Rak piersi zapalny – Patofizjologia i mechanizm

Rak piersi zapalny
Patofizjologia i mechanizm

Zapalny rak piersi (IBC) to rzadka, ale wysoce agresywna forma miejscowo zaawansowanego raka piersi, stanowiąca 1-5% wszystkich przypadków, lecz odpowiadająca za 7-10% zgonów z powodu raka piersi w USA. Charakteryzuje się szybkim przebiegiem i złym rokowaniem, z medianą przeżycia poniżej 4 lat mimo leczenia wielokierunkowego. Patognomonicznym objawem jest obecność licznych zatorów nowotworowych w naczyniach limfatycznych skóry piersi, co prowadzi do obrzęku, zaczerwienienia i charakterystycznego wyglądu „skórki pomarańczowej” obejmującego co najmniej 1/3 powierzchni skóry piersi. IBC rzadko tworzy wyczuwalny guz, co utrudnia diagnostykę. W patogenezie kluczową rolę odgrywa mikrośrodowisko guza bogate w makrofagi typu M2 (TAMs) i limfocyty, które wspierają proliferację komórek nowotworowych, angiogenezę oraz immunosupresję. Komórki IBC wykazują nadekspresję E-kadheryny, co sprzyja tworzeniu embolizatów nowotworowych i pasywnemu rozprzestrzenianiu się przerzutów, a także aktywację szlaków NF-κB, JAK/STAT i COX-2, które nasilają agresywność guza.

Definicja i charakterystyka zapalnego raka piersi
Patofizjologia zapalnego raka piersi

Rola mikroklimatu guza
Mechanizm szerzenia się nowotworu

Szlaki molekularne i genetyczne w zapalnym raku piersi

Zmiany molekularne
Zmiany genetyczne

Charakterystyka histopatologiczna zapalnego raka piersi

Cechy molekularne guza

Mechanizmy oporności na leczenie w zapalnym raku piersi
Podsumowanie mechanizmów patogenezy zapalnego raka piersi

Kolejne rozdziały

Definicja i charakterystyka zapalnego raka piersi

Zapalny rak piersi (ang. inflammatory breast cancer, IBC) to rzadka i wysoce agresywna postać miejscowo zaawansowanego raka piersi, stanowiąca około 1-5% wszystkich przypadków raka piersi, ale odpowiadająca za około 7-10% zgonów związanych z rakiem piersi w Stanach Zjednoczonych¹². Mimo swojej niskiej częstości występowania, IBC charakteryzuje się wyjątkowo złym rokowaniem i szybkim przebiegiem – mediana przeżycia całkowitego wynosi mniej niż 4 lata nawet przy zastosowaniu wielokierunkowego leczenia³.

Cechą patognomoniczną dla IBC jest obecność licznych zatorów nowotworowych w naczyniach limfatycznych skóry brodawkowej i siateczkowatej pokrywającej gruczoł piersiowy⁴⁵. Ważną cechą kliniczną jest gwałtowne pojawienie się objawów, które rozwijają się w ciągu kilku tygodni do 6 miesięcy⁶. Charakterystycznymi objawami są: zaczerwienienie, obrzęk (często o wyglądzie „skórki pomarańczowej”), ucieplenie i powiększenie piersi, które obejmują co najmniej 1/3 powierzchni skóry piersi⁷⁸.

W odróżnieniu od innych typów raka piersi, IBC rzadko tworzy wyczuwalny guz, co znacznie utrudnia diagnostykę⁹¹⁰. Zmiany skórne charakterystyczne dla IBC są spowodowane nie przez naciek komórek zapalnych, lecz przez obrzęk limfatyczny wywołany obecnością zatorów nowotworowych w naczyniach limfatycznych skóry¹¹.

Patofizjologia zapalnego raka piersi

Patogeneza zapalnego raka piersi jest złożona i obejmuje wiele procesów komórkowych i molekularnych. W przeciwieństwie do swojej nazwy, IBC wytwarza niewielkie ilości większości cytokin zapalnych, takich jak interleukina-12, interleukina-1 i interferon gamma¹². Mimo braku klasycznej odpowiedzi zapalnej, IBC charakteryzuje się wysokim potencjałem angiogennym i angioinwazyjnym¹³¹⁴.

Rola mikroklimatu guza

Patogeneza i ewolucja IBC są silnie uzależnione od mikrośrodowiska guza, które charakteryzuje się obecnością licznych makrofagów/monocytów i limfocytów¹⁵¹⁶. Makrofagi związane z guzem (TAMs) wytwarzają wysokie poziomy mediatorów zapalnych, które promują przeżycie i proliferację komórek nowotworowych oraz antagonizują przeciwnowotworową aktywność limfocytów T CD8-dodatnich¹⁷¹⁸.

Mikrośrodowisko guza zawiera zwiększoną liczbę komórek macierzystych gruczołu sutkowego i makrofagów, które mogą wpływać na fenotyp IBC¹⁹. Komórki IBC indukują polaryzację makrofagów w kierunku alternatywnie aktywowanych makrofagów M2 (TAMs), które antagonizują przeciwnowotworową aktywność limfocytów T CD8+, wspierają przeżycie i proliferację komórek nowotworowych oraz przyczyniają się do procesu przerzutowania i angiogenezy poprzez wytwarzanie mediatorów zapalnych, immunosupresję i pośredniczenie w przebudowie macierzy pozakomórkowej guza²⁰.

Obfitość cytokin i chemokin w mikrośrodowisku guza IBC może być odpowiedzialna za wysoką agresywność tego nowotworu oraz za zwiększenie procesów angiogennych i unikanie nadzoru immunologicznego²¹²².

Mechanizm szerzenia się nowotworu

W zapalnym raku piersi komórki nowotworowe rozwijają się i blokują naczynia limfatyczne w skórze piersi, co powoduje, że pierś wygląda na zaczerwienioną, obrzękniętą i zaognioną²³²⁴. Komórki nowotworowe odrywają się od miejsca, w którym zaczęły rosnąć, i przemieszczają do naczyń limfatycznych w skórze. Tam namnażają się, zatykając naczynia, co prowadzi do zmiany koloru skóry, obrzęku i powstawania charakterystycznych wgłębień w skórze²⁵.

IBC wykazuje unikalny wzorzec rozprzestrzeniania się poprzez tworzenie skupisk komórek (embolizatów), które szybko rozprzestrzeniają się w formie ciągłej inwazji znanej jako przerzuty pasywne²⁶²⁷. W IBC E-kadheryna jest nadekspresjonowana i wspiera tworzenie embolizatów guza poprzez promowanie interakcji między komórkami nowotworowymi, zamiast ich przylegania do podścieliska²⁸.

Zasugerowano, że zatykanie naczyń limfatycznych odpowiada za wysoki potencjał przerzutowy IBC²⁹. Ta blokada prowadzi do obrzęku limfatycznego, który powoduje charakterystyczny wygląd skóry „peau d’orange”³⁰.

Szlaki molekularne i genetyczne w zapalnym raku piersi

Z patogenezą i agresywnym fenotypem IBC związanych jest wiele szlaków molekularnych i zmian genetycznych, które mogą wyjaśniać jego wyjątkową biologię i odpowiedź na leczenie.

Zmiany molekularne

W IBC opisano liczne zmiany molekularne, takie jak mutacje genów ERBB2, KRAS, BRAF, EGFR, PIK3CA, PTEN, AKT1 i AKT3, które mogą sugerować stratyfikację terapeutyczną pacjentów z IBC przy zastosowaniu kombinacji różnych terapii celowanych biologicznie³¹³².

Z regulacją procesów zapalnych w IBC związane są różne szlaki molekularne³³³⁴:

Wiele genów docelowych NF-κB jest nadekspresjonowanych w ER-ujemnym IBC w porównaniu z ER-ujemnym rakiem nie-IBC³⁵³⁶
Cytokiny zapalne IL-6 i IL-8, najlepiej scharakteryzowane geny docelowe NF-κB, są produkowane i wydzielane na wysokim poziomie w IBC³⁷³⁸
Enzymy cyklooksygenazy (COX), w szczególności COX-2, indukowane w odpowiedzi na bodźce prozapalne, są nadekspresjonowane w IBC w porównaniu z guzami nie-IBC, co znajduje odzwierciedlenie w większej obfitości prostaglandyny E2 w pierwotnych i przerzutowych guzach IBC³⁹⁴⁰

Aktywacja szlaków JAK/STAT, NF-κB i COX-2 odgrywa istotną rolę w progresji IBC⁴¹. Aktywacja NF-κB odgrywa główną rolę w promowaniu nietypowego fenotypu i agresywności IBC⁴².

Zmiany genetyczne

Co najmniej połowa IBC wykazuje utratę heterozygotyczności. Najczęściej utracone allele to 17q, 13q, 11q, 8p, 6p i 3p⁴³⁴⁴. Akumulacja białka p53 lub mutacja w genie supresorowym p53 została stwierdzona w 20% do 50% raków piersi u ludzi. Nieprawidłowości te są często obserwowane w dziedzicznych zespołach raka piersi, takich jak rodzinny rak piersi i jajnika (np. zespół Li-Fraumeni)⁴⁵⁴⁶.

GTPaza RhoC jest nadekspresjonowana w 90% guzów IBC w porównaniu z 38% guzów nie-IBC. RhoC-GTPaza odgrywa kluczową rolę w zachowaniu przerzutowym IBC poprzez zwiększenie wszystkich aspektów procesów przerzutowych, takich jak ruchliwość i inwazja komórek, formowanie cytoszkieletu i adhezja komórek⁴⁷.

Zaburzenie regulacji WISP3 może powodować zwiększenie ekspresji RhoC GTPazy i zwiększać agresywność IBC⁴⁸. Rodzina RhoC GTPaz jest potężnym regulatorem zarówno metabolizmu glutaminy, jak i N-acetyloasparaginanu w komórkach IBC SUM149, ujawniając nową rolę w regulacji metabolizmu komórek nowotworowych⁴⁹.

Nadekspresja czynnika inicjującego translację eIF4GI w większości przypadków IBC przeprogramowuje maszynerię syntezy białka, zwiększając translację mRNA z wewnętrznymi miejscami wejścia rybosomu (IRESs), które promują przeżycie komórek nowotworowych IBC i tworzenie zatorów nowotworowych⁵⁰⁵¹.

Charakterystyka histopatologiczna zapalnego raka piersi

Klasycznym histologicznym znaleziskiem w zapalnym raku piersi w biopsji zajętej skóry jest inwazja limfatyczna skóry przez komórki nowotworowe⁵²⁵³. Te same złośliwe komórki z zatorów nowotworowych są odpowiedzialne za chorobę miejscową i przerzutową⁵⁴.

IBC nie jest uważany za specyficzny podtyp histologiczny raka piersi i nie ma specyficznych diagnostycznych kryteriów patologicznych⁵⁵. Większość IBC to inwazyjne raki przewodowe o wysokim stopniu złośliwości histologicznej⁵⁶⁵⁷.

Zatykanie naczyń limfatycznych przez komórki nowotworowe jest zjawiskiem charakterystycznym dla IBC, ale nie jest bezwzględnie wymagane do postawienia diagnozy⁵⁸. Chociaż zajęcie limfatyczne skóry potwierdza diagnozę zapalnego raka piersi, nie jest ono ani konieczne, ani wystarczające przy braku klasycznych objawów klinicznych⁵⁹.

Komórki tworzące zatykające naczynia limfatyczne zatoki są zwykle wysokiego stopnia złośliwości z dużym jądrem⁶⁰. Nadekspresja E-kadheryny jest uważana za znak rozpoznawczy guza inwazyjnego i zatorów limfonaczyniowych u pacjentów z zapalnym rakiem piersi⁶¹.

Cechy molekularne guza

Większość przypadków IBC jest ujemna pod względem receptorów hormonalnych⁶²⁶³. Raki piersi z ujemnym statusem receptorów estrogenowych (ER) i receptorów progesteronowych (PgR) są generalnie związane z krótszym przeżyciem wolnym od choroby i gorszym rokowaniem niż guzy receptor-dodatnie⁶⁴⁶⁵.

IBC charakteryzuje się również wysokimi wskaźnikami proliferacji i nadekspresją receptora ludzkiego naskórkowego czynnika wzrostu 2 (HER2)⁶⁶⁶⁷. Około 17% do 30% przypadków IBC jest potrójnie ujemnych, a 18% do 44% wykazuje nadekspresję receptora ludzkiego naskórkowego czynnika wzrostu 2 (HER2)⁶⁸.

Dodatkowo IBC charakteryzuje się:

Nadekspresją p53
Wysoką ekspresją E-kadheryny
Wysokim indeksem proliferacji MIB1
Cytoplazmatyczną nadekspresją MUC-1
Wyraźną angiogenezą spowodowaną nadekspresją genów związanych z angiogenezą⁶⁹

Szlak receptora naskórkowego czynnika wzrostu (EGFR) jest powszechnie aktywny w zapalnym raku piersi, co ma kliniczne znaczenie, ponieważ terapia celowana na EGFR może być skuteczna w IBC⁷⁰.

Mechanizmy oporności na leczenie w zapalnym raku piersi

Zapalny rak piersi często charakteryzuje się opornością na standardowe leczenie, co przyczynia się do jego złego rokowania. Zidentyfikowano kilka mechanizmów leżących u podstaw tej oporności.

