Breast Cancer最新文献

Background: Resveratrol, a natural compound, may be an alternative to improving conventional breast cancer therapy. Thus, we assessed the capability of resveratrol at a low dose to enhance the in vitro effect of conventional theray in estrogen receptor (ER) and human epidermal growth factor receptor type 2 (HER2)-positive breast cancer cells.

Methods: Cell viability of breast cancer cells was measured with neutral red uptake assay. Apoptosis, autophagy, cell cycle progression and cell proliferation were detected through hypotonic fluorescent solution assay, formation of acidic vesicular organelles, flow cytometry, and bromodeoxyuridine assay, respectively. Western blotting was performed to study the expression of pro-apoptotic, anti-apoptotic and autophagic proteins, and estrogen receptors.

Results: Resveratrol combined with tamoxifen metabolites or trastuzumab reduced cell viability of ER- and HER2-positive breast cancer cells, respectively. This effect was mainly associated with induction of apoptosis due to a greater formation of hypodiploid nuclei, reduced protein expression of procaspase-7, Bcl-2, Bcl-xL, and PARP; and increased expression of cleaved PARP. Resveratrol decreased the expression of ERα and increased that of ERβ, contributing to the reduced viability on breast cancer cells. Combined treatments induced autophagy, evidenced by increased levels of acidic vesicular organelles and degradation of p62/SQSTM1 protein. Nevertheless, on inhibiting autophagy with 3-methyladenine, cell viability was further reduced and apoptosis was induced, suggesting a pro-survival role of autophagy, impairing apoptosis.

Conclusions: Resveratrol increasead the in vitro cytotoxic effect of conventional therapy in breast cancer cells. However, it was necessary to block resveratrol-induced autophagy to improve the therapeutic response.

Introduction: The axillary lymph node status (ALNS) and internal mammary lymph nodes (IMLN) expression associated with breast cancer are closely linked to prognosis. This study aimed to establish a nomogram to predict survival at 3, 5, and 10 years in patients with various lymph node statuses.

Methods: We obtained data from patients with breast cancer between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER database). Chi-square analysis was performed to test for differences in the pathological characteristics of the groups, and Kaplan-Meier analysis and the log-rank test were used to plot and compare the correlation between overall survival (OS) and breast cancer specific survival (BCSS). The log-rank test was used for the univariate analysis, and statistically significant characteristics were included in the multivariate and Cox regression analyses. Finally, Independent factor identification was included in constructing the nomogram using R studio 4.2.0; area under curve (AUC) values were calculated, and receiver operating characteristic (ROC) curve, calibration, and decision curve analysis (DCA) curves were plotted for evaluation.

Results: A total of 279,078 patients were enrolled and analysed, demonstrating that the isolated tumour cells (ITC) group had clinicopathological characteristics similar to those of micrometastases (Mic). Multivariate analysis was performed to identify each subgroup's independent risk factors and construct a nomogram. The AUC values were 74.7 (95% CI 73.6-75.8), 72.8 (95% CI 71.9-73.8), and 71.2 (95% CI 70.2-72.2) for 3-, 5-, and 10-year OS, respectively, and 82.2 (95% CI 80.9-83.6), 80.1 (95% CI 79.0-81.2), and 75.5 (95% CI 74.3-76.8) for BCSS in overall breast cancer cases, respectively. AUC values for 3-, 5-, and 10-year OS in the ITC group were 64.8 (95% CI 56.5-73.2), 67.7 (95% CI 62.0-73.4), and 65.4 (95% CI 60.0-70.7), respectively. For those in the Mic group, AUC values for 3-, 5-, and 10-year OS were 72.9 (95% CI 70.7-75.1), 72.4 (95% CI 70.6-74.1), and 71.3 (95% CI 69.6-73.1), respectively, and AUC values for BCSS were 77.8 (95% CI 74.9-80.7), 75.7 (95% CI 73.5-77.9), and 70.3 (95% CI 68.0-72.6), respectively. In the IMLN group, AUC values for 3-, 5-, and 10-year OS were 75.2 (95% CI 71.7-78.7), 73.4 (95% CI 70.0-76.8), and 74.0 (95% CI 69.6-78.5), respectively, and AUC values for BCSS were 76.6 (95% CI 73.0-80.3), 74.1 (95% CI 70.5-77.7), and 74.7 (95% CI 69.8-79.5), respectively. The ROC, calibration, and DCA curves verified that the nomogram had better predictability and benefits.

Conclusion: This study is the first to investigate the predictive value of different axillary lymph node statuses and internal mammary lymph node metastases in breast cancer, providing clinicians with additional aid in treatment decisions.

Purpose: Breast-conserving surgery (BCS) plus radiotherapy and mastectomy exhibit highly comparable prognoses for early-stage breast cancer; however, the safety of BCS for T1-2N3M0 breast cancer remains unclear. This study compared long-term survival for BCS versus (vs.) modified radical mastectomy (MRM) among patients with T1-2N3M0 breast cancer.

