Materiały źródłowe

• #1 Pathways to Breast Cancer Recurrence

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3603357/

  Breast cancer recurrence is clinically a huge problem and one that is largely not well understood. […] This phenomenon is tumor recurrence and the subject of our discussion here. […] Recurrence of breast cancer is a major clinical manifestation and represents the principal cause of breast cancer-related deaths. […] A differential pattern of recurrence between different breast cancer subtypes has been suggested, and it appears that ER-negative breast cancers are associated with higher risk of recurrence during the initial 5 years after diagnosis, compared to ER-positive breast cancers. […] The existence of such subtypes, which are at time overlapping but most of the time so distinct, presents a challenge to the choice of appropriate therapy. […] Irrespective of the underlying breast cancer subtype, a large number of advanced stage breast cancers are marked by metastases to lymph nodes, and, overall, the presence of axillary lymph node metastases is associated with considerable poor disease-free as well as overall survival.

• #2 Breast Cancer Recurrence: Rates, Signs & Treatment

  https://my.clevelandclinic.org/health/diseases/8328-breast-cancer-recurrence

  Breast cancer recurrence is when cancer comes back after treatment. Recurrent breast cancer may develop where it started, or spread to nearby lymph nodes or to more distant areas of your body. Healthcare providers can treat recurrent breast cancer, but it can come back again. […] Breast cancer recurrence happens when treatment doesnt kill all the cancer cells in your breast. Breast cancer treatments are effective, but breast cancer cells can be tricky: Treatment can shrink breast cancer tumors to the point that tests dont detect weakened cancer cells. But the cells are still there, and over time, they can return stronger, start to grow and create tumors. […] According to the American Cancer Society, inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) are more likely to come back than other breast cancer types and subtypes.

• #3 Recurrent breast cancer – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/recurrent-breast-cancer/symptoms-causes/syc-20377135

  Recurrent breast cancer is breast cancer that comes back after initial treatment. Although the initial treatment is aimed at eliminating all cancer cells, a few may have evaded treatment and survived. These undetected cancer cells multiply, becoming recurrent breast cancer. […] Recurrent breast cancer occurs when cells that were part of your original breast cancer break away from the original tumor and hide nearby in the breast or in another part of your body. Later, these cells begin growing again. […] The chemotherapy, radiation, hormone therapy or other treatment you may have received after your first breast cancer diagnosis was intended to kill any cancer cells that may have remained after surgery. But sometimes these treatments aren’t able to kill all of the cancer cells. […] Sometimes cancer cells may be dormant for years without causing harm. Then something happens that activates the cells, so they grow and spread to other parts of the body. It’s not clear why this occurs.

• #4 Breast Cancer Recurrence: Rates, Signs & Treatment

  https://my.clevelandclinic.org/health/diseases/8328-breast-cancer-recurrence

  Breast cancer recurrence is when cancer comes back after treatment. Recurrent breast cancer may develop where it started, or spread to nearby lymph nodes or to more distant areas of your body. Healthcare providers can treat recurrent breast cancer, but it can come back again. […] Breast cancer recurrence happens when treatment doesnt kill all the cancer cells in your breast. Breast cancer treatments are effective, but breast cancer cells can be tricky: Treatment can shrink breast cancer tumors to the point that tests dont detect weakened cancer cells. But the cells are still there, and over time, they can return stronger, start to grow and create tumors. […] According to the American Cancer Society, inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) are more likely to come back than other breast cancer types and subtypes.

• #5 The lingering mysteries of metastatic recurrence in breast cancer | British Journal of Cancer

  https://www.nature.com/articles/s41416-020-01161-4

  Metastatic recurrence is a significant problem in patients with breast cancer, the most frequently diagnosed malignancy and the second leading cause of cancer-related death among women worldwide. […] Protracted intervals between diagnosis and recurrence have been proposed to be the result of tumour dormancy, whereby clinically undetectable minimal residual disease (MRD) can lie asymptomatic for many years to decades. […] This phenomenon appears to reflect not only the metastatic behaviour of cancer cells that are able to escape from the primary tumour and spawn multiple distant metastases prior to diagnosis, but also their ability to remain dormant in secondary sites and thereby resistant to anti-proliferative agents. […] Despite the urgency, however, an understanding of the biological underpinnings of relapse is still lacking.

• #6 Breast Cancer Recurrence | Breast Cancer Surgery Melbourne, VIC

  https://www.melbournebreastcancersurgery.com.au/breast-cancer-recurrence.html

  These cells can begin to grow right away or can remain dormant for many years before beginning to grow and travel further through the body. […] Many recurrences are detected in the five years after diagnosis, especially after triple negative breast cancer. However, on occasions recurrence can occur more than 20 years after the first diagnosis. […] Your individual chance of breast cancer returning is also determinate on a number of factors including the type of breast cancer, tumour size, genetic factors and treatment types. […] In most cases, even the smallest breast cancer detected has been growing for some time before it was caught. […] During this period of growth, the cancer cells multiplied and divided over and over again, and some cancer cells may splinter off from the main tumour and escaped into the surrounding blood and lymphatic vessels.

• #7 The lingering mysteries of metastatic recurrence in breast cancer | British Journal of Cancer

  https://www.nature.com/articles/s41416-020-01161-4

  This review focuses on the questions surrounding metastatic relapse, using breast cancer as a key example, given its wide window of recurrence spanning from months to decades from initial treatment. […] This range in recurrence intervals is likely to reflect, at least in part, tumour cell dissemination, the balance between cell-extrinsic and cell-intrinsic factors in the metastatic environment and the putative dormancy of metastatic cells at distant sites. […] Metastatic relapse is attributed to the outgrowth of cancer cells that have escaped from the primary tumour and take up residence in secondary sites. […] The process whereby DTCs transform a localised cancer into a systemic disease is called the metastatic cascade. […] In this regard, findings from breast cancer mouse models have suggested that early DTCs might be more capable of metastatic seeding, yet less competent at forming primary tumours upon transplantation compared with late DTCs.

• #8 Pathways to Breast Cancer Recurrence

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3603357/

  The majority of research investigations on the role of CSCs in tumor recurrence have focused on their role in the context of resistance against chemotherapy; however, it is increasingly being advocated that CSCs determine the resistance to radiation therapy as well. […] The process of EMT has attracted much interest in recent years with regard to breast cancer aggression. Its association with CSC phenotype further underscores its importance in recurrence of breast tumors. […] Similar to Notch signaling, a role of Wnt signaling in breast tumor recurrence has also been suggested. […] There is evidence to suggest a correlation between Hh signaling and tumor recurrence. […] The causes for such breast cancer recurrence remain completely unknown, except for many putative molecular markers that are under active investigation for their possible role in determining the recurrence. […] The last few years have seen an exponential increase in the number of investigations focused on the functionality of miRNAs in breast cancer progression. There has also been an interest in studying miRNAs with possible implications in predicting breast cancer recurrence.

• #9 Breast cancer: pathogenesis and treatments

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11836418/

  The tumor microenvironment, characterized by interactions between tumor cells, stromal cells, and immune cells, further modulates carcinogenesis. Understanding these mechanisms is vital for developing preventive strategies and targeted therapies. […] Cancer stem cells (CSCs) constitute a minor fraction of the tumor population, characterized by their capacity for self-renewal and differentiation. A plethora of compelling evidence substantiates that CSCs play a pivotal role in driving tumor initiation, conferring resistance to treatment, facilitating recurrence, and promoting metastasis. […] The stemness of tumor cells is regulated by internal signals and influenced by the tumor microenvironment. […] The emergence of novel therapeutic concepts and drugs represents a paradigm shift towards personalized medicine. Evidence suggests that optimal diagnosis and treatment models tailored to individual patient risk and expected subtypes are crucial, supporting the era of precision oncology for breast cancer.

