18P - Association of DNA methylation profiles with pathologic complete response in early triple negative breast cancer patients receiving neoadjuvant chemoimmunotherapy

Background

Immunotherapy (IO) has become an important component of systemic treatment in early-stage triple-negative breast cancer (eTNBC). Considering toxicity and financial burden, identifying reliable biomarkers of response is urgently warranted. Therefore, we investigated blood cell DNA methylation profiles as biomarker for achieving a pathologic complete response (pCR) at surgery after neoadjuvant chemoimmunotherapy.

Methods

eTNBC patients receiving systemic chemoimmunotherapy before surgery at the Medical University of Vienna were included in this analysis. DNA from peripheral blood mononuclear cells (PBMCs) was isolated from whole blood samples collected at start of neoadjuvant therapy and methylation profiling was performed with Infinium Methylation EPIC microarrays. Routine histologic work-up from surgery determined a pCR or non-pCR according to pathologic standard procedures.

Results

Seven eTNBC patients (all women), median age of 63 years (range 40-83 years), were available for this analysis. All patients received neoadjuvant chemoimmunotherapy with pembrolizumab plus weekly paclitaxel/carboplatin followed by pembrolizumab plus epirubicin/cyclophosphamide. Three out of 7 (42.9%) patients achieved a pCR, while 4/7 (57.1%) had residual disease at surgery. Notably, when focusing on their methylation patterns, patients with pCR and non-pCR could be clearly segregated into two distinct groups. This distinction was based on the methylation profiles of the top 500 differentially methylated CpG sites.

Conclusions

Our results revealed differentially methylated genes between patients w/o pCR that might play a role in response to chemoimmunotherapy. Blood cell methylation profiles might serve as predictive biomarker for pCR in eTNBC and larger patient cohorts are needed to validate our findings.

Legal entity responsible for the study

The authors.

Funding

Christian Doppler Laboratory for Personalized Immunotherapy, Department of Medicine I, Medical University of Vienna.

Disclosure

A.M. Starzer: Financial Interests, Personal, Invited Speaker, Lecture honoraria: AstraZeneca; Financial Interests, Institutional, Research Grant, Industry partner of institutional Christian Doppler Laboratory: Roche; Non-Financial Interests, Personal, Member, National Oncology Society: OeGHO; Non-Financial Interests, Personal, Member, Oncology society of USA: ASCO; Other, Personal, Other, Travel support for conference participation: MSD, Lilly. M. Preusser: Financial Interests, Personal, Advisory Board: Bayer, Bristol Myers Squibb, Novartis, Gerson Lehrman, CMC Contrast, GSK, Mundipharma, Roche, BMJ Journals, MedMedia, AstraZeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dohme, Tocagen, Adastra, Gan & Lee Pharmaceuticals; Financial Interests, Institutional, Research Grant, Clinical Trials and research: Boehringer Ingelheim, Bristol Meyers Squibb, Roche, Daiichi Sankyo, Merck Sharp & Dohme, Novocure, GSK, AbbVie; Financial Interests, Institutional, Coordinating PI: PharmaMar; Non-Financial Interests, Personal, Leadership Role, Brain Tumor Group Chair (current): EORTC; Non-Financial Interests, Personal, Leadership Role, EANO Past-President (current): EANO; Non-Financial Interests, Personal, Other, Member Multi-Site Guideline Advisory Group: ASCO. R. Bartsch: Financial Interests, Personal, Invited Speaker: AstraZeneca, Seagen, Roche, Novartis, Eli-Lilly, Pierre Fabre, Daiichi, Gilead, MSD, Pfizer, Eisai, Gruenenthal; Financial Interests, Personal, Advisory Board: Daiichi, AstraZeneca, Roche, Novartis, Eli Lilly, Pierre Fabre, MSD, Gilead, Seagen, Eisai, Gruenenthal; Financial Interests, Institutional, Funding, Investigator Initiated Trial: Daiichi; Financial Interests, Institutional, Coordinating PI, Drug support for investigator initiated trial: MSD. A.S. Berghoff: Financial Interests, Personal, Research Funding: Daiichi Sankyo, Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, Bristol Meyers Squibb, Merck, Daiichi Sankyo, AstraZeneca, CeCaVa; Financial Interests, Personal, Other, travel support: Roche; Financial Interests, Personal, Other, Travel support: Amgen, AbbVie. All other authors have declared no conflicts of interest.