Long-term survival outcomes of neoadjuvant chemotherapy in stage II-III HR+/HER2- breast cancer

Abstract Breast cancer is the most common malignant tumor among women worldwide. Hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer is the largest subgroup among these cases. The application of neoadjuvant chemotherapy (NACT) has rapidly increased in recent years, but its impact on lo...

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Main Authors: Jiaxing Liu, Likuan Tan, Hongyu Zhang, Chengzhi Ma, Gang Qin, Shaolong Huang, Yang Long, Feng-hui He, Yao Huang, Miao-Miao Jiao, Yufei Liu, Guanghui Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-14012-0
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author Jiaxing Liu
Likuan Tan
Hongyu Zhang
Chengzhi Ma
Gang Qin
Shaolong Huang
Yang Long
Feng-hui He
Yao Huang
Miao-Miao Jiao
Yufei Liu
Guanghui Wang
author_facet Jiaxing Liu
Likuan Tan
Hongyu Zhang
Chengzhi Ma
Gang Qin
Shaolong Huang
Yang Long
Feng-hui He
Yao Huang
Miao-Miao Jiao
Yufei Liu
Guanghui Wang
author_sort Jiaxing Liu
collection DOAJ
description Abstract Breast cancer is the most common malignant tumor among women worldwide. Hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer is the largest subgroup among these cases. The application of neoadjuvant chemotherapy (NACT) has rapidly increased in recent years, but its impact on long-term survival in HR+/HER2- breast cancer remains debated. This retrospective cohort study analyzed 21,299 stage II-III HR+/HER2- breast cancer patients from the SEER database (2010–2021), employing propensity score matching (PSM) to balance intergroup differences. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to identify significant prognostic factors. Among 21,299 patients, 17.8% received NACT. After propensity score matching (PSM; n = 6,930), the NACT group still showed poorer OS (5-year 83.7% vs. 89.6%; 10-year 69.9% vs. 76.7%; P < 0.001) and BCSS (85.9% vs. 91.6%; 10-year 75.3% vs. 81.8%; P < 0.001). Multivariate analysis confirmed NACT as an independent risk factor for mortality (HR 1.44, 95% CI 1.30–1.59, p < 0.001). Notably, achieving Pathological Complete Response (pCR) (17.3% of NACT patients) did not improve survival, while non-pCR patients had worse outcomes than adjuvant chemotherapy (ACT) recipients (OS HR 1.58, BCSS HR 1.68, p < 0.001). Stratified analyses revealed consistent survival disadvantages for NACT in stage IIB–IIIC, T1–T3, and N0–N2 subgroups. For stage III patients undergoing Breast-Conserving Surgery(BCS), NACT was associated with significantly lower OS and BCSS compared to ACT. NACT in stage II-III HR+/HER2- breast cancer is associated with inferior long-term survival outcomes compared to ACT, particularly in patients with T1–T3 tumors or N0–N2 lymph node involvement. While NACT may enhance BCS rates, its use should be cautiously weighed against potential survival trade-offs. These findings highlight the need for personalized treatment strategies and further validation through prospective trials, especially given the limitations of retrospective SEER data.