• #10

  https://www.alliedacademies.org/articles/advances-in-diagnosis-and-treatment-of-breast-cancer-recurrence-20809.html

  The estimated lifetime risk of developing breast cancer for women with BRCA1 and BRCA2 mutations is 40% to 85% respectively and carriers with a history of breast cancer have an increased risk as high as 5% per year of contralateral disease that is either a metastatic lesion or the second primary cancer. […] Sometimes after treatment, the residual tumor cells are still detected in most patients. These tumors remain dormant for years before resuming their growth. This results in tumor recurrence with time. […] The cells which play an important role in the formation, growth, and recurrence of tumors, particularly following therapeutic intervention are the cancer stem cells. […] Hence, it is imperative to understand and investigate these mechanisms to design strategies to prevent the recurrence of breast cancer.

• #11

  https://www.alliedacademies.org/articles/advances-in-diagnosis-and-treatment-of-breast-cancer-recurrence-20809.html

  In breast cancer, these cells are identified as CD44(+)/CD24(-). […] With respect to breast cancer, aberrant expression of notch receptors has been seen on epithelial metaplastic lesions and neoplastic lesions inferring that they might play the role of a proto-oncogene. […] It is for this reason; the five-year survival rate for TNBC patients tends to be lower (77%) than other breast cancer types (93%). […] Despite advancements in breast cancer treatment, there is still a significant proportion of patients who continue to experience recurrence even after adjuvant chemotherapy treatment and the survival of stage IV solid tumors still remains low. […] The lymph node status, HER-2 status, and age are significant risk factors for ipsilateral breast tumor recurrence on univariate analysis.

• #12

  https://link.springer.com/article/10.1245/s10434-008-0037-5

  We aimed to identify mechanisms driving local recurrence in a model of breast-conserving surgery (BCS) for breast cancer. […] Breast cancer recurrence after BCS remains a clinically significant, but poorly understood problem. […] Gene expression studies suggested roles for the PI3K/Akt system and local immunosuppression driving the altered growth kinetics. […] Investigating therapies which target tumour survival pathways such as PI3K/Akt and boost immune surveillance in the perioperative period may be useful adjuncts to contemporary breast cancer treatment.

• #13 Pathophysiology and Diagnosis of Breast cancer

  https://www.longdom.org/open-access/pathophysiology-and-diagnosis-of-breast-cancer-92567.html

  Breast cancer can be classified as either primary or metastatic. […] Various types of breast cancer include angiosarcoma, paget disease, inflammatory breast cancer, lobular carcinoma, ductal carcinoma, recurrent breast cancer etc. […] Breast cancer occurs due to contact between an environmental (external) factor and a genetically vulnerable host. […] When cells lose their ability to stop dividing, adhere to other cells and die at the appropriate moment, and finally become malignant. […] One of the protecting pathways is the PI3K/AKT pathway; another is the RAS/MEK/ ERK pathway. […] In some breast cancers, the gene for the PTEN protein is metamorphosed, so the PI3K/AKT pathway is trapped in the „on” position, and the cancer cell does not self-destruct.

• #14 Breast Cancer Metastasis: Mechanisms and Therapeutic Implications

  https://www.mdpi.com/1422-0067/23/12/6806

  Metastasis is the multiple process by which an original primary tumor develops into a distal secondary tumor. It is a representative hallmark of cancer and leads to treatment failure, leading to the death of many patients. Therefore, the patient’s prognosis is closely related to metastasis. The diagnosis of metastatic cancer is considered the final stage in most cancer types. Metastasis is highly complex and involves multiple cellular mechanisms including division from the primary tumor, invasion, evasion of immune surveillance, and regulation of the tissue microenvironment. In particular, epithelial–mesenchymal transition (EMT) is required for metastasis in most cancers. […] EMT, a phenomenon in which epithelial cell polarity and intercellular cohesion are lost, is required for the initiation of metastasis in breast cancer. The pleiotropic transcription factors including SNAIL, TWIST, and zinc finger E-box-binding (ZEB) are important molecules in the regulation of EMT. Recent studies have demonstrated that the loss of expression or dysfunction of GATA3 promotes breast cancer metastasis by regulating G9A and metastatic tumor antigen (MTA) family proteins recruited by ZEB2.

• #15 Breast cancer – Wikipedia

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

  Some mutations associated with cancer, such as p53, BRCA1 and BRCA2, occur in mechanisms to correct errors in DNA. The inherited mutation in BRCA1 or BRCA2 genes can interfere with repair of DNA crosslinks and double-strand breaks (known functions of the encoded protein). These carcinogens cause DNA damage such as DNA crosslinks and double-strand breaks that often require repairs by pathways containing BRCA1 and BRCA2. […] GATA-3 directly controls the expression of estrogen receptor (ER) and other genes associated with epithelial differentiation, and the loss of GATA-3 leads to loss of differentiation and poor prognosis due to cancer cell invasion and metastasis.

• #16 Breast cancer: pathogenesis and treatments | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-02108-4

  Breast cancer, characterized by unique epidemiological patterns and significant heterogeneity, remains one of the leading causes of malignancy-related deaths in women. The mechanisms of tumorigenesis and progression of breast cancer have been central to scientific research, with investigations spanning various perspectives such as tumor stemness, intra-tumoral microbiota, and circadian rhythms. […] Understanding these factors can help in breast cancer prevention and early detection. In addition, the progression of tumor is influenced by various factors operating through distinct mechanisms (such as tumor stemness, intra-tumoral microbiota, and circadian rhythms), and a comprehensive investigation into these mechanisms is essential for identifying potential clinical therapeutic targets. […] The precise mechanisms of breast cancer progression are not fully understood. As mentioned above, the etiology of breast cancer involves a complex array of genetic and environmental factors that contribute to the malignant transformation of breast cells. The tumor microenvironment, characterized by interactions between tumor cells, stromal cells, and immune cells, further modulates carcinogenesis. Understanding these mechanisms is vital for developing preventive strategies and targeted therapies.

• #17 Breast cancer: pathogenesis and treatments | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-02108-4

  Hence, breast carcinogenesis is a multistep process involving the accumulation of genetic alterations and the influence of various risk factors. […] The tumor microenvironment is also populated by lymphocytes, macrophages, myeloid lineage cells, etc., which predominantly play roles in immune reactions. […] Breast cancer exhibits unique mechanisms of immune evasion that contribute to its progression and resistance to immunotherapy. […] The interplay between breast cancer cells and host antitumor immunity determines co-existing mechanisms of immune escape within the same patient, highlighting the need for combinatory immunotherapies and biomarker development. […] The dormancy and reactivation of long-established disseminated tumor cells (DTCs) in distant organs following primary tumor resection constitute a pivotal factor contributing to tumor recurrence and pose a significant challenge in antitumor therapy.

• #18 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Breast-Cancer-Pathophysiology.aspx

  Breast cancer is a malignant tumor that starts in the cells of the breast. […] Damage to the DNA and genetic mutations can lead to breast cancer have been experimentally linked to estrogen exposure. […] The immune system normally seeks out cancer cells and cells with damaged DNA and destroys them. Breast cancer may be a result of failure of such an effective immune defence and surveillance. […] These are several signalling systems of growth factors and other mediators that interact between stromal cells and epithelial cells. Disrupting these may lead to breast cancer as well.

