Hans Tesch (Frankfurt am Main, Germany)

Onkologie Bethanien

Author Of 1 Presentation

Poster Display session (ID 9)

24P - Intermediate biopsies during neoadjuvant chemotherapy for breast cancer to predict patient outcome (ID 42)

Abstract

Background

Intermediate biopsies during neoadjuvant treatment might offer opportunities for prediction of pathological complete response (pCR) and patient outcome, which could be a basis for de-escalation of treatment. However, their relevance for clinical decisions is not clear.

Methods

We evaluated intermediate biopsies that were taken during neoadjuvant treatment from 297 patients with invasive breast cancer from three prospective, randomized trials (GeparQuattro, -Quinto, -Sixto). We evaluated the presence of invasive breast cancer, tumor-infiltrating lymphocytes (TILs) and Ki-67 expression and compared the results to pre-treatment samples. We explored the association of residual cancer in the intermediate biopsies as well as dynamics in Ki-67 and TILs with pCR rates and disease-free survival.

Results

Of the 297 tumors, 87 (29%) samples were triple-negative (TNBC), 138 (46%) HR+/HER2- and 72 (24%) HER2+. We found invasive tumor cells in 70% of biopsies, with significant differences between the subtypes (HR+/HER2-: 84%; TNBC: 62%, HER2+: 51%; p<0.001). In the complete cohort, 8% of patients with invasive tumor cells in intermediate biopsies achieved a pCR after completion of treatment (pCR rate in patients with residual tumor: TNBC: 19%, HR+/HER2: 3%; HER2+: 11%). If no residual cancer was present, pCR rate was 50% in the complete cohort (TNBC: 48%, HR+/HER2-: 27%; HER2+: 66%). An increase in TILs from baseline biopsy to intermediate biopsy was associated with a higher probability of pCR in the overall study cohort (p=0.001). A similar or increased Ki-67 was associated with a low probability of pCR in the overall study cohort (p=0.004) and with a shorter disease-free survival in patients with TNBC (p=0.04).

Conclusions

Intermediate biopsies can identify patients that are unlikely to achieve a pCR after therapy. After further validation, this may be useful for adaptation of treatment. For translational biomarker research, intermediate biopsies are useful tool to study mechanisms of therapy resistance and biomarker discovery. Additional studies will be needed to demonstrate if standardized sampling procedures can further improve response prediction through intermediate biopsies.

Legal entity responsible for the study

German Breast Group.

Funding

Has not received any funding.

