475P - Dynamics of TROP2 expression in triple-negative breast cancer

Background

With the approval of antibody drug conjugates (ADC) for metastatic TNBC (mTNBC), understanding prevalence and changes in ADC target expression from early-stage to metastatic breast cancer is key. Here we report TROP2 expression in a cohort of patients (pts) diagnosed with TNBC with collection of matched tumor samples over time.

Methods

Pts were identified from an institutional database of pts who underwent surgery for stage I-III TNBC at Dana-Farber/Brigham Cancer Center between 2015-2018, and a prospective biopsy protocol for pts who developed mTNBC. TROP2 immunohistochemistry (IHC), RNA and exome sequencing were performed in samples at diagnosis (DX), residual disease (RD) post-neoadjuvant therapy (if applicable), and recurrence (MR). TROP2 IHC (tumor cell membrane expression) was scored by a trained pathologist and classified: low, L (H score <100); medium, M (100-<200); high, H (200-300). RNA expression was quantified using log2p1-transformed and normalized transcripts per million.

Results

TROP2 IHC was performed in 161 samples (62 DX, 54 RD, 45 MR) from 94 pts (Table). TROP2 H/M distribution was similar at DX (90.3%; 56/62) vs MR (88.9%; 40/45). In samples with available TROP2 and HER2 IHC, TROP2 H/M distribution was 88.8% (71/80) in HER2-0 and 91.3% (42/46) in HER2-low TNBC. In 20 pts with paired DX and RD, TROP2 IHC was discordant (H/M vs L) in 15% (3/20). Of 17 TROP2 H/M DX tumors, 2 (11.8%) were L at RD. In 15 pts with paired DX and MR, TROP2 IHC was discordant in 26.7% (4/15). Of 14 TROP2 H/M DX tumors, 3 (21.4%) were L at MR. Correlation between TROP2 IHC and TACSTD2 expression was observed (n=53; Pearson r=0.38; p=0.005). TACSTD2 expression was numerically higher in TROP2 H/M vs L (p=0.09). Increased gene expression was also observed for L vs H (p=0.06) and M vs H (p=0.047). No TACSTD2 mutations were identified. Table: 475P

Distribution and changes in TROP2 IHC (n samples) in pts diagnosed with TNBC. A) TROP2 IHC by sample type; B) From DX to RD; C) From DX to MR. Discordant cases (H/M vs L) are highlighted in bold

Conclusions

TROP2 IHC was H/M in the majority of samples, with similar distribution at DX and MR, and between HER2-0 and HER2-low TNBC. In paired DX/RD or DX/MR, discordance between TROP2 H/M and L groups was low.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Dana-Farber Cancer Institute.

Funding

AstraZeneca.

Disclosure

A.C. Garrido-Castro: Financial Interests, Institutional, Funding, Research funding: AstraZeneca, Daiichi Sankyo, Gilead Sciences, Merck, Zenith Epigenetics, Bristol Myers Squibb, Novartis; Other, Travel to scientific meeting: Roche/Genentech. J. Gomez Tejeda Zanudo: Financial Interests, Personal, Stocks or ownership: CNCR, IDNA, IBB, XBI, Adaptive Biotechnologies, 2seventy bio, Bluebird bio. A.M. Barkell: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. R.J. Hill: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. T.A. King: Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Personal, Speaker, Consultant, Advisor: Exact Sciences. E.A. Mittendorf: Financial Interests, Personal, Advisory Board: Merck, BioNTech; Financial Interests, Institutional, Research Grant, I have a grant from SU2C funded by Roche/Genentech that supports the conduct of a clinical trial: Roche/Genentech; Financial Interests, Institutional, Coordinating PI, Gillead provides clinical trial support to my institution for a study that I am the PI on: Gillead; Financial Interests, Personal, Steering Committee Member: Roche/Genentech, BMS; Non-Financial Interests, Member of Board of Directors: American Society of Clinical Oncology; Non-Financial Interests, Advisory Role, I serve in an advisory role as a Komen Scholar: Komen for the Cure. M.C. Rebelatto: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. D. Carroll: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. N.U. Lin: Financial Interests, Personal, Advisory Board, Ad board participation: Seattle Genetics, Daiichi Sankyo, Prelude Therapeutics; Financial Interests, Personal, Advisory Board, Ad board/Steering Committee participation; consultant: AstraZeneca; Financial Interests, Personal, Other, Consultant: Denali Therapeutics, Blueprint Medicines, Janssen, Affinia Therapeutics; Financial Interests, Personal, Advisory Board, Ad board/Steering committee participation: Olema Pharmaceuticals; Financial Interests, Personal, Advisory Board, Advisory Board: Atera Inc.; Financial Interests, Personal, Royalties, Royalties for book chapter(s): Up to Date; Financial Interests, Institutional, Funding, Trial funding to institute (and steering committee): Olema Pharmaceuticals, AstraZeneca, Seattle Genetics; Financial Interests, Institutional, Funding, Trial funding to institute: Zion Pharmaceuticals; Financial Interests, Institutional, Funding, trial funding to institute: Pfizer, Genentech. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad board participant/consultant: 4D Pharma, ARC Therapeutics, Daiichi Sankyo, Eisai, Genentech/Roche, Gilead, Novartis, Sanofi, SeaGen; Financial Interests, Personal, Other, Consulting: Aadi BioPharma; Financial Interests, Personal, Advisory Board, Ad board participation: Artios, Incyte Corp, BeyondSprings; Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board, Advisory Board participation: Bayer, Infinity Therapeutics, Myovant, OncXerna, Umoja Biopharma, Zentalis, Zetagen; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb, Ellipses Pharma, Mersana Therapeutics; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Advisory Board, Advisory Board participation/consulting: Menarini/Stemline; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Institutional, Funding: AstraZeneca, Eli Lilly, Pfizer, Sanofi, SeaGen, Odonate, Cyclacel, Exelixis, Gilead, Bristol Myers Squibb, Eisai, Merck, Novartis, Nektar, Genentech/Roche; Financial Interests, Personal and Institutional, Steering Committee Member: CytomX. E.C. De Bruin: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. All other authors have declared no conflicts of interest.