Impact of germline BRCA1/2 mutations on response to neoadjuvant systemic therapy and prognosis in breast cancer: a propensity score matched cohort study

Abstract Background We investigated whether germline BRCA1/2 pathogenic variants (PVs) influence treatment response and survival outcomes in breast cancer patients treated with neoadjuvant chemotherapy (NCT). Using propensity score matching (PSM) to control for variations in treatment and clinicopat...

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Main Authors: Hyunyou Kim, Jung Whan Chun, Jinha Hwang, Seung Gyu Yun, Jinseob Kim, Seung Pil Jung, Hyeong-Gon Moon, Eun-Shin Lee, Wonshik Han
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Breast Cancer Research
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Online Access:https://doi.org/10.1186/s13058-025-02041-6
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author Hyunyou Kim
Jung Whan Chun
Jinha Hwang
Seung Gyu Yun
Jinseob Kim
Seung Pil Jung
Hyeong-Gon Moon
Eun-Shin Lee
Wonshik Han
author_facet Hyunyou Kim
Jung Whan Chun
Jinha Hwang
Seung Gyu Yun
Jinseob Kim
Seung Pil Jung
Hyeong-Gon Moon
Eun-Shin Lee
Wonshik Han
author_sort Hyunyou Kim
collection DOAJ
description Abstract Background We investigated whether germline BRCA1/2 pathogenic variants (PVs) influence treatment response and survival outcomes in breast cancer patients treated with neoadjuvant chemotherapy (NCT). Using propensity score matching (PSM) to control for variations in treatment and clinicopathological characteristics, this study aimed to evaluate the influence of BRCA1/2 mutations on prognosis and treatment efficacy, providing insights for optimizing therapeutic strategies and improving patient outcomes. Methods We conducted a retrospective cohort study using data from two institutions. The study analyzed breast cancer patients who underwent germline BRCA1/2 testing and received NCT followed by curative resection and standard adjuvant therapy from January 2001 to January 2019. PSM was used to balance confounding variables. Results Among 411 patients included, 86 have BRCA1/2 mutations. After matching, BRCA1/2 PV carriers had a higher pCR rate (40.0%) compared to wild-type patients (26.5%, OR = 1.85, 95% CI: 1.07–3.22, P = 0.029). They also exhibited a significantly lower 5-year DM rate (4.7% vs. 18.2%, OR = 0.22, 95% CI: 0.08–0.65, P = 0.006). Among pCR patients, outcomes were excellent regardless of BRCA1/2 status. For non-pCR patients, BRCA1/2 PV carriers had better DMFS (hazard ratio (HR) = 0.27, 95% confidence interval (CI) = 0.09–0.81, P = 0.02), though overall survival differences were not significant (HR = 0.47, 95% CI = 0.15–1.47, P = 0.197). Conclusions and relevance Germline BRCA1/2 mutations are associated with higher pCR rates and improved DMFS in breast cancer patients treated with NCT. These findings emphasize the enhanced chemosensitivity of BRCA-associated tumors and the importance of genetic testing in treatment planning. Further research is needed to validate these findings and optimize treatment strategies.
