Breast Cancer Research and Treatment最新文献

Aim: Cancer-related cognitive impairment (CRCI) is one of the severe side effects affecting the quality of life of breast cancer (BC) patients. However, the mechanisms underlying CRCI are still unclear. The study aimed to examine the multiple mediating roles of resilience, social support, cortisol, and neutrophil-lymphocyte ratio (NLR) in the relationship between perceived stress and cognitive function.

Design: The study was a descriptive, cross-sectional study.

Methods: The study investigated 450 BC patients with chemotherapy in China. Convenience sampling was conducted from February to August 2023. The study used the Perceived Stress Scale, the Connor-Davidson Resilience Scale, the Social Support Rating Scale, the Functional Assessment of Cancer Therapy-Cognitive Function, the Montreal Cognitive Assessment, salivary cortisol, and NLR. SPSS 25.0 and AMOS 26.0 conducted bivariate correlations and multiple mediation analysis.

Results: The correlations of magnitude variables ranged from no correlation to moderate level (r = - 0.002 to - 0.617). The multiple mediation path demonstrated that resilience and morning cortisol levels mediated the relationship between perceived stress and cognitive function, with a 95% confidence interval (CI) not including 0 for the direct, indirect, and total effects.

Conclusions: The study confirmed that when BC patients endure physical and psychological stress during diagnosis and treatment, individuals' resilience can buffer the stress on cognitive function. Morning salivary cortisol levels, as the product and indicator of the hypothalamic-pituitary-adrenal (HPA) axis function, may play a significant role in the effect of perceived stress on cognitive function while incapable of finding NLR as the marker of individuals' immune inflammatory response and social support play a role in this relationship. The study, based on a stress perspective, explored the regulatory mechanisms by which perceived stress affects cognitive function in patients undergoing chemotherapy for breast cancer, providing intervenable targets for subsequent improvement of patients' cognitive function.

Purpose: This study aimed to evaluate treatment patterns and clinical outcomes in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) initiating at least one chemotherapy for metastatic disease in real-world settings in Japan.

Methods: In this observational retrospective cohort study, data of 2697 patients with HR+/HER2- mBC from a Japanese medical claims database who initiated the first chemotherapy in metastatic setting between January 1, 2017, and March 31, 2022, were analyzed. The study assessed treatment patterns, time to next treatment or death (TTNTD), time to treatment discontinuation, medical costs, and adverse events of interest for those receiving first-, second-, and third-line chemotherapies for mBC.

Results: The most common regimens were S-1 (20.1%), eribulin (12.2%), and paclitaxel + bevacizumab (6.9%) for each line of therapy, respectively. The TTNTD decreased as treatment advanced, with medians of 8.2, 7.3, and 6.0 months for each line. Monthly medical costs were 277.1, 340.9, and 378.4 thousand yen for each line of therapy, respectively. Nausea/vomiting and neutropenia/leukopenia occurred in 62.6% and 20.5% of patients, respectively.

Conclusion: This study highlights current chemotherapy practices for HR+/HER2- mBC in Japan, where treatment patterns largely align with clinical guidelines but vary according to patient characteristics. Notably, the TTNTD shortens with successive treatments, and medical costs increase, intensifying the financial burden on patients. These findings indicate unmet needs for improved treatment options that enhance outcomes and reduce patient burden in advanced therapy lines.

Purpose: This study aimed to identify preferences of patients with high-risk hormone receptor positive/human epidermal growth factor receptor 2 negative (HR + /HER2-) early breast cancer (EBC) related to adjuvant endocrine therapy (ET) using the Adaptive Choice-Based Conjoint (ACBC) method.

Methods: A stepwise multimodal study was conducted in Germany between October 2021 and March 2022 consisting of desk research, qualitative interviews, and quantitative online surveys. Included patients had a high risk of recurrence at the time of their HR + /HER2- EBC diagnosis, completed primary therapy (surgery ± radiation + (neo)adjuvant chemotherapy), and were prescribed or undertaking adjuvant ET. In the desk research phase, online resources, patient material, and existing studies were reviewed. In the qualitative phase, interviews were conducted with 6 gynaecologists, 6 oncologists, 20 patients, and 5 caretakers. In the quantitative phase, 85 patients completed the ACBC analysis survey.

Results: Included patients were aged 49.4 years (mean) among which 69.4% were still working. In the ACBC absolute rating, diarrhoea, arthralgia, and nausea were least relevant attributes to patients. Relative assessment of ET attributes against each other revealed that achieving the ET goal, namely the reduction of risk of tumour recurrence, had the highest relevance, while avoiding side effects and maintaining quality of life were less relevant. Overall, 35% have considered taking a break or discontinuing adjuvant ET due to side effects.

Conclusion: Reduction of tumour recurrence was the attribute of highest relative importance for patients with high-risk HR + /HER2- EBC followed by side effect avoidance and quality-of-life maintenance, reflecting their importance in treatment decisions.

