Breast Cancer : Basic and Clinical Research最新文献

Despite recent improvements in detecting and managing breast cancer (BC), it continues to be a major worldwide health concern that annually affects millions of people. Exploring the anti-BC potentials of natural compounds has received a lot of scientific attention due to their multi-target mode of action and good safety profiles because of these unmet needs. Drugs made from herbs are secure and have a lot fewer negative effects than those made from synthetic materials. Early stage patients benefit from breast-conserving surgery, but the risk of local recurrence remains, necessitating implanted scaffolds. These scaffolds provide residual cancer cell killing and tailored drug delivery. This review looks at plant extract-infused tissue engineering scaffolds, which provide a novel approach to treating BC. By offering patient individualized, safer treatments, these scaffolds could completely change how BC is treated.

Prior to the advent of the HER2-targeted monoclonal antibody trastuzumab, HER2+ breast cancer (BC) was considered an aggressive disease with a poor prognosis. Over the past 25 years, innovations in molecular biology, pathology, and early therapeutics have transformed the treatment landscape. With the advent of multiple HER2-directed therapies, there have been immense improvements in oncological outcomes in both adjuvant and metastatic settings. Currently, 8 HER2-targeted therapies are approved by the Food and Drug Administration (FDA) for the treatment of early-stage and/or advanced/metastatic disease. Nonetheless, approximately 25% of patients develop recurrent disease or metastasis after HER2-targeted therapy and most patients with HER2+ metastatic breast cancer (MBC) die from their disease. Given the many mechanisms of resistance to HER2-directed therapy, there is a pressing need to further personalize care for patients with HER2+ MBC, by the identification of reliable predictive biomarkers, and the development of novel therapies and combination regimens to overcome therapeutic resistance. Of particular interest are established and novel antibody-drug conjugates, as well as other novel therapeutics and multifaceted approaches to harness the immune system (checkpoint inhibitors, bispecific antibodies, and vaccine therapy). Herein, we discuss standard-of-care treatment of HER2+ MBC, including the management of breast cancer brain metastases (BCBM). Furthermore, we highlight novel treatment approaches for HER2+ MBC, including endeavors to personalize therapy, and discuss ongoing controversies and challenges.

Background: Male breast cancer (MBC) accounts for 1% of global breast cancer cases. On account of its rarity, very few prospective clinical trials have been carried out on MBC. Pakistan has the highest incidence of breast cancer in Asia, but very limited data are available on MBC.

Objectives: The objective is to determine the clinicopathological characteristics and treatment patterns of MBC in Pakistani population.

Design: This is a retrospective cross-sectional study.

Methods: A retrospective cross-sectional study carried out using the cancer database of Shaukat Khanum Memorial Cancer Hospital & Research Center. Men with a histologically proven breast cancer, stage 0 to III disease and requiring surgical intervention were included. The Kaplan-Meier curve and log-rank test were used for survival analysis.

Results: Sixty-eight patients with MBC were included with a median age at diagnosis of 55 years. Most patients were stage II (47.1%). Invasive ductal carcinoma (IDC) was the commonest type (89.7%). Estrogen receptor (ER), progesterone receptor (PR), and Her-2 receptor positivity were 92.6%, 86.8%, and 32.4%, respectively. Mastectomy was performed in 95.6% of the cases. Neoadjuvant and adjuvant chemotherapy was administered in 25 (36.8%) and 26 (38.2%) patients, respectively. Fifty-five (80.9%) patients received adjuvant radiotherapy. Most of the patients (89.7%) received tamoxifen. The 5-year overall and disease-free survival was 88.2% and 80.9%, respectively. Patients receiving neoadjuvant chemotherapy had a better overall and disease-free survival (P = .025).

Conclusions: Male breast cancer occurs at a relatively earlier age in Pakistani population as compared with Western men. Mastectomy is the preferred surgical option for MBC on account of the advanced disease and delayed presentation. Neoadjuvant chemotherapy has a statistically significant effect on overall and disease-free survival, but in spite of these benefits, it remains underutilized.