Methods: Data of patients with T1-2N3M0 breast cancer were extracted from the Surveillance, Epidemiology, and End Results database. Eligible patients were divided into 2 groups, BCS and MRM; Pearson's chi-squared test was used to estimate differences in clinicopathological features. Propensity score matching (PSM) was used to balance baseline characteristics. Univariate and multivariate analyses were performed to investigate the effects of surgical methods and other factors on breast cancer-specific survival (BCSS) and overall survival (OS).

Results: In total, 2124 patients were included; after PSM, 596 patients were allocated to each group. BCS exhibited the same 5-year BCSS (77.9% vs. 77.7%; P = 0.814) and OS (76.1% vs. 74.6%; P = 0.862) as MRM in the matched cohorts. Multivariate survival analysis revealed that BCS had the same BCSS and OS as MRM (hazard ratios [HR] 0.899 [95% confidence intervals (CI) 0.697-1.160], P = 0.413 and HR 0.858 [95% CI 0.675-1.089], P = 0.208, respectively); this was also seen in most subgroups. BCS demonstrated better BCSS (HR 0.558 [95% CI 0.335-0.929]; P = 0.025) and OS (HR 0.605 [95% CI 0.377-0.972]; P = 0.038) than MRM in those with the triple-negative subtype.

Conclusions: BCS has the same long-term survival as MRM in T1-2N3M0 breast cancer and may be a better choice for triple-negative breast cancer.

Background: Insufficient data available for older patients with breast cancer complicates decision-making regarding optimal treatment. A systematic review that uses real-world data is required for assessing the effectiveness and potential adverse effects of various therapies for this age group of patients.

Methods: Databases of PubMed, Embase, and Cochrane Library were searched. We included clinical studies that evaluated various treatments for geriatric breast cancer, including adjuvant radiation therapy, hypofractionated radiation therapy (hypo-RT) and accelerated and partial breast irradiation (APBI), endocrine therapy, chemotherapy, and targeted therapy.

Results: A total of 71 studies were retrieved. Adjuvant radiation therapy significantly improved overall survival (OS) compared with no radiation [hazard ratio (HR) = 0.60, 95% confidence interval (CI) 0.54-0.67]. The pooled estimates of OS for hypo-RT and APBI demonstrated no inferiority compared with conventional radiation. Both endocrine treatment (HR = 0.63, 95% CI 0.43-0.92) and chemotherapy (HR = 0.76, 95% CI 0.65-0.88) significantly increased OS compared with no treatment. Trastuzumab monotherapy significantly enhanced OS compared with no trastuzumab use (HR = 0.23, 95% CI 0.07-0.73).

Conclusion: Despite concerns about potential complications during treatment in older patients, proactive therapies significantly increase their survival rates. For patients who are frailer, hypo-RT and APBI offer survival rates comparable to traditional modalities. Additionally, targeted therapy as a monotherapy holds promise as a viable option for patients with HER2-positive breast cancer who cannot undergo chemotherapy. Therefore, by conducting thorough general assessments and clinical evaluations, the side effects of postoperative treatments can be effectively managed.

Background: Talazoparib monotherapy in patients with germline BRCA-mutated, early-stage triple-negative breast cancer (TNBC) showed activity in the neoadjuvant setting in the phase II NEOTALA study (NCT03499353). These biomarker analyses further assessed the mutational landscape of the patients enrolled in the NEOTALA study.

Methods: Baseline tumor tissue from the NEOTALA study was tested retrospectively using FoundationOne^®CDx. To further hypothesis-driven correlative analyses, agnostic heat-map visualizations of the FoundationOne^®CDx tumor dataset were used to assess overall mutational landscape and identify additional candidate predictive biomarkers of response.

Results: All patients enrolled (N = 61) had TNBC. In the biomarker analysis population, 75.0% (39/52) and 25.0% (13/52) of patients exhibited BRCA1 and BRCA2 mutations, respectively. Strong concordance (97.8%) was observed between tumor BRCA and germline BRCA mutations, and 90.5% (38/42) of patients with tumor BRCA mutations evaluable for somatic-germline-zygosity were predicted to exhibit BRCA loss of heterozygosity (LOH). No patients had non-BRCA germline DNA damage response (DDR) gene variants with known/likely pathogenicity, based on a panel of 14 non-BRCA DDR genes. Ninety-eight percent of patients had TP53 mutations. Genomic LOH, assessed continuously or categorically, was not associated with response.

Conclusion: The results from this exploratory biomarker analysis support the central role of BRCA and TP53 mutations in tumor pathobiology. Furthermore, these data support assessing germline BRCA mutational status for molecular eligibility for talazoparib in patients with TNBC.

Background: The safety and outcome of breast reconstruction after radiotherapy are controversial, and the aesthetic aspects have not been studied extensively. We compared the results of vascular anastomosis, the incidence of postoperative complications, and aesthetic appearance between patients who had and had not received radiotherapy who then had undergone delayed breast reconstruction with autologous free flaps from the abdomen, thighs, and buttocks.