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spelling doaj-art-ae658a7f9ba14161bd3546e311dd1d292025-08-20T03:08:35ZengBMCBreast Cancer Research1465-542X2025-05-012711910.1186/s13058-025-02041-6Impact of germline BRCA1/2 mutations on response to neoadjuvant systemic therapy and prognosis in breast cancer: a propensity score matched cohort studyHyunyou Kim0Jung Whan Chun1Jinha Hwang2Seung Gyu Yun3Jinseob Kim4Seung Pil Jung5Hyeong-Gon Moon6Eun-Shin Lee7Wonshik Han8Department of Surgery, Korea University Hospital, Korea University College of MedicineDepartment of Surgery, Seoul National University College of MedicineDepartment of Laboratory Medicine, Korea University Hospital, Korea University College of MedicineDepartment of Laboratory Medicine, Korea University Hospital, Korea University College of MedicineZarathu Co., LtdDepartment of Surgery, Korea University Hospital, Korea University College of MedicineDepartment of Surgery, Seoul National University College of MedicineDepartment of Surgery, Korea University Hospital, Korea University College of MedicineDepartment of Surgery, Seoul National University College of MedicineAbstract Background We investigated whether germline BRCA1/2 pathogenic variants (PVs) influence treatment response and survival outcomes in breast cancer patients treated with neoadjuvant chemotherapy (NCT). Using propensity score matching (PSM) to control for variations in treatment and clinicopathological characteristics, this study aimed to evaluate the influence of BRCA1/2 mutations on prognosis and treatment efficacy, providing insights for optimizing therapeutic strategies and improving patient outcomes. Methods We conducted a retrospective cohort study using data from two institutions. The study analyzed breast cancer patients who underwent germline BRCA1/2 testing and received NCT followed by curative resection and standard adjuvant therapy from January 2001 to January 2019. PSM was used to balance confounding variables. Results Among 411 patients included, 86 have BRCA1/2 mutations. After matching, BRCA1/2 PV carriers had a higher pCR rate (40.0%) compared to wild-type patients (26.5%, OR = 1.85, 95% CI: 1.07–3.22, P = 0.029). They also exhibited a significantly lower 5-year DM rate (4.7% vs. 18.2%, OR = 0.22, 95% CI: 0.08–0.65, P = 0.006). Among pCR patients, outcomes were excellent regardless of BRCA1/2 status. For non-pCR patients, BRCA1/2 PV carriers had better DMFS (hazard ratio (HR) = 0.27, 95% confidence interval (CI) = 0.09–0.81, P = 0.02), though overall survival differences were not significant (HR = 0.47, 95% CI = 0.15–1.47, P = 0.197). Conclusions and relevance Germline BRCA1/2 mutations are associated with higher pCR rates and improved DMFS in breast cancer patients treated with NCT. These findings emphasize the enhanced chemosensitivity of BRCA-associated tumors and the importance of genetic testing in treatment planning. Further research is needed to validate these findings and optimize treatment strategies.https://doi.org/10.1186/s13058-025-02041-6Breast cancerBRCA1/2 mutationNeoadjuvant chemotherapyPathologic complete responseDistant metastasis-free survival
spellingShingle Hyunyou Kim
Jung Whan Chun
Jinha Hwang
Seung Gyu Yun
Jinseob Kim
Seung Pil Jung
Hyeong-Gon Moon
Eun-Shin Lee
Wonshik Han
Impact of germline BRCA1/2 mutations on response to neoadjuvant systemic therapy and prognosis in breast cancer: a propensity score matched cohort study
Breast Cancer Research
Breast cancer
BRCA1/2 mutation
Neoadjuvant chemotherapy
Pathologic complete response
Distant metastasis-free survival
title Impact of germline BRCA1/2 mutations on response to neoadjuvant systemic therapy and prognosis in breast cancer: a propensity score matched cohort study
title_full Impact of germline BRCA1/2 mutations on response to neoadjuvant systemic therapy and prognosis in breast cancer: a propensity score matched cohort study
title_fullStr Impact of germline BRCA1/2 mutations on response to neoadjuvant systemic therapy and prognosis in breast cancer: a propensity score matched cohort study
title_full_unstemmed Impact of germline BRCA1/2 mutations on response to neoadjuvant systemic therapy and prognosis in breast cancer: a propensity score matched cohort study
title_short Impact of germline BRCA1/2 mutations on response to neoadjuvant systemic therapy and prognosis in breast cancer: a propensity score matched cohort study
title_sort impact of germline brca1 2 mutations on response to neoadjuvant systemic therapy and prognosis in breast cancer a propensity score matched cohort study
topic Breast cancer
BRCA1/2 mutation
Neoadjuvant chemotherapy
Pathologic complete response
Distant metastasis-free survival
url https://doi.org/10.1186/s13058-025-02041-6
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