Background: Surgical staging procedures of the axilla in initially clinically node-positive (cN +) breast cancer patients receiving neoadjuvant chemotherapy (NACT) vary across countries. Different procedures such as axillary lymph node dissection, sentinel lymph node biopsy, target lymph node biopsy and targeted axillary dissection are currently in use. To date, data on radar reflectors as a non-wire and non-radioactive technique for marking target lymph nodes are limited. The present study aims at examining the detection rate, the rate of lost markers, and magnetic resonance imaging artifacts after TLN marking using a radar reflector before NACT in the largest available cohort of breast cancer patients enrolled in the international prospective AXSANA study.

Methods: AXSANA (EUBREAST-03) is an international prospective cohort study including cN + patients managed with different surgical axillary staging techniques after NACT. Eligible patients have cT1-4c cN + breast cancer and receive neoadjuvant chemotherapy. Patients are followed up for 5 years. In the present subgroup analysis, only patients with a TLN marked by a radar reflector were included.

Results: A TLN was marked by radar reflector insertion in 158 patients prior to NACT. Of these, 136 had final surgery results available at the time of analysis, and in 135 out of these 136 patients, localization of TLN was attempted. All radar markers were successfully removed. While lymphoid tissue corresponding to the TLN was identified in 132 patients (97.8%), no lymphoid tissue was detected on histopathology in three patients. It remains unclear whether the TLN was excised in these cases or not. In 1 out of 27 patients (3.7%) who underwent preoperative MRI, image assessment was compromised due to artifacts after radar marker placement.

Conclusion: To the best of our knowledge, this is the largest prospective series of patients receiving a radar reflector for the marking of a TLN prior to NACT for breast cancer. Our data demonstrate that radar reflectors are a reliable tool for marking target lymph nodes before neoadjuvant treatment.

Trial registration number: NCT04373655 (date of registration May 4, 2020).

Purpose: Women residing in disadvantaged neighborhoods experience disparities in breast cancer (BC) survival which persist when accounting for individual-level socioeconomic/treatment factors. The chronic stress of living in a disadvantaged neighborhood may compound the stress of a new cancer diagnosis, leading to neuroendocrine dysregulation. Cognitive Behavioral Stress Management (CBSM) has shown efficacy at reducing distress and modulating neuroendocrine functioning, but it is unknown whether it is efficacious in this population.

Methods: This is a secondary analysis of a randomized trial of 10-week group-based CBSM (versus a psycho-educational control) in women with nonmetastatic BC. The Area Deprivation Index (ADI) was calculated, and women were categorized as living in low (n = 175) versus high disadvantage (n = 50). Women completed a measure of cancer-related distress (Impact of Events Scale-Intrusions) and underwent blood draws to collect PM cortisol at baseline, 6 months, and 12 months. Hierarchical linear modeling tested whether condition predicted the slope of outcomes, and whether ADI moderated these relationships.

Results: CBSM was associated with greater reductions in cancer-specific distress and cortisol, though these effects were not found to be moderated by ADI. Exploratory simple slope analyses showed that CBSM was associated with decreased cancer-related distress across ADI categories, while CBSM resulted in decreased cortisol among low ADI women only.

Conclusion: CBSM reduced cancer-related distress across neighborhoods, but this was only accompanied by cortisol changes among those in advantaged neighborhoods. Neighborhood disadvantage may represent a particularly salient stressor that is distinct from cancer-specific distress. Future interventions targeting this population should consider modifications to increase relevance and accessibility.

Purpose: Unclear or suspicious breast findings are typically clarified by interventional breast biopsy. Lesions with uncertain malignant potential are grouped as B3 lesions in histopathology. The B3 group according to the European Working Group for Breast Screening Pathology (EWGBSP) comprises various breast lesions with different upgrade rates to invasive breast cancer (BC) or ductal carcinoma in situ (DCIS) if surgical removal is performed. The objective of this study was to investigate malignant upgrade rates to DCIS and/or invasive breast cancer (BC) after open surgical excision for the different B3 lesions.

Methods: A total of 192 patients with histologically verified B3 lesions were followed up retrospectively for this analysis. Patients with the B3 lesions atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), and classical lobular neoplasia (LN1-2) were combined into one group, while cellular fibroepithelial lesions (CFL) and phyllodes tumors without suspicion of malignancy, as well as papillomas and radial scars/complex sclerosing lesions (RS/CSL) were summarized in two other groups. We investigated the association of the different B3 lesions with invasive BC or DCIS after open surgical excision.

Results: Histopathological investigation revealed in 21 (10.9%) of the 192 patients invasive BC or DCIS after open surgical excision. The rate of patients with BC and/or DCIS significantly differed between the patient groups (p < 0.01, Fisher's exact test): The highest rate was 17.5% (95% confidence interval (CI), 10.7-26.2) in patients within the group of ADH, FEA, and LN1-2. In the other two groups, fewer malignant lesions occurred. In the group with papillomas and RS/CSL the malignant upgrade rate was 4.3% (95% CI, 0.9-12.2), while within the group with CFL and phyllodes tumors without suspicion of malignancy no malignant upgrade was observed (0.0%, 95% CI, 0.0-16.9).

Conclusions: B3 lesions harbor the risk of malignant upgrade after surgical excision. In our collective ADH, FEA, and LN1-2 had significant higher upgrade rates than other B3 lesions.

