Materiały źródłowe

• #1 The morphologic spectrum of lobular carcinoma in situ (LCIS) observations on clinical significance, management implications and diagnostic pitfalls of classic, florid and pleomorphic LCIS – PubMed

  https://pubmed.ncbi.nlm.nih.gov/35567633/

  Lobular carcinoma in situ (LCIS) is a non-invasive proliferation of atypical dyscohesive epithelial cells characterized by loss or functional alteration of E-cadherin-mediated cell adhesion. The morphologic spectrum of LCIS encompasses classic (C-LCIS), florid (F-LCIS) and pleomorphic LCIS (P-LCIS), as recently defined by the World Health Organization (WHO) Expert Consensus Group. Atypical lobular hyperplasia (ALH) is also part of this spectrum. This article highlights the morphologic and immunohistochemical features of the three forms of LCIS and summarizes their management implications and prognosis, with emphasis on F-LCIS and P-LCIS.

• #2 Lobular Carcinoma in Situ | LCIS | American Cancer Society

  https://www.cancer.org/cancer/types/breast-cancer/non-cancerous-breast-conditions/lobular-carcinoma-in-situ.html

  Lobular carcinoma in situ (LCIS) is a type of breast change that is sometimes seen when a breast biopsy is done. In LCIS, cells that look like cancer cells are growing in the lining of the milk-producing glands (lobules) of the breast, but they dont invade through the wall of the lobules. […] LCIS is not considered cancer, and it typically does not spread beyond the lobule (that is, it doesn’t become invasive breast cancer) if it isnt treated. But having LCIS does increase your risk of later developing an invasive breast cancer in either breast. […] Women with LCIS have about a 7 to 12 times higher risk of developing invasive cancer in either breast. For this reason, doctors typically recommend that women with LCIS have regular breast cancer screening tests and follow-up visits with a health care provider for the rest of their lives.

• #3 Lobular Carcinoma in Situ (LCIS)

  https://my.clevelandclinic.org/health/diseases/21791-lobular-carcinoma-in-situ-lcis

  Lobular carcinoma in situ (LCIS) is a rare breast condition. It causes abnormal cells in your lobules the glands in your breasts that produce breast milk. LCIS isnt breast cancer but it does increase the chance youll have breast cancer. […] Researchers know genetic mutations cause normal cells in your lobules to change into abnormal cells. But they dont know what triggers the change. […] While it doesnt happen often, lobular carcinoma in situ may develop into ductal carcinoma in situ (DCIS) or lobular breast cancer. Studies show that 1 in 10 people with LCIS develop DCIS or lobular breast cancer. […] Your treatment depends on the type of LCIS. For example, if you have classic LCIS, your healthcare provider may recommend active surveillance or preventive therapy. If you have pleomorphic or florid LCIS, you may need surgery.

• #4

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4453073/

  Lobular carcinoma in situ (LCIS) is considered to be a risk factor for the development of invasive breast carcinoma, but it may also be a non-obligate precursor to invasive lobular carcinoma (ILC). […] Many LCIS lesions do not progress to ILC, and the molecular changes that are necessary for progression from LCIS to ILC are poorly understood. Disruption in the E-cadherin complex is the hallmark of lobular lesions, but other signaling molecules, such as PIK3CA and c-src, are consistently altered in LCIS. […] Currently, no diagnostic tools exist which can reliably predict if a woman will subsequently develop IBC after diagnosis of LCIS. […] The key to determining whether a LCIS lesion will progress will lie in the molecular characteristics of the lesion, including genetic aberrations in important signaling pathways, and alterations in EMT pathways. […] A deeper understanding of the drivers of LCIS toward progression to invasive cancer may illuminate possible diagnostic targets that can allow clinicians to differentiate benign pre-invasive lesions from potentially malignant ones.