• #19 Breast Cancer Metastasis: Mechanisms and Therapeutic Implications

  https://www.mdpi.com/1422-0067/23/12/6806

  Immune cells and the tumor microenvironment (TME) may also contribute to breast cancer metastasis. Tumor-associated macrophages (TAMs) play different roles in various microenvironmental signaling. In breast cancer, TAM, a macrophage subtype M2, is often activated by IL-4 secreted by CD4+ T cells. TAM-secreting cytokines including chemokines, inflammatory factors, and growth factors are strongly associated with metastasis by increasing the adhesion to the extracellular matrix (ECM). Therefore, these immune cells and secreted factors could be targets for the treatment of metastatic breast cancer. […] Metastasis is important in breast cancer treatment because it can be both a therapeutic target and a detectable marker. Targeted therapeutics for breast cancer include substances or drugs that block cancer growth by interfering with the function of certain molecules responsible for tumor cell proliferation and survival. Targeted treatment for metastatic breast cancer is determined by the presence or absence of hormone receptors, Her2, cancer recurrence, metastasis rate, and metastasis site. In particular, personalized treatment for individual patients can enhance the therapeutic efficacy and minimize chemotherapy-induced toxicity in breast cancer. However, the possibility of recurrence and metastasis of all types of breast cancer still exists. Additionally, there is still no standard treatment for patients with TNBC, the most aggressive and recurrent type, and results in intensive metastasis. Therefore, this review highlights recent advances in breast cancer treatment, clinical potential and limitations, and presents a more in-depth knowledge of metastatic breast cancer.

• #20 Estrogen a more powerful breast cancer culprit than we realized — Harvard Gazette

  https://news.harvard.edu/gazette/story/2023/05/estrogen-a-more-powerful-breast-cancer-culprit-than-we-realized/

  In what may turn out to be a long-missing piece in the puzzle of breast cancer, Harvard Medical School researchers have identified the molecular sparkplug that ignites cases of the disease currently unexplained by the classical model of breast-cancer development. […] We have identified what we believe is the original molecular trigger that initiates a cascade culminating in breast tumor development in a subset of breast cancers that are driven by estrogen, said study senior investigator Peter Park, professor of Biomedical Informatics in the Blavatnik Institute at HMS. […] The study also shows that the sex hormone estrogen is the culprit behind this molecular dysfunction because it directly alters a cells DNA. […] The new work, however, shows that estrogen causes mischief in a far more direct manner.

• #21 Estrogen a more powerful breast cancer culprit than we realized — Harvard Gazette

  https://news.harvard.edu/gazette/story/2023/05/estrogen-a-more-powerful-breast-cancer-culprit-than-we-realized/

  Our work demonstrates that estrogen can directly induce genomic rearrangements that lead to cancer, so its role in breast cancer development is both that of a catalyst and a cause, said study first author Jake Lee, a former research fellow in the Park lab who is now a medical oncology fellow at Memorial Sloan Kettering Cancer Center. […] When the researchers zoomed onto the hot spots of cancer-gene activation, they noticed that these areas were curiously close to estrogen-binding areas on the DNA. […] This offered a strong clue that estrogen might be somehow involved in the genomic reshuffling that gave rise to cancer-gene activation. […] Estrogen is already known to fuel breast cancer growth by promoting the proliferation of breast cells. However, the new observations cast this hormone in a different light.

• #22 Estrogen a more powerful breast cancer culprit than we realized — Harvard Gazette

  https://news.harvard.edu/gazette/story/2023/05/estrogen-a-more-powerful-breast-cancer-culprit-than-we-realized/

  They show estrogen is a more central character in cancer genesis because it directly alters how cells repair their DNA. […] In light of our results, we propose that these drugs may also prevent estrogen from initiating cancer-causing genomic rearrangements in the cells, in addition to suppressing mammary cell proliferation, Lee said. […] The findings suggest that estrogen-suppressing drugs such as tamoxifen often given to patients with breast cancer to prevent disease recurrence work in a more direct manner than simply reducing breast cell proliferation.

• #23 Breast cancer – Wikipedia

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

  Breast cancer, like other cancers, occurs because of an interaction between an environmental (external) factor and a genetically susceptible host. Normal cells divide as many times as needed, and stop. They attach to other cells and stay in place in tissues. Cells become cancerous when they lose their ability to stop dividing, to attach to other cells, to stay where they belong, and to die at the proper time. […] Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure. Additionally, G-protein coupled estrogen receptors have been associated with various cancers of the female reproductive system including breast cancer. […] Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth. In breast adipose tissue, overexpression of leptin leads to increased cell proliferation and cancer.

• #24 Recurrent Breast Cancer

  https://www.texasoncology.com/types-of-cancer/breast-cancer/recurrent-breast-cancer

  Research indicates that the addition of Avastin to chemotherapy in the treatment of patients with advanced breast cancer produces more anti-cancer responses and longer cancer-free survival than chemotherapy alone. […] The type of second-line therapy that is selected and its effectiveness depends on which first-line chemotherapy the patient received. […] Patients typically develop resistance to drugs that were previously used to treat their cancer. […] The growth of some breast cancer cells can be prevented or slowed by reducing the exposure to estrogen. […] The growth of ER-positive breast cancer cells can be prevented or slowed by reducing their exposure to estrogen. […] Therapy for recurrent, hormone-resistant breast cancer may differ based on which treatment was previously administered.

• #25

  https://www.xiahepublishing.com/2996-3427/OnA-2024-00027

  Discordance in receptor expression between primary and recurrent breast cancer was common, highlighting the importance of re-biopsy in recurrent or metastatic breast cancer, if possible. Patients who lost hormone receptors experienced worse outcomes, suggesting the development of treatment-resistant tumor clones. […] The literature suggests that ER and PR expression is not only discordant during breast cancer recurrence (following diagnosis and subsequent treatment) but also unstable during the metastatic process. […] The hypothesis is that HR receptor loss leads to a shift toward a more aggressive phenotype, which is more likely to metastasize, is associated with tumor recurrence, and is less responsive to treatment, leading to poorer prognosis. […] This systematic review of the literature provides evidence for receptor discordance between primary and recurrent breast cancer. This review adds to the existing evidence refuting the assumption that primary and recurrent breast cancer cells have uniform receptor profiles.

• #26 Breast Cancer: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/1947145-overview

  The current understanding of breast cancer etiopathogenesis is that invasive cancers arise through a series of molecular alterations at the cell level. These alterations result in breast epithelial cells with immortal features and uncontrolled growth. […] This view of breast cancer not as a set of stochastic molecular events, but as a limited set of separable diseases of distinct molecular and cellular origins has altered thinking about breast cancer etiology, type-specific risk factors, and prevention and has had a substantial impact on treatment strategies and breast cancer research. […] Evidence from The Cancer Genome Atlas Network (TCGA) confirms the following four main breast tumor subtypes, with distinct genetic and epigenetic aberrations: Luminal A, Luminal B, Basal-like, HER2-positive.

• #27 Late Recurrence of Breast Cancer

  https://www.verywellhealth.com/late-recurrence-of-breast-cancer-4766608

  Some breast cancers may come back 10, 15, or 20-plus years later […] The „late recurrence” or relapse of breast cancer refers to cancers that come back after five years, but may not return for 10 years, 20 years, or even more. For people who have estrogen receptor-positive breast cancer, the recurrence rate is actually higher after five years than in the first five years. […] In contrast to the common belief that surviving for five years after cancer treatment is equivalent to a cure, with hormone-sensitive (estrogen and/or progesterone receptor-positive) breast tumors, there is a steady rate of recurrence risk for at least 20 years after the original diagnosis, even with very small node-negative tumors. […] Overall, the chance that an estrogen receptor-positive tumor will recur (distant recurrence) between five years and 20 years after diagnosis ranges from 10% to over 41%. People with these tumors remain at risk for the remainder of their lives.

