Breast Cancer最新文献

Background: Adipose-derived stem cells (ADSCs)-assisted fat grafting has emerged as a widely used procedure for breast reconstruction post mastectomy and for aesthetic augmentation. Given the limited cases of breast cancer following grafting, the oncological safety of this procedure remains controversial.

Methods: The effects of ADSCs on the oncogenic features of premalignant MCF-10AT cells were investigated using co-culture and xenograft models. We further evaluated the malignancy-promoting effect of ADSCs in a 7,12-Dimethylbenz(a)anthracene (DMBA)-induced breast cancer model. RNA-sequencing was performed on ADSCs, MCF-10AT cells, and ADSC-co-cultured MCF-10AT cells. Protein changes in ADSC/MCF-10AT co-culture medium and MCF-10AT cells were determined by proteomic analysis. Pathway inhibitors were used to investigate signaling pathways involved in the ADSC-induced oncogenic changes of MCF-10AT cells.

Results: We found that ADSCs promoted the proliferation and migration of MCF-10AT cells, and co-injection of ADSCs increased the tumor incidence of MCF-10AT cells from 29% to 58% in nude mice. Additionally, grafted ADSCs significantly enhanced tumor incidence, growth, and distant metastasis in the DMBA-induced rats, while it could not induce tumorigenesis in normal breast tissues. Combined RNA-sequencing and proteomic analysis demonstrated that the paracrine factors secreted by ADSCs robustly activated the oncogenic PI3K-AKT signaling in MCF-10AT cells. We also revealed the auto-activated TGF-beta and Wnt pathways in co-cultured MCF-10AT cells, which may be synergistic in tumor formation and progression. As expected, blocking these pathways, especially the PI3K-AKT pathway, strongly diminished the promoting effects of ADSCs, suggesting their potential as therapeutic targets for ADSC grafting-associated breast tumors.

Conclusions: Our data illustrated the synergistic effect between ADSC paracrine factors and MCF-10AT auto-activated pathways in the carcinogenesis of MCF-10AT cells through activation of the oncogenic PI3K-AKT pathway. Based on these findings, we strongly recommend pre-operative examinations for breast cancer risk factors before ADSC-associated transplantation.

Background: The MonarchE trial demonstrated the additional benefit of abemaciclib as an adjuvant endocrine therapy for high-risk patients with hormone receptor (HR)-positive HER2-negative breast cancer. Meanwhile, the ACOSOG Z0011 trial established the omission of axillary lymph-node dissection (ALND) as a standard practice in certain patients with positive sentinel lymph-node biopsy (SNB). However, as the MonarchE eligibility criteria include the presence of four or more lymph-node metastases, omitting ALND may hinder the assessment of abemaciclib eligibility in some cases.

Methods: The study population consisted of patients with clinically node-negative, HR-positive, HER2-negative breast cancer who underwent SNB at our institution between January 2008 and December 2021. The proportion of patients meeting the MonarchE cohort1 criteria, and the potential impact of ALND omission on abemaciclib eligibility were assessed.

Results: Among the 1537 patients, 189 underwent SNB followed by ALND due to the presence of one or more positive sentinel nodes. Of these, 69 (36.5%) were eligible for abemaciclib. Eligibility was uncertain without ALND in 138 patients. Among the 138 patients, 124 were candidates for ALND omission, including 11 who were found to have four or more metastatic lymph nodes after completing ALND.

Conclusions: A few cases were identified in which abemaciclib eligibility was not properly determined due to ALND omission. This suggests that omitting ALND following SNB, when two of fewer positive nodes are detected, may not significantly impact the determination of abemaciclib eligibility.

Background: Early prediction and management are crucial for treating breast cancer-related lymphedema (BCRL), yet the risk factors remain poorly understood. This study aims to explore the relationship between postoperative changes in serum cholesterol levels and the development of lymphedema.

Methods: This retrospective study analyzed breast cancer patients who underwent surgery between March 2014 and March 2019. We assessed the development of lymphedema and changes in high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), and total cholesterol (TC) levels. Preoperative values were compared with those measured within 6 months post-surgery, and logistic regression models were used for statistical analysis.

