Cargando…
BRCA Mutation Status in Triple-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Pivotal Role for Treatment Decision-Making
SIMPLE SUMMARY: In this retrospective observational study, we evaluated data from patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NACT) in order to better define the impact of germline BRCA1/2 (gBRCA1/2) mutation status on outcomes in this patient population...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9559391/ https://www.ncbi.nlm.nih.gov/pubmed/36230495 http://dx.doi.org/10.3390/cancers14194571 |
_version_ | 1784807640504729600 |
---|---|
author | Pavese, Francesco Capoluongo, Ettore Domenico Muratore, Margherita Minucci, Angelo Santonocito, Concetta Fuso, Paola Concolino, Paola Di Stasio, Enrico Carbognin, Luisa Tiberi, Giordana Garganese, Giorgia Corrado, Giacomo Di Leone, Alba Generali, Daniele Fragomeni, Simona Maria D’Angelo, Tatiana Franceschini, Gianluca Masetti, Riccardo Fabi, Alessandra Mulè, Antonino Santoro, Angela Belli, Paolo Tortora, Giampaolo Scambia, Giovanni Paris, Ida |
author_facet | Pavese, Francesco Capoluongo, Ettore Domenico Muratore, Margherita Minucci, Angelo Santonocito, Concetta Fuso, Paola Concolino, Paola Di Stasio, Enrico Carbognin, Luisa Tiberi, Giordana Garganese, Giorgia Corrado, Giacomo Di Leone, Alba Generali, Daniele Fragomeni, Simona Maria D’Angelo, Tatiana Franceschini, Gianluca Masetti, Riccardo Fabi, Alessandra Mulè, Antonino Santoro, Angela Belli, Paolo Tortora, Giampaolo Scambia, Giovanni Paris, Ida |
author_sort | Pavese, Francesco |
collection | PubMed |
description | SIMPLE SUMMARY: In this retrospective observational study, we evaluated data from patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NACT) in order to better define the impact of germline BRCA1/2 (gBRCA1/2) mutation status on outcomes in this patient population. Our results show that patients with BRCA1/2 mutation had a higher pathologic complete response (pCR) rate than non-mutated patients; nevertheless, the benefit was confirmed only in the subset of patients who received a platinum-based NACT. Furthermore, pCR was associated with improved Event Free Survival (EFS) and Overall Survival (OS), regardless of BRCA1/2 mutation status and type of NACT received. Long-term follow-up analyses are needed to further define the impact of gBRCA mutation status in patients with early-TNBC. ABSTRACT: Triple-negative breast cancer (TNBC) is characterized by earlier recurrence and shorter survival compared with other types of breast cancer. Moreover, approximately 15 to 25% of all TNBC patients harbor germline BRCA (gBRCA) 1/2 mutations, which confer a more aggressive phenotype. However, TNBC seems to be particularly sensitive to chemotherapy, the so-called ‘triple negative paradox’. Therefore, Neoadjuvant chemotherapy (NACT) is currently considered the preferred approach for early-stage TNBC. BRCA status has also been studied as a predictive biomarker of response to platinum compounds. Although several randomized trials investigated the addition of carboplatin to standard NACT in early-stage TNBC, the role of BRCA status remains unclear. In this retrospective analysis, we evaluated data from 136 consecutive patients with Stage I-III TNBC who received standard NACT with or without the addition of carboplatin, in order to define clinical features and outcomes in BRCA 1/2 mutation carriers and non-carrier controls. Between January 2013 and February 2021, 67 (51.3%) out of 136 patients received a standard anthracyclines/taxane regimen and 69 (50.7%) patients received a platinum-containing chemotherapy regimen. Deleterious germline BRCA1 or BRCA2 mutations were identified in 39 (28.7%) patients. Overall, patients with deleterious gBRCA1/2 mutation have significantly higher pCR rate than non-carrier patients (23 [59%] of 39 vs. 33 [34%] of 97; p = 0.008). The benefit of harboring a gBRCA mutation was confirmed only in the subset of patients who received a platinum-based NACT (17 [65.4%] of 26 vs. 13 [30.2%] of 43; p = 0.005) while no differences were found in the platinum-free subgroup. Patients who achieved pCR after NACT had significantly better EFS (OR 4.5; 95% CI 1.9–10.7; p = 0.001) and OS (OR 3.3; 95% CI 1.3–8.9; p = 0.01) than patients who did not, regardless of BRCA1/2 mutation status and type of NACT received. Our results based on real-world evidence show that TNBC patients with the gBRCA1/2 mutation who received platinum-based NACT have a higher pCR rate than non-carrier patients, supporting the use of this chemotherapy regimen in this patient population. Long-term follow-up analyses are needed to further define the role of gBRCA mutation status on clinical outcomes in patients with early-TNBC. |
format | Online Article Text |
id | pubmed-9559391 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95593912022-10-14 BRCA Mutation Status in Triple-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Pivotal Role for Treatment Decision-Making Pavese, Francesco Capoluongo, Ettore Domenico Muratore, Margherita Minucci, Angelo Santonocito, Concetta Fuso, Paola Concolino, Paola Di Stasio, Enrico Carbognin, Luisa Tiberi, Giordana Garganese, Giorgia Corrado, Giacomo Di Leone, Alba Generali, Daniele Fragomeni, Simona Maria D’Angelo, Tatiana Franceschini, Gianluca Masetti, Riccardo Fabi, Alessandra Mulè, Antonino Santoro, Angela Belli, Paolo Tortora, Giampaolo Scambia, Giovanni Paris, Ida Cancers (Basel) Article SIMPLE SUMMARY: In this retrospective observational study, we evaluated data from patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NACT) in order to better define the impact of germline BRCA1/2 (gBRCA1/2) mutation status on outcomes in this patient population. Our results show that patients with BRCA1/2 mutation had a higher pathologic complete response (pCR) rate than non-mutated patients; nevertheless, the benefit was confirmed only in the subset of patients who received a platinum-based NACT. Furthermore, pCR was associated with improved Event Free Survival (EFS) and Overall Survival (OS), regardless of BRCA1/2 mutation status and type of NACT received. Long-term