Methods: In total, 257 flaps in 241 patients were investigated; 194 and 63 flaps implanted in patients who did not receive radiotherapy and who received radiotherapy before breast reconstruction, respectively. Of the 257 flaps, 221, 20, 14, and 2 came from the abdomen, thighs, buttocks, and other anatomic locations, respectively. We evaluated aesthetic outcomes in 105 patients who had not received radiotherapy and 35 who had.

Results: We found no significant differences between the two groups in the incidence of vascular reanastomosis, the time required for anastomosis, or the incidence of unplanned reoperation. Complications such as flap necrosis were rare in both groups. Aesthetic outcomes were significantly better in the patients who had not received radiotherapy.

Conclusions: Breast reconstruction with autologous free flaps can be performed safely in patients who have received radiotherapy, but the aesthetic result is slightly inferior to that in patients who had not received radiotherapy.

Background: A history of severe nausea and vomiting during pregnancy (SNVP) is a risk factor for postoperative nausea and vomiting (PONV). This study aimed to explore potentially effective treatment strategies and potential genetic factors underlying SNVP risk-related PONV.

Methods: A total of 140 female patients undergoing breast cancer surgery were assigned to either the study group (70 with SNVP) or the control group (70 with mild to moderate nausea and vomiting during pregnancy (MNVP)). Patients in each group were randomly assigned to two different treatment subgroups and received either ondansetron plus dexamethasone (OD) or OD + TEAS (ODT) (transcutaneous electrical acupoint stimulation, TEAS). Blood samples were collected from patients before induction (D0) and 24 h (D1) after surgery for growth differentiation factor 15 (GDF-15) evaluation. The primary outcome was the incidence of PONV within 36 h. The secondary outcome was the serum GDF-15 level.

Results: The incidence of PONV in the SNVP group was significantly higher than that in the MNVP group within 24 h (P < 0.005). In the SNVP group, ODT-treated patients had less PONV than those in the OD-treated group during the 6-12 h (P = 0.033) and 12-24 h (P = 0.008) intervals, while within 6 h, there were fewer vomiting cases in the ODT-treated group (SNVP-ODT vs. SNVP-OD, 7/33 vs. 19/35, P = 0.005). The preoperative GDF-15 serum levels in patients with SNVP were significantly higher (P = 0.004). Moreover, higher preoperative GDF-15 serum levels correlated with a higher incidence of PONV (P = 0.043).

Conclusions: TEAS showed significant effect on PONV treatment in patients with SNVP. A higher serum GDF-15 level was associated with a history of SNVP, as well as a higher risk of PONV.

Background: Immediate breast reconstruction (IBR) is a common oncoplastic procedure used in breast cancer surgery. This study aims to investigate compliance with prosthetic breast reconstruction guidelines and its impact on perioperative treatment.

Methods: We reviewed data from the National Clinical Database-Breast Cancer Registry between January 2019 and December 2020. We compared perioperative treatment implementation between the IBR and non-IBR groups by subtype matching for age, menopausal status, T stage, N stage, and histology.

Results: A total of 8,860 patients with breast cancer who underwent IBR (6,075 breast prostheses, 2,492 autologous tissues, and 293 others) were identified. The compliance rate with the guidelines for prosthetic breast reconstruction was 97.7%. After matching, chemotherapy for luminal A-like diseases was significantly less frequent in the IBR group than in the non-IBR group (16.3% vs 20.5%, p < 0.001), and radiotherapy was less frequent in luminal A-like and HER2-positive patients (7.2% vs 9.0%, p = 0.010 and 7.1% vs 11.4%, p = 0.005, respectively). Among the 1-3 node-positive cases, fewer patients with prosthetic IBR received radiotherapy than those without IBR (15.7% vs 26.4%, p < 0.001).

Conclusion: Prosthetic breast reconstruction was performed with strict adherence to the Japanese guidelines. The implementation rates of chemotherapy and radiotherapy were lower in the specific IBR group than those in the non-IBR group. Therefore, large-scale, long-term follow-up data are required.

Objective: To develop and authenticate a neoadjuvant chemotherapy (NACT) pathological complete remission (pCR) model based on the expression of Reg IV within breast cancer tissues with the objective to provide clinical guidance for precise interventions.

Method: Data relating to 104 patients undergoing NACT were collected. Variables derived from clinical information and pathological characteristics of patients were screened through logistic regression, random forest, and Xgboost methods to formulate predictive models. The validation and comparative assessment of these models were conducted to identify the optimal model, which was then visualized and tested.

Result: Following the screening of variables and the establishment of multiple models based on these variables, comparative analyses were conducted using receiver operating characteristic (ROC) curves, calibration curves, as well as net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Model 2 emerged as the most optimal, incorporating variables such as HER-2, ER, T-stage, Reg IV, and Treatment, among others. The area under the ROC curve (AUC) for Model 2 in the training dataset and test dataset was 0.837 (0.734-0.941) and 0.897 (0.775-1.00), respectively. Decision curve analysis (DCA) and clinical impact curve (CIC) further underscored the potential applications of the model in guiding clinical interventions for patients.

Conclusion: The prediction of NACT pCR efficacy based on the expression of Reg IV in breast cancer tissue appears feasible; however, it requires further validation.