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| Item Type: | Article |
|---|---|
| Title: | Genetic alterations, therapy response, and survival among patients with triple-negative breast cancer: a secondary analysis of a randomized clinical trial |
| Creators Name: | Richters, L., Gluz, O., Weber-Lassalle, N., Christgen, M., Haverkamp, H., Kuemmel, S., Kayali, M., Kates, R.E., Grischke, E.M., Altmüller, J., Forstbauer, H., Thiele, H., Braun, M., Warm, M., Ossowski, A., Wuerstlein, R., Ernst, C., Graeser, M., Linn, S.C., Nitz, U., Hauke, J., Kreipe, H.H., Schmutzler, R.K., Hahnen, E. and Harbeck, N. |
| Abstract: | IMPORTANCE: Subgroup definitions for possible deescalation of neoadjuvant cancer treatment are urgently needed in clinical practice. OBJECTIVE: To investigate the effect of BRCA1 and/or BRCA2 tumor pathogenic variants (tPVs) by comparing 2 deescalated neoadjuvant regimens (nab-paclitaxel plus either carboplatin or gemcitabine) on pathologic complete response (pCR), invasive disease-free survival (IDFS), and overall survival (OS) of patients with early-stage triple-negative breast cancer (TNBC). DESIGN, SETTING, AND PARTICIPANTS: This was a preplanned secondary analysis of a phase 2 prospective randomized clinical trial (ADAPT-TN) conducted by the West German Study Group (WSG) at 45 sites in Germany between June 2013 and February 2015. The trial enrolled patients with noninflammatory early-stage TNBC (clinical tumor size ≥1 cm; estrogen receptor and progesterone receptor expression <1%; and ERBB2 negative). DNA samples from pretreatment biopsies were obtained. Genetic analysis was performed between January 2018 and March 2020. Final data analyses took place in September 2023. EXPOSURE: Patients were randomized to 12 weeks of treatment with nab-paclitaxel plus either carboplatin or gemcitabine; omission of otherwise mandatory anthracycline-containing chemotherapy was allowed in the case of pCR. tPVs in 20 cancer-associated genes, including BRCA1 and BRCA2, were analyzed using a customized gene panel. MAIN OUTCOMES AND MEASURES: The prevalence of BRCA1 and/or BRCA2 tPVs and their effect on pCR rate, IDFS, and OS were evaluated using logistic and Cox proportional hazards regression. RESULTS: Of the 307 patients with DNA samples from pretreatment biopsies available, tumor next-generation sequencing analyses were successful for 266 patients. The 266 patients included in this analysis were female, with a median age of 51 years (range, 26-76 years). A total of 162 patients (60.9%) had a clinical tumor size of 2 cm or greater, and 70 (26.3%) had clinical node-positive disease. BRCA1 and/or BRCA2 tPVs were detected in 42 patients (15.8%). The highest pCR rate among patients with BRCA1 and/or BRCA2 tPVs was seen in the nab-paclitaxel plus carboplatin group (9 of 14 patients [64.3%]) compared with the nab-paclitaxel plus gemcitabine group (10 of 28 [35.7%]) (odds ratio, 3.24 [95% CI, 0.85-12.36]; P = .08); the highest numeric 5-year IDFS and OS rates (84.4% and 92.9%, respectively) were seen in the nab-paclitaxel plus carboplatin group. CONCLUSIONS AND RELEVANCE: In this secondary analysis of the WSG-ADAPT-TN randomized clinical trial on tPVs, deescalated nab-paclitaxel plus carboplatin was superior to nab-paclitaxel plus gemcitabine, particularly in patients with BRCA1 and/or BRCA2 tPVs. These findings suggest that BRCA1 and/or BRCA2 tPV status could be a candidate marker for a deescalation strategy in early-stage TNBC; however, prospective validation of survival outcomes in larger cohorts with differentiation between germline and somatic pathogenic variants is necessary. |
| Keywords: | Albumins, Antineoplastic Combined Chemotherapy Protocols, BRCA1 Protein, BRCA2 Protein, Carboplatin, Deoxycytidine, Disease-Free Survival, Gemcitabine, Germany, Neoadjuvant Therapy, Paclitaxel, Prospective Studies, Triple Negative Breast Neoplasms |
| Source: | JAMA Network Open |
| ISSN: | 2574-3805 |
| Publisher: | American Medical Association |
| Volume: | 8 |
| Number: | 2 |
| Page Range: | e2461639 |
| Date: | February 2025 |
| Official Publication: | https://doi.org/10.1001/jamanetworkopen.2024.61639 |
| PubMed: | View item in PubMed |
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