• #28 Breast Cancer – Gynecology and Obstetrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gynecology-and-obstetrics/breast-cancer/breast-cancer

  Breast cancer invades locally and spreads through the regional lymph nodes, bloodstream, or both. Metastatic breast cancer may affect almost any organ in the bodymost commonly, lungs, liver, bone, brain, and skin. Some breast cancers may recur sooner than others; recurrence can often be predicted based on tumor markers. For example, metastatic breast cancer may occur within 3 years in patients who are negative for tumor markers or occur 10 years after initial diagnosis and treatment in patients who have an estrogen-receptor positive tumor. […] BRCA1 and BRCA2 gene mutations increase the risk of developing breast cancer to 70%. Prophylactic bilateral mastectomy reduces the risk of breast cancer by 90% and should be offered to women with a BRCA mutation. Other genetic mutations that increase the risk of developing breast cancer include mutations in CHEK2, PALB2, ATM, RAD51C, RAD51D, BARD1, and TP53, which are usually included in panel genetic testing.

• #29

  https://www.alliedacademies.org/articles/advances-in-diagnosis-and-treatment-of-breast-cancer-recurrence-20809.html

  The high-risk factors of recurrence after Breast-Conserving Therapy (BCT) are ER/ PR, HER-2, age, lymph node involvement, tumor diameter, neoadjuvant chemotherapy, and pathological status. […] The expression of MMP2 and MMP9 is associated with high metastasis potential in breast cancer. Strong expression of MMP9 was observed in recurring tumors. […] NSD2 overexpression has been seen in multiple types of aggressive solid tumors including breast cancer and can be used as a valuable biomarker to check for recurrence and prognosis of a tumor. […] The use of biomarkers has improved breast cancer diagnosis, prognosis, prediction of therapeutic response, and follow up of disease during and after treatment. […] For example, Cyclin E, a protein expressed in the late phase of the cell cycle can be considered as an acceptable biomarker as its overexpression has been seen to correlate with an increased risk in breast cancer recurrence.

• #30 Breast Cancer Recurrence | Breast Cancer Surgery Melbourne, VIC

  https://www.melbournebreastcancersurgery.com.au/breast-cancer-recurrence.html

  However, everyone who has had breast cancer is at potential risk of recurrence, and that is why in most cases, there is a recommendation for treatment in addition to surgery, which is known as adjuvant therapy. […] The risk of recurrence can never be entirely eliminated, but the aim of adjuvant therapy is to reduce recurrence risk to the absolute minimum. […] Some breast cancers, when diagnosed very early when small and without lymph node involvement, have an excellent prognosis and are very unlikely to recur. […] On the contrary, larger cancers, with lymph node involvement or with a more invasive behaviour, are unfortunately at a higher risk of recurrence. […] The late recurrence or relapse of breast cancer refers to cancers that come back after five years, but may not return for 10 years, 20 years, or even more.

• #31 Late Recurrence of Breast Cancer

  https://www.verywellhealth.com/late-recurrence-of-breast-cancer-4766608

  Hormonal therapy can have a significant effect on the risk of recurrence. […] Late recurrences can differ from early relapse (within five years) with regard to sites of metastases and survival. […] Factors such as initial tumor size, number of nodes involved, and receptor status play into the risk of late recurrence, but tumor biology appears to have the greatest effect. […] With estrogen receptor-positive breast cancer (hormone-sensitive tumors), more than half of recurrences occur after five years. […] The impact of late distant recurrence cannot be stressed enough. Once breast cancer is metastatic, it is no longer curable. […] The reasons why cancer cells can lie dormant for extended periods of time have eluded researchers to date and are very difficult to study. […] It’s thought that in most cases, breast cancer cells metastasize (in small numbers or micrometastases) before cancer is detected, and roughly 30% of people with early-stage breast cancer have been found to have cancer cells in their bone marrow.

• #32 Promising approach to prevent breast cancer recurrence • healthcare-in-europe.com

  https://healthcare-in-europe.com/en/news/prevent-breast-cancer-recurrence.html

  Finnish cancer researchers discovered a mechanism that wakes up these dormant breast cancer cells and demonstrated that preventing the mechanism can significantly improve treatment outcomes in experimental models. […] The reasons why dormant breast cancer cells awake even after several years are not well understood. However, identifying these reasons could provide an opportunity to develop new therapies to prevent cancer recurrence. […] By sequencing the molecular changes in the cells, the group identified the DUSP6 protein, whose expression closely followed the development of therapy resistance. […] The leading researcher Majid Momeny was also able to show that when the activity of the DUSP6 protein was blocked during cancer treatment, breast cancer cells lost their ability to grow.

• #33 Late Recurrence of Breast Cancer

  https://www.verywellhealth.com/late-recurrence-of-breast-cancer-4766608

  The tumor microenvironment also likely plays a role no matter the mechanism. […] The constant rate of recurrence means that the risk that an estrogen receptor-positive breast cancer will recur between 15 years and 16 years post-diagnosis is the same as the risk that it will recur between five years and six years after diagnosis. […] Several hypotheses have been proposed to explain how these cells remain dormant and how they may be reactivated or „wake up.” […] Given the importance of dormant cancer cells, the United Kingdom has set up a challenge (Grand Challenge Award) for scientists to identify and target dormant cancer cells. […] Research is in progress not only to better understand who may have a late recurrence but also to evaluate potential methods to reduce these recurrences.

• #34 Breast cancer recurrence may be triggered by chemotherapy injury to non-cancer cells – ecancer

  https://ecancer.org/en/news/23718-breast-cancer-recurrence-may-be-triggered-by-chemotherapy-injury-to-non-cancer-cells

  Breast cancer recurrence may be triggered by chemotherapy injury to non-cancer cells. A standard chemotherapy drug injures surrounding non-cancer cells, which can then awaken dormant cancer cells and promote cancer growth, according to a new study published in the open-access journal PLOS Biology by Ramya Ganesan of Emory University, US, and colleagues. The finding is important for understanding cancer recurrence and may point to important new targets to prevent it. […] Recurrence occurs when dormant cells re-awaken and start dividing again. […] Some studies have indicated that chemotherapy itself may promote escape from dormancy, but the mechanism of this effect has not been clear. […] The driver of this reawakening of dormant cells, the authors showed, was release of two key cell signalling molecules, granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) by the injured stromal cells, which acted on the dormant cells to promote their growth, both in vitro and in vivo.

• #35 Breast cancer recurrence may be triggered by chemotherapy injury to non-cancer cells | EurekAlert!

  https://www.eurekalert.org/news-releases/1000529

  Breast cancer recurrence may be triggered by chemotherapy injury to non-cancer cells. A standard chemotherapy drug injures surrounding non-cancer cells, which can then awakens dormant cancer cells and promotes cancer growth, according to a new study publishing September 12th in the open access journal PLOS Biology by Ramya Ganesan of Emory University, US, and colleagues. The finding is important for understanding cancer recurrence and may point to important new targets to prevent it. […] Some studies have indicated that chemotherapy itself may promote escape from dormancy, but the mechanism of this effect has not been clear. […] The driver of this reawakening of dormant cells, the authors showed, was release of two key cell signaling molecules, granulocyte colony stimulating factor (G-CSF) and interleukin-6 (IL-6) by the injured stromal cells, which acted on the dormant cells to promote their growth, both in vitro and in vivo.