Background: The scaffolding protein, caveolin-1 (Cav-1), participates in multiple cellular functions including promotion of sodium excretion from the kidney. Loss of expression of Cav-1 is associated with tumorigenesis of various types of cancer. We have shown the potential link between hypertension and breast cancer via abnormal function of the G protein-coupled receptor kinase type 4 (GRK4).

Objective: The current studies tested the hypothesis that Cav-1 acts as a tumor-suppressive factor in breast cancer cells and enhances the sensitivity to the inhibitory effect of the type 1 dopaminergic receptor (D₁R).

Methods: Michigan Cancer Foundation (MCF) MCF-7 cells stably expressing a Cav-1/mCherry fusion protein or mCherry alone were used as models to examine the effect of Cav-1 on cell growth, apoptosis, and senescence. Cell proliferation was determined by cell counting, cell cycle analysis (flow cytometry), and BrdU incorporation. Apoptosis was determined using the Cell Death Detection ELISA kit from Roche Diagnosis. Senescence was determined using the senescence associated beta galactosidase (SA-β-gal) assay. Reactive oxygen species (ROS) was measured using 2',7'-dichlorodihydrofluorescein diacetate. Western blot analysis was used to measure activation of signaling pathway molecules. All statistical analyses were conducted with Microsoft Excel.

Results: Overexpression of Cav-1 in MCF-7 cells reduced cellular growth rate. Both inhibition of proliferation and induction of cell death are contributing factors. Multiple signaling pathways were activated in Cav-1-expressing MCF-7 cells. Activation of Akt was prominent. In MCF-7-expressing Cav-1 (MCF-7 Cav-1) cells, the levels of phosphorylated Akt at S⁴⁷³ and T³⁰⁸ were increased 28- and 8.7-fold, respectively. Instead of protecting cells from apoptosis, extremely high levels of activated Akt resulted in increased levels of ROS which led to apoptosis and senescence. The tumor-suppressive effect plus downregulation of GRK4 makes Cav-1-expressing MCF-7 cells significantly more sensitive to the inhibitory effect of the D₁R agonist, SKF38393.

Conclusion: Caveolin-1 acts as a tumor-suppressing factor via extreme activation of Akt and down regulation of survival factors such as GRK4, survivin, and cyclin D1.

Background: Breast magnetic resonance imaging (MRI) is an important imaging tool for the management of breast cancer patients and for screening women at high risk for breast cancer.

Objectives: To examine long-term trends in the distribution of histologic diagnoses obtained from MRI-guided breast biopsies.

Design: Retrospective analysis.

Methods: We retrospectively reviewed the distribution of histologic diagnoses of MRI-guided breast biopsies from 2004 to 2019. All cases underwent central pathology review and lesions were classified based on the most prominent histologic finding present. Magnetic resonance imaging features were extracted from radiology reports when available and correlated with pathology diagnoses.

Results: Four hundred ninety-four MRI-guided biopsies were performed on 440 patients; overall, 73% of biopsies were benign and 27% were malignant. The annual percentages of benign and malignant diagnoses remained similar throughout the 16-year period. Of the benign entities commonly identified, the percentage of benign papillary and sclerosing lesions detected in the benign biopsies increased significantly (13% in 2004-2011 vs 31% in 2012-2019, P = .03). The mean size of malignant lesions was larger than benign lesions (30.1 mm compared with 14.2 mm, P = .045); otherwise, there were no distinguishing radiologic features between benign and malignant lesions.

Conclusion: The specificity of breast MRI remained constant over a 16-year period; however, there was a shift in the distribution of benign diagnoses with increased detection and biopsy of benign papillary and sclerosing lesions. Monitoring the distribution of breast MRI biopsy diagnoses over time with radiology-pathology correlation might improve the suboptimal specificity of breast MRI.