Badacze z Roswell Park Cancer Institute (RPCI) zidentyfikowali mechanizm komórek raka piersi, który prowadzi do oporności na chemioterapię w zapalnym raku piersi⁷¹. Te przedkliniczne odkrycia dostarczają dowodów na potencjalne podejście terapeutyczne, które przywróci wrażliwość na chemioterapię i poprawi leczenie guzów zapalnego raka piersi⁷².

Wykazano, że bisfenol A (BPA) wspomaga przeżycie komórek zapalnego raka piersi, ujawniając potencjalny mechanizm rozwoju choroby⁷³⁷⁴. BPA zwiększał sygnalizację poprzez receptory komunikujące się ze szlakiem MAPK, a obecność BPA może prowadzić do oporności na leki przeciwnowotworowe ukierunkowane na ten szlak⁷⁵⁷⁶.

Istotną cechą IBC jest obecność licznych spójnych skupisk w naczyniach limfatycznych i ich oporność na wiele terapii⁷⁷. Skupiska te mają akumulację E-kadheryny z powodu jej zmienionego transportu, co może wspomagać bierne rozprzestrzenianie się tych embolizatów⁷⁸.

Nadmierna ekspresja czynnika inicjującego translację eIF4GI prowadzi do rozwoju IBC poprzez zwiększoną translację mRNA zawierających wewnętrzne miejsca wejścia rybosomu (IRES), które promują przeżycie komórek guza IBC i tworzenie zatorów nowotworowych⁷⁹.

W oparciu o analizę wcześniej opracowanych modeli terapeutycznie opornego IBC, badacze postawili hipotezę, że dysregulacja apoptotyczna i mechanizmy adaptacji redoks są kluczowe dla fenotypu oporności na leki w komórkach IBC, a ukierunkowanie na te mechanizmy może przezwyciężyć oporność terapeutyczną⁸⁰.

Podsumowanie mechanizmów patogenezy zapalnego raka piersi

Patogeneza zapalnego raka piersi jest złożonym procesem obejmującym wiele czynników molekularnych, komórkowych i mikrośrodowiskowych. Kluczowe mechanizmy obejmują:

Zatykanie naczyń limfatycznych skóry przez komórki nowotworowe, prowadzące do charakterystycznego wyglądu skóry „peau d’orange”⁸¹
Nadekspresję E-kadheryny, która promuje tworzenie skupisk komórek nowotworowych zamiast ich przylegania do podścieliska⁸²
Aktywację szlaków sygnałowych, takich jak NF-κB, JAK/STAT i COX-2, które promują procesy zapalne i agresywny fenotyp IBC⁸³
Bogate mikrośrodowisko guza z licznymi makrofagami i cytokinami, które przyczyniają się do angiogenezy i inwazyjności⁸⁴
Nadekspresję czynnika eIF4GI, który przeprogramowuje maszynerię syntezy białka, zwiększając translację określonych mRNA⁸⁵
Dysregulację genów RhoC GTPazy i WISP3, które zwiększają potencjał przerzutowy guza⁸⁶

Zrozumienie tych mechanizmów molekularnych może prowadzić do identyfikacji nowych celów terapeutycznych i rozwoju skuteczniejszych strategii leczenia zapalnego raka piersi⁸⁷. Identyfikacja znaczących zmian molekularnych w IBC pomogłaby w diagnostyce, przewidywaniu odpowiedzi na leczenie i opracowaniu nowych celów terapeutycznych⁸⁸.

Ostatecznie, łączne dowody mocno wskazują, że różnorodne komórki, bioaktywne cząsteczki i powiązane z nimi szlaki transdukcji sygnału w mikrośrodowisku guza IBC komunikują się i oddziałują ze sobą, tworząc skomplikowaną sieć, przypuszczalnie zapośredniczoną przez różne molekularne i komórkowe mechanizmy biologiczne kontrolujące powstawanie, rozwój i progresję IBC⁸⁹.

Kolejne rozdziały

Zapraszamy do dalszego czytania naszego leksykonu.

Wybierz kolejny rozdział z menu poniżej, aby otworzyć nową podstronę kompedium wiedzy i uzyskać szczegółowe informację o leku, substancji lub chorobie.

