Cha CD, et al. J Breast Cancer. 2024 Oct;27:e32. https://doi.org/10.4048/jbc.2024.0213

Radiotherapy (RT) is the standard of care following breast-conserving operation in breast cancer patients. The neutrophil-to-lymphocyte ratio (NLR) reflects the systemic change caused as a result of the radiotherapy. We aimed to evaluate the association between RT and the change in NLR following the receipt of RT, and to investigate the prognostic impact. We retrospectively reviewed NLR values of breast cancer patients taken before the administration of the first and the last session of RT. The cut-off point for the NLR was determined using the Youden index and receiver operating characteristic (ROC) curve within the training set. Recurrence-free survival (RFS), distant metastasis free survival, and overall survival were the main outcomes. Patients with an NLR higher than 3.49 after RT were classified to an RT-induced high NLR group and showed a significantly higher recurrence rate compared to those with low NLR (p < 0.001). In a multivariate Cox proportional hazards model, RT-induced high NLR remained a significant prognostic factor (HR 2.194, 95% CI 1.230–3.912, p = 0.008 for tumor recurrence. We demonstrated that an increase in NLR over the course of RT has a negative impact on survival, putting these patients with RT-susceptible host immunity at a higher risk of tumor recurrence.

Incorporating dual human epidermal growth factor receptor 2 (HER2) blockade into neoadjuvant systemic therapy (NST) led to higher response in patients with HER2-positive breast cancer. However, axillary response to treatment regimens, including single or dual HER2 blockade, in patients with clinically node-positive breast cancer remains uncertain. Our study aimed to examine the pathologic axillary response according to the type of NST, that is, single or dual HER2 blockade. In our study, 546 patients with clinically node-positive, HER2-positive breast cancer who received NST followed by axillary surgery were retrospectively selected and divided into three groups: chemotherapy alone, chemotherapy + trastuzumab and chemotherapy + trastuzumab with pertuzumab. The primary outcome was the axillary pathologic complete response (pCR). Among 471 patients undergoing axillary lymph node dissection, the axillary pCR rates were 43.5%, 74.5% and 68.8% in patients who received chemotherapy alone, chemotherapy + trastuzumab and chemotherapy + trastuzumab with pertuzumab, respectively. There was no difference in axillary pCR rates between patients who received single or dual HER2 blockade (P = .379). Among patients receiving chemotherapy + trastuzumab, patients without breast pCR had the greatest risk for residual axillary metastases (relative risk, 9.8; 95% confidence interval, 3.2-14.9; P < .0001). In conclusion, adding trastuzumab to chemotherapy increased the axillary pCR rate in patients with clinically node-positive, HER2-positive breast cancer; furthermore, dual HER2-blockade with trastuzumab and pertuzumab did not elevate the axillary response compared with trastuzumab alone. Breast pCR could be a strong predictor for axillary pCR in clinically node-positive patients treated with HER2-targeting therapy.

Importance: Patients with sporadic breast cancer have comparable prognoses after undergoing either breast-conserving treatment (BCT) or mastectomy. However, there are limited and inconsistent data on the assessment of oncologic outcomes between BCT and mastectomy in patients with pathogenic variants in BRCA1 or BRCA2.Objective: To investigate the outcomes of BCT on recurrence and survival in patients with breast cancer with BRCA1 or BRCA2 pathogenic variants.Design, Setting, and Participants: This retrospective multicenter cohort study analyzed patients from 13 institutions in South Korea with primary breast cancer with BRCA1 or BRCA2 pathogenic variants who underwent either BCT or mastectomy from January 2008 through December 2015. The median (IQR) follow-up period was 8.3 (6.4-9.6) years. Data were analyzed from September 2023 to August 2024.Exposure: BRCA1 or BRCA2 pathogenic variant and BCT.Main Outcomes and Measures: Primary outcomes were logoregional recurrence–free survival, distant recurrence–free survival, and overall survival. Propensity score matching (PSM) using the greedy nearest neighbor method was performed to match covariates to minimize potential selection bias.Results: A total of 575 female patients with BRCA1 or BRCA2 pathogenic variants were identified, all of whom were South Korean with a mean (SD) age of 42.0 (9.7) years. Among them, 367 patients (66.2%) received BCT and 186 (33.8%) were treated with mastectomy. BCT was not a factor associated with oncologic outcomes, including locoregional recurrence, compared with mastectomy. After adjusting for clinicopathologic characteristics through 1:1 PSM, there were still no statistically significant differences in oncologic outcomes between the BCT group and the mastectomy group. Multivariate analysis showed that the type of breast surgery was not significantly associated with oncologic outcomes. In subgroup analysis among matched patients based on BRCA1 or BRCA2 status, tumor size, lymph node metastasis, histologic grade, and subtype, BCT was also not a factor associated with risk for recurrence.Conclusions and Relevance: The findings from this cohort study of patients with BRCA1 or BRCA2 pathogenic variants suggested that there were no significant differences in oncologic outcomes between patients who underwent BCT and those who underwent mastectomy. Therefore, breast conservation with close surveillance can be considered a viable treatment option for BRCA1 or BRCA2 pathogenic variant carriers. Further studies incorporating prospectively collected data are warranted to validate our findings.