Recent advances in understanding breast cancer and emerging therapies with a focus on luminal and triple-negative breast cancer

Hachem, Georges El; Gombos, Andrea; Awada, Ahmad

doi:10.12688/f1000research.17542.1

Cited by 19 publications

(13 citation statements)

References 84 publications

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“…Good clinical outcomes have been observed after anti-hormonal therapies in tumors expressing ER, although these therapies lead to resistance, limiting the effectiveness of hormone-based therapy (3). Triple-negative breast cancer (TNBC) is a subtype in which PR, ER and EGFR2 are not expressed (4)(5)(6). With no approved targeted therapy, TNBC is the most aggressive breast cancer, with the worst prognosis and the highest mortality rates (5).…”

Section: Introductionmentioning

confidence: 99%

“…Triple-negative breast cancer (TNBC) is a subtype in which PR, ER and EGFR2 are not expressed (4)(5)(6). With no approved targeted therapy, TNBC is the most aggressive breast cancer, with the worst prognosis and the highest mortality rates (5). The primary treatment options for TNBC include radiation-and chemotherapies, and surgical resection, which have limited e cacy and are accompanied with severe side effects (4).…”

Section: Introductionmentioning

confidence: 99%

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CDK12/13 inhibition induces immunogenic cell death and enhances anti-PD-1 anticancer activity in breast cancer

Zhang

et al. 2020

Cancer Letters

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Background: The T cell response against different tumors is improved by immunogenic cell death (ICD), indicating a role for ICD in augmenting antitumor immunity elicited by the anti-checkpoint antibody antiprogrammed death 1 (anti-PD-1). Methods: The effect of SR-4835 on breast cancer was analyzed by cell proliferation and ow cytometry. Calreticulin translocation and HMGB1 and ATP release were detected by ow cytometry, ELISA and luminescence assay, respectively. Immunogenicity in vitro was analyzed by co-culturing of SR-4835 treated cancer cells with bone-marrow derived dendritic cells (BMDCs) and rate of maturation of BMDCs and production of IL-6 in the supernatant were measured. The in vivo antitumor effect was analyzed by syngeneic mouse model followed by ow cytometry for TILs. Results: In the present study, we report a synergistic and durable immune-mediated antitumor response elicited by the combined treatment of SR-4835, a CDK12/13 speci c inhibitor, with PD-1 blockade in a murine model of 4T1 breast cancer. The developed combination therapy elicited antitumor activity in immunocompetent mouse tumor models. Furthermore, the SR-4835-treated tumor cells exhibited characteristics of ICD, including the release of high mobility group box 1 (HMGB1) and ATP and the translocation of surface calreticulin (CRT). This activity led to a significant T-cell dependent regression of tumors. The enhanced in ltration of T cells and dendritic cell (DC) activation in the tumors of mice treated with both SR-4835 and anti-PD-1 indicate that this combination treatment promotes an improved immune response and suggests a potential mechanism involving anti-PD-1 and SR-4835 activity that enhances anti-PD-1 effects. Conclusion: The results of the present study demonstrate the potential of CDK12/13 inhibition combined with checkpoint inhibition in breast cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CDK12/13 inhibition induces immunogenic cell death and enhances anti-PD-1 anticancer activity in breast cancer

Zhang

et al. 2020

Cancer Letters

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“…There are currently three CDK4/6 inhibitors approved to treat HR+/HER2- metastatic BC: palbociclib, ribociclib, and abemaciclib. They can be administered as first-line treatment combined with AIs or as second-line treatment combined with fulvestrant [ 258 ].…”

Section: New Strategies and Challenges For Breast Cancer Treatmentmentioning

confidence: 99%

Breast Cancer Treatments: Updates and New Challenges

Burguin

Diorio

Durocher

2021

JPM

212

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Breast cancer (BC) is the most frequent cancer diagnosed in women worldwide. This heterogeneous disease can be classified into four molecular subtypes (luminal A, luminal B, HER2 and triple-negative breast cancer (TNBC)) according to the expression of the estrogen receptor (ER) and the progesterone receptor (PR), and the overexpression of the human epidermal growth factor receptor 2 (HER2). Current BC treatments target these receptors (endocrine and anti-HER2 therapies) as a personalized treatment. Along with chemotherapy and radiotherapy, these therapies can have severe adverse effects and patients can develop resistance to these agents. Moreover, TNBC do not have standardized treatments. Hence, a deeper understanding of the development of new treatments that are more specific and effective in treating each BC subgroup is key. New approaches have recently emerged such as immunotherapy, conjugated antibodies, and targeting other metabolic pathways. This review summarizes current BC treatments and explores the new treatment strategies from a personalized therapy perspective and the resulting challenges.

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“…7 Evolution of breast cancer is slow and silent and the breast tumor can progressively spread hematologically and lymphatically to distant metastasis leading to poor prognosis. 8 Mostly the breast cancer is detected accidentally during routine checkups or due to some physical changes like change in breast shape or size or change in the rate of nipple discharge. 9 Delayed diagnosis of breast cancer leading to late implementation of treatment strategies (surgery, chemotherapy, radiation) increases the risk of patient mortality and lowers the survival rate.…”

Section: Introductionmentioning

confidence: 99%

The study of role of mammography and fine needle aspiration cytology in the diagnosis of early breast carcinoma

Stephen

Manoj

2021

Int Surg J

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Background: Epidemiologically breast cancer is the most common form of cancer among women. Prevalence rate of breast cancer is higher in urban women of middle age group. Early diagnosis of breast carcinoma is required for effective treatment else it may lead to mortality if advanced to stage 3 or 4. At present, there are different diagnosis modalities for early stage breast carcinoma. Currently triple diagnostic assessment including clinical, radiological and pathological examinations with 99% sensitivity is used in diagnosing all palpable breast lumps. The aim of the study was to determine the sensitivity and specificity of mammogram and Fine needle aspiration cytology (FNAC) in diagnosing breast cancer.Methods: A cross sectional study was conducted on total 80 female patients above 30 years of age with a palpable breast lump. Patients were sent for mammography, fine needle aspiration cytology and histopathological examinations. Results of mammography, FNAC and HPR were compared and statistically correlated.Results: Sensitivity of mammogram diagnosis was observed to be 92.857%, specificity as 86.842%, positive and negative predictive values to be 88.636% and 91.667% respectively. Therefore, current study findings revealed accuracy of mammogram to be 90.000%. Sensitivity of FNAC diagnosis was observed to be 92.857% and specificity to be 100%, positive and negative predictive values were observed to be 100% and 92.683% respectively. The study results revealed that FNAC diagnosis exhibited accuracy of 96.250%.Conclusions: Current investigation findings revealed that FNAC has more accuracy in predicting breast cancer than mammogram. Also, it was concluded that there is a significant association between FNAC and mammogram diagnosis.

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Recent advances in understanding breast cancer and emerging therapies with a focus on luminal and triple-negative breast cancer

Cited by 19 publications

References 84 publications

CDK12/13 inhibition induces immunogenic cell death and enhances anti-PD-1 anticancer activity in breast cancer

CDK12/13 inhibition induces immunogenic cell death and enhances anti-PD-1 anticancer activity in breast cancer

Breast Cancer Treatments: Updates and New Challenges

The study of role of mammography and fine needle aspiration cytology in the diagnosis of early breast carcinoma

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