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spelling doaj-art-2f93d65d8a3442619d601a7ba3cd402c2025-08-24T11:27:27ZengNature PortfolioScientific Reports2045-23222025-08-0115111410.1038/s41598-025-14012-0Long-term survival outcomes of neoadjuvant chemotherapy in stage II-III HR+/HER2- breast cancerJiaxing Liu0Likuan Tan1Hongyu Zhang2Chengzhi Ma3Gang Qin4Shaolong Huang5Yang Long6Feng-hui He7Yao Huang8Miao-Miao Jiao9Yufei Liu10Guanghui Wang11Department of Breast and Thyroid Surgery, Tongren People’s HospitalDepartment of Breast and Thyroid Surgery, Tongren People’s HospitalDepartment of Breast and Thyroid Surgery, Tongren People’s HospitalDepartment of Breast and Thyroid Surgery, Tongren People’s HospitalDepartment of Breast and Thyroid Surgery, Tongren People’s HospitalDepartment of Breast and Thyroid Surgery, Tongren People’s HospitalDepartment of Breast and Thyroid Surgery, Tongren People’s HospitalDepartment of Breast and Thyroid Surgery, Tongren People’s HospitalDepartment of Breast and Thyroid Surgery, Tongren People’s HospitalDepartment of Breast and Thyroid Surgery, Tongren People’s HospitalDepartment of Breast and Thyroid Surgery, Tongren People’s HospitalDepartment of Breast Surgery, Guizhou Provincial People’s HospitalAbstract Breast cancer is the most common malignant tumor among women worldwide. Hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer is the largest subgroup among these cases. The application of neoadjuvant chemotherapy (NACT) has rapidly increased in recent years, but its impact on long-term survival in HR+/HER2- breast cancer remains debated. This retrospective cohort study analyzed 21,299 stage II-III HR+/HER2- breast cancer patients from the SEER database (2010–2021), employing propensity score matching (PSM) to balance intergroup differences. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to identify significant prognostic factors. Among 21,299 patients, 17.8% received NACT. After propensity score matching (PSM; n = 6,930), the NACT group still showed poorer OS (5-year 83.7% vs. 89.6%; 10-year 69.9% vs. 76.7%; P < 0.001) and BCSS (85.9% vs. 91.6%; 10-year 75.3% vs. 81.8%; P < 0.001). Multivariate analysis confirmed NACT as an independent risk factor for mortality (HR 1.44, 95% CI 1.30–1.59, p < 0.001). Notably, achieving Pathological Complete Response (pCR) (17.3% of NACT patients) did not improve survival, while non-pCR patients had worse outcomes than adjuvant chemotherapy (ACT) recipients (OS HR 1.58, BCSS HR 1.68, p < 0.001). Stratified analyses revealed consistent survival disadvantages for NACT in stage IIB–IIIC, T1–T3, and N0–N2 subgroups. For stage III patients undergoing Breast-Conserving Surgery(BCS), NACT was associated with significantly lower OS and BCSS compared to ACT. NACT in stage II-III HR+/HER2- breast cancer is associated with inferior long-term survival outcomes compared to ACT, particularly in patients with T1–T3 tumors or N0–N2 lymph node involvement. While NACT may enhance BCS rates, its use should be cautiously weighed against potential survival trade-offs. These findings highlight the need for personalized treatment strategies and further validation through prospective trials, especially given the limitations of retrospective SEER data.https://doi.org/10.1038/s41598-025-14012-0Breast cancerHR+/HER2-Neoadjuvant chemotherapyOverall survivalBreast cancer-specific survivalPropensity score matching
spellingShingle Jiaxing Liu
Likuan Tan
Hongyu Zhang
Chengzhi Ma
Gang Qin
Shaolong Huang
Yang Long
Feng-hui He
Yao Huang
Miao-Miao Jiao
Yufei Liu
Guanghui Wang
Long-term survival outcomes of neoadjuvant chemotherapy in stage II-III HR+/HER2- breast cancer
Scientific Reports
Breast cancer
HR+/HER2-
Neoadjuvant chemotherapy
Overall survival
Breast cancer-specific survival
Propensity score matching
title Long-term survival outcomes of neoadjuvant chemotherapy in stage II-III HR+/HER2- breast cancer
title_full Long-term survival outcomes of neoadjuvant chemotherapy in stage II-III HR+/HER2- breast cancer
title_fullStr Long-term survival outcomes of neoadjuvant chemotherapy in stage II-III HR+/HER2- breast cancer
title_full_unstemmed Long-term survival outcomes of neoadjuvant chemotherapy in stage II-III HR+/HER2- breast cancer
title_short Long-term survival outcomes of neoadjuvant chemotherapy in stage II-III HR+/HER2- breast cancer
title_sort long term survival outcomes of neoadjuvant chemotherapy in stage ii iii hr her2 breast cancer
topic Breast cancer
HR+/HER2-
Neoadjuvant chemotherapy
Overall survival
Breast cancer-specific survival
Propensity score matching
url https://doi.org/10.1038/s41598-025-14012-0
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