Breast Cancer : Targets and Therapy最新文献

We present a case report on a case of invasive apocrine carcinoma of breast during pregnancy at a tertiary referral hospital in Ethiopia. The patient's case in this report signifies the challenging clinical situation that the patient, developing fetus and treating physicians have to go through and the need to improve maternal-fetal medicine and oncologic setup and treatment guidelines in Ethiopia. Our case also illustrates the huge disparity between the management of both breast cancer and its occurrence during pregnancy in low-income countries like Ethiopia and developed nations elsewhere. Our case report shows a rare histological finding. The patient has invasive apocrine carcinoma of the breast. To our knowledge, it is the first case to be reported in the country.

Metastatic breast cancer is difficult to cure and has a worse prognosis with higher rates of mortality. Recently, breast surgery is believed to improve the survival rates among these women, but due to limited evidence, definite conclusions cannot be made. Therefore, we undertook this narrative review to synthesize the evidence from existing studies to assess the effectiveness of locoregional surgery and surgery of metastatic sites in improving the outcomes among women diagnosed with metastatic cancer disease along with the summary of current treatment guidelines. We reviewed PubMed and Embase and included both observational studies and randomized controlled trials (RCTs) that were published in English between 2000 and 2021. Outcomes were either survival, quality of life, toxicity related to local treatment assessed by mortality at the end of one month, progression-free survival, and breast cancer-specific survival. The main effect size assessed was hazard ratio with their 95% CIs. After literature search, we found 8 observational studies and 3 RCTs. The findings of the observational studies revealed that breast cancer surgery improves survival from 30% to 50% among women. However, findings from RCTs were mixed for local and distant progression survival. Surgery improved the local progression-free survival but worsened the distant progression-free survival. Besides, there was no effect of breast surgery on quality of life. Regarding the surgery of metastatic site, studies are complex with mixed findings and variation in survival depending upon the type of metastatic site and response to initial systematic therapy and other factors. Based on the existing mixed evidence, it is not possible to make firm and definite conclusions about the effectiveness of breast surgery in improving the survival or quality of life among women with metastatic breast cancer. In future, more RCTs are required with a larger sample size to confirm the findings of observational studies.

Objective: To detect the activation of the EGFR and mTOR signaling pathways in the triple negative breast cancer cell line MDA-MB-468 and investigate the inhibitory effect of gefitinib, an epidermal growth factor receptor inhibitor, and everolimus, a target protein inhibitor of rapamycin, on triple negative breast cancer cells.

Methods: Triple negative human breast cancer MDA-MB-468 cells were cultured and blank control group, single EGFR inhibitor gefitinib group, single mTOR inhibitor everolimus group, and two drug combination group were set up respectively to detect the effects of single and combined drugs on cell proliferation activity, cell cycle and apoptosis, and the expression of EGFR and mTOR signal pathway proteins in cell lines after single and combined drug intervention was detected again by Western blot.

Results: The level of EGFR and p-mTOR protein in triple negative breast cancer was higher than in non triple negative breast cancer (P<0.05). The level of mTOR, S6K1, p-EGFR, p-S6K1 was significantly increased when treated with EGF (0ng/mL, 10ng/mL, 100ng/mL) for 1h, compared to without EGF stimulation (P<0.05). The level of p-EGFR, p-mTOR, p-S6K1 protein increased significantly when the cells were exposed to EGF for 2h, respectively (P<0.05). EGFR inhibitor gefitinib alone and the mTOR inhibitor everolimus alone could significantly inhibit the proliferation of human triple negative breast cancer MDA-MB-468 cells in a dose-dependent manner (P<0.05). The level of p-4EBP1 protein in EGFR and mTOR signal pathway was significantly increased after the intervention of gefitinib alone, everolimus alone, and the combination of two drugs (P<0.05).

Conclusion: EGFR and mTOR signaling pathways can be activated in triple negative breast cancer; Both the EGFR inhibitor gefitinib alone and the mTOR inhibitor everolimus alone can significantly inhibit the proliferation of human triple negative breast cancer MDA-MB-468 cells. The combination of the EGFR inhibitor gefitinib and the mTOR inhibitor everolimus may achieve anti-tumor effect similar to that of single drug by reducing the drug dose.

Background: Metaplastic breast cancer (MBC) is an extremely rare malignant breast disease that has rarely been reported. The molecular subtype of MBC is mostly triple-negative, with a high recurrence rate and a worse prognosis. Due to its low HR- and HER2-positive rate, reports on endocrine and targeted therapy are very limited.

Case report: We report a case of infrequent triple-negative MBC, which, although at an early stage, quickly developed multiple recurrent lesions in the chest wall. The tumor relapsed repeatedly after comprehensive treatment, including surgery, chemotherapy and radiotherapy. However, pathological results after the third surgery suggested that the molecular subtype had changed from triple-negative to HER2-positive. The previous comprehensive treatment had not been able to effectively control the disease, but the patient achieved a long progression-free survival time through chemotherapy and trastuzumab targeted therapy after the subtype change. To date, there has been no recurrence for over eight years.

