Abstract 146P
Background
Early stage tumor-infiltrating lymphocytes (TIL)-low triple-negative breast cancers (TNBC) are characterized by bad prognosis. The RAD51 test can identify Homologous Recombination Repair (HRR)-deficient (HRD) tumors and may add prognostic value in this subset of patients, potentially guiding post-neoadjuvant treatments in order to improve survival.
Methods
We quantified functional HRD detecting RAD51 and BRCA1 nuclear foci by immunofluorescence, content of TIL by H&E and IHC and expression of immune markers on diagnostic tumor biopsies of 148 high-risk BC patients, namely histologically confirmed TNBC or early onset BC (≤ 35 years old) or gBRCA1/2-mutated BC. Patients were admitted at 6 Italian Hospitals of the “Gruppo Oncologico Italiano di Ricerca Clinica” (GOIRC) and at the Bordet Institute in Brussels and treated with (neo)adjuvant chemotherapy based on anthracyclines, taxanes and cyclophosphamide. Functional HRD was predefined as RAD51 score ≤10% (RAD51-low).
Results
RAD51 was successfully scored in 123/148 (83%) samples. 43/123 (35%) patients presented HRR mutations: 35 gBRCA1 (28%), 6 gBRCA2 (5%), and 2 gPALB2 (2%) mutations. 99/123 (81%) tumors were HRD by RAD51: 41/43 (95%) HRR-mutated and 58/80 (72%) HRR-WT tumors. 39/80 (49%) HRR-WT tumors presented BRCA1-low nuclear foci, surrogate of lack of BRCA1 function likely due to epigenetic silencing. pCR rates, TIL extent and PD-L1 Combined Positive Score (CPS) did not correlate with HRD status. DFS did not differ between HRD and HRR proficient (HRP)-tumors. Instead, patients with HRD tumors had a statistically significant higher 5y-OS than patients with HRP-tumors (88% vs 59%, p=0.032). Within TIL-low tumors, the 5y-OS benefit was greater in HRD vs HRP (92% vs 49%, p=0.004). In support, HRD/TIL-low tumors showed lower PD-L1 CPS compared to others (p=0.0011); no statistically significant differences were found in CD3+ and CD20+ TIL.
Conclusions
The RAD51 test is able to identify HRR-altered tumors, beyond gBRCA1/2 mutations, and to select a cohort of HRD/TIL-low patients with good prognosis in a platinum-free (neo)adjuvant chemotherapy setting. Biomarker analyses on a larger cohort of patients are ongoing. Results will be available for the congress.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Azienda Ospedaliero-Universitaria di Parma.
Funding
EraPerMed (Horizon 2020 Program).
Disclosure
B. Pellegrino: Non-Financial Interests, Institutional, Other, meeting grant: Pfizer, Lilly; Financial Interests, Personal and Institutional, Writing Engagements: MSD. A. Frassoldati: Financial Interests, Personal, Advisory Board, and travel grant: Roche, Novartis, AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board: Daichii, Seagen, Gilead; Non-Financial Interests, Personal, Other, travel grant: Pfizer, Amgen. M. Lambertini: Financial Interests, Personal, Other, Consultant and speaker honoraria: Roche, Novartis, Lilly, MSD; Financial Interests, Personal, Other, Consultant: AstraZeneca, Exact Sciences, Pfizer, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: Takeda, Ipsen, Knight, Sandoz, Libbs. M.V. Dieci: Financial Interests, Personal, Other, Personal Fees: Eli Lilly, MSD, Exact Sciences, Novartis, Pfizer, Seagen. L. Cortesi: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Gilead; Financial Interests, Personal, Other, Honoraria and consulting: Novartis, Pfizer, MSD. J. Balmaña: Non-Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer; Financial Interests, Institutional, Other, Steering Committee Member: AstraZeneca; Financial Interests, Institutional, Principal Investigator: MedSir, Pfizer. V. Serra: Financial Interests, Personal, Research Grant, and personal fees: AstraZeneca; Financial Interests, Personal, Research Grant: Tesaro; Financial Interests, Personal, Other, Personal Fees: AbbVie; Financial Interests, Personal and Institutional, Other, Patent WO2019122411A1: Other. A. Musolino: Financial Interests, Personal and Institutional, Research Grant: Roche; Financial Interests, Personal and Institutional, Research Grant, and personal fees: Lilly; Financial Interests, Personal, Other, Personal Fees: Eisai, Seagen, Daiichi Sankyo. All other authors have declared no conflicts of interest.