Materiały źródłowe

#1 Inflammatory Breast Cancer | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/111445
Inflammatory breast cancer (IBC) is a rare subtype of locally advanced breast cancer according to the TNM breast cancer staging system. It accounts for about 2% to 4% of breast cancer cases in the United States. Despite its low incidence, IBC contributes to 7% of breast cancer caused mortality. It is clinically characterized by diffuse induration of the skin with an erysipeloid appearance, and there is usually no underlying mass. […] A high body mass index is an independent risk factor for inflammatory breast cancer. Possible risk factors that need further investigation are viral infections and chronic inflammation, younger age at first live birth, smoking, and breastfeeding. […] Inflammatory breast cancer is the most aggressive entity of breast cancer. The median overall survival among women is less than 4 years, even with multimodality treatment options. However, increased survival in recent years has been noted with the improvement of chemotherapeutic management.
#2 Inflammatory Breast Cancer: A Literature Review | Mamouch | World Journal of Oncology
https://www.wjon.org/index.php/wjon/article/view/1161/893
The multidisciplinary management of inflammatory breast cancer (IBC), which is the most aggressive form of breast cancer due to its rapid proliferation, has changed over the past three decades thanks to advances in medical treatments that represent the basis of treatment, without eliminating the use of locoregional treatments including surgery and radiotherapy in the localized stages. The molecular profile determination of IBC allows the orientation towards new targeted therapeutic strategies with an impact on survival. […] Inflammatory breast cancer (IBC) is a rare and aggressive clinicopathological entity of breast cancer. It represents 1% to 6% of all cases of breast cancer. […] IBC is also characterized by rapid progression and higher metastatic potential. The 5-year survival of patients with this cancer type is low compared to other breast cancers. However, the combinations of neoadjuvant chemotherapy, surgery and radiotherapy led to an improvement in prognosis. Optimal management of IBC requires coordination between oncologists, surgeons and radiation therapists.
#3 Inflammatory Breast Cancer – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK564324/
Inflammatory breast cancer (IBC) is a rare subtype of locally advanced breast cancer according to the TNM breast cancer staging system. Despite its low incidence, IBC contributes to 7% of breast cancer caused mortality. […] Inflammatory breast cancer is the most aggressive entity of breast cancer. The median overall survival among women is less than 4 years, even with multimodality treatment options. However, increased survival in recent years has been noted with the improvement of chemotherapeutic management. […] An angioinvasive nature is intrinsic to primary IBC. Normal experimental studies have evaluated the role of hormone receptor status and genetic changes, the p53 tumor suppressor gene, cytokines, and other genetic determinants. […] The majority of IBCs are hormone receptor-negative. Breast cancers with negative estrogen receptors (ER) and progesterone receptors (PGR) are generally associated with shorter disease-free survival and poor prognosis than receptor-positive tumors. IBCs also have high proliferative rates and also overexpress human epidermal growth factor receptor 2 (HER 2). These molecular markers may identify patients who have a worse prognosis.
#4 Pathological and molecular characteristics of inflammatory breast cancer
https://pmc.ncbi.nlm.nih.gov/articles/PMC8798351/
Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer characterized by the presence of many dermal tumor emboli in the papillary and reticular dermis of the skin overlying the breast. […] The pathogenesis and evolution of IBC are strongly dependent upon tumor microenvironment, characterized by several macrophages/monocytes and lymphocytes. […] In addition, several molecular alterations are described in this tumor, such as mutations of ERBB2, KRAS, BRAF, EGFR, PIK3CA, PTEN, AKT1, and AKT3 genes that could suggest a therapeutic stratification of IBC patients with the combination of different biological target therapies. […] Many experimental pieces of evidence have suggested that the etiology and pathogenesis of IBC may be closely related to inflammation and changes in the tumor microenvironment.
#5 Pathological and molecular characteristics of inflammatory breast cancer – Di Bonito – Translational Cancer Research
https://tcr.amegroups.org/article/view/28003/22777
Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer characterized by the presence of many dermal tumor emboli in the papillary and reticular dermis of the skin overlying the breast. […] The pathogenesis and evolution of IBC are strongly dependent upon tumor microenvironment, characterized by several macrophages/monocytes and lymphocytes. […] Several molecular alterations are described in this tumor, such as mutations of ERBB2, KRAS, BRAF, EGFR, PIK3CA, PTEN, AKT1, and AKT3 genes that could suggest a therapeutic stratification of IBC patients with the combination of different biological target therapies. […] Many experimental pieces of evidence have suggested that the etiology and pathogenesis of IBC may be closely related to inflammation and changes in the tumor microenvironment.
#6 Inflammatory breast cancer: Pathology and molecular pathogenesis – UpToDate
https://www.uptodate.com/contents/inflammatory-breast-cancer-pathology-and-molecular-pathogenesis
Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer. De novo IBC refers to primary disease. These patients typically present with pain and a tender, firm, and enlarged breast. The skin over the breast is reddened, warm, and thickened, with a „peau d’orange” (orange skin) appearance. In comparison, the inflammatory recurrence of a noninflammatory breast cancer is called secondary disease. It usually develops on the chest wall at the site of previous mastectomy, but can also occur rarely as a distant cutaneous recurrence. The signs and symptoms of IBC arise rapidly compared to non IBC, typically within weeks to six months. […] The 2017 American Joint Committee on Cancer and the International Union for Cancer Control (AJCC-UICC) Tumor, Node, Metastasis (TNM) breast cancer staging system defines IBC as a clinical-pathologic entity characterized by diffuse erythema and edema (peau d’orange) involving a third or more of the skin of the breast. These „inflammatory” skin changes are not due to infiltration of inflammatory cells but rather to lymphedema caused by tumor emboli within the dermal lymphatics. However, the diagnosis is based upon the clinical presentation. Although dermal lymphatic involvement supports the diagnosis of inflammatory breast cancer, it is neither necessary nor sufficient in the absence of classical clinical findings.
#7 Inflammatory breast cancer: Pathology and molecular pathogenesis – UpToDate
https://www.uptodate.com/contents/inflammatory-breast-cancer-pathology-and-molecular-pathogenesis
Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer. De novo IBC refers to primary disease. These patients typically present with pain and a tender, firm, and enlarged breast. The skin over the breast is reddened, warm, and thickened, with a „peau d’orange” (orange skin) appearance. In comparison, the inflammatory recurrence of a noninflammatory breast cancer is called secondary disease. It usually develops on the chest wall at the site of previous mastectomy, but can also occur rarely as a distant cutaneous recurrence. The signs and symptoms of IBC arise rapidly compared to non IBC, typically within weeks to six months. […] The 2017 American Joint Committee on Cancer and the International Union for Cancer Control (AJCC-UICC) Tumor, Node, Metastasis (TNM) breast cancer staging system defines IBC as a clinical-pathologic entity characterized by diffuse erythema and edema (peau d’orange) involving a third or more of the skin of the breast. These „inflammatory” skin changes are not due to infiltration of inflammatory cells but rather to lymphedema caused by tumor emboli within the dermal lymphatics. However, the diagnosis is based upon the clinical presentation. Although dermal lymphatic involvement supports the diagnosis of inflammatory breast cancer, it is neither necessary nor sufficient in the absence of classical clinical findings.
#8 Inflammatory Breast Carcinoma Presenting with Two Different Patterns of Cutaneous Metastases: Carcinoma Telangiectaticum and Carcinoma Erysipeloides | JCAD – The Journal of Clinical and Aesthetic Dermatology
https://jcadonline.com/inflammatory-breast-carcinoma-presenting-with-two-different-patterns-of-cutaneous-metastases-carcinoma-telangiectaticum-and-carcinoma-erysipeloides/
Inflammatory breast cancer (IBC) is an aggressive and infiltrative malignancy that most frequently presents with a myriad of nonspecific symptoms and signs of inflammation. The classic peu dorange presentation represents edema and erythema of the breast skin. It is a rare presentation of breast malignancy with an incidence of up to six percent in the United States population. The international expert panel on inflammatory breast cancer has advised the following criteria supporting a diagnosis of IBC: rapid onset (less than or equal to three months) of edema, erythema (greater than or equal to one-third of the breast), warmth, presence of a palpable mass or adenopathy, nipple retraction/crusting/flattening, core needle biopsy-proven IBC, previously diagnosed mastitis unresponsive to a seven-day course of antibiotics, overall duration less than six months, and skin punch biopsy revealing intralymphatic tumor emboli. Diagnostic imaging, such as ultrasonography, mammography, and magnetic resonance imaging, are often unsuccessful in detecting breast masses; however, these modalities may aid in localizing areas of concern and may identify metastases since up to 30 percent of incidental cases of IBC have been shown to have distant metastases. In fact, a retrospective review of IBC-confirmed patients concluded that a breast mass was visible on mammography in only 15 percent of patients. Other nonspecific findings, however, such as distortion of trabeculae, were very common. IBC clinically mimics a benign bacterial infection of the breast and/or skin, such as mastitis, cellulitis, or abscess. No evidence of breast masses or lumps are usually detected on physical examination. Diagnosing IBC as infection and treatment with antibiotics represents the leading cause of misdiagnosis and delay of treatment. The authors report a rare case of IBC presenting with two types of cutaneous metastases: lymphangioma circumscriptum-like (carcinoma telangiectaticum) and erysipelas-like lesions (carcinoma erysipeloides).
#9 Inflammatory breast cancer – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/inflammatory-breast-cancer/symptoms-causes/syc-20355413
Inflammatory breast cancer happens when a growth of cells forms in the breast tissue. The cells break away from where they started to grow and travel to the lymphatic vessels in the skin. The cells grow to clog the vessels. The blockage in the lymphatic vessels causes skin color changes, swelling and dimpled skin. This skin is a classic sign of inflammatory breast cancer. […] Inflammatory breast cancer is a form of breast cancer that causes breast swelling and skin changes. […] Inflammatory breast cancer is considered a locally advanced cancer. When a cancer is locally advanced, that means it has spread from where it started to nearby tissue and possibly to nearby lymph nodes. […] Inflammatory breast cancer can easily be confused with a breast infection, which is a much more common cause of breast swelling and skin changes.
#10 Inflammatory Breast Cancer: Signs, Symptoms, Causes & Treatment
https://my.clevelandclinic.org/health/diseases/17925-inflammatory-breast-cancer
Inflammatory breast cancer (IBC) is a rare type of cancer that spreads quickly. Unlike most breast cancers, IBC doesn’t usually cause lumps in breast tissue. Instead, it appears as a rash, creating skin texture on the affected breast similar to an orange peel. IBC causes pain, redness, swelling and dimpling on the affected breast. […] IBC results when cancer cells block lymph vessels the small, hollow tubes that allow lymph fluid to drain out of your breast. The blockage leads to inflammation, causing symptoms that make it easy to mistake IBC for an infection. […] Most inflammatory breast cancer is considered invasive ductal carcinoma. Ductal carcinoma is cancer that forms from cells lining your milk ducts. An invasive ductal carcinoma is cancer that spreads beyond your milk ducts, invading healthy tissue. Researchers don’t know what causes these cells to become malignant (cancerous).
#11 Inflammatory breast cancer: Pathology and molecular pathogenesis – UpToDate
https://www.uptodate.com/contents/inflammatory-breast-cancer-pathology-and-molecular-pathogenesis
Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer. De novo IBC refers to primary disease. These patients typically present with pain and a tender, firm, and enlarged breast. The skin over the breast is reddened, warm, and thickened, with a „peau d’orange” (orange skin) appearance. In comparison, the inflammatory recurrence of a noninflammatory breast cancer is called secondary disease. It usually develops on the chest wall at the site of previous mastectomy, but can also occur rarely as a distant cutaneous recurrence. The signs and symptoms of IBC arise rapidly compared to non IBC, typically within weeks to six months. […] The 2017 American Joint Committee on Cancer and the International Union for Cancer Control (AJCC-UICC) Tumor, Node, Metastasis (TNM) breast cancer staging system defines IBC as a clinical-pathologic entity characterized by diffuse erythema and edema (peau d’orange) involving a third or more of the skin of the breast. These „inflammatory” skin changes are not due to infiltration of inflammatory cells but rather to lymphedema caused by tumor emboli within the dermal lymphatics. However, the diagnosis is based upon the clinical presentation. Although dermal lymphatic involvement supports the diagnosis of inflammatory breast cancer, it is neither necessary nor sufficient in the absence of classical clinical findings.
#12 Inflammatory Breast Cancer – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK564324/
At least half of IBCs have a loss of heterozygosity. The most frequent lost alleles are 17 q., 13 q., 11 q., 8P, 6P, and 3P. […] Accumulation of p53 protein or mutation in p53 TSG was reported in 20% to 50% of human breast cancers. These abnormalities are often seen in hereditary breast cancer syndromes like familial breast and ovarian cancers (e.g., Li-Fraumeni syndrome). […] IBC is a misnomer, it produces negligible levels of most inflammatory cytokines such as interleukin-12, interleukin-1, and interferon-gamma. Inflammatory breast cancer tends to be highly vascular because of its angiogenic and angioinvasive potential. […] The classic histologic finding in inflammatory breast cancer on biopsy of the affected skin is dermal lymphatic invasion by tumor cells. The same malignant cells from tumor emboli are responsible for local and metastatic disease. […] Inflammatory breast cancer is associated with very poor prognosis and a high risk of early recurrence. The current evidence suggests that for the same stage of locally advanced breast cancer, inflammatory breast cancer has a poorer prognosis.
#13 POE – Inflammatory Breast Cancer Pathology – MD Anderson Cancer Center
https://streaming.mdanderson.org/transcript/poe-ibc-pathology-krishnamurthy.htm
Overall, inflammatory breast tumors are more angiogenic, lymphangiogenic, and vasculogenic than non-inflammatory breast carcinomas. […] Increased cancer stem cells may have a potential role in creating an aggressive phenotype for inflammatory breast carcinoma. These stem cells are linked to tumor progression through their ability to undergo the process of epithelial – mesenchymal transition, or EMT. […] It is to be recognized that inflammatory breast carcinoma is a distinct entity of breast cancer. The etiology and risk factors of this variant of breast carcinoma is not fully identified.
#14 Inflammatory Breast Cancer – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK564324/
At least half of IBCs have a loss of heterozygosity. The most frequent lost alleles are 17 q., 13 q., 11 q., 8P, 6P, and 3P. […] Accumulation of p53 protein or mutation in p53 TSG was reported in 20% to 50% of human breast cancers. These abnormalities are often seen in hereditary breast cancer syndromes like familial breast and ovarian cancers (e.g., Li-Fraumeni syndrome). […] IBC is a misnomer, it produces negligible levels of most inflammatory cytokines such as interleukin-12, interleukin-1, and interferon-gamma. Inflammatory breast cancer tends to be highly vascular because of its angiogenic and angioinvasive potential. […] The classic histologic finding in inflammatory breast cancer on biopsy of the affected skin is dermal lymphatic invasion by tumor cells. The same malignant cells from tumor emboli are responsible for local and metastatic disease. […] Inflammatory breast cancer is associated with very poor prognosis and a high risk of early recurrence. The current evidence suggests that for the same stage of locally advanced breast cancer, inflammatory breast cancer has a poorer prognosis.
