261P - Subtyping of residual disease (RD) following neoadjuvant chemotherapy (NACT) for triple negative breast cancer (TNBC): Evolution and prognostic impact

Background

RD following NACT in TNBC is associated with poor prognosis. However, significant heterogeneity exists within the biology of the RD, and genomic subtyping may enable a more accurate prognostic classification. We already reported the predictive and prognostic value of baseline TNBCtype. Here, we focus on the evolution of TNBCtype after NACT and its prognostic value.

Methods

We present a prospective cohort of stage I-III TNBC patients from 10 hospitals across Spain and Peru, treated with 6 cycles of NACT with carboplatin and docetaxel (NCT01560663). Response was evaluated according to the Symmans Residual Cancer Burden score (RCB). RNAseq was performed on the basal biopsy and the RD following NACT. The TNBCtype classification was done on the TNBCtype online tool.

Results

Paired RNAseq and TNBCtype subtypes from pre- and post-NACT was available for 74 patients. 64.9% of the patients had RCB-2, 29.7% RCB-3 and 5.4% were not evaluable for the RCB classification. Baseline TNBCtype distribution was: BL1 25.7%, BL2 13.5%, LAR 17.6%, M 37.8% and 4 patients were considered as ER+. TNBCtype distribution after NACT was 20.3% BL1, 20.3% BL2, 18.9% M, 18.9% LAR and 21.6% ER+. However, correlation between pre- and post-NACT subtyping was poor, with 55.4% of the samples changing their subtype. Changes occurred within all the subtypes, although tumors initially classified as LAR were the most stable (76.9% concordance), as opposed to M and BL1 (32.1% and 36.8%). Intrinsic subtypes were highly concordant, with only 13.5% changes and most of these changes between non-basal subtypes. With a median follow-up of 55 months, there were 21 distant recurrences and 18 deaths. Post-NACT BL1 and M patients showed the worse long-term survival, with 5y DRFS of 65% and 62.5% as compared to 86.2% and 77.9% for BL2 and LAR. Table: 261P

Conclusions

TNBCtype significantly differs after exposure to NACT and subtyping of the RD enables a more accurate prognostic classification.

Clinical trial identification

NCT01560663.

Editorial acknowledgement

Legal entity responsible for the study

Hospital General Universitario Gregorio Marañon.

Funding

Instituto de Salud Carlos III.

Disclosure

I. Echavarria Diaz-Guardamino: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, AstraZeneca, Pierre Fabre, Lilly, Gilead; Financial Interests, Personal, Advisory Board: Daichi Sankyo, Lilly. S. Lopez-Tarruella Cobo: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly, Gilead, GSK, Roche, Pierre Fabre, Seagen, Menarini_Stemline, Gebro Pharma, Veracyte, MSD; Financial Interests, Personal, Invited Speaker: Lilly; Non-Financial Interests, Member of Board of Directors: GEICAM, SEOM. Y. Jerez Gilarranz: Financial Interests, Personal, Invited Speaker: Daichii, Novartis, roche, pfizer. F. Moreno Anton: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Daiichi Sankyo, MSD, Gilead; Financial Interests, Institutional, Research Grant: pfizer. T. Massarrah: Financial Interests, Personal, Advisory Board: GSK, Novartis. B. Herrero Lopez: Financial Interests, Personal, Invited Speaker: Roche, Novartis, Pharmamar, Eisai, AstraZeneca, Daichii Sankyo, Pfizer, Teva, Kiowa Kirin, GSK, Gilead. C. Bueno Muiño: Financial Interests, Personal, Invited Speaker: Novartis, Daiichi Sankyo, AstraZeneca, GSK, Lilly; Financial Interests, Personal, Advisory Board: Pfizer. M. Martin Jimenez: Financial Interests, Personal, Advisory Board: Astrazeneca, Lilly, Roche/Genentech, Daiichi Sankyo, Menarinio-Stemline; Financial Interests, Personal, Invited Speaker: Pfizer, Astrazeneca, Lilly, Novartis, Roche/Genentech; Financial Interests, Institutional, Research Grant: Novartis, Roche, Puma; Non-Financial Interests, Member of Board of Directors: TRIO; Non-Financial Interests, Leadership Role: GEICAM; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Advisory Board: SEOM. All other authors have declared no conflicts of interest.