Results: Among the 906 patients studied, 87 (9.6%) developed lymphedema, with a median onset of 15 months. An increase in serum HDL levels relative to baseline was associated with a reduced risk of lymphedema (odds ratio [OR] 0.94 per unit increase, 95% confidence interval [CI]: 0.92-0.95), even after adjusting for established factors such as body mass index, type of axillary surgery, number of lymph nodes removed, regional radiotherapy, and chemotherapy. In contrast, elevated serum TG levels were linked to a higher risk of lymphedema (OR 1.003 per unit increase, 95% CI: 1.001-1.006). No significant associations were found with changes in LDL or TC levels (p > 0.05).

Conclusion: Postoperative changes in HDL and TG levels are significantly associated with the risk of developing lymphedema, suggesting their potential role as early indicators. These results have important clinical implications for guiding follow-up care and early intervention strategies, although further validation is needed.

Background: This study investigated fluctuations in levels of chosen cytokines among patients with breast cancer before to after chemotherapy. Contemporaneous changes in cognitive function were examined.

Methods: Adult patients with breast cancer stages I-III without brain metastasis were invited to participate in this longitudinal follow-up study. A multidimensional neuropsychological examination was administered at two timepoints evaluating multiple subjective and objective cognitive domains, depression, anxiety, or fatigue before and at least 3 months after chemotherapy, and baseline demographic information. Cytokine levels were taken at the same times. Stepwise multivariate Generalized Linear Mixed Model was used to examine changes in cytokines and associations with changes in cognitive function.

Results: Over a mean interval of 10.46 months, Event-based prospective memory (p<0.001), Word list immediate (p<0.001) or delayed recall (p = 0.024), and self- perceived cognitive impairment (p = 0.026) were significantly improved following chemotherapy. Higher levels of IFNγ and worse performance on the Color Trails Test Part 1, inverse associations of IFNγ or IL-12p70 with Block Design, and TNFα with Digit Symbol Substitution were found, but no significant time effects were noted. However, significant group and time effects were only observed in IL-2 and IL-12p70 with improvements in Event-based prospective memory. That is, from baseline to follow-up, each increase in log values of IL-12p70 and IL-2 were associated with 2.18 (SE = 0.65, p = 0.001) and 2.16 (0.68, p = 0.002) points of increase in Event-based prospective memory. No significant effects were detected for other cytokines or cognitive tests.

Conclusion: Improvements in Event-based prospective memory were positively associated with contemporaneous changes in IL-2 and IL-12p70. Our finding may not only reduce BC patients' concerns about chemotherapy-related cognitive adverse effects, but also demonstrates the possible needs for further replications and investigations on interactions of systemic cytokines, inflammation, and cognitive functions associated with cancer and chemotherapy.

Background: Recurrent breast cancer (BC) has poor prognosis. To ascertain the survival time after recurrence (STR) is necessary for improving QOL and for selecting appropriate treatment. An investigation was conducted to determine whether certain biomarkers would improve prognosis and whether the disease-free interval (DFI) and biomarkers can predict STR.

Methods: Cases (n = 1,254) with recurrent BC from January 2000 to December 2023 were enrolled in this study. The cases were divided into the 2000-2005 group (n = 182), 2006-2011 group (n = 331), 2012-2017 group (n = 369), and 2018-2023 group (n = 366). A simple linear regression model was used to identify the relationship between STR and DFI.

Results: Survival rates after recurrence significantly increased in cases after 2012. No improvement was observed in cases with a HER2-0 status and a Ki-67 index value < 15%. A multivariate analysis revealed that the Ki-67 index value was a significant factor in the 2000-2005 group. The ER and HER2 status were significant after 2012. The most significant correlation was found between DFI and STR in deceased patients with a Ki-67 index value > 30%, followed by HER2-low, tumor size ≤ 2 cm and ER < 1%. The following formula was developed to predict STR; $\text{STR (mons)}={\alpha }_0+{\beta }_0\bullet \text{DFI}+{\sum }_{i=1}^5{F}_i\left({\alpha }_i,+,{\beta }_i,\bullet ,\text{DFI}\right)$ CONCLUSION: Prognosis after recurrence clearly improved from 2012. In recurrent deceased patients, there was a strong correlation between DFI and STR in cases with a Ki-67 index value > 30% and a HER2-low status. Further studies need to be conducted in clinical settings to verify the accuracy of the predictive formula developed for STR.

Background: In patients with breast cancer staged ypN1 after neoadjuvant chemotherapy (NAC), there is limited evidence-based guidance regarding exemption from axillary lymph node dissection (ALND).

