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Abstract
Introduction. Germline BRCA1/2 mutations are present in 5–10% of patients with luminal, HER2-negative breast cancer (BC) and are associated with a more aggressive form of the disease and reduced sensitivity to hormone therapy ± CDKi. This study was initiated due to the limited data available on the efficacy of neoadjuvant chemotherapy (NACT) in this population.
Materials and methods. This retrospective study included all patients with luminal (ER >10%, ≥4 Allred score), HER2-negative, stage II–III BC with class 4 or 5 pathogenicity germline BRCA1/2 mutations who received anthracycline- and taxane-containing NACT between September 2017 and December 2023. The study analyzed the pathological complete response (pCR) rate and the predictors of achieving a pCR, as well as the indicators of disease-free and overall survival (OS).
Results. A total of 31 patients were included in the study. Among them, 14 (45.2 %) had a BRCA1 mutation (mut), 16 (51.6 %) had a BRCA2mut, and one patient (3.2 %) had both mutations. The mean age was 40.5 years (range: 27–58), and 29 patients (93.5 %) were premenopausal. Most patients had locally advanced disease — 23 (74.2 %), with cT4 in 18 (58 %) cases and lymph node involvement (N+) in 26 (83.9 %) cases. Estrogen receptor (ER) expression ≥ 50 % (6-8 Allred score) was observed in 27 (87.1 %) cases, and progesterone receptor (PR) expression ≥ 20 % (4-8 Allred score) was found in 20 (64.5 %) cases. The tumor subtype was classified as luminal B and A in 29 (93.5 %) and 2 (6.5 %) cases retrospectively. The median of ki67 was 49,6 % (17-85). Most patients had a tumor grade of G2 (n = 23; 74.2 %), while 8 (25.8 %) had G3 tumors. The overall pCR rate was 45.2 % (14/31), with 64.3 % (9/14) in the BRCA1 mutation subgroup and 31.3 % (5/16) in the BRCA2 subgroup (p = 0.07). The 3-year invasive disease-free survival (iDFS) was 83.3 %, and the 3-year OS was 94.4 %.
Conclusion. Thus, this study confirms the high sensitivity of BRCAmut luminal HER2-negative BC to neoadjuvant chemotherapy, especially in the BRCA1 subgroup.
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