Impact of homologous recombination deficiency biomarkers on outcomes in patients with triple-negative breast cancer treated with adjuvant doxorubicin and cyclophosphamide (SWOG S9313)

Abstract

Int0137 (The trial pre-dates Clinicaltrial.Gov website establishment).

Comprehensive molecular comparison of BRCA1 hypermethylated and BRCA1 mutated triple negative breast cancers

“…This lends support to the reproducibility and generalizability of our results in the context of the studied patient demographics for both molecular and patient outcome findings, despite limited sample numbers for some comparisons. In the total SCAN-B cohort, 24.1% of TNBC patients were BRCA1 hypermethylated, a proportion in the lower to mid-range of previous reports [14][15][16][17][18][19][20] . However, in comparison to the observed BRCA1-null rate of 10.5% among all SCAN-B patients, BRCA1 hypermethylation is more than twice as frequent.…”

“…DNA promoter hypermethylation could be an alternative mechanism of inactivating BRCA1. BRCA1 promoter hypermethylation has been reported in 16-57% of TNBCs across studies [14][15][16][17][18][19][20] , superseding the frequency of germline BRCA1 alterations, however, with conflicting reports about association with prognosis (e.g. refs.…”

Combination Immunotherapy Strategies in Breast Cancer

“…Deficiencies in homologous recombination correlate with improved response to platinum-based chemotherapy and PARP inhibitors [48][49][50][51], particularly in breast cancers with germline/somatic mutations in the BRCA1/2 gene [47]. There is emerging interest in combination ICI with PARP inhibitors [52].…”

New approaches in the neoadjuvant systemic therapy of breast cancer

“…The Homologous Recombination Deficiency (HRD) score is an unweighted sum of three independent DNA-based measures of genomic instability and reflects the function of the homologous recombination repair pathway. The HRD score seemed to be a predictor of platinum sensitivity [25], but its specificity was disproved by Sharma et al [26]. According to their experience, adjuvant doxorubicin and cyclophosphamide treatment produced equally good disease-free survival in the HRD scorepositive cases [26].…”

“…OncotypeDX ® provides prognosis and predicts benefit of a certain systemic therapy. In clinical practice, three risk groups are distinguished by the assay: in cancers with low recurrence score (<18), the risk of relapse is very low, and the use of exclusive endocrine therapy is sufficient; cancers with intermediate recurrence score (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) sole endocrine therapy or sequential chemotherapy-endocrine therapy are individually selected; cases with high risk recurrence score (>31) show poorer prognosis, and the addition of chemotherapy significantly improves outcome. In fact, the recent results of the TAILOR-x study indicate that below the risk score of 26, there is no benefit of adjuvant chemotherapy among small and node-negative HR-positive and HER2-negative cases [18].…”