#15 Pathological and molecular characteristics of inflammatory breast cancer
https://pmc.ncbi.nlm.nih.gov/articles/PMC8798351/
Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer characterized by the presence of many dermal tumor emboli in the papillary and reticular dermis of the skin overlying the breast. […] The pathogenesis and evolution of IBC are strongly dependent upon tumor microenvironment, characterized by several macrophages/monocytes and lymphocytes. […] In addition, several molecular alterations are described in this tumor, such as mutations of ERBB2, KRAS, BRAF, EGFR, PIK3CA, PTEN, AKT1, and AKT3 genes that could suggest a therapeutic stratification of IBC patients with the combination of different biological target therapies. […] Many experimental pieces of evidence have suggested that the etiology and pathogenesis of IBC may be closely related to inflammation and changes in the tumor microenvironment.
#16 Pathological and molecular characteristics of inflammatory breast cancer – Di Bonito – Translational Cancer Research
https://tcr.amegroups.org/article/view/28003/22777
Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer characterized by the presence of many dermal tumor emboli in the papillary and reticular dermis of the skin overlying the breast. […] The pathogenesis and evolution of IBC are strongly dependent upon tumor microenvironment, characterized by several macrophages/monocytes and lymphocytes. […] Several molecular alterations are described in this tumor, such as mutations of ERBB2, KRAS, BRAF, EGFR, PIK3CA, PTEN, AKT1, and AKT3 genes that could suggest a therapeutic stratification of IBC patients with the combination of different biological target therapies. […] Many experimental pieces of evidence have suggested that the etiology and pathogenesis of IBC may be closely related to inflammation and changes in the tumor microenvironment.
#17 Pathological and molecular characteristics of inflammatory breast cancer
https://pmc.ncbi.nlm.nih.gov/articles/PMC8798351/
Tumor-associated macrophages (TAMs) produce high levels of inflammatory mediators that promote survival and proliferation of tumor cells and also antagonize the antitumor activity of CD8-positive T cells. […] The abundance of cytokines and chemokines in the IBC tumor microenvironment could be responsible for the high aggressiveness of this tumor and for the increase of angiogenic processes and evasion of immune surveillance. […] A series of different molecular pathways have been associated with the regulation of inflammatory processes in IBC. […] Many NF-B target genes are upregulated in ER-negative IBC compared with ER-negative non-IBC tissues. […] Moreover, the inflammatory cytokines IL-6 and IL-8, the best characterized NF-B target genes, are produced and secreted at high levels within IBC. […] Finally, cyclooxygenase (COX) enzymes, in particular of COX-2, induced in response to proinflammatory stimuli, is overexpressed in IBC compared to non-IBC tumors, and this is also reflected by more abundant prostaglandin E2 in primary and metastatic IBC tumors.
#18 Pathological and molecular characteristics of inflammatory breast cancer – Di Bonito – Translational Cancer Research
https://tcr.amegroups.org/article/view/28003/22777
Tumor-associated macrophages (TAMs) produce high levels of inflammatory mediators that promote survival and proliferation of tumor cells and also antagonize the antitumor activity of CD8-positive T cells. […] The abundance of cytokines and chemokines in the IBC tumor microenvironment could be responsible for the high aggressiveness of this tumor and for the increase of angiogenic processes and evasion of immune surveillance. […] A series of different molecular pathways have been associated with the regulation of inflammatory processes in IBC. […] Many NF-B target genes are upregulated in ER-negative IBC compared with ER-negative non-IBC tissues. […] Moreover, the inflammatory cytokines IL-6 and IL-8, the best characterized NF-B target genes, are produced and secreted at high levels within IBC. […] Finally, cyclooxygenase (COX) enzymes, in particular of COX-2, induced in response to proinflammatory stimuli, is overexpressed in IBC compared to non-IBC tumors, and this is also reflected by more abundant prostaglandin E2 in primary and metastatic IBC tumors.
#19 Biomarkers for Inflammatory Breast Cancer: Diagnostic and Therapeutic | BCTT
https://www.dovepress.com/biomarkers-for-inflammatory-breast-cancer-diagnostic-and-therapeutic-u-peer-reviewed-fulltext-article-BCTT
The tumor microenvironment contains increased mammary stem cells and macrophages, which may influence the phenotype of IBC. […] IBC cells induce the polarisation of macrophages into alternatively activated M2 tumor-associated macrophages (TAMs). TAMs antagonize the antitumor activity of CD8 T-cells, support survival, and proliferation of tumor cells and contribute to metastasis process and angiogenesis by the production of inflammatory mediators, immunosuppression, and by mediating tumor extracellular matrix remodeling. […] The communication between intrinsic and extrinsic components of IBC and the abundance of cytokines and chemokines in the TME strongly contribute to the aggressiveness and high angiogenic potential of this tumor. Critical modes of interaction are cytokine-mediated communication and direct intercellular contact between cancer cells and tumor microenvironment with a variety of pathway crosstalk.
#20 Biomarkers for Inflammatory Breast Cancer: Diagnostic and Therapeutic | BCTT
https://www.dovepress.com/biomarkers-for-inflammatory-breast-cancer-diagnostic-and-therapeutic-u-peer-reviewed-fulltext-article-BCTT
The tumor microenvironment contains increased mammary stem cells and macrophages, which may influence the phenotype of IBC. […] IBC cells induce the polarisation of macrophages into alternatively activated M2 tumor-associated macrophages (TAMs). TAMs antagonize the antitumor activity of CD8 T-cells, support survival, and proliferation of tumor cells and contribute to metastasis process and angiogenesis by the production of inflammatory mediators, immunosuppression, and by mediating tumor extracellular matrix remodeling. […] The communication between intrinsic and extrinsic components of IBC and the abundance of cytokines and chemokines in the TME strongly contribute to the aggressiveness and high angiogenic potential of this tumor. Critical modes of interaction are cytokine-mediated communication and direct intercellular contact between cancer cells and tumor microenvironment with a variety of pathway crosstalk.
#21 Pathological and molecular characteristics of inflammatory breast cancer
https://pmc.ncbi.nlm.nih.gov/articles/PMC8798351/
Tumor-associated macrophages (TAMs) produce high levels of inflammatory mediators that promote survival and proliferation of tumor cells and also antagonize the antitumor activity of CD8-positive T cells. […] The abundance of cytokines and chemokines in the IBC tumor microenvironment could be responsible for the high aggressiveness of this tumor and for the increase of angiogenic processes and evasion of immune surveillance. […] A series of different molecular pathways have been associated with the regulation of inflammatory processes in IBC. […] Many NF-B target genes are upregulated in ER-negative IBC compared with ER-negative non-IBC tissues. […] Moreover, the inflammatory cytokines IL-6 and IL-8, the best characterized NF-B target genes, are produced and secreted at high levels within IBC. […] Finally, cyclooxygenase (COX) enzymes, in particular of COX-2, induced in response to proinflammatory stimuli, is overexpressed in IBC compared to non-IBC tumors, and this is also reflected by more abundant prostaglandin E2 in primary and metastatic IBC tumors.
#22 Pathological and molecular characteristics of inflammatory breast cancer – Di Bonito – Translational Cancer Research
https://tcr.amegroups.org/article/view/28003/html
The abundance of cytokines and chemokines in the IBC tumor microenvironment could be responsible for the high aggressiveness of this tumor and for the increase of angiogenic processes and evasion of immune surveillance. […] A series of different molecular pathways have been associated with the regulation of inflammatory processes in IBC. […] Many NF-B target genes are upregulated in ER-negative IBC compared with ER-negative non-IBC tissues. […] Moreover, the inflammatory cytokines IL-6 and IL-8, the best characterized NF-B target genes, are produced and secreted at high levels within IBC. […] Finally, cyclooxygenase (COX) enzymes, in particular of COX-2, induced in response to proinflammatory stimuli, is overexpressed in IBC compared to non-IBC tumors, and this is also reflected by more abundant prostaglandin E2 in primary and metastatic IBC tumors.
#23 Inflammatory breast cancer – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/inflammatory-breast-cancer/symptoms-causes/syc-20355413
Inflammatory breast cancer happens when a growth of cells forms in the breast tissue. The cells break away from where they started to grow and travel to the lymphatic vessels in the skin. The cells grow to clog the vessels. The blockage in the lymphatic vessels causes skin color changes, swelling and dimpled skin. This skin is a classic sign of inflammatory breast cancer. […] Inflammatory breast cancer is a form of breast cancer that causes breast swelling and skin changes. […] Inflammatory breast cancer is considered a locally advanced cancer. When a cancer is locally advanced, that means it has spread from where it started to nearby tissue and possibly to nearby lymph nodes. […] Inflammatory breast cancer can easily be confused with a breast infection, which is a much more common cause of breast swelling and skin changes.
#24 Inflammatory breast cancer – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/inflammatory-breast-cancer/symptoms-causes/syc-20355413
Inflammatory breast cancer doesn’t commonly form a lump, as occurs with other forms of breast cancer. Instead, signs and symptoms of inflammatory breast cancer include: Fast change in the appearance of one breast, over the course of several weeks. […] Inflammatory breast cancer happens when cells in the breast develop changes in their DNA. A cell’s DNA holds the instructions that tell the cell what to do. In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions tell the cells to die at a set time. In cancer cells, the DNA changes give different instructions. The changes tell the cancer cells to make many more cells quickly. Cancer cells can keep living when healthy cells would die. This causes too many cells. […] In inflammatory breast cancer, the cancer cells break away from where they started. They travel to the lymphatic vessels in the breast skin. The cells grow to clog the vessels. The blockage in the lymphatic vessels causes skin color changes, swelling and dimpled skin. This skin is a classic sign of inflammatory breast cancer.
#25 Inflammatory breast cancer – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/inflammatory-breast-cancer/symptoms-causes/syc-20355413
Inflammatory breast cancer happens when a growth of cells forms in the breast tissue. The cells break away from where they started to grow and travel to the lymphatic vessels in the skin. The cells grow to clog the vessels. The blockage in the lymphatic vessels causes skin color changes, swelling and dimpled skin. This skin is a classic sign of inflammatory breast cancer. […] Inflammatory breast cancer is a form of breast cancer that causes breast swelling and skin changes. […] Inflammatory breast cancer is considered a locally advanced cancer. When a cancer is locally advanced, that means it has spread from where it started to nearby tissue and possibly to nearby lymph nodes. […] Inflammatory breast cancer can easily be confused with a breast infection, which is a much more common cause of breast swelling and skin changes.
#26 Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer | Nature Cell Biology
https://www.nature.com/articles/ncb1900
Inflammatory breast cancer (IBC) is the most lethal form of primary breast cancer. IBC lethality derives from generation of tumour emboli, which are non-adherent cell clusters that rapidly spread by a form of continuous invasion known as passive metastasis. In IBC, E-cadherin is overexpressed and supports formation of tumour emboli by promoting tumour cell interactions rather than adherence to stroma. We show that the unique pathogenic properties of IBC result in part from overexpression of the translation initiation factor eIF4GI in most IBCs. eIF4GI reprograms the protein synthetic machinery for increased translation of mRNAs with internal ribosome entry sites (IRESs) that promote IBC tumour cell survival and formation of tumour emboli. Overexpression of eIF4GI promotes formation of IBC tumour emboli by enhancing translation of IRES-containing p120 mRNAs. […] These findings provide a new understanding of translational control in the development of advanced breast cancer.
#27 Inflammatory breast cancer: a model for investigating cluster-based dissemination | npj Breast Cancer
https://www.nature.com/articles/s41523-017-0023-9
Metastases claim more than 90% of cancer-related patient deaths and are usually seeded by a subset of circulating tumor cells shed off from the primary tumor. […] In this review, we highlight recent insights into molecular mechanisms that can enable the formation of these clusters(a) hybrid epithelial/mesenchymal phenotype of cells that couples their ability to migrate and adhere, and (b) intercellular communication that can spatially coordinate the cluster formation and provide survival signals to cancer cells. […] Finally, we discuss the highly aggressive Inflammatory Breast Cancer as an example of a carcinoma that can metastasize via clusters and corroborates the proposed molecular mechanisms. […] In this review, we highlight recent work that offers novel insights into mechanisms that can contribute to cluster formation and ascribe heightened metastatic potential to them. We then focus on a highly aggressive diseaseInflammatory Breast Cancer (IBC)that forms clustered lymphatic emboli as a major means of metastasis and note several lines of evidence suggesting distant metastases also occur via clusters.
#28 Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer | Nature Cell Biology
https://www.nature.com/articles/ncb1900
Inflammatory breast cancer (IBC) is the most lethal form of primary breast cancer. IBC lethality derives from generation of tumour emboli, which are non-adherent cell clusters that rapidly spread by a form of continuous invasion known as passive metastasis. In IBC, E-cadherin is overexpressed and supports formation of tumour emboli by promoting tumour cell interactions rather than adherence to stroma. We show that the unique pathogenic properties of IBC result in part from overexpression of the translation initiation factor eIF4GI in most IBCs. eIF4GI reprograms the protein synthetic machinery for increased translation of mRNAs with internal ribosome entry sites (IRESs) that promote IBC tumour cell survival and formation of tumour emboli. Overexpression of eIF4GI promotes formation of IBC tumour emboli by enhancing translation of IRES-containing p120 mRNAs. […] These findings provide a new understanding of translational control in the development of advanced breast cancer.
#29 Inflammatory Breast Cancer â Does the Confirmation of Dermal Lymphatic Invasion Predict the Worst Outcome? | touchONCOLOGY
https://touchoncology.com/breast-cancer/journal-articles/inflammatory-breast-cancer-does-the-confirmation-of-dermal-lymphatic-invasion-predict-the-worst-outcome/
It could be speculated that prognosis of patients with the above-mentioned three types of IBC differs, and that a combination of DLI with a full inflammatory component might be the worst. […] In fact, it has been proposed that DLI is responsible for the high metastatic potential of IBC. […] The main conclusion is that DLI and IBC are independent predictors of poor outcome, but also that patients with both characteristics have a worse prognosis with increased risk for local and distant relapse.
#30 Inflammatory Breast Cancer: Causes, Symptoms, Diagnosis & Treatment
https://www.ganeshdiagnostic.com/blog/inflammatory-breast-cancer-causes-symptoms-diagnosis-and-treatment
