Breast Cancer最新文献

Background: Patients living with and beyond breast cancer frequently exhibit several side effects that can impact quality of life and physical functioning way beyond diagnosis and cancer therapies. Traditional on-land exercise has shown to be effective in reducing several symptoms of BC but little is known about the role of water-based exercise in improving physical and psychological well-being.

Objectives: To compare land- vs. water-based exercise training for BC survivors to improve Health-Related Quality of Life (HRQoL), cancer-related fatigue (CRF), physical functioning, body composition and physical activity in patients with BC.

Methods: A randomised, parallel group (1:1) controlled trial was conducted between 2020 and 2022. Patients were randomly allocated to complete a similar exercise training twice weekly during 12 weeks either on land (LG) using traditional gym equipment or in a swimming pool (WG) using body-weight exercises and water-suitable accessories. Both groups were supervised and monitored by an experienced physiotherapist. Main outcome was HRQoL (EORTC QLQ C30 and B23 module) and CRF measured with the Piper Scale. Secondary variables included functional capacity with the 6 Minutes Walking Test (6MWT), upper and lower body strength (handgrip strength and 30″ Sit-to-Stand (STS) test), body composition and objectively measured physical activity.

Results: 28 patients were assessed and randomised during the study period. One patient did not receive the allocated intervention due to skin issues and one patient was dropped out during the intervention. A significant effect of time was found for both symptom severity (F(₂,₅₂) = 6.46, p = 0.003) and overall functioning (F_1.67,43.45 = 5.215, p =0 .013) but no interaction was found between group and time. No effects were reported for CRF. Similar findings were reported for functional capacity (time effect F_1.231,32.019 = 16.818, p < 0.001) and lower body strength (time effect F_2,52 = 15.120, p < 0.001) as well as fat mass (time effect F_2,52 = 4.38, p = 0.017). Notably, a significant time per group interaction was reported for physical activity (F_2,52 = 6.349, p =0.003) with patients in the WG significantly improving PA levels over time while patients in the LG exhibited a marked decreased.

Conclusions: Exercise training either in water or on land can decrease symptom severity and improve functionality and body composition. Water-based training seems more effecting than land-based exercise to improve physical activity patterns over time.

Background: The prognosis in patients with breast cancer with isolated locoregional recurrence (ILRR) without simultaneous distant metastases after immediate breast reconstruction (IBR) remains unknown. We aimed to investigate the prognosis in this patient population.

Methods: This multi-institutional retrospective observational study evaluated 3295 patients with primary breast cancer who underwent IBR at 12 Japanese medical facilities between January 1, 2008 and December 31, 2016. The outcome measures were the prognostic factors for ILRR after IBR, 5-year distant metastasis-free interval (DMFI), and 5-year overall survival (OS).

Results: Mastectomy or skin-sparing mastectomy was performed in 3295 patients. ILRR occurred in 70 patients, and the median observation period from ILRR diagnosis was 39.3 months. Of the 70 patients, 9 (12.9%) had axillary lymph node recurrence (ALNR) at the time of ILRR diagnosis. The 5-year DMFI and OS rates after ILRR were 92.4% and 91.2%, respectively. Pathological lymph node metastasis at primary surgery (P = 0.041) and ALNR (P = 0.022) at ILRR were significantly associated with DMFI in the univariate analysis. ALNR was the only independent prognostic factor in the multivariate analysis (P = 0.041). Post-mastectomy radiation therapy (PMRT; P = 0.022) and ALNR (P = 0.043) were significantly associated with OS in the univariate analysis, and both PMRT (P = 0.010) and ALNR (P = 0.028) were independent prognostic factors in the multivariate analysis for OS.

Conclusions: Although patients with breast cancer who had ILRR after IBR have favorable prognosis, ALNR may lead to poor prognosis. To the best of our knowledge, this study is the first to report the prognosis of these patients.

Background: Peripherally inserted central catheters (PICCs) and new type of arm-port, the PICC-port, are currently used for neoadjuvant chemotherapy treatment in patients with breast cancer. We aimed to compare Quality of Life (QoL) of patients receiving one of these two devices investigating overall satisfaction, psychological impact, as well as the impact on professional, social and sport activities, and local discomfort.

Methods: We did a prospective observational before-after study of PICCs versus PICC-ports. Adult (aged ≥ 18 years) females with breast cancer candidate to neoadjuvant chemotherapy were included. The primary outcome was QoL according to the Quality-of-Life Assessment Venous Device Catheters (QLAVD) questionnaire assessed 12 months after device implantation.

Results: Between May 2019 and November 2020, of 278 individuals screened for eligibility, 210 were enrolled. PICC-ports were preferred over PICCs with a QLAVD score of 29 [25; 32] vs 31 [26; 36.5] (p = 0.014). Specifically, most QLAVD constructs related to psychological impact, social aspects, and discomfort were in favor of PICC-ports vs PICC, especially in women under the age of 60. Overall, pain scores at insertion and during therapy administration were not significantly different between the two groups, as well as infection, secondary malpositioning, thrombosis, or obstruction of the device.

Conclusions: In women with breast cancer undergoing neoadjuvant chemotherapy, PICC-ports were overall better accepted than PICCs in terms of QoL, especially in those who were younger. Device-related complications were similar.

Background: Breast cancer (BC) presents persistent challenges due to subtype-specific limited efficacy and potential resistance to standard therapy, influenced by the dynamic reversible nature of epigenetic plasticity. This study aims to comprehensively explore the evolving BC epigenetic landscape, analyzing trends and evaluating the therapeutic potential of epigenetic drugs (epi-drugs) for BC treatment.

Methods: We conducted a cross-sectional study of BC epigenetic trials using ClinicalTrials.gov until July 18, 2023. Additionally, results from randomized controlled trials were retrieved from the registry or PubMed using trial registration numbers.

Results: In total, 22 epi-drugs were investigated in 100 trials, with 11 currently being studied in 38 ongoing trials for BC. Over the years, epigenetic clinical trials for BC have notably increased, with histone deacetylase inhibitors constituting 45.45% of the candidate agents in the development pipeline. All ongoing trials are enrolling human epidermal growth factor receptor2 (HER2)-negative BC patients. Epi-drugs are commonly explored in combination with multiple anti-cancer therapies, such as aromatase or microtubule inhibitors, using an intermittent sequential administration approach. Emerging strategies include new-generation epi-drugs and combination involving immunotherapy or targeted therapy. Among candidate drugs, tucidinostat and entinostat, in combination with exemestane, demonstrated significant improvements in progression-free survival in phase III trials for hormone receptor-positive, HER2-negative BC patients.

Conclusion: This study highlights the growing interest in BC epigenetics, suggesting a potential shift from a one-size-fits-all approach to precision medicine, and emphasizes the necessity for robust evidence on their efficacy and safety to support continuous development and approval, addressing the unmet needs in BC treatment.

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.