Conclusion: Among repeatedly relapsed MBC patients, further investigation should be taken into consideration. As in the case presented in our study, it is possible that the HER2 status can convert from negative to overexpression. Moreover, for HER2-positive MBC patients, anti-HER2 therapy is recommended. The decision-making process requires multidisciplinary involvement.

Purpose: To investigate the HER2 status and clinicopathological features in invasive breast cancer with HER2 ≥4.0 and <6.0, which has always been controversial.

Methods: Forty breast cancer cases with HER2 ≥4.0 and <6.0 by fluorescence in situ hybridization (FISH) were collected and classified into two groups based on the HRE2/CEP17 ratio (Group A: ≥2.0, n=22; Group B: <2.0, n=18). Clinicopathological characteristics, HER2 status, risk classification, and molecular typing were further analyzed and compared by 21-Gene expression assay and MammaPrint plus BluePrint test.

Results: The majority of cases in both groups were invasive carcinoma (NOS), with histological grade II, HR+, Ki-67 ≥20%, HER2 2+, and a high risk of recurrence, although younger patients and lymph node metastases were more common in Group A. Surprisingly, all HR+ breast cancers in both groups were classified as luminal-type, HR- cases were all basal-type or unknown, and the index of HER2 in all cases was <0.000 using the BluePrint test, which indicated that HER2 status should be negative. Furthermore, the level of HER2 mRNA expression in all cases of both groups was <10.7, which was defined as HER2 negative by the 21-Gene expression assay. In addition, 10 patients of Group A received anti-HER2 neoadjuvant therapy; only one patient with HR- achieved Grade 5 based on the Miller-Payne system, whereas none of the patients achieved pathological complete response (pCR) based on the Residual Cancer Burden system.

Conclusion: Group A breast cancer, which has always been unquestionably diagnosed as HER2 amplification, was more likely to be HER2 negative and derived less benefit from anti-HER2 neoadjuvant chemotherapy. Group A breast cancer should be distinguished from classical HER2-positive breast cancers when assessing HER2 FISH, and a larger cohort of Group A patients should be included in further studies.

More than 50% of breast cancers are currently defined as "Human epidermal growth factor receptor 2 (HER2) low breast cancer (BC)", with HER2 immunohistochemistry (IHC) scores of +1 or +2 with a negative fluorescence in situ hybridization (FISH) test. In most studies that compared the clinical and biological characteristics of HER2-low BC with HER2-negative BC, HER2-low was not associated with unique clinical and molecular characteristics, and it seems that the importance of HER2 in these tumors is being a docking site for the antibody portion of antibody drug conjugates (ADCs). Current pathological methods may underestimate the proportion of BCs that express low levels of HER2 due to analytical limitations and tumor heterogeneity. In this review we summarize and contextualize the most recent literature on HER2-low breast cancers, including clinical and translational studies We also review the challenges of assessing low HER2 expression in BC and discuss the current and future therapeutic landscape for these tumors.

Objective: Breast cancer (BC) is a major public health problem in Saudi Arabia and worldwide and significantly affects the health of Saudi women. This study investigates the awareness and predictors of breast cancer among medical students at the University of Bisha, Saudi Arabia.

Methods: This cross-sectional study involved 391 medical students from the University of Bisha (Medicine and Applied Medical sciences) conducted from June to December 2022. Data were collected using a questionnaire with 27 questions. Data were analyzed using Stata/ BE 17.0 for Mac (Intel 64-bit) 1985-2021 Stata Corp LLC. All ethical issues were addressed honestly, including IRB and student consent.

Results: In our study, almost half of the participants (49.36%) had suboptimal knowledge of general BC awareness, which was statistically significantly related to gender and previous participation in BC education (p-value < 0.05). Of the students (57%) showed a positive intention to participate in BC activities. Logistic regression models were used to identify factors that positively predicted student participation and engagement in BC activities. These factors showed a statistically significant relationship (p-value < 0.05), including previous participation (OR =1.557143), female (OR =1.412844), living in rural areas (OR =1.7075471), and medical applied sciences students (OR =1.439252).

Conclusion: Despite half of the participants having suboptimal awareness of BC, there was a significant willingness to engage in BC prevention activities. Therefore, we recommend further analysis to identify gaps in the medical curriculum and update it accordingly, as well as to plan an extracurricular activity to increase student awareness of breast cancer as part of the University of Bisha's social accountability.

Objective: The effect of chemotherapy in patients with breast cancer (BC) is uncertain. This study attempted to analyze serum microRNAs (miRNAs) in NAC resistant and sensitive BC patients and develop a miRNA-based nomogram model. To further help clinicians make treatment decisions for hormone receptor-positive patients.

Methods: A total of 110 BC patients with NAC were recruited and assigned in sensitive and resistant group, and 4 sensitive patients and 3 resistant patients were subjected to high-throughput sequencing. The functions of their target genes were analyzed by GO and KEGG. Five BC-related reported miRNAs were selected for expression pattern measurement by RT-qPCR and multivariate logistic analysis. The nomogram model was developed using R 4.0.1, and its predictive efficacy, consistency and clinical application value in development and validation groups were evaluated using ROC, calibration and decision curves.

