269P - Her2-low/HRR proficient early triple negative breast cancer is characterized by good prognosis

Background

Her2-low status fails to distinguish between early TNBC with different prognoses. RAD51 test can identify HRD tumors and may enhance prognostic value in this subset of patients.

Methods

We assessed Her2 status using IHC/FISH, detected functional HRD by observing RAD51 nuclear foci through immunofluorescence, and evaluated TIL content through H&E and IHC on diagnostic tumor biopsies of 86 histologically confirmed TNBC patients. Patients were admitted at 6 Italian Hospitals of the “Gruppo Oncologico Italiano di Ricerca Clinica” (GOIRC) and treated with neo-adjuvant chemo(immune)therapy. Functional HRD was predefined as RAD51 score ≤10% (RAD51-low). HER2-low status was predefined as HER2 IHC score of 1+ or 2+ with negative FISH, and HER2-neg if they had a HER2 IHC score of 0. Tumors with TIL extent ≥ 30% were predefined as High-TIL.

Results

14/34 (41%) of Her2-low patients presented HRR mutations: 9 gBRCA1 (26%), 4 gBRCA2 (29%), and 1 gPALB2 (7%) mutations. 11/52 (21%) of Her2-neg patients presented HRR mutations: 9 gBRCA1 (82%), 1 gATM (2%) and 1 gPALB2 (2%) mutations. 23/34 (68%) Her2-low tumors were HRD by RAD51; 21/52 (40%) of Her2-neg tumors were HRD by RAD51. pCR rates did not differ between Her2-low and Her2-neg TNBC but they were higher in Her2-low/HRR proficient (HRP) compared to Her2-neg/HRP tumors (Table). Her2-low samples presented a higher percentage of High-TIL tumors compared to Her2-neg; HRD status did not affect TIL extent (Table). Her2 status did not influence survival in our cohort (5y-DFS 89% vs 79%, respectively; p=0.2). However, patients with Her2-low/HRP tumors appeared to have a higher 5y-DFS than patients with Her2-neg/HRP-tumors (100% vs 70%, respectively), although the difference was not statistically significant (p=0.07). Table: 269P

Conclusions

Combining Her2 and HRD status appeared to be useful in identifying a subgroup of TNBC with an excellent prognosis. Biomarker analyses on a larger cohort of patients are ongoing, and results will be available for the congress.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Massimo Fabi.

Funding

Has not received any funding.

Disclosure

B. Pellegrino: Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Other, Travel grant: Lilly; Financial Interests, Personal, Invited Speaker: Gilead, Pfizer; Financial Interests, Personal, Expert Testimony: MSD. C. Casarini: Financial Interests, Personal, Funding: Exact Science, Novartis, Lilly, Roche, Gilead, MSD, Pfizer, Amgen. G. Zoppoli: Financial Interests, Personal, Ownership Interest, Co-ownership: Immunomica Srl. M. Lambertini: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Menarini, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Takeda, Sandoz, Ipsen, Libbs, Knight, Daiichi Sankyo, Lilly, Pfizer, Novartis, Roche, AstraZeneca, Menarini, Gilead; Financial Interests, Personal, Other, Travel grant to attend ASCO 2022: Gilead; Financial Interests, Personal, Other, Travel grant to attend ASCO 2023 and ASCO 2024: Daiichi Sankyo; Financial Interests, Personal, Other, Travel grant to attend SABCS 2023: Roche; Financial Interests, Institutional, Coordinating PI, 2-year research grant paid to my Institution: Gilead; Non-Financial Interests, Leadership Role, Chair of the ESMO Young Oncologists Committee from 01/2023 to 12/2024: ESMO; Non-Financial Interests, Member of Board of Directors, Member of the national council of the Italian Association of Medical Oncology (AIOM): AIOM. M. Botosso: Financial Interests, Personal, Funding: Lilly. L. Cortesi: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD; Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Gilead. A. Musolino: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Seagen, Lilly, Gilead, Novartis, Pfizer, Daiichi Sankyo; Financial Interests, Personal, Research Funding: Lilly, Roche; Financial Interests, Personal, Funding: Novartis, Gilead, Roche, Seagen, Pfizer, Daiichi Sankyo. All other authors have declared no conflicts of interest.