Abstract 129P
Background
TROP-2 is involved in regulating cancer growth and invasion in different tumour types. It is also a potent therapeutic target, being addressed by antibody drug conjugates (ADC). This study evaluates the impact of TROP-2 on breast cancer prognosis in high-risk, node-positive BC of the German adjuvant intergroup node-positive (GAIN) cohort.
Methods
Tissue microarrays (TMAs) were generated from FFPE-pre-therapeutic surgical resection tissue (n = 1358). Immunohistochemical staining was performed with human TROP-2 antibody SP295. Membranous and cytoplasmic expression of TROP-2 in invasive tumor cells was assessed. The Cutoff Finder web application was used for identification of the best cutoff point according to disease-free survival (DFS) and overall survival (OS). For n = 996 patients, data on hormone receptor (HR), HER2 and Ki67 status were available. The association of membranous (m)TROP-2 and cytoplasmic (c)TROP-2 expression with molecular intrinsic subgroups, TNM stages, age, proliferation and HR status were evaluated.
Results
For 1186 TMA spots valid TROP-2 evaluation was available. The Cutoff Finder identified 70 % as best cutoff for cTROP-2 expression. cTROP-2 ≤ 70 % was significantly associated with better grading (p < 0.001). In multivariate Cox regression analysis, cTROP-2 ≤ 70% was associated with improved DFS in HR+/HER2- (p = 0.006) and luminal A-like tumors (p = 0.013). For mTROP-2, a product score (IRS) of grouped percentage and staining intensity showed better DFS and OS for IRS > 3 (also identified by Cutoff Finder) in HER2+/HRany and HER2+/HR+ patients (uni-/multivariate). Detailed data incl. molecular subtypes will be presented.
Conclusions
TROP-2 is commonly expressed in breast cancer with its cellular localization differentially affecting survival. The results are relevant for biomarker strategies for future therapeutic concepts. In the SASCIA trial investigating Sacituzumab TROP-2 is prospectively assessed.
Clinical trial identification
NCT01690702.
Legal entity responsible for the study
The authors.
Funding
Roche.
Disclosure
P. Jank: Other, Personal, Stocks/Shares: Myriad Genetics. W. Janni: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Gilead; Financial Interests, Personal, Full or part-time Employment: Universitätsklinikum Ulm; Financial Interests, Institutional, Invited Speaker: Novartis, GSK, Sanofi, Amgen, Roche, Lilly; Non-Financial Interests, Leadership Role: Chair of AGO Breast Council. P.A. Fasching: Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, AstraZeneca, Hexal, Lilly, Pierre Fabre, Seagen, Agendia, Sanofi Aventis; Financial Interests, Personal, Invited Speaker: Novartis, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, AstraZeneca, Lilly, Seagen, Gilead; Financial Interests, Personal, Other, Medical Writing Support: Roche; Financial Interests, Institutional, Invited Speaker: BionTech, Cepheid; Non-Financial Interests, Member: ASCO, Arbeitsgemeinschaft für Gynäkologische Onkologie e.V., Translational Research in Oncology, Deutsche Gesellschaft für Senologie e.v. F. Marmé: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK/Tesaro, Clovis, Pfizer, Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Novartis, Roche, Gilead/immunomedics, EISAI, PharmaMar, GenomicHealth, Myriad, Seagen; Financial Interests, Institutional, Invited Speaker: Seagen, Daiichi Sankyo, GSK, AstraZeneca, Roche, AstraZeneca, Novartis, Roche, Eisai, Gilead/Immunomedics, MSD, German Breast Group, AGO Research GmbH, Vaccibody, GSK; Financial Interests, Institutional, Advisory Board: Roche, Immunicom; Financial Interests, Institutional, Funding: AstraZeneca, Lilly, Seagen. M. Schmidt: Financial Interests, Institutional, Research Grant: AtraZeneca, BioNTech, Eisai, GBG, Genentech, Novartis, Pantarhei Bioscience, Pfizer, PierreFabre, Roche; Financial Interests, Personal, Other, Consulting fees: AstraZeneca, BioNTech, Eisai, Daichi-Sankyo, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, Seagen; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Novartis, Pfizer, Roche, Segaen; Financial Interests, Personal, Other, Travel support: Pfizer, Roche; Financial Interests, Personal, Other, Patent: EP 2951317 B1, EP 2390370 B1; Financial Interests, Personal, Advisory