• #36 Promising approach to prevent recurrence of breast cancer | ScienceDaily

  https://www.sciencedaily.com/releases/2024/06/240617173550.htm

  Treatment outcomes for breast cancer have become better over the years, but proportion of breast cancers still recur even after long periods without signs of cancer remaining dormant in the body. […] The reasons why dormant breast cancer cells awake even after several years are not well understood. However, identifying these reasons could provide an opportunity to develop new therapies to prevent cancer recurrence. […] By sequencing the molecular changes in the cells, the group identified the DUSP6 protein, whose expression closely followed the development of therapy resistance. […] The leading researcher Majid Momeny was also able to show that when the activity of the DUSP6 protein was blocked during cancer treatment, breast cancer cells lost their ability to grow. […] Blocking the protein also made the previously treatment-resistant cancer cells more sensitive to HER2 inhibitors.

• #37 Promising Approach To Prevent Breast Cancer Recurrence Identified | Technology Networks

  https://www.technologynetworks.com/cancer-research/news/promising-approach-to-prevent-breast-cancer-recurrence-identified-387870

  Researchers have identified a targetable pathway that triggers breast cancer recurrence. […] Finnish cancer researchers discovered a mechanism that wakes up these dormant breast cancer cells and demonstrated that preventing the mechanism can significantly improve treatment outcomes in experimental models. […] The reasons why dormant breast cancer cells awake even after several years are not well understood. However, identifying these reasons could provide an opportunity to develop new therapies to prevent cancer recurrence. […] By sequencing the molecular changes in the cells, the group identified the DUSP6 protein, whose expression closely followed the development of therapy resistance. […] The leading researcher Majid Momeny was also able to show that when the activity of the DUSP6 protein was blocked during cancer treatment, breast cancer cells lost their ability to grow.

• #38 Could blocking a protein stop breast cancer from recurring?

  https://www.medicalnewstoday.com/articles/metastatic-breast-cancer-scientists-find-new-mechanism-to-prevent-recurrence

  Patients with estrogen receptor (ER)-positive breast cancer are at risk of cancer recurrence even decades after treatment. […] This is because cancer cells that spread to other organs can remain dormant for many years before reawakening to form tumors. […] A new study found that disseminated cancer cells remain dormant in the lungs of young, healthy mice, but in older mice or mice with lung damage, they grow rapidly to form tumors. […] The researchers attribute this difference to a protein called PDGF-C, which is present in low levels in the lungs of young, healthy mice, but is elevated in older mice or mice with lung damage. […] These findings suggest that blocking PDGF-C using a drug could potentially prevent cancer recurrence in patients with ER-positive breast cancer. […] In mice with aging or damaged lungs, disseminated cancer cells rapidly grew into large tumors.

• #39 PAQR8 promotes breast cancer recurrence and confers resistance to multiple therapies | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-022-01559-3

  Breast cancer mortality is principally due to recurrent disease that becomes resistant to therapy. We recently identified copy number (CN) gain of the putative membrane progesterone receptor PAQR8 as one of four focal CN alterations that preferentially occurred in recurrent metastatic tumors compared to primary tumors in breast cancer patients. […] Notably, PAQR8 CN gain in recurrent tumors was mutually exclusive with activating ESR1 mutations in patients treated with anti-estrogen therapies and occurred in 50% of both patients treated with anti-estrogen therapies and those treated with chemotherapy or anti-Her2 agents. […] We show that PAQR8 is necessary and sufficient for efficient mammary tumor recurrence in mice, spontaneously upregulated and CN gained in recurrent tumors that arise following therapy in multiple mouse models, and associated with poor survival following recurrence as well as poor overall survival in breast cancer patients. […] PAQR8 promoted resistance to therapy by enhancing tumor cell survival following estrogen receptor pathway inhibition by fulvestrant or estrogen deprivation, Her2 pathway blockade by lapatinib or Her2 downregulation, and treatment with chemotherapeutic agents.

• #40 PAQR8 promotes breast cancer recurrence and confers resistance to multiple therapies | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-022-01559-3

  Our findings that PAQR8 can function independently of progesterone are consistent with a study in yeast that employed a heterologous reporter construct containing a portion of the FET3 promoter that is repressed by the yeast PAQR protein Izh2p. […] Thus, the extent to which progesterone-dependent and independent effects of PAQR8 may be context-dependent, or may differ from those of PAQR7, remains to be clarified. […] We provide the first functional evidence to support the hypothesis that PAQR8 may function as a ceramidase by demonstrating that knockdown of endogenous PAQR8 increases ceramide levels, whereas PAQR8 overexpression decreases ceramide levels while increasing levels of S1P. […] Together, our findings indicate that Paqr8 expression decreases ceramide levels, increases S1P levels, and thereby decreases the ceramide:S1P ratio, which would be anticipated to favor cell survival. […] In aggregate, our studies provide in vivo evidence that PAQR8 plays a functional role in cancer, implicate PAQR8, ceramide metabolism, and cAMP in breast cancer recurrence, and identify a novel mechanism of resistance to multiple antineoplastic therapies.

• #41 Osteopontin: a new therapeutic alarm clock in breast cancer recurrence | Research Communities by Springer Nature

  https://communities.springernature.com/posts/osteopontin-a-new-therapeutic-alarm-clock-in-breast-cancer-recurrence

  When the time comes to wake up, recurrent breast cancers adapt and overcome many therapies, from targeted to immune-based. […] In a recent paper, we show a multi-pronged mechanism of osteopontin-driven breast cancer recurrence and its therapeutic potential. […] Osteopontin is a therapeutic target that drives breast cancer recurrence. […] In our recent study, we pinpoint osteopontin, an extracellular matrix protein and secreted cytokine, to be a rather loud alarm that drives breast cancer recurrence. […] Our work untangled the many ways by which osteopontin contributes to cancer recurrence. […] Altogether, osteopontin’s multifaceted influence is vital for the tumor’s ability to thrive and recur. […] One of the most exciting findings of our study is the potential of targeting osteopontin.

• #42 UM’s latest study discovers new mechanism to block recurrence and metastasis of breast cancer – Faculty of Health Sciences (FHS)

  https://fhs.um.edu.mo/en/ums-latest-study-discovers-new-mechanism-to-block-recurrence-and-metastasis-of-breast-cancer/

  A research team led by Chuxia DENG, dean of the University of Macau (UM) Faculty of Health Sciences (FHS), recently found that breast cancer susceptibility gene 1 (BRCA1) plays an important role in regulating mitophagy and mitochondrial dynamics: it maintains a healthy mitochondrial network and reduces inflammasome activity, which blocks the recurrence and metastasis of breast cancer after surgery. […] BRCA1 plays an important role in regulating mitophagy and mitochondrial dynamics: it maintains a healthy mitochondrial network and reduces inflammasome activity, which blocks recurrence and metastasis of breast cancer after surgery. […] This study indicates that BRCA1 has dual roles in regulating mitochondrial dynamics. […] Unbalanced mitochondrial dynamics leads to elongated mitochondria and prevents isolating damaged organelles from healthy mitochondrial network in BRCA1 mutant cells.