Methods: This study analyzed ypN1 breast cancer patients post-NAC from the Surveillance, Epidemiology, and End Results databases. Patients were categorized into the breast-conserving surgery (BCS) group and the total mastectomy (TM) group, and further divided by the number of positive lymph nodes (LNs). The effects of three axillary management strategies, ALND, sentinel lymph node biopsy combined with radiotherapy (SLNB + RT), and ALND + RT were compared. The overall survival (OS) and breast cancer-specific survival (BCSS) of all subgroups and their independent risk factors were analyzed. Independent prognostic factors selected from multivariate Cox analysis were utilized to create nomograms for predicting OS and BCSS.

Results: A total of 3641 patients were involved, with 1331 in the BCS group and 2310 in the TM group. In the TM group, patients with 3 residual positive LNs exhibited significant improvements in OS and BCSS when treated with ALND + RT. For patients with 1 or 2 residual positive LNs in the TM group and all BCS patients, no significant survival differences in survival outcomes were observed among the three axillary management methods. The accuracy of the nomograms was validated via calibration curves, receiver operating characteristic curves, and decision curve analysis curves.

Conclusion: For TM group patients with 3 residual positive LNs after NAC, ALND + RT is recommended. For other subgroups of ypN1 patients, SLNB + RT can be considered an alternative to ALND. The nomogram developed to predict OS and BCSS in ypN1 breast cancer patients demonstrated excellent predictive ability.

Background: Neoadjuvant pembrolizumab plus chemotherapy and adjuvant pembrolizumab have been established as the optimal systemic therapies for patients with early stage triple-negative breast cancer (TNBC); however, their efficacy and feasibility in the Japanese population remain unexplored.

Methods: This study included patients with early stage TNBC or low estrogen receptor (ER) positivity (1-9%) with human epidermal growth factor receptor type 2- (HER2-) negative breast cancer who received neoadjuvant pembrolizumab plus chemotherapy from October 2022 at Cancer Institute Hospital of Japanese Foundation for Cancer Research. Information regarding clinicopathological features, systemic therapy, treatment outcomes, and adverse events of patients who underwent surgery by February 2024 was retrospectively collected.

Results: Overall, 69 patients received neoadjuvant pembrolizumab plus carboplatin and paclitaxel therapy, and 46 underwent surgery by February 2024. The median age of the patients was 53.5 years, and 80.4% and 19.6% had stage II and III disease, respectively. TNBC and ER-low HER2-negative breast cancer accounted for 82.6% and 17.4% cases, respectively. Overall pathological complete response rate was 56.5%, with 87.5% in patients with ER-low HER2-negative tumors. The completion rates for neoadjuvant pembrolizumab, chemotherapy, and pembrolizumab plus chemotherapy were 65.2%, 56.5%, and 52.2%, respectively. Furthermore, 80.4% and 15.2% of patients experienced grade 3 or higher treatment-related adverse events and immune-related adverse events, respectively, and 34% experienced unexpected hospitalization during neoadjuvant treatment.

Conclusions: The efficacy and safety profiles of neoadjuvant pembrolizumab plus chemotherapy in the Japanese population are consistent with previous reports. This regimen may have therapeutic potential against ER-low HER2-negative tumors and TNBC.

Purpose: Understanding individuals at high risk of breast cancer, as well as patients and survivors, underscores the critical role of genetic counseling in the diagnosis and treatment of breast cancer.

Methods: This systematic review adhered to the guidelines outlined in the Reporting Items for Systematic Review and Meta-Analysis (PRISMA). The review process was managed using Covidence systematic review software, facilitating data extraction according to predefined eligibility criteria by two independent reviewers. Quality appraisal and narrative synthesis were conducted following data extraction.

Results: Out of 1089 articles screened, nineteen (19) studies met the inclusion criteria and were included in this review. These studies were categorized into categories based on their relevance to breast cancer genetic counseling. Rapid Genetic Counseling and Testing (RGCT): 3 studies (15.78%), racial differences: 2 studies (10.52%), limited health literacy: 4 studies (21.05%), breast cancer survivorship: 3 studies (15.78%), risk perceptions and cancer worry: 5 studies (26.31%) and telephone delivery and computer aid programs: 2 studies (10.52%) based on specific focus areas of each study in relation to breast cancer genetic counseling.

Conclusion: Genetic counseling has shown to improve client outcomes across the majority of reviewed studies, contributing to the advancement of evidence-based practice in this field. However, to further promote evidence-based advancements in breast cancer genetic counseling, it is imperative to pay close attention to potential sources of bias and uphold rigorous quality standards in future research endeavors.