Breast Cancer Research and Treatment最新文献

Purpose: To determine whether automated quantification of background parenchymal enhancement (BPE) from dynamic contrast-enhanced MRI (DCE-MRI) can serve as an imaging biomarker for clinical outcomes including overall survival (OS), recurrence-free survival (RFS), and pathological complete response (pCR) in breast cancer.

Methods: The multi-institutional data consisted of 922 biopsy-confirmed invasive breast cancer patients from the Duke-Breast-Cancer-MRI dataset and 152 patients with whole-breast pre- (T₀) and/or post (T₃) DCE-MRI from the I-SPY2 dataset for validation. Automated fibroglandular tissue (FGT) segmentation and BPE quantification were performed on DCE-MRI. The optimal intensity enhancement threshold by volume-based method was established against four radiologist-defined BPE categories. The area under the curve (AUC) was obtained for classification of BPE categories. Cox proportional hazards models were used to predict OS and RFS. Logistic regression was used to predict pCR.

Results: Peak-contrast BPE showed strong correlation with radiologist-defined BPE, achieving the best performance at a 55% signal enhancement threshold (AUC 0.70-0.86). The calculated BPE decreased after neoadjuvant chemotherapy. A reduction in calculated BPE grade after neoadjuvant chemotherapy was predictive of pCR for the high baseline BPE group (adjusted odds ratio = 5.88 [1.03, 33.33]) and for the low baseline BPE group (adjusted odds ratio = 6.54 [1.26, 33.94]). Baseline BPE was independently associated with improved OS (adjusted hazard ratio 0.58 [0.34, 0.99]) but not associated with RFS.

Conclusion: Automated quantification of BPE from DCE-MRI provides an objective and reproducible imaging biomarker associated with treatment response and overall survival in breast cancer. These results support its potential utility for individualized risk stratification and therapeutic decision-making.

Purpose: The retinoblastoma protein (Rb) is a critical cell-cycle regulator, and its loss of function can lead to resistance to CDK4/6 inhibitors (CDK4/6i), which are the standard first-line treatment for estrogen receptor (ER)-positive metastatic breast carcinoma (mBC). Thus, identifying Rb-deficient mBC is crucial for optimal personalized breast cancer management. This study aimed to determine the prevalence of Rb loss by immunohistochemistry (IHC) in a cohort of ER + mBC and to assess its correlation with RB1 genetic inactivation.

Methods: We analyzed Rb IHC in 50 consecutive ER-positive mBC. Histopathologic and clinical features were analyzed. p16 IHC was performed in a subset of Rb-deficient cases. Targeted next-generation tumor-normal sequencing (NGS) data using MSK-IMPACT were retrospectively analyzed in 38 mBCs.

Results: Rb loss was identified in 20% (10/50) of mBC, and was either partial (8%, 4/50) or complete (12%, 6/50). In all evaluable cases (100%, 9/9), Rb loss was associated with p16 positivity. Neuroendocrine (NE) features were observed in 40% (4/10) of mBCs with Rb loss. MSK-IMPACT data were available for six Rb-deficient cases and revealed pathogenic RB1 alterations in two (33%). None of the tumors with preserved Rb expression (80%, 40/50) showed RB1 genetic alterations or NE features. Notably, one mBC case demonstrated disease progression on CDK4/6 inhibitor therapy, accompanied by acquired Rb loss and acquisition of an NE phenotype.

Conclusion: Rb loss in mBC can be reliably detected by Rb IHC, especially when interpreted alongside p16, offering a rapid and cost-effective means of assessing Rb status. This approach may identify Rb-deficient tumors that are missed by conventional methods, such as next-generation sequencing, and help guide personalized therapeutic strategies in patients with mBC.

Purpose: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) improves outcomes in breast cancer (BC); however it may not prevent brain metastases. We evaluated central nervous system (CNS) recurrence patterns in early-stage BC following NAC according to pCR.

Methods: All consecutive stage I-III BC treated with NAC and surgery at a single center between 2007 and 2018 were analyzed. Endpoints included the impact of pCR on CNS recurrence across BC subtypes-hormone receptor-positive(HR)/HER2-negative, HER2-positive and triple-negative (TNBC), CNS recurrence patterns and overall survival (OS) after CNS relapse. Statistical comparisons included Fisher's Exact test, Chi-square, Kaplan-Meier, and regression analyses.

Results: Among 1147 patients, 537 had HR-positive/HER2-negative, 301 HER2-positive, 309 TNBC, mostly stage III, treated with anthracycline + taxane NAC, and trastuzumab if HER2-positive. Three hundred sixty-five achieved pCR (59/537 HR-positive/HER2-negative, 158/301 HER2-positive, 148/309 TNBC). CNS recurrence occurred in 72 (6.2%) patients, with no difference between pCR and non-pCR (4.7 vs. 7.0%, p = 0.15). Across subtypes, there was no difference for HR-positive/HER2-negative (3.4 vs. 4%, p = 1.0), TNBC (5.4 vs. 9.3%, p = 0.2), however there was a reduction in HER2-positive (4.4 vs. 14.7%, p = 0.003) after pCR. Isolated CNS relapse was the predominant pattern of CNS metastasis (82.4%) in pCR, particularly in HER2-positive. Median OS after CNS relapse was 12 months. Multivariate analysis identified HER2-positive, TNBC, and cN2-3 status as independent predictors of CNS recurrence.