Inflammatory breast cancer (IBC) is an occasional and assertive variety of breast cancer that accounts for about 1-5% of all breast cancer cases. […] The phrase „inflammatory” is introduced as it regularly submits signs of inflammation, such as redness, warmth, and swelling of the breast. […] These signs are precipitated by most cancer cells that block the lymphatic vessels in the pores and skin of the breast, mainly to a buildup of fluid and an attribute look recognized as „peau d’orange” (orange peel). […] IBC additionally tends to be extra aggressive than different kinds of breast cancers and is regularly recognized at a later stage. […] The pathogenesis of inflammatory breast cancers (IBC) is complicated and includes a couple of mobile and molecular processes. […] One key function of IBC is its inflammatory nature. Inflammation is a regular response to tissue harm or infection; however, persistent irritation can make contributions to the improvement and development of cancer.
#31 Pathological and molecular characteristics of inflammatory breast cancer
https://pmc.ncbi.nlm.nih.gov/articles/PMC8798351/
Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer characterized by the presence of many dermal tumor emboli in the papillary and reticular dermis of the skin overlying the breast. […] The pathogenesis and evolution of IBC are strongly dependent upon tumor microenvironment, characterized by several macrophages/monocytes and lymphocytes. […] In addition, several molecular alterations are described in this tumor, such as mutations of ERBB2, KRAS, BRAF, EGFR, PIK3CA, PTEN, AKT1, and AKT3 genes that could suggest a therapeutic stratification of IBC patients with the combination of different biological target therapies. […] Many experimental pieces of evidence have suggested that the etiology and pathogenesis of IBC may be closely related to inflammation and changes in the tumor microenvironment.
#32 Pathological and molecular characteristics of inflammatory breast cancer – Di Bonito – Translational Cancer Research
https://tcr.amegroups.org/article/view/28003/html
Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer characterized by the presence of many dermal tumor emboli in the papillary and reticular dermis of the skin overlying the breast. […] The pathogenesis and evolution of IBC are strongly dependent upon tumor microenvironment, characterized by several macrophages/monocytes and lymphocytes. […] In addition, several molecular alterations are described in this tumor, such as mutations of ERBB2, KRAS, BRAF, EGFR, PIK3CA, PTEN, AKT1, and AKT3 genes that could suggest a therapeutic stratification of IBC patients with the combination of different biological target therapies. […] Many experimental pieces of evidence have suggested that the etiology and pathogenesis of IBC may be closely related to inflammation and changes in the tumor microenvironment.
#33 Pathological and molecular characteristics of inflammatory breast cancer
https://pmc.ncbi.nlm.nih.gov/articles/PMC8798351/
Tumor-associated macrophages (TAMs) produce high levels of inflammatory mediators that promote survival and proliferation of tumor cells and also antagonize the antitumor activity of CD8-positive T cells. […] The abundance of cytokines and chemokines in the IBC tumor microenvironment could be responsible for the high aggressiveness of this tumor and for the increase of angiogenic processes and evasion of immune surveillance. […] A series of different molecular pathways have been associated with the regulation of inflammatory processes in IBC. […] Many NF-B target genes are upregulated in ER-negative IBC compared with ER-negative non-IBC tissues. […] Moreover, the inflammatory cytokines IL-6 and IL-8, the best characterized NF-B target genes, are produced and secreted at high levels within IBC. […] Finally, cyclooxygenase (COX) enzymes, in particular of COX-2, induced in response to proinflammatory stimuli, is overexpressed in IBC compared to non-IBC tumors, and this is also reflected by more abundant prostaglandin E2 in primary and metastatic IBC tumors.
#34 Pathological and molecular characteristics of inflammatory breast cancer – Di Bonito – Translational Cancer Research
https://tcr.amegroups.org/article/view/28003/html
The abundance of cytokines and chemokines in the IBC tumor microenvironment could be responsible for the high aggressiveness of this tumor and for the increase of angiogenic processes and evasion of immune surveillance. […] A series of different molecular pathways have been associated with the regulation of inflammatory processes in IBC. […] Many NF-B target genes are upregulated in ER-negative IBC compared with ER-negative non-IBC tissues. […] Moreover, the inflammatory cytokines IL-6 and IL-8, the best characterized NF-B target genes, are produced and secreted at high levels within IBC. […] Finally, cyclooxygenase (COX) enzymes, in particular of COX-2, induced in response to proinflammatory stimuli, is overexpressed in IBC compared to non-IBC tumors, and this is also reflected by more abundant prostaglandin E2 in primary and metastatic IBC tumors.
#35 Pathological and molecular characteristics of inflammatory breast cancer
https://pmc.ncbi.nlm.nih.gov/articles/PMC8798351/
Tumor-associated macrophages (TAMs) produce high levels of inflammatory mediators that promote survival and proliferation of tumor cells and also antagonize the antitumor activity of CD8-positive T cells. […] The abundance of cytokines and chemokines in the IBC tumor microenvironment could be responsible for the high aggressiveness of this tumor and for the increase of angiogenic processes and evasion of immune surveillance. […] A series of different molecular pathways have been associated with the regulation of inflammatory processes in IBC. […] Many NF-B target genes are upregulated in ER-negative IBC compared with ER-negative non-IBC tissues. […] Moreover, the inflammatory cytokines IL-6 and IL-8, the best characterized NF-B target genes, are produced and secreted at high levels within IBC. […] Finally, cyclooxygenase (COX) enzymes, in particular of COX-2, induced in response to proinflammatory stimuli, is overexpressed in IBC compared to non-IBC tumors, and this is also reflected by more abundant prostaglandin E2 in primary and metastatic IBC tumors.
#36 Pathological and molecular characteristics of inflammatory breast cancer – Di Bonito – Translational Cancer Research
https://tcr.amegroups.org/article/view/28003/html
The abundance of cytokines and chemokines in the IBC tumor microenvironment could be responsible for the high aggressiveness of this tumor and for the increase of angiogenic processes and evasion of immune surveillance. […] A series of different molecular pathways have been associated with the regulation of inflammatory processes in IBC. […] Many NF-B target genes are upregulated in ER-negative IBC compared with ER-negative non-IBC tissues. […] Moreover, the inflammatory cytokines IL-6 and IL-8, the best characterized NF-B target genes, are produced and secreted at high levels within IBC. […] Finally, cyclooxygenase (COX) enzymes, in particular of COX-2, induced in response to proinflammatory stimuli, is overexpressed in IBC compared to non-IBC tumors, and this is also reflected by more abundant prostaglandin E2 in primary and metastatic IBC tumors.
#37 Pathological and molecular characteristics of inflammatory breast cancer
https://pmc.ncbi.nlm.nih.gov/articles/PMC8798351/
Tumor-associated macrophages (TAMs) produce high levels of inflammatory mediators that promote survival and proliferation of tumor cells and also antagonize the antitumor activity of CD8-positive T cells. […] The abundance of cytokines and chemokines in the IBC tumor microenvironment could be responsible for the high aggressiveness of this tumor and for the increase of angiogenic processes and evasion of immune surveillance. […] A series of different molecular pathways have been associated with the regulation of inflammatory processes in IBC. […] Many NF-B target genes are upregulated in ER-negative IBC compared with ER-negative non-IBC tissues. […] Moreover, the inflammatory cytokines IL-6 and IL-8, the best characterized NF-B target genes, are produced and secreted at high levels within IBC. […] Finally, cyclooxygenase (COX) enzymes, in particular of COX-2, induced in response to proinflammatory stimuli, is overexpressed in IBC compared to non-IBC tumors, and this is also reflected by more abundant prostaglandin E2 in primary and metastatic IBC tumors.
#38 Pathological and molecular characteristics of inflammatory breast cancer – Di Bonito – Translational Cancer Research
https://tcr.amegroups.org/article/view/28003/html
The abundance of cytokines and chemokines in the IBC tumor microenvironment could be responsible for the high aggressiveness of this tumor and for the increase of angiogenic processes and evasion of immune surveillance. […] A series of different molecular pathways have been associated with the regulation of inflammatory processes in IBC. […] Many NF-B target genes are upregulated in ER-negative IBC compared with ER-negative non-IBC tissues. […] Moreover, the inflammatory cytokines IL-6 and IL-8, the best characterized NF-B target genes, are produced and secreted at high levels within IBC. […] Finally, cyclooxygenase (COX) enzymes, in particular of COX-2, induced in response to proinflammatory stimuli, is overexpressed in IBC compared to non-IBC tumors, and this is also reflected by more abundant prostaglandin E2 in primary and metastatic IBC tumors.
#39 Pathological and molecular characteristics of inflammatory breast cancer
https://pmc.ncbi.nlm.nih.gov/articles/PMC8798351/
Tumor-associated macrophages (TAMs) produce high levels of inflammatory mediators that promote survival and proliferation of tumor cells and also antagonize the antitumor activity of CD8-positive T cells. […] The abundance of cytokines and chemokines in the IBC tumor microenvironment could be responsible for the high aggressiveness of this tumor and for the increase of angiogenic processes and evasion of immune surveillance. […] A series of different molecular pathways have been associated with the regulation of inflammatory processes in IBC. […] Many NF-B target genes are upregulated in ER-negative IBC compared with ER-negative non-IBC tissues. […] Moreover, the inflammatory cytokines IL-6 and IL-8, the best characterized NF-B target genes, are produced and secreted at high levels within IBC. […] Finally, cyclooxygenase (COX) enzymes, in particular of COX-2, induced in response to proinflammatory stimuli, is overexpressed in IBC compared to non-IBC tumors, and this is also reflected by more abundant prostaglandin E2 in primary and metastatic IBC tumors.
#40 Pathological and molecular characteristics of inflammatory breast cancer – Di Bonito – Translational Cancer Research
https://tcr.amegroups.org/article/view/28003/html
The abundance of cytokines and chemokines in the IBC tumor microenvironment could be responsible for the high aggressiveness of this tumor and for the increase of angiogenic processes and evasion of immune surveillance. […] A series of different molecular pathways have been associated with the regulation of inflammatory processes in IBC. […] Many NF-B target genes are upregulated in ER-negative IBC compared with ER-negative non-IBC tissues. […] Moreover, the inflammatory cytokines IL-6 and IL-8, the best characterized NF-B target genes, are produced and secreted at high levels within IBC. […] Finally, cyclooxygenase (COX) enzymes, in particular of COX-2, induced in response to proinflammatory stimuli, is overexpressed in IBC compared to non-IBC tumors, and this is also reflected by more abundant prostaglandin E2 in primary and metastatic IBC tumors.
#41 Targeting Signaling Pathways in Inflammatory Breast Cancer
https://www.mdpi.com/2072-6694/12/9/2479
The tumor microenvironment (TME), which includes T cells, tumor-associated macrophages (TAMs), fibroblasts, mast cells, and mesenchymal stem cells (MSCs), has been shown to play critical roles in promoting IBC aggressiveness. […] The JAK/STAT, NF-ÎºB, and COX-2 inflammatory pathways are important in the progression of IBC. […] The activation of NF-ÎºB plays a major role in promoting the unusual phenotype and aggressiveness of IBC. […] COX-2 is overexpressed in a wide range of malignancies, including colon, bladder, prostate, pancreatic, and breast cancers, and it is associated with tumor growth and invasiveness. […] The expression of COX-2 is regulated by the EGFR pathway and is correlated with EGFR expression in IBC specimens. […] The dysregulation of WISP3 can upregulate RhoC GTPase and enhance the aggressiveness of IBC. […] The RhoC GTPase family is a potent regulator of both glutamine and N-acetylaspartate metabolism in IBC SUM149 cells, revealing a novel role in regulating tumor cell metabolism. […] The clinical relevance of targeting RhoC GTPase in IBC needs further investigation.
#42 Targeting Signaling Pathways in Inflammatory Breast Cancer
https://www.mdpi.com/2072-6694/12/9/2479
The tumor microenvironment (TME), which includes T cells, tumor-associated macrophages (TAMs), fibroblasts, mast cells, and mesenchymal stem cells (MSCs), has been shown to play critical roles in promoting IBC aggressiveness. […] The JAK/STAT, NF-ÎºB, and COX-2 inflammatory pathways are important in the progression of IBC. […] The activation of NF-ÎºB plays a major role in promoting the unusual phenotype and aggressiveness of IBC. […] COX-2 is overexpressed in a wide range of malignancies, including colon, bladder, prostate, pancreatic, and breast cancers, and it is associated with tumor growth and invasiveness. […] The expression of COX-2 is regulated by the EGFR pathway and is correlated with EGFR expression in IBC specimens. […] The dysregulation of WISP3 can upregulate RhoC GTPase and enhance the aggressiveness of IBC. […] The RhoC GTPase family is a potent regulator of both glutamine and N-acetylaspartate metabolism in IBC SUM149 cells, revealing a novel role in regulating tumor cell metabolism. […] The clinical relevance of targeting RhoC GTPase in IBC needs further investigation.
#43 Inflammatory Breast Cancer – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK564324/
At least half of IBCs have a loss of heterozygosity. The most frequent lost alleles are 17 q., 13 q., 11 q., 8P, 6P, and 3P. […] Accumulation of p53 protein or mutation in p53 TSG was reported in 20% to 50% of human breast cancers. These abnormalities are often seen in hereditary breast cancer syndromes like familial breast and ovarian cancers (e.g., Li-Fraumeni syndrome). […] IBC is a misnomer, it produces negligible levels of most inflammatory cytokines such as interleukin-12, interleukin-1, and interferon-gamma. Inflammatory breast cancer tends to be highly vascular because of its angiogenic and angioinvasive potential. […] The classic histologic finding in inflammatory breast cancer on biopsy of the affected skin is dermal lymphatic invasion by tumor cells. The same malignant cells from tumor emboli are responsible for local and metastatic disease. […] Inflammatory breast cancer is associated with very poor prognosis and a high risk of early recurrence. The current evidence suggests that for the same stage of locally advanced breast cancer, inflammatory breast cancer has a poorer prognosis.
#44 Inflammatory Breast Cancer | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/111445
An angioinvasive nature is intrinsic to primary IBC. Normal experimental studies have evaluated the role of hormone receptor status and genetic changes, the p53 tumor suppressor gene, cytokines, and other genetic determinants. […] The majority of IBCs are hormone receptor-negative. Breast cancers with negative estrogen receptors (ER) and progesterone receptors (PGR) are generally associated with shorter disease-free survival and poor prognosis than receptor-positive tumors. IBCs also have high proliferative rates and also overexpress human epidermal growth factor receptor 2 (HER 2). These molecular markers may identify patients who have a worse prognosis. […] At least half of IBCs have a loss of heterozygosity. The most frequent lost alleles are 17 q., 13 q., 11 q., 8P, 6P, and 3P. […] Accumulation of p53 protein or mutation in p53 TSG was reported in 20% to 50% of human breast cancers. These abnormalities are often seen in hereditary breast cancer syndromes like familial breast and ovarian cancers (e.g., Li-Fraumeni syndrome).
#45 Inflammatory Breast Cancer – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK564324/
At least half of IBCs have a loss of heterozygosity. The most frequent lost alleles are 17 q., 13 q., 11 q., 8P, 6P, and 3P. […] Accumulation of p53 protein or mutation in p53 TSG was reported in 20% to 50% of human breast cancers. These abnormalities are often seen in hereditary breast cancer syndromes like familial breast and ovarian cancers (e.g., Li-Fraumeni syndrome). […] IBC is a misnomer, it produces negligible levels of most inflammatory cytokines such as interleukin-12, interleukin-1, and interferon-gamma. Inflammatory breast cancer tends to be highly vascular because of its angiogenic and angioinvasive potential. […] The classic histologic finding in inflammatory breast cancer on biopsy of the affected skin is dermal lymphatic invasion by tumor cells. The same malignant cells from tumor emboli are responsible for local and metastatic disease. […] Inflammatory breast cancer is associated with very poor prognosis and a high risk of early recurrence. The current evidence suggests that for the same stage of locally advanced breast cancer, inflammatory breast cancer has a poorer prognosis.