Purpose: Growing breast cancer is associated with an inherent risk of metastasis. If surgical treatment of breast cancer is delayed, the prognosis worsens with increasing tumor size. This justifies the search for a safe time interval between diagnosis and surgery.

Methods: The 2022 population-based data on incidence and the time interval to initial surgery for the United States (U.S.) and Germany are used. Tumor growth and initiation of metastases can be calculated using public data on hormone receptor status, volume doubling time, and tumor size-dependent relative survival. Our assumptions are based on an initial 19.8 mm mean tumor size. 15-year BC-specific mortality in both countries is assumed to be 19.6% without surgical delay. Volume doubling time stratified by hormone receptor status, assumed to be continuous may differ by a factor of 2.4.

Results: The U.S. and Germany report 287,850/71,375 new breast cancers for the year 2022 and 2019. If tumor removal is delayed by 8 weeks, mortality rate increases by 2.25/4.79% (HR + /HR-) as estimated by our model. The currently reported mean delay in the U.S. and Germany of 33.7/26.0 days or 4.8/3.7 weeks, respectively, would lead to an estimated 4,676/918 additional BC deaths or a 1.6/1.2% rise in the 15-year BC-specific mortality rate.

Conclusions: This study offers reasonable evidence that confirmed cases of breast cancer should be prioritized and treated according to hormone receptor status and tumor size as soon as possible. Effective screening measures should be followed by timely treatment.

Background: The prognostic value of pathological complete response (pCR) in HR+/HER2- breast cancer patients following neoadjuvant chemotherapy (NAC) is limited, as many of these patients achieve long-term survival regardless of pCR status. The effectiveness of current tools-residual cancer burden (RCB), the Miller-Payne (MP) score, CPS-EG score and the immunohistochemical 4 (IHC4)-in this subgroup remains uncertain. In this study, we validated the prognostic role of these approaches and developed a COMBINED score capable of more accurately stratifying patients into distinct risk groups, effectively identifying low-risk patients with favorable outcomes who may be suitable for treatment de-escalation.

Methods: This study retrospectively analyzed 601 HR+/HER2- breast cancer patients at Sun Yat-sen Memorial Hospital who did not achieve pCR following NAC. Patients were stratified using the IHC4, RCB, MP, CPS-EG, and a novel COMBINE score (integrating CPS-EG and IHC4). Survival outcomes, including disease-free survival (DFS) and overall survival (OS), were evaluated using Kaplan-Meier analysis and Cox regression, with time-dependent ROC and concordance index (C-index) calculations to assess prognostic performance.

Results: The IHC4 and CPS-EG scores outperformed the RCB and MP scores in predicting DFS and OS for non-pCR HR+/HER2- patients. The COMBINE score further enhanced prognostic accuracy, stratifying patients into four risk groups with significant differences in 5-year DFS (96.5% for low-risk vs. 55.1% for high-risk) and OS (100% for low-risk vs. 63.4% for high-risk). The COMBINE score consistently demonstrated superior AUC and C-index values compared to the CPS-EG and IHC4 scores individually at all time points (all p-values < 0.05).

Conclusion: The IHC4 score adds prognostic value beyond the CPS-EG score in HR+/HER2- breast cancer patients post-NAC. The COMBINE score, integrating both systems, offers superior prognostic stratification, highlighting the importance of combining clinical staging with tumor biology. Future studies with independent datasets are needed to validate these findings. This study provides valuable insights for optimizing treatment decisions in HR+/HER2- breast cancer.

Introduction: Triple-negative breast cancer (TNBC), is a highly aggressive tumor. Formosanin C (FC) is a diosgenin with immunomodulatory and antitumor properties, the precise mechanism through which it is against TNBC remains uncertain.

Objective: Clarifying the mechanism of FC against TNBC.

Materials and methods: The impact of FC on two TNBC cell lines for 24 h was investigated through various techniques including the CCK8 assay, flow cytometry, transwell assay, scratch tests, immunoblot assay, and immunofluorescence. To elucidate the mechanism behind the anti-TNBC effect of FC, MDA-MB-231 cells were subjected to STAT3 overexpression. Moreover, the in vivo efficacy of FC was examined using a xenograft nude mice (BALB/C). Mice were divided into the control group (equal amount of PBS), the napabucasin group (5 mg/kg) and the FC groups (1 mg/kg, 2 mg/kg). The study duration was 30 days.

Results: FC exhibited inhibitory effects against MDA-MB-231 and Hs578T cells. FC can decrease the migratory capacity of TNBC cells by inhibiting epithelial-mesenchymal transition (EMT). Meanwhile, we demonstrated that the inhibition of phosphorylation of STAT3 (Y705) is the crucial mechanism of FC against TNBC. Moreover, FC also hindered the polarization of macrophage M2.

Discussion and conclusion: This study is the first to show that FC restrains the EMT of TNBC cells by obstructing the STAT3 pathway and hinders the M2 polarization of macrophages and immune evasion. Therefore, FC holds the possibility of being utilized as a therapeutic remedy for TNBC.