• #43 A New Mechanism for Inhibiting Breast Cancer Metastasis and Recurrence – Faculty of Health Sciences (FHS)

  https://fhs.um.edu.mo/en/a-new-mechanism-for-inhibiting-breast-cancer-metastasis-and-recurrence/

  Prof. Chuxia DENG, dean of the Faculty of Health Sciences (FHS) and director of its Cancer Centre, and Dr. Qiang CHEN, a senior instructor in FHS, have uncovered a new mechanism for inhibiting breast cancer metastasis and recurrence, bringing new hope for patients. […] The teams latest study found that the susceptibility gene BRCA1 can inhibit postsurgery breast cancer metastasis and recurrence by promoting mitochondrial autophagy and reducing the activity of inflammatory bodies. […] He says, Even after chemotherapy and mastectomy, the risk of TNBC recurrence within the first five years is still higher than other types of breast cancer, because surgery often stimulates the bodys own immune system, causing it to release growthpromoting factors that lead to cancer recurrence and metastasis.

• #44 Breast cancer recurrence: Could chemotherapy cause what it’s trying to stop? • healthcare-in-europe.com

  https://healthcare-in-europe.com/en/news/breast-cancer-recurrence-chemotherapy-cause.html

  The finding is important for understanding cancer recurrence and may point to important new targets to prevent it. […] Recurrence occurs when dormant cells re-awaken and start dividing again. […] Our paper highlights a deleterious effect of cancer chemotherapy: release of stromal IL-6 and G-CSF by taxane chemotherapy awakened dormant breast cancer cells, a postulated mechanism for tumor relapse. […] The driver of this reawakening of dormant cells, the authors showed, was release of two key cell signaling molecules, granulocyte colony stimulating factor (G-CSF) and interleukin-6 (IL-6) by the injured stromal cells, which acted on the dormant cells to promote their growth, both in vitro and in vivo. […] These findings have several important implications. […] They provide a possible mechanistic foundation for the observation that high serum levels of IL-6 are associated with early recurrence in breast cancer patients receiving chemotherapy, potentially strengthening the utility of that biomarker in planning treatment.

• #45 Breast cancer recurrence: Could chemotherapy cause what it’s trying to stop? • healthcare-in-europe.com

  https://healthcare-in-europe.com/en/news/breast-cancer-recurrence-chemotherapy-cause.html

  Our paper highlights a deleterious effect of cancer chemotherapy: release of stromal IL-6 and G-CSF by taxane chemotherapy awakened dormant breast cancer cells, a postulated mechanism for tumor relapse. Transient blockade of cytokine signaling during chemotherapy administration may prevent tumor recurrence.

• #46 Finding biomarkers and mechanisms for chemotherapy resistance in breast cancer

  https://frontlinegenomics.com/finding-biomarkers-and-mechanisms-for-chemotherapy-resistance-in-breast-cancer/

  In the fight against breast cancer, it’s useful to be able to prepare for the next move and see as far ahead as possible. Chemotherapy-resistant and recurring breast cancer cells are a challenge to clinicians and patients, but hope exists in new research into mechanisms of, and biomarkers for, chemotherapy resistance. […] Researchers in the Netherlands have identified new biomarkers and mechanisms of chemotherapy resistance in breast cancer cells. […] Pathological complete response (pCR) to chemotherapy is prognostically positive, while partial or non-response often results in recurrences of tumours. A partial pathological response to chemotherapy could indicate that part of the tumour is resistant to treatment, or a resistance mechanism has occurred as a cellular stress response. […] Most tumours show at least partial non-response to chemotherapy, and the extent of this non-responsiveness is predictive of recurrence-free survival.

• #47 Multimodal recurrence risk prediction model for HR+/HER2- early breast cancer following adjuvant chemo-endocrine therapy: integrating pathology image and clinicalpathological features | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-025-01968-0

  In HR+/HER2- early breast cancer (EBC) patients, approximately one-third of stage II and 50% of stage III patients experience recurrence, with poor outcomes after recurrence. […] Given that these patients commonly undergo adjuvant chemo-endocrine therapy (C-ET), accurately predicting the recurrence risk is crucial for optimizing treatment strategies and improving patient outcomes. […] To predict the recurrence risk in HR+/HER2- EBC patients following adjuvant C-ET, we developed two deep learning pipelines based on pretrained tissue-specific feature extractors and multi-instance learning with attention mechanisms. […] Currently, no established model exists for predicting the recurrence risk of HR+/HER2- EBC patients following adjuvant C-ET. […] This approach enables the identification of high-risk patients who may still experience recurrence, ultimately aiding in the formulation of precise therapeutic strategies.

• #48 Multimodal recurrence risk prediction model for HR+/HER2- early breast cancer following adjuvant chemo-endocrine therapy: integrating pathology image and clinicalpathological features | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-025-01968-0

  Our multimodal recurrence risk prediction model is a practical and reliable tool that enhances the predictive power of existing systems relying solely on clinicopathological parameters. […] The high prognostic value of the multimodal model was demonstrated in the five-fold cross-validation test sets, with AUCs of 0.8750.037, 0.8640.031, and 0.8660.029 for recurrence prediction at 3-, 5-, and 7-years, respectively. […] This study identified the pathological and molecular characteristics of high-risk patients through an integrated analysis of morphological features from pathological slides and patient transcriptomic data. […] Immune microenvironment analysis revealed lower proportions of gamma-delta T cells and higher proportions of monocytes in high-risk patients, indicating that the immune microenvironment plays a crucial role in tumor recurrence. […] GSEA revealed that differentially expressed genes in high-risk patients were significantly enriched in pathways such as IFN-/ response, transplant rejection, and KRAS signaling, which may contribute to recurrence mechanisms.

• #49 Promising approach to prevent recurrence of breast cancer | ScienceDaily

  https://www.sciencedaily.com/releases/2024/06/240617173550.htm

  Another important finding was that by inhibiting DUSP6, it was possible to slow the growth of breast cancer metastases in the brain in mouse models. […] Based on our findings, blocking the DUSP6 protein could therefore provide a basis for effective combination therapy also in HER2 breast cancer cases that have already lost response to treatment. […] Importantly, the drug was shown to significantly enhance the therapeutic effect of several existing HER2 inhibitors. […] These newly-published basic research results provide important evidence that DUSP6 is a very promising target protein for future cancer drug development and worth investigating.

• #50 Promising approach to prevent breast cancer recurrence • healthcare-in-europe.com

  https://healthcare-in-europe.com/en/news/prevent-breast-cancer-recurrence.html

  Blocking the protein also made the previously treatment-resistant cancer cells more sensitive to HER2 inhibitors. […] Another important finding was that by inhibiting DUSP6, it was possible to slow the growth of breast cancer metastases in the brain in mouse models. […] Based on our findings, blocking the DUSP6 protein could therefore provide a basis for effective combination therapy also in HER2 breast cancer cases that have already lost response to treatment. […] The significance of the study is highlighted by the group’s access to experimental drug molecules that inhibit the DUSP6 protein. […] Importantly, the drug was shown to significantly enhance the therapeutic effect of several existing HER2 inhibitors. […] These newly-published basic research results provide important evidence that DUSP6 is a very promising target protein for future cancer drug development and worth investigating.

• #51 Overcoming recurrence – how research is bringing new hope for breast cancer patients

  https://www.icr.ac.uk/research-and-discoveries/cancer-blogs/detail/science-talk/overcoming-recurrence—how-research-is-bringing-new-hope-for-breast-cancer-patients

  While advances in research mean that breast cancer is being treated more successfully than ever before, the worry of recurrence remains for many patients. […] However, breast cancer still has a powerful trick up its sleeve: recurrence. Various factors, including the type of breast cancer and its stage at diagnosis, can affect the risk of recurrence, which decreases over time but never disappears. Recurrence is still possible decades after the initial treatment, and this unpredictability places a significant psychological burden on many survivors. […] Earlier this year, our scientists showed that it was possible to predict the recurrence of breast cancer in high-risk patients even years ahead by analysing blood samples for tumour DNA, which cancer cells release into the bloodstream. This could improve the chances of detecting cancer early should it reappear.