#46 Inflammatory Breast Cancer | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/111445
An angioinvasive nature is intrinsic to primary IBC. Normal experimental studies have evaluated the role of hormone receptor status and genetic changes, the p53 tumor suppressor gene, cytokines, and other genetic determinants. […] The majority of IBCs are hormone receptor-negative. Breast cancers with negative estrogen receptors (ER) and progesterone receptors (PGR) are generally associated with shorter disease-free survival and poor prognosis than receptor-positive tumors. IBCs also have high proliferative rates and also overexpress human epidermal growth factor receptor 2 (HER 2). These molecular markers may identify patients who have a worse prognosis. […] At least half of IBCs have a loss of heterozygosity. The most frequent lost alleles are 17 q., 13 q., 11 q., 8P, 6P, and 3P. […] Accumulation of p53 protein or mutation in p53 TSG was reported in 20% to 50% of human breast cancers. These abnormalities are often seen in hereditary breast cancer syndromes like familial breast and ovarian cancers (e.g., Li-Fraumeni syndrome).
#47 Inflammatory Breast Cancer: A Literature Review | Mamouch | World Journal of Oncology
https://www.wjon.org/index.php/wjon/article/view/1161/893
Studies have suggested that IBC does not have a specific molecular signature. Recently, they have identified in vivo and in vitro genes that can contribute to the aggressive phenotype of IBC. […] IBC cells are characterized by overexpression of E-cadherin, which is essential for cell adhesion, tumor emboli formation, and progression of metastasis which implies poor prognosis. In addition, RhoC-GTPase is overexpressed in 90% of IBC tumors compared to 38% of non-IBC tumors. Indeed, RhoC-GTPase plays a critical role in the metastatic behavior of IBC by increasing all aspects of metastatic processes such as motility and cell invasion, cytoskeletal assembly, and cell adhesion. […] The diagnosis of IBC remains above all a clinical diagnosis supported by a histological evidence of infiltrating carcinoma, and the therapeutic approach can only be multidisciplinary. The ability to identify new targeted therapies allows us to control the aggressive phenotype of IBC. Molecular biology and genomics are very likely to play an important role in the diagnosis and management of IBC.
#48 Targeting Signaling Pathways in Inflammatory Breast Cancer
https://www.mdpi.com/2072-6694/12/9/2479
The tumor microenvironment (TME), which includes T cells, tumor-associated macrophages (TAMs), fibroblasts, mast cells, and mesenchymal stem cells (MSCs), has been shown to play critical roles in promoting IBC aggressiveness. […] The JAK/STAT, NF-ÎºB, and COX-2 inflammatory pathways are important in the progression of IBC. […] The activation of NF-ÎºB plays a major role in promoting the unusual phenotype and aggressiveness of IBC. […] COX-2 is overexpressed in a wide range of malignancies, including colon, bladder, prostate, pancreatic, and breast cancers, and it is associated with tumor growth and invasiveness. […] The expression of COX-2 is regulated by the EGFR pathway and is correlated with EGFR expression in IBC specimens. […] The dysregulation of WISP3 can upregulate RhoC GTPase and enhance the aggressiveness of IBC. […] The RhoC GTPase family is a potent regulator of both glutamine and N-acetylaspartate metabolism in IBC SUM149 cells, revealing a novel role in regulating tumor cell metabolism. […] The clinical relevance of targeting RhoC GTPase in IBC needs further investigation.
#49 Targeting Signaling Pathways in Inflammatory Breast Cancer
https://www.mdpi.com/2072-6694/12/9/2479
The tumor microenvironment (TME), which includes T cells, tumor-associated macrophages (TAMs), fibroblasts, mast cells, and mesenchymal stem cells (MSCs), has been shown to play critical roles in promoting IBC aggressiveness. […] The JAK/STAT, NF-ÎºB, and COX-2 inflammatory pathways are important in the progression of IBC. […] The activation of NF-ÎºB plays a major role in promoting the unusual phenotype and aggressiveness of IBC. […] COX-2 is overexpressed in a wide range of malignancies, including colon, bladder, prostate, pancreatic, and breast cancers, and it is associated with tumor growth and invasiveness. […] The expression of COX-2 is regulated by the EGFR pathway and is correlated with EGFR expression in IBC specimens. […] The dysregulation of WISP3 can upregulate RhoC GTPase and enhance the aggressiveness of IBC. […] The RhoC GTPase family is a potent regulator of both glutamine and N-acetylaspartate metabolism in IBC SUM149 cells, revealing a novel role in regulating tumor cell metabolism. […] The clinical relevance of targeting RhoC GTPase in IBC needs further investigation.
#50 Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer | Nature Cell Biology
https://www.nature.com/articles/ncb1900
Inflammatory breast cancer (IBC) is the most lethal form of primary breast cancer. IBC lethality derives from generation of tumour emboli, which are non-adherent cell clusters that rapidly spread by a form of continuous invasion known as passive metastasis. In IBC, E-cadherin is overexpressed and supports formation of tumour emboli by promoting tumour cell interactions rather than adherence to stroma. We show that the unique pathogenic properties of IBC result in part from overexpression of the translation initiation factor eIF4GI in most IBCs. eIF4GI reprograms the protein synthetic machinery for increased translation of mRNAs with internal ribosome entry sites (IRESs) that promote IBC tumour cell survival and formation of tumour emboli. Overexpression of eIF4GI promotes formation of IBC tumour emboli by enhancing translation of IRES-containing p120 mRNAs. […] These findings provide a new understanding of translational control in the development of advanced breast cancer.
#51 Key Gene In Deadly Inflammatory Breast Cancer Identified | ScienceDaily
https://www.sciencedaily.com/releases/2009/06/090614153255.htm
Aggressive, deadly and often misdiagnosed, inflammatory breast cancer (IBC) is the most lethal form of primary breast cancer, often striking women in their prime and causing death within 18 to 24 months. […] Now, scientists from The Cancer Institute at NYU Langone Medical Center have identified a key gene eIF4G1 that is overexpressed in the majority of cases of IBC, allowing cells to form highly mobile clusters that are responsible for the rapid metastasis that makes IBC such an effective killer. […] Dr. Schneider and his colleagues found that the overexpression of the gene eIF4G1 reprograms how the IBC tumor cells make proteins. Other researchers have identified genes associated with IBC, but this is the first gene shown to orchestrate how IBC tumor cells form special structures unique to this disease known as „tumor emboli.” These small clusters of highly mobile tumor cells are responsible for the rapid metastasis of IBC.
#52 Inflammatory Breast Cancer – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK564324/
At least half of IBCs have a loss of heterozygosity. The most frequent lost alleles are 17 q., 13 q., 11 q., 8P, 6P, and 3P. […] Accumulation of p53 protein or mutation in p53 TSG was reported in 20% to 50% of human breast cancers. These abnormalities are often seen in hereditary breast cancer syndromes like familial breast and ovarian cancers (e.g., Li-Fraumeni syndrome). […] IBC is a misnomer, it produces negligible levels of most inflammatory cytokines such as interleukin-12, interleukin-1, and interferon-gamma. Inflammatory breast cancer tends to be highly vascular because of its angiogenic and angioinvasive potential. […] The classic histologic finding in inflammatory breast cancer on biopsy of the affected skin is dermal lymphatic invasion by tumor cells. The same malignant cells from tumor emboli are responsible for local and metastatic disease. […] Inflammatory breast cancer is associated with very poor prognosis and a high risk of early recurrence. The current evidence suggests that for the same stage of locally advanced breast cancer, inflammatory breast cancer has a poorer prognosis.
#53 Inflammatory Breast Cancer | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/111445
IBC is a clinicopathological diagnosis that requires an interprofessional approach for diagnosis. A core needle biopsy of the breast should be obtained to make the initial diagnosis of invasive carcinoma. The classic histologic finding in inflammatory breast cancer on biopsy of the affected skin is dermal lymphatic invasion by tumor cells. […] Patients with inflammatory breast cancer typically present with pain or a rapidly growing breast lump associated with itching and enlargement of the breast. Almost all have lymph node involvement at the time of presentation, and about one-third will have distant metastasis. […] The diagnosis of inflammatory breast cancer is based upon the characteristic clinical presentation and core needle biopsy showing invasive carcinoma of the breast. […] Both national comprehensive cancer network and international inflammatory breast cancer expert guidelines recommend intensive therapy for patients with primary inflammatory breast cancer to achieve the best local control and survival outcome via a tri-modality approach: Systemic therapy, surgery, and radiation therapy.
#54 Inflammatory Breast Cancer – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK564324/
At least half of IBCs have a loss of heterozygosity. The most frequent lost alleles are 17 q., 13 q., 11 q., 8P, 6P, and 3P. […] Accumulation of p53 protein or mutation in p53 TSG was reported in 20% to 50% of human breast cancers. These abnormalities are often seen in hereditary breast cancer syndromes like familial breast and ovarian cancers (e.g., Li-Fraumeni syndrome). […] IBC is a misnomer, it produces negligible levels of most inflammatory cytokines such as interleukin-12, interleukin-1, and interferon-gamma. Inflammatory breast cancer tends to be highly vascular because of its angiogenic and angioinvasive potential. […] The classic histologic finding in inflammatory breast cancer on biopsy of the affected skin is dermal lymphatic invasion by tumor cells. The same malignant cells from tumor emboli are responsible for local and metastatic disease. […] Inflammatory breast cancer is associated with very poor prognosis and a high risk of early recurrence. The current evidence suggests that for the same stage of locally advanced breast cancer, inflammatory breast cancer has a poorer prognosis.
#55 Inflammatory Breast Cancer: A Literature Review | Mamouch | World Journal of Oncology
https://www.wjon.org/index.php/wjon/article/view/1161/893
Currently, there are no established risk factors for IBC. However, many epidemiological studies clarify the characteristics of IBC that have been studied. The most important suspected risk factors associated with this disease are: black race, body mass index (BMI), age and region. […] At present, there are no definitive molecular or pathological diagnosis criteria for IBC. Therefore, the diagnosis is entirely based on clinical symptoms such as the rapid onset of signs like erythema and edema of the breast skin (orange peel), i.e. the possibility of misleading between IBC and benign bacterial infections such as mastitis is high, that is why it is important to note that IBC is not usually associated with symptoms of infection such as fever. […] IBC is not considered as a specific histological subtype of breast carcinomas, and it has no specific diagnostic pathological criteria. Most IBC are ductal carcinoma and had a high histological nuclear grade. About 17 % to 30% of IBC cases are triple negative and 18% to 44% are epidermal growth factor receptor 2 (HER2) positive.
#56 Inflammatory Breast Cancer: A Literature Review | Mamouch | World Journal of Oncology
https://www.wjon.org/index.php/wjon/article/view/1161/893
Currently, there are no established risk factors for IBC. However, many epidemiological studies clarify the characteristics of IBC that have been studied. The most important suspected risk factors associated with this disease are: black race, body mass index (BMI), age and region. […] At present, there are no definitive molecular or pathological diagnosis criteria for IBC. Therefore, the diagnosis is entirely based on clinical symptoms such as the rapid onset of signs like erythema and edema of the breast skin (orange peel), i.e. the possibility of misleading between IBC and benign bacterial infections such as mastitis is high, that is why it is important to note that IBC is not usually associated with symptoms of infection such as fever. […] IBC is not considered as a specific histological subtype of breast carcinomas, and it has no specific diagnostic pathological criteria. Most IBC are ductal carcinoma and had a high histological nuclear grade. About 17 % to 30% of IBC cases are triple negative and 18% to 44% are epidermal growth factor receptor 2 (HER2) positive.
#57 Inflammatory Breast CA : Pathology
https://www.webpathology.com/images/breast/breast-carcinomas/infiltrating-ductal-carcinoma/33525
Inflammatory Breast Carcinoma (IBC) shows diffuse erythema and edema (peau d’orange) of the breast skin. By definition, there is involvement of at least a third or more of the skin overlying the breast (AJCC-TNM Staging System) and is classified as cT4d. IBC is primarily a clinical diagnosis and not a specific histologic subtype. The cutaneous changes of IBC are due to lymphedema caused by widespread carcinomatous emboli within dermal lymphatic channels. The tumor emboli are generally present throughout the breast but may or may not be seen in a small skin biopsy. Therefore, the presence of tumor emboli in dermal lymphatics is not required to make the diagnosis of IBC. Conversely, tumor emboli in dermal lymphatics in the absence of skin changes do not qualify as IBC. The diagnosis of IBC should not be applied to a patient with neglected locally advanced breast cancer that may be fungated or ulcerated. Grossly, the tumor is often indistinct in the mastectomy specimen. The entire breast is diffusely enlarged and indurated due to involvement by the tumor. The skin is visibly thickened. Microscopically, IBC is usually high-grade invasive ductal carcinoma of no specific type. IBC is characterized by negativity for ER and PR and overexpression of HER2. In addition, there is overexpression of p53, high E-cadherin expression, high MIB1 proliferation index, and cytoplasmic MUC-1 overexpression. There is prominent angiogenesis due to upregulation of angiogenesis-related genes. Bevacizumab – a recombinant monoclonal antibody to VEGF appears to have a role in the treatment of IBC. Most patients with IBC are treated by neoadjuvant chemotherapy followed by mastectomy and radiation.
#58 Inflammatory breast cancer: Pathology and molecular pathogenesis – UpToDate
https://www.uptodate.com/contents/inflammatory-breast-cancer-pathology-and-molecular-pathogenesis
Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer. De novo IBC refers to primary disease. These patients typically present with pain and a tender, firm, and enlarged breast. The skin over the breast is reddened, warm, and thickened, with a „peau d’orange” (orange skin) appearance. In comparison, the inflammatory recurrence of a noninflammatory breast cancer is called secondary disease. It usually develops on the chest wall at the site of previous mastectomy, but can also occur rarely as a distant cutaneous recurrence. The signs and symptoms of IBC arise rapidly compared to non IBC, typically within weeks to six months. […] The 2017 American Joint Committee on Cancer and the International Union for Cancer Control (AJCC-UICC) Tumor, Node, Metastasis (TNM) breast cancer staging system defines IBC as a clinical-pathologic entity characterized by diffuse erythema and edema (peau d’orange) involving a third or more of the skin of the breast. These „inflammatory” skin changes are not due to infiltration of inflammatory cells but rather to lymphedema caused by tumor emboli within the dermal lymphatics. However, the diagnosis is based upon the clinical presentation. Although dermal lymphatic involvement supports the diagnosis of inflammatory breast cancer, it is neither necessary nor sufficient in the absence of classical clinical findings.
#59 Inflammatory breast cancer: Pathology and molecular pathogenesis – UpToDate
https://www.uptodate.com/contents/inflammatory-breast-cancer-pathology-and-molecular-pathogenesis
Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer. De novo IBC refers to primary disease. These patients typically present with pain and a tender, firm, and enlarged breast. The skin over the breast is reddened, warm, and thickened, with a „peau d’orange” (orange skin) appearance. In comparison, the inflammatory recurrence of a noninflammatory breast cancer is called secondary disease. It usually develops on the chest wall at the site of previous mastectomy, but can also occur rarely as a distant cutaneous recurrence. The signs and symptoms of IBC arise rapidly compared to non IBC, typically within weeks to six months. […] The 2017 American Joint Committee on Cancer and the International Union for Cancer Control (AJCC-UICC) Tumor, Node, Metastasis (TNM) breast cancer staging system defines IBC as a clinical-pathologic entity characterized by diffuse erythema and edema (peau d’orange) involving a third or more of the skin of the breast. These „inflammatory” skin changes are not due to infiltration of inflammatory cells but rather to lymphedema caused by tumor emboli within the dermal lymphatics. However, the diagnosis is based upon the clinical presentation. Although dermal lymphatic involvement supports the diagnosis of inflammatory breast cancer, it is neither necessary nor sufficient in the absence of classical clinical findings.
#60 POE – Inflammatory Breast Cancer Pathology – MD Anderson Cancer Center
https://streaming.mdanderson.org/transcript/poe-ibc-pathology-krishnamurthy.htm
Inflammatory breast carcinoma is a rare and aggressive type of breast cancer that comprises from 1 percent to 5 percent of all newly diagnosed breast cancers. This entity is characterized by rapid progression, aggressive behavior, and an overall survival that is lower than other breast cancers. […] Inflammatory breast carcinoma is characterized by the presence of numerous dermal tumor emboli in papillary and reticular dermis of the skin overlying breast. This is regarded as the pathognomonic feature for the distinction of inflammatory breast carcinoma from non-inflammatory breast carcinoma. […] The tumor cells comprising the lymphovascular tumor emboli are generally high grade with large nucleus. […] E-cadherin overexpression is regarded as a hallmark of the invasive tumor and also the lymphovascular tumor emboli in patients with inflammatory breast carcinoma.
#61 POE – Inflammatory Breast Cancer Pathology – MD Anderson Cancer Center
https://streaming.mdanderson.org/transcript/poe-ibc-pathology-krishnamurthy.htm
Inflammatory breast carcinoma is a rare and aggressive type of breast cancer that comprises from 1 percent to 5 percent of all newly diagnosed breast cancers. This entity is characterized by rapid progression, aggressive behavior, and an overall survival that is lower than other breast cancers. […] Inflammatory breast carcinoma is characterized by the presence of numerous dermal tumor emboli in papillary and reticular dermis of the skin overlying breast. This is regarded as the pathognomonic feature for the distinction of inflammatory breast carcinoma from non-inflammatory breast carcinoma. […] The tumor cells comprising the lymphovascular tumor emboli are generally high grade with large nucleus. […] E-cadherin overexpression is regarded as a hallmark of the invasive tumor and also the lymphovascular tumor emboli in patients with inflammatory breast carcinoma.
#62 Inflammatory Breast Cancer – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK564324/
Inflammatory breast cancer (IBC) is a rare subtype of locally advanced breast cancer according to the TNM breast cancer staging system. Despite its low incidence, IBC contributes to 7% of breast cancer caused mortality. […] Inflammatory breast cancer is the most aggressive entity of breast cancer. The median overall survival among women is less than 4 years, even with multimodality treatment options. However, increased survival in recent years has been noted with the improvement of chemotherapeutic management. […] An angioinvasive nature is intrinsic to primary IBC. Normal experimental studies have evaluated the role of hormone receptor status and genetic changes, the p53 tumor suppressor gene, cytokines, and other genetic determinants. […] The majority of IBCs are hormone receptor-negative. Breast cancers with negative estrogen receptors (ER) and progesterone receptors (PGR) are generally associated with shorter disease-free survival and poor prognosis than receptor-positive tumors. IBCs also have high proliferative rates and also overexpress human epidermal growth factor receptor 2 (HER 2). These molecular markers may identify patients who have a worse prognosis.
#63 Inflammatory Breast Cancer | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/111445
An angioinvasive nature is intrinsic to primary IBC. Normal experimental studies have evaluated the role of hormone receptor status and genetic changes, the p53 tumor suppressor gene, cytokines, and other genetic determinants. […] The majority of IBCs are hormone receptor-negative. Breast cancers with negative estrogen receptors (ER) and progesterone receptors (PGR) are generally associated with shorter disease-free survival and poor prognosis than receptor-positive tumors. IBCs also have high proliferative rates and also overexpress human epidermal growth factor receptor 2 (HER 2). These molecular markers may identify patients who have a worse prognosis. […] At least half of IBCs have a loss of heterozygosity. The most frequent lost alleles are 17 q., 13 q., 11 q., 8P, 6P, and 3P. […] Accumulation of p53 protein or mutation in p53 TSG was reported in 20% to 50% of human breast cancers. These abnormalities are often seen in hereditary breast cancer syndromes like familial breast and ovarian cancers (e.g., Li-Fraumeni syndrome).
#64 Inflammatory Breast Cancer – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK564324/
Inflammatory breast cancer (IBC) is a rare subtype of locally advanced breast cancer according to the TNM breast cancer staging system. Despite its low incidence, IBC contributes to 7% of breast cancer caused mortality. […] Inflammatory breast cancer is the most aggressive entity of breast cancer. The median overall survival among women is less than 4 years, even with multimodality treatment options. However, increased survival in recent years has been noted with the improvement of chemotherapeutic management. […] An angioinvasive nature is intrinsic to primary IBC. Normal experimental studies have evaluated the role of hormone receptor status and genetic changes, the p53 tumor suppressor gene, cytokines, and other genetic determinants. […] The majority of IBCs are hormone receptor-negative. Breast cancers with negative estrogen receptors (ER) and progesterone receptors (PGR) are generally associated with shorter disease-free survival and poor prognosis than receptor-positive tumors. IBCs also have high proliferative rates and also overexpress human epidermal growth factor receptor 2 (HER 2). These molecular markers may identify patients who have a worse prognosis.
#65 Inflammatory Breast Cancer | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/111445
An angioinvasive nature is intrinsic to primary IBC. Normal experimental studies have evaluated the role of hormone receptor status and genetic changes, the p53 tumor suppressor gene, cytokines, and other genetic determinants. […] The majority of IBCs are hormone receptor-negative. Breast cancers with negative estrogen receptors (ER) and progesterone receptors (PGR) are generally associated with shorter disease-free survival and poor prognosis than receptor-positive tumors. IBCs also have high proliferative rates and also overexpress human epidermal growth factor receptor 2 (HER 2). These molecular markers may identify patients who have a worse prognosis. […] At least half of IBCs have a loss of heterozygosity. The most frequent lost alleles are 17 q., 13 q., 11 q., 8P, 6P, and 3P. […] Accumulation of p53 protein or mutation in p53 TSG was reported in 20% to 50% of human breast cancers. These abnormalities are often seen in hereditary breast cancer syndromes like familial breast and ovarian cancers (e.g., Li-Fraumeni syndrome).
#66 Inflammatory Breast Cancer – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK564324/
Inflammatory breast cancer (IBC) is a rare subtype of locally advanced breast cancer according to the TNM breast cancer staging system. Despite its low incidence, IBC contributes to 7% of breast cancer caused mortality. […] Inflammatory breast cancer is the most aggressive entity of breast cancer. The median overall survival among women is less than 4 years, even with multimodality treatment options. However, increased survival in recent years has been noted with the improvement of chemotherapeutic management. […] An angioinvasive nature is intrinsic to primary IBC. Normal experimental studies have evaluated the role of hormone receptor status and genetic changes, the p53 tumor suppressor gene, cytokines, and other genetic determinants. […] The majority of IBCs are hormone receptor-negative. Breast cancers with negative estrogen receptors (ER) and progesterone receptors (PGR) are generally associated with shorter disease-free survival and poor prognosis than receptor-positive tumors. IBCs also have high proliferative rates and also overexpress human epidermal growth factor receptor 2 (HER 2). These molecular markers may identify patients who have a worse prognosis.
#67 Inflammatory Breast Cancer | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/111445
An angioinvasive nature is intrinsic to primary IBC. Normal experimental studies have evaluated the role of hormone receptor status and genetic changes, the p53 tumor suppressor gene, cytokines, and other genetic determinants. […] The majority of IBCs are hormone receptor-negative. Breast cancers with negative estrogen receptors (ER) and progesterone receptors (PGR) are generally associated with shorter disease-free survival and poor prognosis than receptor-positive tumors. IBCs also have high proliferative rates and also overexpress human epidermal growth factor receptor 2 (HER 2). These molecular markers may identify patients who have a worse prognosis. […] At least half of IBCs have a loss of heterozygosity. The most frequent lost alleles are 17 q., 13 q., 11 q., 8P, 6P, and 3P. […] Accumulation of p53 protein or mutation in p53 TSG was reported in 20% to 50% of human breast cancers. These abnormalities are often seen in hereditary breast cancer syndromes like familial breast and ovarian cancers (e.g., Li-Fraumeni syndrome).
#68 Inflammatory Breast Cancer: A Literature Review | Mamouch | World Journal of Oncology
https://www.wjon.org/index.php/wjon/article/view/1161/893
Currently, there are no established risk factors for IBC. However, many epidemiological studies clarify the characteristics of IBC that have been studied. The most important suspected risk factors associated with this disease are: black race, body mass index (BMI), age and region. […] At present, there are no definitive molecular or pathological diagnosis criteria for IBC. Therefore, the diagnosis is entirely based on clinical symptoms such as the rapid onset of signs like erythema and edema of the breast skin (orange peel), i.e. the possibility of misleading between IBC and benign bacterial infections such as mastitis is high, that is why it is important to note that IBC is not usually associated with symptoms of infection such as fever. […] IBC is not considered as a specific histological subtype of breast carcinomas, and it has no specific diagnostic pathological criteria. Most IBC are ductal carcinoma and had a high histological nuclear grade. About 17 % to 30% of IBC cases are triple negative and 18% to 44% are epidermal growth factor receptor 2 (HER2) positive.
#69 Inflammatory Breast CA : Pathology
https://www.webpathology.com/images/breast/breast-carcinomas/infiltrating-ductal-carcinoma/33525
Inflammatory Breast Carcinoma (IBC) shows diffuse erythema and edema (peau d’orange) of the breast skin. By definition, there is involvement of at least a third or more of the skin overlying the breast (AJCC-TNM Staging System) and is classified as cT4d. IBC is primarily a clinical diagnosis and not a specific histologic subtype. The cutaneous changes of IBC are due to lymphedema caused by widespread carcinomatous emboli within dermal lymphatic channels. The tumor emboli are generally present throughout the breast but may or may not be seen in a small skin biopsy. Therefore, the presence of tumor emboli in dermal lymphatics is not required to make the diagnosis of IBC. Conversely, tumor emboli in dermal lymphatics in the absence of skin changes do not qualify as IBC. The diagnosis of IBC should not be applied to a patient with neglected locally advanced breast cancer that may be fungated or ulcerated. Grossly, the tumor is often indistinct in the mastectomy specimen. The entire breast is diffusely enlarged and indurated due to involvement by the tumor. The skin is visibly thickened. Microscopically, IBC is usually high-grade invasive ductal carcinoma of no specific type. IBC is characterized by negativity for ER and PR and overexpression of HER2. In addition, there is overexpression of p53, high E-cadherin expression, high MIB1 proliferation index, and cytoplasmic MUC-1 overexpression. There is prominent angiogenesis due to upregulation of angiogenesis-related genes. Bevacizumab – a recombinant monoclonal antibody to VEGF appears to have a role in the treatment of IBC. Most patients with IBC are treated by neoadjuvant chemotherapy followed by mastectomy and radiation.
#70 Inflammatory breast cancer – Wikipedia
https://en.wikipedia.org/wiki/Inflammatory_breast_cancer
Inflammatory breast cancer (IBC) is one of the most aggressive types of breast cancer. It is referred to as „inflammatory” due to its frequent presentation with symptoms resembling a skin inflammation, such as erysipelas. […] IBC is characterised by the presence of cancer cells in the subdermal lymphatics on skin biopsy. Consequently, IBC is always staged at stage IIIB or above, as that type of locally advanced disease is a classic prognostic indicator. […] Inflammatory breast cancer is a high-grade aneuploid cancer, with mutations and overexpression of p53, high levels of E-cadherin and abnormal cadherin function. It is often regarded as a systemic cancer. […] The epidermal growth factor receptor (EGFR) pathway is commonly active in inflammatory breast cancer; this has the clinical implication that EGFR targeting therapy may be effective in inflammatory breast cancer.
#71 Chemo Resistance Mechanisms Identified in Inflammatory Breast Cancer – Cancer Therapy Advisor
https://www.cancertherapyadvisor.com/home/cancer-topics/breast-cancer/chemo-resistance-mechanisms-identified-in-inflammatory-breast-cancer/
Researchers at Roswell Park Cancer Institute (RPCI) have identified a mechanism of breast cancer cells that leads to chemotherapy resistance in inflammatory breast cancer. […] These preclinical findings, published online ahead of print in the International Journal of Oncology, provide evidence for a potential therapeutic approach that will restore sensitivity to chemotherapy and improve treatment of inflammatory breast cancer tumors. […] This study forms the basis for future research in patients with breast cancer and offers hope for targeted therapy for patients with aggressive triple-negative inflammatory breast cancer, said lead researcher Mateusz Opyrchal, MD, PhD, Assistant Professor of Oncology at RPCI.
#72 Chemo Resistance Mechanisms Identified in Inflammatory Breast Cancer – Cancer Therapy Advisor
https://www.cancertherapyadvisor.com/home/cancer-topics/breast-cancer/chemo-resistance-mechanisms-identified-in-inflammatory-breast-cancer/
Researchers at Roswell Park Cancer Institute (RPCI) have identified a mechanism of breast cancer cells that leads to chemotherapy resistance in inflammatory breast cancer. […] These preclinical findings, published online ahead of print in the International Journal of Oncology, provide evidence for a potential therapeutic approach that will restore sensitivity to chemotherapy and improve treatment of inflammatory breast cancer tumors. […] This study forms the basis for future research in patients with breast cancer and offers hope for targeted therapy for patients with aggressive triple-negative inflammatory breast cancer, said lead researcher Mateusz Opyrchal, MD, PhD, Assistant Professor of Oncology at RPCI.
#73 Study Shows How BPA May Affect Inflammatory Breast Cancer | Duke Department of Surgery
https://surgery.duke.edu/news/study-shows-how-bpa-may-affect-inflammatory-breast-cancer
Study is the first to identify how chemicals might encourage deadly cancers growth. […] The chemical bisphenol A, or BPA, appears to aid the survival of inflammatory breast cancer cells, revealing a potential mechanism for how the disease grows according to a study led by researchers in the Department of Surgery at Duke University School of Medicine and the Duke Cancer Institute. […] Inflammatory breast cancer (IBC) is the most lethal and fastest-growing form of breast cancer and quickly develops resistance to treatments. […] The study is the first to show that BPA increased signaling through receptors that communicate with the MAPK pathway and that the presence of BPA may lead to resistance to cancer drugs targeting this pathway. […] Previous studies have theorized that BPA and other endocrine-disrupting chemicals — ones that mimic hormones like estrogen in the body — may promote the development of breast tissue tumors.
#74 Study shows how BPA may affect inflammatory breast cancer