Disclosure

M. Untch: Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Amgen GmbH; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: AstraZeneca; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: BMS; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Celgene GmbH; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Daiichi Sankyo; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Eisai; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Lilly Deutschland; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Lilly Int.; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: MSD Merck; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Myriad Genetics; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Pfizer GmbH; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Roche Pharma AG; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Sanofi Aventis Deutschland GmbH; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Novartis; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Pierre Fabre; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Clovis Oncology; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Seatlle Genetics; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Seagen; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: GSK; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Gilead. T. Karn: Other, Personal, Other, Patent pending: EP18209672. M. van Mackelenbergh: Financial Interests, Institutional, Other, Honoraria: Amgen; Financial Interests, Institutional, Other, Honoraria: AstraZeneca; Financial Interests, Institutional, Other, Honoraria: Novartis; Financial Interests, Institutional, Other, Honoraria: Pfizer; Financial Interests, Institutional, Other, Honoraria: Pierre Fabre; Financial Interests, Institutional, Other, Honoraria: Lilly; Financial Interests, Institutional, Other, Honoraria: Genomic Health; Financial Interests, Institutional, Other, Honoraria: Molecular Health; Financial Interests, Institutional, Other, Honoraria: Roche; Financial Interests, Institutional, Other, Honoraria: Gilead; Financial Interests, Institutional, Other, Honoraria: Seagen; Financial Interests, Institutional, Other, Honoraria: GSK. J. Huober: Financial Interests, Personal, Other, personal fees: Gilead; Financial Interests, Personal, Other, personal fees: Seagen; Financial Interests, Personal and Institutional, Research Grant, Grant, personal fees: Lilly; Financial Interests, Personal and Institutional, Research Grant, Grant, Travel, personal fees: Novartis; Financial Interests, Personal, Other, Travel, personal fees, Other: Pfizer; Financial Interests, Personal, Other, Travel, personal fees, Other: Daiichi; Financial Interests, Personal, Other, personal fees: Roche; Financial Interests, Personal, Other, personal fees: MSD; Financial Interests, Personal, Other, personal fees: AbbVie; Financial Interests, Personal, Other, personal fees: Eisai; Financial Interests, Institutional, Research Grant, Grant: Hexal; Financial Interests, Institutional, Research Grant, Grant, Travel, Other: BMS. W.D. Schmitt: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: GlaxoSmithKline; Financial Interests, Personal, Funding: Myriad Genetics. F. Marmé: Financial Interests, Personal, Other, Personal Fees: Roche/Genentech; Financial Interests, Personal, Other, Personal Fees: AstraZeneca; Financial Interests, Personal, Other, Personal Fees: Pfizer; Financial Interests, Personal, Other, Personal Fees: Tesaro; Financial Interests, Personal, Other, Personal Fees: Novartis; Financial Interests, Personal, Other, Personal Fees: Amgen; Financial Interests, Personal, Other, Personal Fees: PharmaMar; Financial Interests, Personal, Other, Personal Fees: Genomic Health; Financial Interests, Personal, Other, Personal Fees: CureVac; Financial Interests, Personal, Other, Personal Fees: EISAI; Financial Interests, Personal, Other, Persona Fees: BMS; Financial Interests, Personal, Other, Personal Fees: Clovis Oncology; Financial Interests, Personal, Other, Personal Fees: GSK; Financial Interests, Personal, Other, Personal Fees: MSD; Financial Interests, Personal, Other, Personal Fees: Seagen; Financial Interests, Personal, Other, Personal Fees: Myriad Genetics; Financial Interests, Personal, Other, Personal Fees: Pierre Fabre; Financial Interests, Personal and Institutional, Research Grant, Personal Fees: Gilead/Immunomedics; Financial Interests, Personal, Other, Persona fees: Janssen-Cilag. E. Stickeler: Financial Interests, Personal, Other, personal fees: Roche; Financial Interests, Personal, Other, personal fees: Gilead; Financial Interests, Personal, Other, personal fees: MSD; Financial Interests, Personal, Other, personal fees: Lilly; Financial Interests, Personal, Other, personal fees: Pfizer; Financial Interests, Personal, Other, personal fees: Seagen; Financial Interests, Personal, Other, personal fees: PharmaMar. H. Tesch: Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: Novartis; Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: Roche; Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: GSK; Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: Seagen; Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: Pfizer; Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: Lilly; Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: AstraZeneca; Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: Daiichi; Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: Exact Science. P.A. Fasching: Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Novartis; Financial Interests, Institutional, Research Grant, Grant, Institutional Funding: BioNTech; Financial Interests, Personal and Institutional, Advisory Board, Advisory Board, Invited Speaker, Research Grant: Pfizer; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant, Grant, Institutional Funding: Cepheid; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board, Advisory