Metaplastic breast carcinoma is an invasive carcinoma with a high differentiation rate of the neoplastic epithelium toward mesenchymal-like epithelium. It comprises of only less than 1% of all breast cancers. Although 80% to 90% of metaplastic breast carcinomas are triple-negative cancers, they usually have worse outcomes than other triple-negative breast cancers (TNBCs). Metaplastic carcinoma is also often refractory to cytotoxic chemotherapy. Here, we reported a case of a 61-year-old female patient, presenting with a solitary and pedunculated mass in the right axillary tail breast tissue, whose biopsy revealed metaplastic breast carcinoma with chondroid differentiation. She had failed neoadjuvant chemotherapy and immunotherapy. Although she received debulking surgery, the tumor regrew even faster before surgery. Despite receiving palliative chemotherapy, the patient died 11 weeks after surgery. This case draws attention to physicians that early recognition and surgery may be more beneficial than chemotherapy in combating metaplastic breast carcinoma.

Background: Any treatment protocol that leads to complete elimination of surgery may lead to a better patient acceptance of breast cancer treatments.

Objectives: We conducted this study to assess the feasibility of preoperative vacuum-assisted biopsies in identifying pathological complete response (pCR) and its accuracy in correlation to final histopathology report (HPR), in an Indian setting.

Methods: This was a prospective study conducted between October 1, 2019, and March 31, 2021. Patients with early breast cancer, estrogen and progesterone receptors negative and either Her2 positive or negative, and who were fit to undergo marker placement at the centre of the tumour and to receive third-generation chemotherapy (4 cycles of 3 weekly doxorubicin and cyclophosphamide followed by 4 cycles of 3 weekly docetaxel) were included in the study. Following the enrolment, a tissue marker was placed at the centre of the tumour and appropriate chemotherapy was started. Patients who achieved clinical complete response were subjected to ultrasound-guided vacuum-assisted biopsy (VAB) from the tumour bed before surgery. Pathology results of the VAB and resected specimen were then compared. Descriptive statistics were used in the study.

Results: Eighteen patients were enrolled in the study, with a mean age of 43.6 ± 9.8 years. However, only 10 were eligible for VAB procedure, and sensitivity and specificity were calculated based on the results of these 10 patients only. Vacuum-assisted biopsy showed sensitivity of 50% and specificity of 100% in identifying pCR. Combination of mammography, ultrasonography, and VAB showed sensitivity of 77.8% and specificity of 66.7% in identifying pCR.

Conclusion: Vacuum-assisted biopsy of tumour bed may not be sensitive enough to eliminate surgery even in patients who have had exceptional response to neo-adjuvant chemotherapy.

Background: Breast cancer is the most prominent cancer type to affect women. Surgical treatment of invasive breast cancers involves mastectomy. Due to mastectomy, women are subjected to social, emotional, and cultural problems which need to be addressed.

Objective: The objective of the study is to understand how women cope with body image-related issues, trauma, anxiety, and depression post-mastectomy.

Design: A systematic literature review was conducted for understanding the coping in post-mastectomy patients. The methods for identifying the studies were based on Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) guidelines.

Databases: Medline/PubMed, PsycInfo, and Cochrane databases were used for searching relevant articles. A final of 19 studies were analyzed for the work.

Methods: Search strings such as "coping strategies and post mastectomy," "body image coping and post mastectomy" and "anxiety coping and post mastectomy" were used for identification of references from databases. Eligibility criteria were used for finalizing the references.

Results: Analysis of the 19 studies has clearly shown that women who undergo mastectomy suffer from anxiety, stress, and trauma. This study has observed that women have problems with their body image post-mastectomy along with bouts of depression. Self-coping has been observed in relatively few studies. Psychological interventions before surgery have been observed to be a better coping strategy. In most of the studies, women opted for breast reconstruction to overcome the trauma associated with mastectomy.

Conclusion: Mastectomy has a severe impact on women's appearance and psychology. Breast reconstruction and acceptance have played an important role in coping among these women. However, breast reconstruction is not accepted by many women due to a multitude of factors. Thus, it is essential to have proper intervention programs in place to ensure women can cope with this situation and can lead healthy lives.

Registration: Systematic literature review (SLR) is submitted to PROSPERO. The application confirmation number is 449135.Registration awaited from the database.