https://medicalxpress.com/news/2017-03-bpa-affect-inflammatory-breast-cancer.html
The chemical bisphenol A, or BPA, appears to aid the survival of inflammatory breast cancer cells, revealing a potential mechanism for how the disease grows, according to a study led by researchers in the Department of Surgery at Duke University School of Medicine and the Duke Cancer Institute. […] Inflammatory breast cancer (IBC) is the most lethal and fastest-growing form of breast cancer and quickly develops resistance to treatments. […] Reporting in the March issue of the journal Carcinogenesis, senior author Gayathri Devi, Ph.D., associate professor of surgery at Duke, and co-investigators found that bisphenol A increased the cell signaling pathway known as mitogen-activated protein kinases, or MAPK, in inflammatory breast cancer cells. […] „The study is the first to show that BPA increased signaling through receptors that communicate with the MAPK pathway and that the presence of BPA may lead to resistance to cancer drugs targeting this pathway,” Devi said. „In our cell models, more signaling led to increased growth of the cancer cells.”
#75 Study Shows How BPA May Affect Inflammatory Breast Cancer | Duke Department of Surgery
https://surgery.duke.edu/news/study-shows-how-bpa-may-affect-inflammatory-breast-cancer
Study is the first to identify how chemicals might encourage deadly cancers growth. […] The chemical bisphenol A, or BPA, appears to aid the survival of inflammatory breast cancer cells, revealing a potential mechanism for how the disease grows according to a study led by researchers in the Department of Surgery at Duke University School of Medicine and the Duke Cancer Institute. […] Inflammatory breast cancer (IBC) is the most lethal and fastest-growing form of breast cancer and quickly develops resistance to treatments. […] The study is the first to show that BPA increased signaling through receptors that communicate with the MAPK pathway and that the presence of BPA may lead to resistance to cancer drugs targeting this pathway. […] Previous studies have theorized that BPA and other endocrine-disrupting chemicals — ones that mimic hormones like estrogen in the body — may promote the development of breast tissue tumors.
#76 Study shows how BPA may affect inflammatory breast cancer
https://medicalxpress.com/news/2017-03-bpa-affect-inflammatory-breast-cancer.html
The chemical bisphenol A, or BPA, appears to aid the survival of inflammatory breast cancer cells, revealing a potential mechanism for how the disease grows, according to a study led by researchers in the Department of Surgery at Duke University School of Medicine and the Duke Cancer Institute. […] Inflammatory breast cancer (IBC) is the most lethal and fastest-growing form of breast cancer and quickly develops resistance to treatments. […] Reporting in the March issue of the journal Carcinogenesis, senior author Gayathri Devi, Ph.D., associate professor of surgery at Duke, and co-investigators found that bisphenol A increased the cell signaling pathway known as mitogen-activated protein kinases, or MAPK, in inflammatory breast cancer cells. […] „The study is the first to show that BPA increased signaling through receptors that communicate with the MAPK pathway and that the presence of BPA may lead to resistance to cancer drugs targeting this pathway,” Devi said. „In our cell models, more signaling led to increased growth of the cancer cells.”
#77 Inflammatory Breast Cancer: a model for investigating cluster-based dissemination | bioRxiv
https://www.biorxiv.org/content/10.1101/119479v1.full
Another hallmark of IBC is the presence of numerous cohesive clusters in the lymphatics and their resistance to multiple therapies. […] These clusters or emboli have accumulation of E-cadherin due to its altered trafficking, accumulation which may aid the passive dissemination of these emboli. […] Transfection of dominant negative E-cadherin in MARY-X, a mouse model for IBC that exhibits tight aggregates of individual tumor cells held by E-cadherin in suspension, reduces the formation of these emboli, indicating a role for E-cadherin in maintaining the clustered phenotype. […] Besides maintaining E-cadherin levels, IBC cells often also express mesenchymal proteins such as vimentin, thereby adding to the interpretation of IBC as a manifestation of a hybrid E/M phenotype. […] The predominance of CD24hi CD44hi cells can be an important underlying reason for resistance of IBC against chemotherapy and radiotherapy. […] Overall, observations in IBC mouse and cell line models and in vivo experiments on CTC clusters challenge the hypothesis that a total loss of E-cadherin is necessary for metastasis.
#78 Inflammatory Breast Cancer: a model for investigating cluster-based dissemination | bioRxiv
https://www.biorxiv.org/content/10.1101/119479v1.full
Another hallmark of IBC is the presence of numerous cohesive clusters in the lymphatics and their resistance to multiple therapies. […] These clusters or emboli have accumulation of E-cadherin due to its altered trafficking, accumulation which may aid the passive dissemination of these emboli. […] Transfection of dominant negative E-cadherin in MARY-X, a mouse model for IBC that exhibits tight aggregates of individual tumor cells held by E-cadherin in suspension, reduces the formation of these emboli, indicating a role for E-cadherin in maintaining the clustered phenotype. […] Besides maintaining E-cadherin levels, IBC cells often also express mesenchymal proteins such as vimentin, thereby adding to the interpretation of IBC as a manifestation of a hybrid E/M phenotype. […] The predominance of CD24hi CD44hi cells can be an important underlying reason for resistance of IBC against chemotherapy and radiotherapy. […] Overall, observations in IBC mouse and cell line models and in vivo experiments on CTC clusters challenge the hypothesis that a total loss of E-cadherin is necessary for metastasis.
#79 Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer | Nature Cell Biology
https://www.nature.com/articles/ncb1900
Inflammatory breast cancer (IBC) is the most lethal form of primary breast cancer. IBC lethality derives from generation of tumour emboli, which are non-adherent cell clusters that rapidly spread by a form of continuous invasion known as passive metastasis. In IBC, E-cadherin is overexpressed and supports formation of tumour emboli by promoting tumour cell interactions rather than adherence to stroma. We show that the unique pathogenic properties of IBC result in part from overexpression of the translation initiation factor eIF4GI in most IBCs. eIF4GI reprograms the protein synthetic machinery for increased translation of mRNAs with internal ribosome entry sites (IRESs) that promote IBC tumour cell survival and formation of tumour emboli. Overexpression of eIF4GI promotes formation of IBC tumour emboli by enhancing translation of IRES-containing p120 mRNAs. […] These findings provide a new understanding of translational control in the development of advanced breast cancer.
#80 Identification and Targeting of Therapeutic Resistance Mechanisms in Inflammatory Breast Cancer
https://dukespace.lib.duke.edu/dspace/handle/10161/8087
Inflammatory breast cancer (IBC) is a rare and highly aggressive form of breast cancer that is characterized by survival signaling through overexpression and/or activation of the epidermal growth factor receptors EGFR/ErbB1 and Her2/ErbB2 and defects in the apoptotic program. […] The development of therapeutic resistance is a significant barrier to successful treatment in IBC, and thus, strategies targeting the mechanisms that drive drug resistance could prevent or reverse therapeutic resistance, significantly improving patient prognosis. […] Based on analysis of previously developed models of therapeutic resistant IBC, we hypothesized that apoptotic dysregulation and redox adaptive mechanisms were central to the drug resistant phenotype in IBC cells, and that targeting of these mechanisms could overcome therapeutic resistance.
#81 Inflammatory breast cancer – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/inflammatory-breast-cancer/symptoms-causes/syc-20355413
Inflammatory breast cancer happens when a growth of cells forms in the breast tissue. The cells break away from where they started to grow and travel to the lymphatic vessels in the skin. The cells grow to clog the vessels. The blockage in the lymphatic vessels causes skin color changes, swelling and dimpled skin. This skin is a classic sign of inflammatory breast cancer. […] Inflammatory breast cancer is a form of breast cancer that causes breast swelling and skin changes. […] Inflammatory breast cancer is considered a locally advanced cancer. When a cancer is locally advanced, that means it has spread from where it started to nearby tissue and possibly to nearby lymph nodes. […] Inflammatory breast cancer can easily be confused with a breast infection, which is a much more common cause of breast swelling and skin changes.
#82 Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer | Nature Cell Biology
https://www.nature.com/articles/ncb1900
Inflammatory breast cancer (IBC) is the most lethal form of primary breast cancer. IBC lethality derives from generation of tumour emboli, which are non-adherent cell clusters that rapidly spread by a form of continuous invasion known as passive metastasis. In IBC, E-cadherin is overexpressed and supports formation of tumour emboli by promoting tumour cell interactions rather than adherence to stroma. We show that the unique pathogenic properties of IBC result in part from overexpression of the translation initiation factor eIF4GI in most IBCs. eIF4GI reprograms the protein synthetic machinery for increased translation of mRNAs with internal ribosome entry sites (IRESs) that promote IBC tumour cell survival and formation of tumour emboli. Overexpression of eIF4GI promotes formation of IBC tumour emboli by enhancing translation of IRES-containing p120 mRNAs. […] These findings provide a new understanding of translational control in the development of advanced breast cancer.
#83 Targeting Signaling Pathways in Inflammatory Breast Cancer
https://www.mdpi.com/2072-6694/12/9/2479
The tumor microenvironment (TME), which includes T cells, tumor-associated macrophages (TAMs), fibroblasts, mast cells, and mesenchymal stem cells (MSCs), has been shown to play critical roles in promoting IBC aggressiveness. […] The JAK/STAT, NF-ÎºB, and COX-2 inflammatory pathways are important in the progression of IBC. […] The activation of NF-ÎºB plays a major role in promoting the unusual phenotype and aggressiveness of IBC. […] COX-2 is overexpressed in a wide range of malignancies, including colon, bladder, prostate, pancreatic, and breast cancers, and it is associated with tumor growth and invasiveness. […] The expression of COX-2 is regulated by the EGFR pathway and is correlated with EGFR expression in IBC specimens. […] The dysregulation of WISP3 can upregulate RhoC GTPase and enhance the aggressiveness of IBC. […] The RhoC GTPase family is a potent regulator of both glutamine and N-acetylaspartate metabolism in IBC SUM149 cells, revealing a novel role in regulating tumor cell metabolism. […] The clinical relevance of targeting RhoC GTPase in IBC needs further investigation.
#84 Biomarkers for Inflammatory Breast Cancer: Diagnostic and Therapeutic | BCTT
https://www.dovepress.com/biomarkers-for-inflammatory-breast-cancer-diagnostic-and-therapeutic-u-peer-reviewed-fulltext-article-BCTT
Inflammatory breast cancer (IBC) is a rare and highly aggressive subtype of advanced breast cancer. The aggressive behavior, resistance to chemotherapy, angiogenesis, and high metastatic potential are key intrinsic characteristics of IBC caused by many specific factors. Pathogenesis and behavior of IBC are closely related to tumor surrounding inflammatory and immune cells, blood vessels, and extracellular matrix, which are all components of the tumor microenvironment (TME). […] The communication between intrinsic and extrinsic components of IBC and the abundance of cytokines and chemokines in the TME strongly contribute to the aggressiveness and high angiogenic potential of this tumor. […] Pathogenesis and aggressive behavior of IBC are closely related to tumor surrounding inflammatory and immune cells, blood vessels, and extracellular matrix, which are all components of the tumor microenvironment. The tumor microenvironment has a crucial role in the local immune response.
#85 Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer | Nature Cell Biology
https://www.nature.com/articles/ncb1900
Inflammatory breast cancer (IBC) is the most lethal form of primary breast cancer. IBC lethality derives from generation of tumour emboli, which are non-adherent cell clusters that rapidly spread by a form of continuous invasion known as passive metastasis. In IBC, E-cadherin is overexpressed and supports formation of tumour emboli by promoting tumour cell interactions rather than adherence to stroma. We show that the unique pathogenic properties of IBC result in part from overexpression of the translation initiation factor eIF4GI in most IBCs. eIF4GI reprograms the protein synthetic machinery for increased translation of mRNAs with internal ribosome entry sites (IRESs) that promote IBC tumour cell survival and formation of tumour emboli. Overexpression of eIF4GI promotes formation of IBC tumour emboli by enhancing translation of IRES-containing p120 mRNAs. […] These findings provide a new understanding of translational control in the development of advanced breast cancer.
#86 Inflammatory Breast Cancer: A Literature Review | Mamouch | World Journal of Oncology
https://www.wjon.org/index.php/wjon/article/view/1161/893
Studies have suggested that IBC does not have a specific molecular signature. Recently, they have identified in vivo and in vitro genes that can contribute to the aggressive phenotype of IBC. […] IBC cells are characterized by overexpression of E-cadherin, which is essential for cell adhesion, tumor emboli formation, and progression of metastasis which implies poor prognosis. In addition, RhoC-GTPase is overexpressed in 90% of IBC tumors compared to 38% of non-IBC tumors. Indeed, RhoC-GTPase plays a critical role in the metastatic behavior of IBC by increasing all aspects of metastatic processes such as motility and cell invasion, cytoskeletal assembly, and cell adhesion. […] The diagnosis of IBC remains above all a clinical diagnosis supported by a histological evidence of infiltrating carcinoma, and the therapeutic approach can only be multidisciplinary. The ability to identify new targeted therapies allows us to control the aggressive phenotype of IBC. Molecular biology and genomics are very likely to play an important role in the diagnosis and management of IBC.
#87 Inflammatory breast cancer: Clinical progress and the main problems that must be addressed | Breast Cancer Research | Full Text
https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr608
Inflammatory carcinoma of the breast has distinct biological characteristics that differentiate it from non-inflammatory carcinoma. […] Several genes have been identified that might contribute to the aggressive clinical behavior of inflammatory breast cancer. […] Despite the significant progress that has been made in the treatment of this aggressive form of breast cancer, most women with inflammatory breast cancer will relapse and succumb to this disease. […] Current research on the biologic characteristics of inflammatory carcinoma has made significant strides in the understanding of the aggressive behavior of this tumor, and future research will be vital in developing targeted therapies.
#88 Update on inflammatory breast cancer | Breast Cancer Research | Full Text
https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr997
Inflammatory breast cancer (IBC) is both the least frequent and the most severe form of epithelial breast cancer. […] Identification of the molecular determinants of IBC would probably lead to more specific treatments and to improved survival. […] The main issue in IBC is to identify the specific pattern of genetic changes accounting for this particular phenotype and aggressiveness, so that we can develop more effective targeted treatments. […] It is highly probable that the identification of significant molecular changes in IBC would help with diagnosis, with treatment response prediction, and with the development of new therapeutic targets. […] The rapid onset of IBC in a previously healthy breast, one of the most important characteristics of the disease, is likely to be subtended by particular molecular alterations.
#89 The tumor microenvironment and inflammatory breast cancer
https://www.jcancer.org/v08p1884.htm
In summary, the cumulative evidence up-to-date strongly indicates that the diverse cells, bioactive molecules and their related signal transduction pathways in the tumor microenvironment of IBC communicate and interact with each other, forming a complicated network, presumably mediated through various molecular and cellular biological mechanisms in the control of IBC formation, development and progression.