Board: Hexal; Financial Interests, Personal, Advisory Board, Advisory Board: Agendia; Financial Interests, Personal, Advisory Board, Advisory Board: Sanofi Aventis; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Gilead. A. Schneeweiss: Financial Interests, Personal and Institutional, Research Grant, Research Grant, Travel expenses, Honoraria: BMS; Financial Interests, Personal and Institutional, Research Grant, Research Grant, Expert testimony, Travel expenses, Honoraria: Roche; Financial Interests, Institutional, Research Grant, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant, Research Grant: Molecular Partner; Financial Interests, Personal, Expert Testimony, Expert testimony, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria, Travel expenses: Pfizer; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Tesaro; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Seagen; Financial Interests, Personal, Other, Honoraria: Gilead. V. Müller: Financial Interests, Personal, Invited Speaker, speaker and consultancy honoraria: Amgen; Financial Interests, Personal, Invited Speaker, speaker honoraria: AstraZeneca; Financial Interests, Personal, Invited Speaker, speaker and consultancy honoraria: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, speaker and consultancy honoraria: Eisai; Financial Interests, Personal, Invited Speaker, speaker honoraria: Pfizer; Financial Interests, Personal, Invited Speaker, speaker and consultancy honoraria: MSD; Financial Interests, Personal and Institutional, Invited Speaker, speaker and consultancy honoraria, Institutional research support: Novartis; Financial Interests, Personal and Institutional, Invited Speaker, speaker and consultancy honoraria, Institutional research support: Roche; Financial Interests, Personal, Invited Speaker, speaker honoraria: Teva; Financial Interests, Personal and Institutional, Invited Speaker, speaker honoraria, Institutional research support: Seagen; Financial Interests, Personal, Invited Speaker, speaker and consultancy honoraria: GSK; Financial Interests, Personal, Invited Speaker, speaker and consultancy honoraria: Gilead; Financial Interests, Personal, Advisory Role, consultancy honoraria: Genomic Health; Financial Interests, Personal, Advisory Role, consultancy honoraria: Hexal; Financial Interests, Personal, Advisory Role, consultancy honoraria: Pierre Fabre; Financial Interests, Personal, Advisory Role, consultancy honoraria: ClinSol; Financial Interests, Personal, Advisory Role, consultancy honoraria: Lilly; Financial Interests, Institutional, Other, Institutional research support: Genentech. S. Loibl: Financial Interests, Institutional, Research Grant, Grant, Other: AbbVie; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Other: Amgen; Financial Interests, Institutional, Research Grant, Grant, Other: AstraZeneca; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Other: Bayer; Financial Interests, Institutional, Advisory Board, honorarium for Ad Boards, Other: BMS; Financial Interests, Institutional, Research Grant, Grant, Other: Celgene; Non-Financial Interests, Institutional, Research Grant, Grant, Medical Writing, Other: Daiichi Sankyo; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Other: Eirgenix; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Other: GSK; Non-Financial Interests, Institutional, Research Grant, Grant, Medical Writing, Other: Immunomedics/Gilead; Financial Interests, Institutional, Advisory Board, honorarium for Ad Boards, Other: Lilly; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Other: Merck; Non-Financial Interests, Institutional, Research Grant, Grant, Medical Writing, Other: Novartis; Non-Financial Interests, Institutional, Research Grant, Grant, Medical Writing, Other: Pfizer; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board & Lecture, Other: Pierre Fabre; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board & Lecture, Other: prIME/Medscape; Non-Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Medical Writing, Other: Puma; Financial Interests, Institutional, Advisory Board, honorarium for Lecture, Other: Samsung; Non-Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Medical Writing, Other: Seagen; Non-Financial Interests, Institutional, Advisory Board, honorarium for Ad Boards & Lectures, Medical Writing, Other: Roche; Other, Institutional, Other, Patent Pending, Immunsignature in TNBC: EP14153692.0; Other, Institutional, Other, Patent Pending, Signature for CDK 4/6 Inhibitor: EP21152186.9; Other, Institutional, Other, Patent Issued, Predicting response to an Anti-HER2 containing therapy: EP15702464.7; Other, Institutional, Other, Patent Pending, GeparNuevo: EP19808852.8; Other, Institutional, Royalties, Patent Issued, Royalties, VM Scope GmbH: Digital Ki67 Evaluator. C. Denkert: Financial Interests, Personal, Ownership Interest, Stock and Other Ownership Interests: Sividon Diagnostics; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: MSD Oncology; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Molecular Health; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Merck; Financial Interests, Personal and Institutional, Advisory Role, Consulting or Advisory Role, Research Funding: Roche; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Lilly; Financial Interests, Institutional, Research Grant, Research Funding: Myriad Genetics; Other, Personal, Royalties, Patents, Royalties, Other Intellectual Property: VMScope digital pathology software; Other, Personal, Royalties, Patents, Royalties, Other Intellectual Property: WO2015114146A1; Other, Personal, Royalties, Patents, Royalties, Other Intellectual Property: WO2010076322A1; Other, Personal, Royalties, Patents, Royalties, Other Intellectual Property: WO2020109570A1. All other authors have declared no conflicts of interest.

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