Board: AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, Seagen. V. Mueller: Financial Interests, Institutional, Research Grant, Speaker Honoraria: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead, Pierre Fabre, Medscape; Financial Interests, Institutional, Other, Consultancy Honoraria: Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Sanofi, Seagen, Gilead, Pierre Fabre; Financial Interests, Institutional, Other, Travel Support: Roche, Pfizer, Daiichi Sankyo, Gilead. M. Untch: Financial Interests, Institutional, Other, Supportfor present Abstract: Amgen; Financial Interests, Institutional, Funding, Support for Present Abstract: Roche; Financial Interests, Institutional, Other, Consulting fees: Amgen, AbbVie, Sanofi-Aventis, Pfizer, Agendia, Daiichi, AstraZeneca, Seagen, Gilead, Genzyme, MSD, Lilly, Stemline; Financial Interests, Institutional, Speaker’s Bureau: AstraZeneca, Lilly, Baxter, Pfizer, Gilead, Myriad, Pierre Fabre. C. Schem: Financial Interests, Personal, Advisory Board: Roche, Novartis, Lilly, AstraZeneca, Daichi Sanyo; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Roche, Gilead. V. Nekljudova: Financial Interests, Institutional, Full or part-time Employment: GBG; Financial Interests, Institutional, Research Grant: AbbVie, AstraZeneca, BMS, Daichi-Sankyo, Gilead, Novartis, Pfizer, Roche, Seagen; Non-Financial Interests, Institutional, Writing Engagements: Daiichi Sankyo, Gilead, Novartis, Pfizer, Roche, Seagen; Other, Institutional, Other, EP14153692.0: Patent; Other, Institutional, Other, EP21152186.9: Patent; Other, Institutional, Other, EP15702464.7: Patent; Other, Institutional, Other, EP19808852.8: Patent; Other, Institutional, Royalties: VM Scope GmbH. S. Loibl: Financial Interests, Institutional, Advisory Board, Member: Amgen, AstraZeneca, BMS, Celgene, EirGenix, GSK, Lilly, Pierre Fabre, Roche, Seagen, AbbVie, Sanofi, Gilead, Merck, Novartis, Relay Therapeutics; Financial Interests, Institutional, Invited Speaker: AstraZeneca, DSI, Novartis, Pfizer, Roche, Gilead, Seagen; Financial Interests, Institutional, Advisory Board: DSI, Pfizer, Olema; Financial Interests, Personal, Invited Speaker: Medscape; Financial Interests, Personal, Full or part-time Employment, CEO: GBG Forschungs GmbH; Financial Interests, Institutional, Invited Speaker, Ki67: VM Scope GmbH; Financial Interests, Institutional, Research Grant: AstraZeneca, Celgene, Novartis, Immunomedics/Gilead, Pfizer, Roche, Daiichi Sankyo; Financial Interests, Institutional, Funding: AbbVie, Molecular Health; Financial Interests, Personal, Other, PIPenelope/Padma: Pfizer; Financial Interests, Personal, Other, SC PALOMA3: Pfizer; Financial Interests, Personal, Other, SC SOLAR1: Novartis; Financial Interests, Personal, Other, SC ASCENT: Immunomedics/Gilead; Financial Interests, Personal, Other, SC HERCLIMB: Seagen; Financial Interests, Personal, Other, SC Katherine: Roche; Financial Interests, Personal, Other, SC Capitello; EC Cambria 1: AstraZeneca; Financial Interests, Personal, Other, SC Inavo: Roche; Financial Interests, Personal, Other, SC Destiny B05; SC Destiny B09: Daiichi Sankyo; Non-Financial Interests, Principal Investigator, After publication of primary endpoint: PI Aphinity; Non-Financial Interests, Advisory Role, Group in Germany responsible for breast cancer guidelines: AGO Kommission Mamma; Non-Financial Interests, Member, German Gynaecological Oncology society: AGO; Non-Financial Interests, Member, German Cancer Society: DKG; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member, Member guideline committee; past chair in ESMO Breast: ESMO; Other, EP14153692.0No financial interest, Institutional: Patent; Other, EP21152186.9No financial interest, institutional: Patent; Other, EP15702464.7No financial interest, institutional: Patent; Other, EP19808852.8 No financial interest, Institutional: Patent. C. Denkert: Financial Interests, Personal, Advisory Board: MSD Oncology, Daiichi Sankyo, Molecular Health, AstraZeneca, Roche, Lilly; Financial Interests, Personal, Invited Speaker: AstraZeneca, VmScope digital pathology software; Financial Interests, Institutional, Research Grant: Roche, Myriad, German Breast Group. All other authors have declared no conflicts of interest.