Conclusion: Although pCR was not associated with a lower overall risk of CNS recurrence, it predicted a reduced risk in HER2-positive disease. Isolated CNS relapse predominated, suggesting a sanctuary effect.

Purpose: Socioeconomic inequalities in breast cancer survival persist in the UK. Area-based deprivation measures may underestimate socioeconomic effects by assigning average deprivation levels to all area inhabitants. This study investigated associations between house value (individual-level) and area-based deprivation with breast cancer outcomes in Northern Ireland.

Methods: Women diagnosed with breast cancer from 2011 to 2021 were identified using the Northern Ireland Cancer Registry. House value was determined from Valuation and Lands Agency property valuation data, and area-based deprivation from the Northern Ireland Multiple Deprivation Measure. The primary outcome was breast cancer-specific mortality. Secondary outcomes were stage at diagnosis and all-cause mortality. Cox regression models calculated adjusted hazard ratios (HR) and 95% confidence intervals (95% CIs) for mortality by house value category and deprivation, adjusting for confounders.

Results: Among 12,766 women with breast cancer, women in the lowest versus highest house value category had a 60% increase in mortality (adjusted HR = 1.60 95% CI 1.34, 1.92; per 20 percentile decrease adjusted HR = 1.12 95% CI 1.08, 1.16) and were more likely diagnosed with stage 4 disease (7.5% versus 4.1%; P < 0.001). Women living in the most versus least deprived areas had a 26% increase in mortality (adjusted HR = 1.26 95% CI 1.08, 1.47; per 20 percentile decrease adjusted HR = 1.05 95% CI 1.01, 1.08) but had no difference in stage 4 disease (5.9% vs. 5.0%; P = 0.157).

Conclusion: Individual-level house value demonstrated stronger associations with breast cancer outcomes than area-level deprivation, suggesting it may serve as a more sensitive indicator for monitoring health inequalities in cancer.

Purpose: To investigate long-term outcomes for triple‑negative breast cancer (TNBC) patients enrolled in JBCRG-22.

Methods: TNBC (cT1c-T3, cN0-1, M0) patients were stratified by homologous recombination deficiency (HRD) and germline BRCA mutation (gBRCAm) status. Group A patients (aged < 65 years with HRD-positive tumors, or those with gBRCAm, if available) were randomized to receive 4 cycles of weekly paclitaxel (group A1) or eribulin (group A2), both with carboplatin, followed by 4 cycles of anthracycline. Group B patients (aged < 65 years with HRD-negative tumors or aged ≥ 65 years) were randomized to receive 6 cycles of eribulin plus cyclophosphamide (group B1) or eribulin plus capecitabine (group B2). Five-year invasive disease-free survival (IDFS), distant disease-free survival (DDFS), and overall survival (OS) were assessed. Additionally, data were analyzed by biomarker levels including lymphocyte count (LC) and neutrophil-to-lymphocyte ratio (NLR).

Results: Ninety-nine patients were followed for a median of 5.6 years. In patients who received eribulin-based therapy (groups A2 + B1 + B2), 5-year IDFS and OS rates, respectively, were 95% and 100% in patients who achieved pCR after neoadjuvant therapy (n = 20) and 71.4% and 80.2% in those who did not (n = 56), showing significantly better prognosis in the pCR cohort (p < 0.05). OS tended to be better in patients with baseline LC ≥ 1500/mm³ and NLR < 3, particularly in eribulin-treated patients, although differences were non-significant.

Conclusions: These findings will help guide the development of eribulin-based neoadjuvant chemotherapy for selected TNBC patients. Our exploratory analysis of LC and NLR results may help inform clinical prediction models for eribulin-treated patients.

Trial registration: The study has been registered with the University Hospital Medical Information Network Clinical Trials Registry ( https://www.umin.ac.jp/ctr/index-j.htm ) with unique trial number UMIN000023162. The Japan Breast Cancer Research Group trial number is JBCRG-22.

Purpose: To evaluate whether the omission of axillary surgery impacts clinical outcomes in patients with early-stage breast cancer and clinically negative lymph nodes.

Methods: We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) comparing no axillary surgery with standard axillary interventions (sentinel lymph node biopsy [SLNB] or axillary dissection [AD]). This study followed PRISMA guidelines and was registered in PROSPERO (CRD420250653779). Searches were conducted in PubMed, Web of Science, and Embase through June 2025. Outcomes assessed included overall survival (OS), disease-free survival (DFS), and axillary recurrence (AR). Meta-analyses were performed using RevMan 5.4. Risk of bias was assessed using the RoB 2 tool.