• #5 Lobular carcinoma in situ – Wikipedia

  https://en.wikipedia.org/wiki/Lobular_carcinoma_in_situ

  Cells of lobular neoplasia (LN), including both atypical lobular hyperplasia and LCIS, and ILC share common genetic alterations, perhaps accounting, in part, for the similarities in histologic appearance. Classic LCIS and invasive lobular lesions are low-grade ER and PR-positive cancers, referring to the positive expression of Estrogen and Progesterone receptors on the neoplastic cells (determined via immunohistochemistry). These entities are also both classically negative for HER2 (human epidermal growth factor receptor 2). These hormone and growth factor receptors are clinically significant, as they represent targets for chemotherapy. Chromosomal alterations have also been consistently observed between LCIS and ILC namely, loss of 16q and gain of 1q, referring to the loss of the long arm (designated q) of chromosome 16 and an extra copy of the long arm of chromosome 1. Furthermore, e-cadherin, the transmembrane protein mediating epithelial cell adhesion, exhibits loss of expression on LN cells, and P120 Catenin exhibits cytoplasmic reactivity.

• #5 Lobular carcinoma in situ – Wikipedia

  https://en.wikipedia.org/wiki/Lobular_carcinoma_in_situ

  LCIS often have the same genetic alterations (such as loss of heterozygosity on chromosome 16q, the locus for the e-cadherin gene) as the adjacent area of invasive carcinoma. These observations, along with genomic analysis for clonal relationships between the cells of LCIS and ILC, support LCIS as being a precursor to ILC, and that the lesions encompassed by the broader category of lobular neoplasia (LN) fall on a linear spectrum of progression. LCIS is often found concurrently with foci of invasive carcinoma and multiple studies have shown, using genetic sequencing techniques, that synchronous LCIS and ILC share clonal cell populations, or originate from the same line of mutated cells. […] Lobular carcinoma in situ is both a risk factor and precursor of invasive carcinoma. Furthermore, it is a non-obligate precursor. In other words, LCIS represents a distinct entity in the developmental pathway of cancer that does not guarantee invasive carcinoma.

• #5 Lobular carcinoma in situ – Wikipedia

  https://en.wikipedia.org/wiki/Lobular_carcinoma_in_situ

  Lobular neoplasia is considered pre-cancerous, and LCIS is an indicator (marker) for increased risk of developing invasive breast cancer in women. This risk extends more than 20 years. Most of the risk relates to subsequent invasive ductal carcinoma rather than to invasive lobular carcinoma. […] The relative risk of developing invasive carcinoma after LCIS diagnosis is 8-10 times greater than in the general population.

• #6 Molecular drivers of lobular carcinoma in situ | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-015-0580-5

  Lobular carcinoma in situ (LCIS) is considered to be a risk factor for the development of invasive breast carcinoma, but it may also be a non-obligate precursor to invasive lobular carcinoma (ILC). […] Many LCIS lesions do not progress to ILC, and the molecular changes that are necessary for progression from LCIS to ILC are poorly understood. Disruption in the E-cadherin complex is the hallmark of lobular lesions, but other signaling molecules, such as PIK3CA and c-src, are consistently altered in LCIS. […] In contrast to the role of LCIS as a risk factor for the development of breast cancer, a role for direct progression of LCIS into invasive cancer is less well accepted, and the molecular basis is currently poorly understood. […] Cells may acquire genetic (and/or epigenetic) changes in critical pathways that allow migration into the stroma. Alternatively, or in concert, cells may receive signals that cause progression from the stroma, including fibroblasts, adipocytes, and immune cells.

• #6 Molecular drivers of lobular carcinoma in situ | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-015-0580-5

  Specific chromosomal alterations are found frequently and consistently in LCIS. The chromosomal changes most commonly associated with LCIS are loss of 16q and gain of 1q. […] Results of aCGH experiments have shown that while most chromosomal changes in LCIS are not consistent, those that are most consistent (namely, 16q loss and 1q amplification) are found early in the progression to invasive disease. […] The key to determining whether a LCIS lesion will progress will lie in the molecular characteristics of the lesion, including genetic aberrations in important signaling pathways, and alterations in EMT pathways.