• #52 Overcoming recurrence – how research is bringing new hope for breast cancer patients

  https://www.icr.ac.uk/research-and-discoveries/cancer-blogs/detail/science-talk/overcoming-recurrence—how-research-is-bringing-new-hope-for-breast-cancer-patients

  Ideally, though, we need to stop breast cancer from returning at all. In recent decades, an innovative type of treatment called immunotherapy has provided hope. Immunotherapy, which enhances the body’s ability to detect, target and kill cancer cells, has been shown to reduce the risk of recurrence in aggressive breast cancer. However, more research is needed to understand exactly how these treatments work, how we can maximise their effectiveness while limiting their side effects, and how we can identify those most likely to benefit. […] Other scientists are focusing on alternative treatment avenues. An early-stage study led by Professor Luca Magnani, Leader of our Breast Epigenetic Plasticity and Evolution Group, revealed that hormonal treatment given after surgery can sometimes trigger changes in gene activity that allow breast cancer cells to enter a dormant state. Upon waking up, these cells begin dividing again, causing cancer to return. By inhibiting an enzyme called G9a, the researchers eliminated these cells. This discovery could lead to new treatment approaches that remove any worry of breast cancer returning.

• #53 Breast cancer: pathogenesis and treatments | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-02108-4

  The implication is that the distal site DTCs have remained dormant for numerous years before the clinical detectability of the tumor. […] The specific mechanisms underlying early occult metastasis in breast cancer remain unknown. […] The emergence of cancer immunotherapy has brought about revolutionary advancements in the field of cancer treatment. […] The future treatment landscape of TNBC will probably involve novel combinations to extend the population of patients who might benefit from immunotherapies.

• #54 Analysis of hormone receptor status in primary and recurrent breast cancer via data mining pathology reports

  https://www.degruyter.com/document/doi/10.1515/med-2019-0013/html?lang=en

  Hormone receptors of breast cancer, such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her-2), are important prognostic factors for breast cancer. […] The hormone expression status from 3679 primary and 44 recurrent breast cancer cases was successfully retrieved with the method. Statistical analysis of these data showed that the recurrent disease had a significantly lower positivity rate for ER (54.5% vs 76.5%, p=0.001278) than primary breast cancer and a higher positivity rate for Her-2 (48.8% vs 16.2%, p=9.79e-8). These results corroborated the previous literature. […] This observation that the recurrent disease is more prone to be ER-negative, PR-negative, and Her-2-positive is consistent with the previous literature. […] The present article demonstrated a significant difference in the hormone receptor expression between primary and recurrent breast cancer, which is consistent with previous literature.

• #55 Molecular data can predict breast cancer recurrence | News Center

  https://med.stanford.edu/news/all-news/2019/03/molecular-data-can-predict-breast-cancer-recurrence.html

  Molecular data obtained from breast cancer cells can be used to predict which patients are at a high risk for recurrence even decades after their diagnosis, according to a new study jointly conducted by researchers at the Stanford University School of Medicine and the Cancer Research UK Cambridge Institute, as well as several other institutions. […] In particular, some patients whose tumors express the estrogen receptor but not another receptor called HER2 are at a persistent risk of relapse over time. […] The findings provide researchers and clinicians with a powerful new tool with which to predict a patient’s prognosis and potentially direct clinical decision-making. […] „We found that about 25 percent of women whose tumors express the estrogen receptor and not HER2 have an exceedingly high risk of late distant relapse and account for the vast majority of these events,” Curtis said. „These are the women who seem to be cured but then present with systemic disease many years later. Until now, there has been no good way to identify this subset of women who might benefit from ongoing screening or treatment.”

• #56 Molecular data can predict breast cancer recurrence | News Center

  https://med.stanford.edu/news/all-news/2019/03/molecular-data-can-predict-breast-cancer-recurrence.html

  „This important scientific paper identifies molecular features that determine the timing of cancer recurrence. In the future, this type of genomic classification should help us separate patients who remain at jeopardy – and might warrant additional or ongoing treatment – and those who do not.” […] Importantly, in many cases the study also identified the likely genomic drivers of specific tumors, many of which the researchers believe could serve as targets for drug development. […] Curtis and her colleagues studied the long-term medical histories of more than 3,000 women diagnosed with breast cancer in the United Kingdom and Canada between 1977 and 2005 to learn more about whether, when and where specific breast cancer types are likely to spread after initially successful treatment. […] The researchers were also able to identify a subgroup of women with triple-negative breast cancers – considered to be an aggressive and more difficult form of the disease to treat – who are unlikely to see their cancers recur after five years.

• #57 The Likelihood of Recurrence | Breast Cancer Trials

  https://www.breastcancertrials.org.au/breast-cancer-recurrence/?srsltid=AfmBOoobUyiPJWN05ZDvtshZwef1iAmXbHoJOhDEE04O7rrRxAiaUD0d

  Yes. You are still at risk of breast cancer recurrence if you have had a bilateral mastectomy (surgical removal of both breasts). Undergoing a bilateral mastectomy drastically reduces your chances of local or contralateral breast cancer recurrence as almost all of the breast tissue has been removed. However, there is still a chance that residual breast tissue or cancer cells could recur on the chest wall. […] There is no definitive way to prevent breast cancer from coming back. However, treatments such as surgery, chemotherapy, radiotherapy, targeted therapy (eg trastuzumab for HER2-positive breast cancer) and/or hormone therapy (for hormone receptor positive breast cancer) do reduce the risk of recurrence, depending on the type and stage of the cancer.

• #58 Breast Cancer Recurrence | Breast Cancer Surgery Melbourne, VIC

  https://www.melbournebreastcancersurgery.com.au/breast-cancer-recurrence.html

  Even early-stage cancers that originally had no lymph node involvement can recur and develop metastatic disease. […] While its less common, cancer cells can bypass lymphatics and lymph nodes and travel via surrounding blood vessels. […] If and when cancer comes back, the cancer cells that escaped the breast are to blame. […] Unfortunately, these treatments dont work 100 percent of the time. So if cells have spread, and if the treatments we give dont affect them, the cancer cells can persist and take hold someplace, developing into metastases, or spread. This is why and how recurrence happens. […] It has long been recognized that breast cancer is not always cured by locoregional treatment alone. […] The goal of treating early breast cancer is to remove the cancer and keep it from coming back (breast cancer recurrence).

• #59 Recurrent breast cancer – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/recurrent-breast-cancer/diagnosis-treatment/drc-20377141

  If your doctor suspects you may have recurrent breast cancer based on results of a mammogram or physical exam, or because of signs and symptoms, he or she may recommend additional tests to confirm the diagnosis. […] Your doctor may recommend a biopsy procedure to collect suspicious cells for testing, as this is the only way to confirm whether your cancer has returned. […] A pathologist can determine if the cancer is a recurrence of cancer or a new type of cancer. […] Your treatment options will depend on several factors, including the extent of the disease, its hormone receptor status, the type of treatment you received for your first breast cancer and your overall health. […] Treatment for a local recurrence typically starts with an operation and may include radiation if you haven’t had it before.