Results: Out of 853 records, seven RCTs including 8806 patients met the inclusion criteria. Among them, 2,915 patients underwent no axillary surgery, while 5891 received surgical axillary treatment. Two trials compared no surgery with SLNB, and five compared no surgery with AD. No significant differences were found in OS (OR = 1.02; 95% CI, 0.86-1.20; p = 0.84; I² = 36%) or DFS (OR = 0.80; 95% CI, 0.63-1.00; p = 0.05; I² = 63%). AR was significantly lower in the axillary surgery group (OR = 0.18; 95% CI, 0.10-0.31; p < 0.01; I² = 39%).

Conclusion: The omission of axillary surgery in early-stage breast cancer with clinically negative lymph nodes does not negatively impact overall or disease-free survival. However, it is associated with a higher-though still low-risk of axillary recurrence.

Purpose: Aromatase Inhibitors Associated Musculoskeletal Symptoms (AIMSS) are common side effects among hormone receptor-positive breast cancer patients, significantly affecting patients' treatment adherence and quality of life. The individual genetic susceptibility mechanism underlying AIMSS was not well understood yet. This study aimed to validate the association between genetic polymorphisms and AIMSS among Chinese breast cancer patients.

Methods: This was a cross-sectional study. Participants were recruited from a tertiary hospital in China from May 2023 to June 2024. Musculoskeletal symptoms were measured using the Modified Score for the Assessment of Chronic Rheumatoid Affections of the Hands (M-SACRAH) and the Western Ontario and McMaster Osteoarthritis Index (WOMAC) among hormone receptor-positive patients receiving aromatase inhibitor therapy. Six genes (i.e., ESR1, ESR2, RANK, OPG, TCL1A and CYP19A1) related 20 SNPs were tested. Multivariate linear regression analysis was used to explore the association between different genotypes and the severity of AIMSS.

Results: Among 171 participants, the standardized M-SACRAH score was 3.33 (IQR 0.00-9.17) and the standardized WOMAC score was 5.83 (IQR 2.08-17.29). Patients carrying the ESR1 rs9340799 AG genotype (vs. AA) had a significant reduction in the severity of hand joint symptoms [adjusted β = -4.51, 95% CI: -8.29, -0.73, p = 0.020] and knee/hip joint symptoms [adjusted β = -4.44, 95% CI: -8.49, -0.39, p = 0.032]. The ESR1 rs2077647 TC genotype (vs. TT) was related to lower level of hand joint symptoms [adjusted β = -5.03, 95% CI: -8.69, -1.37, p = 0.007] and knee/hip joint symptoms [adjusted β = -5.04, 95% CI: -8.97, -1.12, p = 0.012]. The ESR1 rs2234693 TC genotype (vs. TT) [adjusted β = -4.06, 95% CI: -8.09, -0.03, p = 0.049] was associated with lower level of knee/hip joint symptoms. No significant associations emerged between ESR2, RANKL, OPG, TCL1A, or CYP19A1 variants and AIMSS.

Conclusions: This study preliminarily validated the association between ESR1 polymorphisms (rs9340799, rs2077647, and rs2234693) and aromatase inhibitor associated musculoskeletal symptoms in hormone receptor-positive breast cancer among Chinese patients. Future research should focus on dissecting their molecular mechanisms, and integrating genetic data with clinical interventions to optimize the management strategies of musculoskeletal toxicity.

Purpose: For early-stage triple-negative breast cancer (TNBC), the KEYNOTE-522 trial established neoadjuvant pembrolizumab plus chemotherapy (CT), followed by adjuvant pembrolizumab, as the standard of care. Nevertheless, uncertainties remain on how to integrate this regimen with other adjuvant therapies such as capecitabine or olaparib. This study evaluated real-world treatment patterns and safety of adjuvant therapies following neoadjuvant chemoimmunotherapy.

Methods: The Neo-Real study includes patients with TNBC treated with neoadjuvant pembrolizumab plus CT in Brazil and Argentina. This study describes real-world adjuvant treatment patterns and safety; survival outcomes are not reported in this analysis.

Results: Among 726 patients included, 692 underwent surgery, and 62.9% achieved pathologic complete response (pCR). Of those with pCR, 84.8% received adjuvant pembrolizumab alone, while 14.3% received no adjuvant therapy. Among patients with residual disease and no germline BRCA1/2 mutations (n = 207), 57.5% received pembrolizumab plus capecitabine, 26.1% pembrolizumab alone, and 12.6% capecitabine alone. In BRCA1/2-mutated patients (n = 26), 57.7% received pembrolizumab plus olaparib, 19.2% pembrolizumab alone, and 11.5% olaparib alone. Safety data were available for 359 patients. Adjuvant pembrolizumab alone caused a lower incidence of grade ≥ 3 AEs (6.7%) compared with combination regimens (P = 0.002). Drug discontinuation due to toxicity occurred in 5.7%, 11.2%, and 7.7% of patients receiving pembrolizumab, pembrolizumab + capecitabine, and pembrolizumab + olaparib, respectively (P = 0.126).

Conclusion: Most patients with pCR continued adjuvant pembrolizumab, while combination strategies predominated among those with residual disease and were associated with higher rates of grade ≥ 3 AEs. The efficacy of these combined regimens remains to be determined.