Results: There were 44 differentially-expressed miRNAs in resistant BC patients. miR-3646, miR-4741, miR-6730-3p, miR-6831-5p and miR-8485 were candidate for resistance diagnosis in BC. Logistic multiple regression analysis showed that miR-4741 (or = 0.30, 95% CI = 0.08-0.63, P = 0.02) and miR-6831-5p (or = 0.48, 95% CI = 0.24-0.78, P = 0.01) were protective factors of BC resistance. The ROC curves showed a sensitivity of 0.884 and 0.750 for miR-4741 and miR-6831-5P as markers of resistance, suggesting that they can be used as independent risk factors for BC resistance. The other 3 miRNAs can be used as calibration factors to establish the risk prediction model of resistance in BC. In risk model, the prediction accuracy of resistance of BC is about 78%. 5-miRNA signature diagnostic models can help clinicians provide personalized treatment for NAC resistance BC patients to improve patient survival.

Conclusion: MiR-4741 and miR-6831-5p are independent risk factors for breast cancer resistance. This study constructed a nomogram model of NAC resistance in BC based on 5 differentially-expressed serum miRNAs.

Purpose: The study aimed to compare the survival outcomes and efficacy of platinum in early breast cancer patients with BRCA1 and BRCA2 mutations.

Methods: Patients diagnosed with stage I-III breast cancer and carrying germline pathogenic/likely pathogenic BRCA mutations in three medical institutions in China from April 2016 to January 2021 were retrospectively analyzed. Data on clinical and pathological characteristics, treatment information, pathogenic variants of BRCA, and survival outcomes were collected for all eligible patients.

Outcomes: One hundred and sixty-nine patients with BRCA mutations were enrolled, including BRCA1 mutation (53.3%, n = 90) and BRCA2 mutation (46.7%, n = 79). The median age was 39 years, and most patients (68.1%, n = 115) were stage I-II. Patients with BRCA1 mutations were characterized by histological grade III (55.6%) and higher Ki-67 index (Ki-67 ≥ 30%, 78.9%) compared with patients with BRCA2 mutations (27.8%, 58.2%). BRCA1 mutation patients accounted for a significantly higher proportion of triple negative breast cancer than BRCA2 mutation patients (71.1% vs 19.0%, P < 0.0001). A total of 142 (84.0%) patients received neo/adjuvant chemotherapy, including anthracycline and/or taxane-based regimens (55.6%) or platinum-based regimens (27.2%). Median follow-up was 33.2 months. Three-year DFS (disease-free survival) and DRFS (distant recurrence-free survival) had no significant differences between patients with BRCA1 and BRCA2 mutations (82.0% vs 85.4%, P = 0.35; 94.3% vs 94.6%, P = 0.39). The 3-year DFS rate in BRCA1 mutation cohort of patients received platinum regimen was significantly higher than patients received non-platinum regimen (96.0% vs 75.2%, P = 0.01). No differences between DFS and DRFS were observed in patients with BRCA2 mutation received platinum regimen and non-platinum regimen.

Conclusion: Similar survival outcomes were observed in early breast cancer patients with BRCA1 and BRCA2 mutation, though they had different biological characteristics. Patients with BRCA1 mutations are more benefit from platinum-regimen. The value of platinum-regimen for early breast cancer patients with BRCA1 and BRCA2 needs to be verified further.

Background: Breast cancer is the most common tumor globally. Automated Breast Volume Scanner (ABVS) and strain elastography (SE) can provide more useful breast information. The use of radiomics combined with ABVS and SE images to predict breast cancer has become a new focus. Therefore, this study developed and validated a radiomics analysis of breast lesions in combination with coronal plane of ABVS and SE to improve the differential diagnosis of benign and malignant breast diseases.

Patients and methods: 620 pathologically confirmed breast lesions from January 2017 to August 2021 were retrospectively analyzed and randomly divided into a training set (n=434) and a validation set (n=186). Radiomic features of the lesions were extracted from ABVS, B-ultrasound, and strain elastography (SE) images, respectively. These were then filtered by Gradient Boosted Decision Tree (GBDT) and multiple logistic regression. The ABVS model is based on coronal plane features for the breast, B+SE model is based on features of B-ultrasound and SE, and the multimodal model is based on features of three examinations. The evaluation of the predicted performance of the three models used the receiver operating characteristic (ROC) and decision curve analysis (DCA).

Results: The area under the curve, accuracy, specificity, and sensitivity of the multimodal model in the training set are 0.975 (95% CI:0.959-0.991),93.78%, 92.02%, and 96.49%, respectively, and 0.946 (95% CI:0.913 -0.978), 87.63%, 83.93%, and 93.24% in the validation set, respectively. The multimodal model outperformed the ABVS model and B+SE model in both the training (P < 0.001, P = 0.002, respectively) and validation sets (P < 0.001, P = 0.034, respectively).

Conclusion: Radiomics from the coronal plane of the breast lesion provide valuable information for identification. A multimodal model combination with radiomics from ABVS, B-ultrasound, and SE could improve the diagnostic efficacy of breast masses.