• #60 Recurrent Breast Cancer

  https://www.texasoncology.com/types-of-cancer/breast-cancer/recurrent-breast-cancer

  Recurrent breast cancer is cancer that progresses during treatment or recurs after a remission. […] Most patients who experience a recurrence of their cancer have disease that has metastasized, or spread, throughout the body. […] Despite effective local control with surgery and radiation, the majority of patients experiencing a local recurrence ultimately develop systemic recurrence of their cancer. […] For this reason, many doctors believe additional treatment with chemotherapy or hormonal therapy may be useful. […] Targeted therapies are treatments that can selectively target cancer cells and minimize damage to normal, healthy cells. […] Overexpression of this protein leads to increased growth of cancer cells. […] Fortunately, the development of treatments that specifically target HER2-positive cells has improved outcomes among women with HER2-positive breast cancer.

• #61 Recurrent breast cancer – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/recurrent-breast-cancer/diagnosis-treatment/drc-20377141

  For recurrent breast cancer that’s confined to the breast, treatment usually involves removing any remaining breast tissue. […] If your first cancer was treated with a lumpectomy, your doctor may recommend a mastectomy to remove all of your breast tissue lobules, ducts, fatty tissue, skin and nipple. […] If your first breast cancer was treated with a mastectomy and the cancer comes back in the chest wall, you may have surgery to remove the new cancer along with a margin of normal tissue. […] A local recurrence may be accompanied by hidden cancer in nearby lymph nodes. […] Radiation therapy uses high-energy beams, such as X-rays or protons, to kill cancer cells. […] Chemotherapy uses drugs to kill cancer cells. […] Medications that block the growth-promoting effects of the hormones estrogen and progesterone may be recommended if your cancer is hormone receptor positive.

• #62 Recurrent breast cancer – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/recurrent-breast-cancer/diagnosis-treatment/drc-20377141

  If testing shows your cancer cells produce excess HER2 protein, medications that target that protein will likely be recommended. […] If it’s possible, surgery to remove the cancer is the recommended treatment for a regional recurrence. […] Sometimes radiation therapy may be used after surgery. […] Many treatments exist for metastatic breast cancer. […] If one treatment doesn’t work or stops working, you may be able to try other treatments. […] In general, the goal of treatment for metastatic breast cancer isn’t to cure the disease. […] Your doctor works to achieve a balance between controlling your symptoms while minimizing toxic effects from treatment. […] If your cancer is hormone receptor positive, you may benefit from hormone therapy. […] Your doctor may recommend chemotherapy if your cancer is hormone receptor negative or if hormone therapy is no longer working. […] Immunotherapy uses your immune system to fight cancer. […] Immunotherapy might be an option if you have triple-negative breast cancer, which means that the cancer cells don’t have receptors for estrogen, progesterone or HER2.

• #63 Treatments for recurrent breast cancer | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/breast/treatment/recurrent

  Hormone therapy may be offered when hormone receptor-negative breast cancer recurs in older people, when it recurs only in 1 or 2 places, or if there is a long period of time between when the cancer was first treated and when it recurred. […] Chemotherapy may be offered for locally recurrent breast cancer to reduce the risk of the cancer coming back again. […] Chemotherapy for recurrent breast cancer may also be combined with targeted therapy or hormone therapy. […] The targeted therapy treatment offered by your healthcare team will depend on any targeted therapy drugs you have been treated with before. […] Targeted therapy may also be combined with hormone therapy or chemotherapy. […] Distant recurrence of breast cancer is treated like metastatic breast cancer.

• #64 Recurrent Breast Cancer | Nebraska Hematology Oncology – Cancer Care Treatment Blood Disorders Clinical Trials Lincoln Nebraska (NE)

  https://www.yourcancercare.com/types-of-cancer/breast-cancer/recurrent-breast-cancer

  The first chemotherapy treatment is called first-line and additional chemotherapy for cancer that has recurred is referred to as second-line. […] The type of second-line therapy that is selected and its effectiveness depends on which first-line chemotherapy the patient received. […] The growth of some breast cancer cells can be prevented or slowed by reducing the exposure to estrogen. This is the goal of hormonal therapy in the treatment for breast cancer. […] Hormonal therapy for recurrent, hormone-resistant breast cancer may differ based on which treatment was previously administered. […] Recurrent breast cancer often includes cancer that has spread to the bones, called metastases. […] Management of bone metastases may include a bisphosphonate drug. […] The development of more effective cancer treatments requires that new and innovative therapies are evaluated with cancer patients. Clinical trials are studies that measure the effectiveness of new drugs or treatment strategies. Future progress in the treatment of recurrent breast cancer will result from the continued evaluation of new treatments in clinical trials.

• #65 Could blocking a protein stop breast cancer from recurring?

  https://www.medicalnewstoday.com/articles/metastatic-breast-cancer-scientists-find-new-mechanism-to-prevent-recurrence

  We now plan to better unpick how patients might benefit from the existing drug imatinib, and in the long term aim to create more specific treatments targeted at the reawakening mechanism. […] One question that will be important to address is: how general is this phenomenon? […] It would seem unlikely that PDGF-C levels found in older patients is linked exclusively to the progression of ER+ breast cancer.

• #66 A patient with stage IIIB advanced breast cancer who is still alive 24 years after surgery: a case report and remarks on the treatment strategies – Yoneto – Translational Cancer Research

  https://tcr.amegroups.org/article/view/67807/html

  Furthermore, we must consider new therapeutic strategies that comprehensively integrate the information not only from tumor cells but also from the hosts immune system. […] Therefore, the accumulation of the information on expression of proteins and genes such as PD-L1 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and their expression intensities in tumor cells, peripheral blood lymphocytes, and TILs in metastatic tissues, as well as surface markers of immune-related cells and transition factors such as CD4, 8, 25, 45R, CCR4/6 and Foxp3 may provide a bridge to new treatments. […] In fact, the latest basic researches have confirmed that CDK4/6is are non-cytotoxic anticancer agents and do not significantly impair the host immune response system, specifically abemaciclib enhances that by suppressing Treg function. […] A paradigm shift in the treatment strategies, such as occurred in HER2+ breast cancer, may occur in postmenopausal HR+ highly advanced or recurrent breast cancer in the future, and therefore the results of the latest basic research must be kept in mind in clinical practice.

• #67 Recurrent Breast Cancer

  https://www.texasoncology.com/types-of-cancer/breast-cancer/recurrent-breast-cancer

  Clinical studies have shown that bisphosphonate therapy can prevent or delay bone destruction, including fractures and related pain, in women with breast cancer that has spread to the bone. […] The development of more effective cancer treatments requires that new and innovative therapies are evaluated with cancer patients.

• #68 A patient with stage IIIB advanced breast cancer who is still alive 24 years after surgery: a case report and remarks on the treatment strategies – Yoneto – Translational Cancer Research

  https://tcr.amegroups.org/article/view/67807/html

  A total mastectomy, including the surrounding tissue, is certainly an important first step toward a complete cure. […] In addition, chemotherapy had been performed in this case, but currently, endocrine therapy is now widely used as the first choice for HR+ recurrent breast cancer patients based on a misinterpretation of the Hortobagyi treatment algorithm, if there are no life-threatening visceral metastases. […] The prognosis for patients could vary greatly depending on which treatment is chosen. […] This fact may be the result of continued treatments that aimed to the complete cure, suggesting that the continuation of aggressive treatment can lead to long-term survival. […] Recently, with rapid advent of agents possessing novel mechanismsit may be possible to completely treat and cure for post-menopausal HR+ HER2 breast cancer with systemic recurrence.

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