follow-up analyses are needed to further define the impact of gBRCA mutation status in patients with early-TNBC. ABSTRACT: Triple-negative breast cancer (TNBC) is characterized by earlier recurrence and shorter survival compared with other types of breast cancer. Moreover, approximately 15 to 25% of all TNBC patients harbor germline BRCA (gBRCA) 1/2 mutations, which confer a more aggressive phenotype. However, TNBC seems to be particularly sensitive to chemotherapy, the so-called ‘triple negative paradox’. Therefore, Neoadjuvant chemotherapy (NACT) is currently considered the preferred approach for early-stage TNBC. BRCA status has also been studied as a predictive biomarker of response to platinum compounds. Although several randomized trials investigated the addition of carboplatin to standard NACT in early-stage TNBC, the role of BRCA status remains unclear. In this retrospective analysis, we evaluated data from 136 consecutive patients with Stage I-III TNBC who received standard NACT with or without the addition of carboplatin, in order to define clinical features and outcomes in BRCA 1/2 mutation carriers and non-carrier controls. Between January 2013 and February 2021, 67 (51.3%) out of 136 patients received a standard anthracyclines/taxane regimen and 69 (50.7%) patients received a platinum-containing chemotherapy regimen. Deleterious germline BRCA1 or BRCA2 mutations were identified in 39 (28.7%) patients. Overall, patients with deleterious gBRCA1/2 mutation have significantly higher pCR rate than non-carrier patients (23 [59%] of 39 vs. 33 [34%] of 97; p = 0.008). The benefit of harboring a gBRCA mutation was confirmed only in the subset of patients who received a platinum-based NACT (17 [65.4%] of 26 vs. 13 [30.2%] of 43; p = 0.005) while no differences were found in the platinum-free subgroup. Patients who achieved pCR after NACT had significantly better EFS (OR 4.5; 95% CI 1.9–10.7; p = 0.001) and OS (OR 3.3; 95% CI 1.3–8.9; p = 0.01) than patients who did not, regardless of BRCA1/2 mutation status and type of NACT received. Our results based on real-world evidence show that TNBC patients with the gBRCA1/2 mutation who received platinum-based NACT have a higher pCR rate than non-carrier patients, supporting the use of this chemotherapy regimen in this patient population. Long-term follow-up analyses are needed to further define the role of gBRCA mutation status on clinical outcomes in patients with early-TNBC. MDPI 2022-09-21 /pmc/articles/PMC9559391/ /pubmed/36230495 http://dx.doi.org/10.3390/cancers14194571 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Pavese, Francesco Capoluongo, Ettore Domenico Muratore, Margherita Minucci, Angelo Santonocito, Concetta Fuso, Paola Concolino, Paola Di Stasio, Enrico Carbognin, Luisa Tiberi, Giordana Garganese, Giorgia Corrado, Giacomo Di Leone, Alba Generali, Daniele Fragomeni, Simona Maria D’Angelo, Tatiana Franceschini, Gianluca Masetti, Riccardo Fabi, Alessandra Mulè, Antonino Santoro, Angela Belli, Paolo Tortora, Giampaolo Scambia, Giovanni Paris, Ida BRCA Mutation Status in Triple-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Pivotal Role for Treatment Decision-Making |
title | BRCA Mutation Status in Triple-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Pivotal Role for Treatment Decision-Making |
title_full | BRCA Mutation Status in Triple-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Pivotal Role for Treatment Decision-Making |
title_fullStr | BRCA Mutation Status in Triple-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Pivotal Role for Treatment Decision-Making |
title_full_unstemmed | BRCA Mutation Status in Triple-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Pivotal Role for Treatment Decision-Making |
title_short | BRCA Mutation Status in Triple-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Pivotal Role for Treatment Decision-Making |
title_sort | brca mutation status in triple-negative breast cancer patients treated with neoadjuvant chemotherapy: a pivotal role for treatment decision-making |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9559391/ https://www.ncbi.nlm.nih.gov/pubmed/36230495 http://dx.doi.org/10.3390/cancers14194571 |
work_keys_str_mv | AT pavesefrancesco brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT capoluongoettoredomenico brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT muratoremargherita brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT minucciangelo brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT santonocitoconcetta brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT fusopaola brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT concolinopaola brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT distasioenrico brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT carbogninluisa brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT tiberigiordana brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT garganesegiorgia brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT corradogiacomo brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT dileonealba brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT generalidaniele brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT fragomenisimonamaria brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT dangelotatiana brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT franceschinigianluca brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT masettiriccardo brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT fabialessandra brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT muleantonino brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT santoroangela brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT bellipaolo brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT tortoragiampaolo brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT scambiagiovanni brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking AT parisida brcamutationstatusintriplenegativebreastcancerpatientstreatedwithneoadjuvantchemotherapyapivotalrolefortreatmentdecisionmaking |