• #6 Molecular drivers of lobular carcinoma in situ | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-015-0580-5

  Another possibility is that tumor suppressive myoepithelial cells may become compromised, allowing LCIS cells to break through and gain access to the stroma. […] It is most likely that the progression of LCIS to IBC occurs through a combination of these events. […] Current research on LCIS has focused on four main areas: (1) prognostic markers, (2) genomic changes, (3) factors related to epithelial to mesenchymal transition (EMT), and (4) signaling pathways. […] The expression of nuclear receptors – especially ER – can be used to predict clinical outcome of tumors; 80 to 100 % of LCIS cases express ER, most of which show moderate to strong immunoreactivity by immunohistochemistry. […] In LCIS, 0 to 11 % of tumors have HER2 amplification. More aggressive LCIS subtypes are more likely to have amplified HER2; 18 % of FLCIS and 31 % of apocrine PLCIS show HER2 amplification.

• #7 Invasive lobular carcinoma of the breast: morphology, biomarkers and ’omics | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-015-0519-x

  Invasive lobular carcinoma (ILC) is the most common special type of breast cancer and presents with a distinct morphology and clinical behaviour compared with invasive carcinoma of no special type (IC-NST). […] E-cadherin loss is responsible for the inherently discohesive phenotype associated with ILCs, and changes at the genomic level account for this loss. […] The characteristic discohesive growth pattern of ILC is the result of the dysregulation of cell-cell adhesion properties, primarily driven by the targeted disruption of the cell adhesion molecule E-cadherin. […] In contrast, approximately 90% of LNs and ILCs, including variants, completely lack E-cadherin protein expression. […] The loss of E-cadherin in ILC also results in the loss of -, – and -catenins, and p120-catenin becomes up-regulated and re-localised to the cytoplasm.

• #7 Invasive lobular carcinoma of the breast: morphology, biomarkers and ’omics | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-015-0519-x

  E-cadherin deregulation occurs in the earliest morphological stage of lobular tumourigenesis (that is, ALH) and is frequently and irreversibly driven by genomic alterations targeting its gene, CDH1 (located at chromosome 16q22.1). […] Molecularly, the patterns of E-cadherin loss often follow Knudsens two hit hypothesis for a classic tumour suppressor gene, involving CDH1 mutation, gene methylation and/or loss of heterozygosity in the region of 16q22.1. […] The somatic copy number loss of 16q in ILC and ER-positive, low-grade IC-NST is extremely frequent, suggesting these tumours share a common pathway of evolution. […] Identical CDH1 genetic mutations have been detected in LCIS and in their adjacent invasive counterpart, which is a key finding implicating LCIS as a direct (but non-obligate) precursor for ILC.

• #7 Invasive lobular carcinoma of the breast: morphology, biomarkers and ’omics | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-015-0519-x

  The acquisition of the mesenchymal phenotype is accompanied by cadherin switching (loss of E-cadherin and activation of N-cadherin), which is driven by transcriptional regulators of E-cadherin, including SNAIL and TWIST. […] Given the loss of E-cadherin and the infiltrating growth pattern of ILC, it is tempting to speculate that EMT plays a mechanistic role in driving this phenotype. […] The functional role of EMT in driving the invasive nature of ILC remains unlikely.

• #8 Understanding Your Pathology Report: Lobular Carcinoma In Situ (LCIS) | American Cancer Society

  https://www.cancer.org/cancer/diagnosis-staging/tests/biopsy-and-cytology-tests/understanding-your-pathology-report/breast-pathology/lobular-carcinoma-in-situ.html

