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Adjuvant versus neoadjuvant chemotherapy in triple-negative breast cancer patients with BRCA mutations.

ABSTRACT: PURPOSE:As triple-negative breast cancers are associated with earlier recurrences and poorer survival, optimal treatment of early-stage breast cancer is essential. Several retrospective studies in triple-negative breast cancer have reported conflicting results in overall survival in patients receiving neoadjuvant or adjuvant systemic therapy. This study aims to analyze outcomes of adjuvant versus neoadjuvant in patients with early-stage triple-negative breast cancer with and without BRCA germline mutations. METHODS:Patients with stage I or II triple-negative breast cancer who had BRCA testing were identified from a prospective cohort study of 4027 patients. Clinical, demographic, genetic test results, chemotherapy, recurrence, and survival data were analyzed. Overall survival and disease-free survival were estimated using the Kaplan-Meier method. RESULTS:319 patients with stage I and II triple-negative breast cancer who met eligibility criteria were included in the analysis. 187 received adjuvant chemotherapy (58.6%) and 132 received neoadjuvant chemotherapy (41.4%). 135 were BRCA positive (42.3%) and 184 were BRCA negative (57.7%). There was no significant association between overall survival or disease-free survival and treatment with neoadjuvant versus adjuvant in the overall cohort. Furthermore, there were no significant differences between patient subgroups (neoadjuvant BRCA positive, neoadjuvant BRCA negative, adjuvant BRCA positive, and adjuvant BRCA negative) with respect to either overall survival or disease-free survival. CONCLUSIONS:Neoadjuvant versus adjuvant with standard anthracycline- and taxane-containing regimens results in similar disease-free survival and overall survival among patients with stage I and II triple-negative breast cancer regardless of BRCA status. Further studies are needed to evaluate whether similar results are observed with newer agents.

SUBMITTER: Clifton K

PROVIDER: S-EPMC5994186 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Adjuvant versus neoadjuvant chemotherapy in triple-negative breast cancer patients with BRCA mutations.

Clifton Katherine K Gutierrez-Barrera Angelica A Ma Junsheng J Bassett Roland R Litton Jennifer J Kuerer Henry H Moulder Stacy S Albarracin Constance C Hortobagyi Gabriel G Arun Banu B

Breast cancer research and treatment 20180222 1

<h4>Purpose</h4>As triple-negative breast cancers are associated with earlier recurrences and poorer survival, optimal treatment of early-stage breast cancer is essential. Several retrospective studies in triple-negative breast cancer have reported conflicting results in overall survival in patients receiving neoadjuvant or adjuvant systemic therapy. This study aims to analyze outcomes of adjuvant versus neoadjuvant in patients with early-stage triple-negative breast cancer with and without BRCA ...[more]

PMID: 29470805

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Project description: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.

Dataset Information

Adjuvant versus neoadjuvant chemotherapy in triple-negative breast cancer patients with BRCA mutations.

Publications

Adjuvant versus neoadjuvant chemotherapy in triple-negative breast cancer patients with BRCA mutations.

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