Aim: This pooled analysis aimed to evaluate locoregional recurrence (LRR) rates of breast cancer (BC) after neoadjuvant chemotherapy (NACT) and to identify independent LRR predictors.
Methods: 10,075 women with primary BC from nine neoadjuvant trials were included. The primary outcome was the cumulative incidence rate of LRR as the first event after NACT. Distant recurrence, secondary malignancy or death were defined as competing events. For identifying LRR predictors, surgery type, pathological complete response (pCR), BC subtypes and other potential risk factors were evaluated.
Results: Median followup was 67 months (range 0-215), overall LRR rate was 9.5%, 4.1% in pCR versus 9.5% in non-pCR patients. Younger age, clinically positive lymph nodes, G3 tumours, non-pCR and TNBC but not surgery type were independent LRR predictors in multivariate analysis. Among BC subtypes, 5-year cumulative LRR rates were associated with higher risk in non-pCR versus pCR patients, which was significant for HR+/HER2- (5.9% vs 3.9%; HR = 2.32 [95%CI 1.22-4.43]; p = 0.011); HR-/HER2+ (14.8% vs 3.1%; HR = 4.26 [94%CI 2.35-7.71]; p < 0.001) and TNBC (18.5% vs 4.2%; HR = 4.10 [95%CI 2.88-5.82]; p < 0.001) but not for HR+/HER2+ (8.1% vs 4.8%; HR = 1.56 [95%CI 0.85-2.85]; p = 0.150). Within non-pCR subgroup, LRR risk was higher for HR-/HER2+ and TNBC vs HR+/HER2- (HR = 2.05 [95%CI 1.54-2.73]; p < 0.001 and HR = 2.77 [95%CI 2.27-3.39]; p < 0.001, respectively).
Conclusions: This pooled analysis demonstrated that young age, node-positive and G3 tumours, as well as TNBC, and non-pCR significantly increased the risk of LRR after NACT. Hence, there is a clear need to investigate better multimodality therapies in the post-neoadjuvant setting for high-risk patients.
Keywords: Breast cancer; Locoregional recurrence; Neoadjuvant therapy; Prognostic factors; Survival.
Copyright © 2020 Elsevier Ltd. All rights reserved.
Conflict of interest statement
Conflict of interest statement H. Tesch reported nonfinancial support, honoraria and travel grants from Lilly, Amgen, Roche and Novartis outside the submitted work. J. Huober reported honoraria und advice board from Lilly, Novartis, Roche, Pfizer, Hexal, Astra Zeneca, MSD, Celgene; research funding from Novartis, Celgene and Travel expenses from Roche, Pfizer, Novartis, Celgene. C. Hanusch reported personal fees from AstraZeneca, Pfizer, Celgene, Lilly, Novartis and Roche outside the submitted work. C. Denkert reported stock and ownership interests from Sividon Diagnostics; honoraria from TEVA, Novartis, Pfizer, Roche, Amgen; consulting or advisor role from MSD Oncology, Amgen, Daiichi Sankyo and patents or other intellectual property from VMScope: digital pathology software, patent application: EP18209672 - cancer immunotherapy, patent application EP20150702464 - therapy response outside the submitted work. D. Krug reported personal fees from Merck Sharp & Dome outside the submitted work. A. Schneeweiss reported grants from Celgene, Roche, AbbVie, Molecular Partner, personal fees from Roche, AstraZeneca, Celgene, Roche, Pfizer, Novartis, MSD, Tesaro, Lilly, outside the submitted work. M. Untch reported personal fees and nonfinancial support to the institute from Lilly, MSD Merck, Mundipharma, Myriad Genetics, Odonate, Pfizer, Roche, Sanofi Aventis Deutschland GmbH, TEVA, Novartis, and personal fee to the institute from PUMA Biotechnology outside the submitted work. C. Jackisch reported personal fees from Roche and Amgen during the conduct of the study. T. Link reported personal fees from Amgen, nonfinancial support from AstraZeneca, personal fees and nonfinancial support from Pfizer, nonfinancial support from Pharma Mar, nonfinancial support from Daiichi Sankyo, personal fees from MSD, personal fees from Novartis, TEVA, Tesaro, personal fees and nonfinancial support from Roche outside the submitted work. S. Loibl reported research grant from Roche during the conduct of the study; honoraria paid to the institute from AbbVie, Amgen, AstraZeneca, Celgene, Novartis, Pfizer, Roche, Seattle Genetics, TEVA, Vifor, PRIME, Daiichi Sankyo outside the submitted work and patent P14153692.0 pending. P.A. Fasching reported grants from Novartis, Biontech, personal fees from Novartis, Roche, Pfizer, Celgene, Daiichi Sankyo, TEVA, Astra Zeneca, Merck Sharp & Dohme, Myelo Therapeutics, Macrogenics, Eisai, Puma, grants from Cepheid during the conduct of the study. K. Rhiem reported personal fees from Tesaro, Pfizer and AstraZeneca outside the submitted work. All remaining authors declare that they have no competing interests.
Predictors of locoregional outcome in HER2-overexpressing breast cancer treated with neoadjuvant chemotherapy.Am J Clin Oncol. 2015 Aug;38(4):348-52. doi: 10.1097/COC.0b013e31829d1eb8. Am J Clin Oncol. 2015. PMID: 23799288
A prognostic index for locoregional recurrence after neoadjuvant chemotherapy.Ecancermedicalscience. 2016 Jun 16;10:647. doi: 10.3332/ecancer.2016.647. eCollection 2016. Ecancermedicalscience. 2016. PMID: 27433280 Free PMC article.
Biological subtype predicts locoregional recurrence after postmastectomy radiotherapy in Chinese breast cancer patients.Cancer Med. 2020 Apr;9(7):2427-2434. doi: 10.1002/cam4.2904. Epub 2020 Feb 12. Cancer Med. 2020. PMID: 32048817 Free PMC article.
Ki67 and lymphocytes in the pretherapeutic core biopsy of primary invasive breast cancer: positive markers of therapy response prediction and superior survival.Horm Mol Biol Clin Investig. 2017 Sep 22;32(2):/j/hmbci.2017.32.issue-2/hmbci-2017-0022/hmbci-2017-0022.xml. doi: 10.1515/hmbci-2017-0022. Horm Mol Biol Clin Investig. 2017. PMID: 28937963 Review.
Axillary treatment for operable primary breast cancer.Cochrane Database Syst Rev. 2017 Jan 4;1(1):CD004561. doi: 10.1002/14651858.CD004561.pub3. Cochrane Database Syst Rev. 2017. PMID: 28052186 Free PMC article. Review.