  Lobular carcinoma in situ (LCIS) is a type of in-situ carcinoma of the breast. While DCIS is considered a pre-cancer, it is unclear whether LCIS is a pre-cancer or if it’s just a general risk factor for developing breast cancer. This is because LCIS rarely seems to turn into invasive cancer if it’s left untreated. Having LCIS does increase a person’s risk of getting breast cancer, but the cancer occurs just as often in the opposite breast (the one without any LCIS). Because it isn’t clear if LCIS is a pre-cancer, many doctors prefer to use the term lobular neoplasia instead of lobular carcinoma in situ. […] LCIS and another type of breast change called atypical lobular hyperplasia (ALH) are types of lobular neoplasia. These are benign (non-cancerous) conditions, but they both increase your risk of breast cancer. […] E-cadherin is a test that might be done to help determine if carcinoma in situ is ductal (DCIS) or lobular (LCIS). (The cells in LCIS are usually negative for E-cadherin.) If your report doesn’t mention E-cadherin, it means that this test wasn’t needed to make the distinction.

• #9 Understanding Lobular Carcinoma In Situ (LCIS) | Breast Cancer Research Foundation

  https://www.bcrf.org/about-breast-cancer/lcis-lobular-carcinoma-in-situ/

  Despite both having lobular in the name, invasive lobular carcinoma and lobular carcinoma in situ (LCIS) are not the same. […] The causes of LCIS are not well known or understood, but some hereditary risk factors have been identified. […] A gene commonly mutated in LCIS is CDH-1, a tumor suppressor gene that provides the instructions for making the protein E-cadherin. […] In some studies, mutations in the PIK3CA gene were found to be just as common as CDH-1 mutations in LCIS. […] Researchers continue to investigate genetic mutations and other molecular drivers of LCIS formation and how they may contribute to an elevated breast cancer risk. […] Other risk factors for LCIS include being over 40 years of age, using a combination (estrogen and progestin) hormone replacement therapy for more than three to five years after menopause, smoking, and excessive alcohol consumption.

• #9 Understanding Lobular Carcinoma In Situ (LCIS) | Breast Cancer Research Foundation

  https://www.bcrf.org/about-breast-cancer/lcis-lobular-carcinoma-in-situ/

  LCIS does not usually cause any symptoms. […] Because of the elevated cancer risk, doctors may recommend more frequent mammogram, ultrasound, and MRI screenings to ensure any cancer that develops is caught at its earliest stage. […] Because no diagnostic tools currently exist that reliably predict who will develop invasive breast cancer after an LCIS diagnosis, it is likely that some women with LCIS are undertreated, and some women are overtreated. […] BCRF researchers are committed to developing more precise, personalized breast cancer screening, especially in women who have an elevated risk of breast cancer. […] Our investigators are developing a deeper understanding of the drivers of disease by identifying the genetic or molecular biomarkers associated with high-risk breast lesions such as DCIS and LCIS.

• #10 Lobular neoplasia: morphology, biological potential and management in core biopsies | Modern Pathology

  https://www.nature.com/articles/modpathol201035

  Lobular neoplasia has been traditionally recognized as a marker of increased risk for subsequent breast carcinoma development; however, molecular studies suggest that it also behaves in a non-obligate precursor manner. […] However, in recent years, there is increasing evidence that LCIS may also act as a non-obligate precursor in the progression to invasive carcinoma. […] The molecular data described above suggest that ALH/LCIS behaves in a non-obligate precursor manner. Loss of 16q and gain at 1q in lobular neoplasia points to the possible progression toward a low-grade invasive phenotype, given the frequency of these alterations in low-grade invasive breast cancer. […] Taken together, however, the molecular genetic and clinicopathological data support lobular neoplasia acting both as a precursor lesion and as a risk indicator for subsequent carcinoma. We cannot, as yet, predict which lobular neoplastic lesions are likely to progress. Further studies are needed to understand and identify the subset of lobular neoplastic lesions that have the highest likelihood of progressing to invasive carcinoma.

• #11 Lobular Breast Cancer And LCIS Characteristics | Food for Breast Cancer

  https://foodforbreastcancer.com/articles/lobular-breast-cancer-and-lcis-characteristics

  However, one study found that LCIS with high Ki-67 (a marker of proliferation) expression is more likely to progress to invasive breast cancer than low Ki-67. […] The picture is more clear for pleomorphic lobular carcinoma in situ (PLCIS), a higher-risk type of LCIS which is more likely to progress.

• #11 Lobular Breast Cancer And LCIS Characteristics | Food for Breast Cancer

  https://foodforbreastcancer.com/articles/lobular-breast-cancer-and-lcis-characteristics

  Women with lobular carcinoma in situ (LCIS) or atypical lobular hyperplasia (a possible precursor of both LCIS and invasive breast cancer) are at significantly higher than average risk for invasive breast cancer, but the risk is higher for developing both ductal and lobular breast cancer. […] One small study reported that 50% of invasive lobular tumors eventually arising in women with LCIS were clonally related, in other words, they were very similar genetically with shared mutations. […] A 2023 study reported that the absence of LCIS at the time of diagnosis was an unfavorable prognostic marker among those with invasive lobular breast cancer. […] One 2024 study reported that LCIS has both an immediate risk (19.3%) and a delayed risk (18.6%) of invasive breast cancer with 91% of such cancer occurring in the same breast as the LCIS and 9% in the opposite (contralateral) breast.

• #12 Contemporary management of ductal carcinoma in situ and lobular carcinoma in situ – Obeng-Gyasi – Chinese Clinical Oncology

  https://cco.amegroups.org/article/view/10361/html

  In addition to being a risk factor, LN has also been shown to be a non-obligate precursor based on comparable histologic and molecular profiles to invasive lobular cancer and a higher risk of ipsilateral breast cancer compared to the contralateral breast. […] Furthermore, in contrast to women of average risk, individuals with LN have an increased probability of developing ILC (18-fold increase) as opposed to IDC (3- to 4-fold increase). […] PLCIS is characterized by enlarged discohesive epithelial cells, irregular shaped nuclei and abundant eosinophilic cytoplasm. […] Additional features such as comedo necrosis and calcifications found in PLCIS make it histopathologically similar to DCIS. […] Such similarities to DCIS have resulted in some authors arguing that PLCIS has an increased probability of progression to invasive cancer.

• #12 Contemporary management of ductal carcinoma in situ and lobular carcinoma in situ – Obeng-Gyasi – Chinese Clinical Oncology

  https://cco.amegroups.org/article/view/10361/html

  Histopathologically, lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS) are differentiated from invasive carcinoma by the confinement of malignant cells to the basement membrane. […] However, recent genomic and transcriptomic analyses indicate molecular similarities in in situ and invasive cancers within the context of histologic grade as opposed to stage of progression. […] Estrogen receptor expression and activation among these lesions has been also been implicated in the progression to invasive disease. […] Moreover, the work of Hanahan et al. on the hallmarks of cancer have contributed to the evolution of our understanding of tumorigenesis and moved us towards consideration of both DCIS and LCIS as non-obligate precursors along the broad spectrum of malignant progression. […] Thus, the progression from DCIS and LCIS to invasive cancer is not assured, but rather a complex process involving interactions between genetics and the microenvironment at the molecular level.

• #13 Case: Lobular Carcinoma in Situ (LCIS) – Radiology | UCLA Health

  https://www.uclahealth.org/departments/radiology/education/breast-imaging-teaching-resources/cases/case-lcis

  Lobular carcinoma in situ (LCIS) is a noninvasive lesion of the breast considered to be a nonobligate precursor of invasive lobular carcinoma. The pathologic definition is proliferation of atypical cells filling and distending at least half of the acini in the lobular unit. In LCIS, cells typically show dyscohesion with loss of E-cadherin expression. Pagetoid spread of cells between the epithelial and myoepithelial layers is another common pathologic feature. […] Besides classic LCIS, less common variants of LCIS have been recognized. Pleomorphic LCIS demonstrates large, pleomorphic nuclei. Florid LCIS involves marked distension of ducts or terminal duct lobular units. Both pleomorphic and florid LCIS subtypes are often associated with calcifications and comedonecrosis.

• #14 :: Journal of Breast Disease

  https://www.jbd.or.kr/m/journal/view.php?number=128

  There is no consensus on management strategies for LCIS. […] Recent guidelines recommend that risk management, including close follow-up, risk-reducing medication, or preventative mastectomy, should be considered for women with LCIS. […] Routine surgical excision, however, is not recommended for the management of LCIS. […] The results of the present study showed an excellent prognosis for LCIS, whether the patient was treated with or without radiation therapy. […] Pleomorphic LCIS is considered an aggressive type of LCIS. […] In the present study, pleomorphic LCIS was found in 3 cases (6.1%), which was lower than what was found in a previously reported study.

• #15 Lobular Carcinoma In-Situ (LCIS)

  https://cbcn.ca/en/lobular-carcinoma-in-situ

  Lobular carcinoma in situ (LCIS) describes a condition in which there is abnormal cell growth in the lining on the lobules that dont invade the wall of the lobules. […] While LCIS is a benign condition and is not considered to be breast cancer, having LCIS puts a person at an approximately 7 to 12 times higher risk of later developing invasive breast cancer. […] Following a diagnosis of classic LCIS, the risk of going on to develop invasive carcinoma is about 9 to 10 times higher as compared to the general population. […] In pleomorphic LCIS, the cells lining the breast lobules and larger and more abnormal looking. […] 72% to 100% of cases of pleomorphic LCIS are positive for estrogen receptors (ER), 50% to 100% of cases are positive for progesterone receptors (PR), and in 1% to 41% of cases HER2 is overexpressed.

• #16 Lobular Carcinoma in Situ (LCIS)

  https://info.iowaradiology.com/lobular-carcinoma-in-situ-lcis

  Lobular carcinoma in situ (LCIS) describes the growth of abnormal cells in the breast lobules, the milk-producing glands at the ends of the milk ducts. In situ means that the abnormal cells are contained in their original place and have not invaded the surrounding tissue. […] Unlike ductal carcinoma in situ (DCIS), LCIS is not considered true breast cancer. Rather, it is a condition that is associated with an increased risk of developing breast cancer in the future. Because of this, some experts prefer the term lobular neoplasia (denoting the development of abnormal lobular cells) rather than referring to this condition as carcinoma. […] Women with LCIS have 8-10 times the average risk of developing invasive breast cancer in either the lobules or the milk ducts. […] When LCIS is diagnosed, its usually a result of a biopsy investigating another breast condition in the vicinity of the abnormal cells.

• #16 Lobular Carcinoma in Situ (LCIS)

  https://info.iowaradiology.com/lobular-carcinoma-in-situ-lcis

  Under a microscope, LCIS can look much like DCIS. Both are described as stage 0, meaning that the abnormality has not spread beyond the original site. […] LCIS is most often diagnosed before menopause, between the ages of 40 and 50. […] More than half of patients are found to have abnormal cells in more than one lobule (called multifocal LCIS), and in about one third of LCIS patients, both breasts are affected. […] Because the presence of LCIS indicates an elevated breast cancer risk, it is especially important that patients with the condition continue to get regular screening mammograms. […] Some patients with LCIS choose to take medications to lower their risk of developing breast cancer (called chemoprevention). […] A recent study found that women with LCIS have a 2% annual risk of developing breast cancer, and those who choose chemoprevention lower that annual risk to below 1%.

• #17 Lobular carcinoma in situ (LCIS): Symptoms, cancer, and more

  https://www.medicalnewstoday.com/articles/lcis

  Of the two conditions, DCIS is more serious. Doctors consider DCIS precancer, but it is not clear if LCIS is definitely precancer or merely a risk factor for breast cancer development. […] Treatment may consist of surgically removing the abnormal cells along with a small amount of healthy tissue surrounding them. […] To reduce the risk of breast cancer, doctors may also recommend a person take estrogen-blocking or estrogen-reducing medications because the hormone may impact breast cancer cell growth. […] The authors of the study also mention a 2017 analysis that found that females with LCIS who develop breast cancer usually get an early-stage diagnosis.

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