Abstract 206P
Background
HER2-low expression is emerging as a predictive biomarker for novel antibody-drug conjugates in breast cancer. However, little is known on its biologic and prognostic significance in IBC.
Methods
Patients (pts) diagnosed with HER2-negative IBC between 12/1999 and 01/2021 were identified from the Dana-Farber Cancer Institute IBC registry. Pts were divided into two groups: HER2-low (IHC 1+ or 2+/FISH-) and HER2-0 (IHC 0). Clinicopathologic features and disease outcomes were compared between HER2-low and HER2-0 IBC, overall and according to estrogen receptor (ER) status.
Results
The study included 276 pts (stage III: 209, stage IV: 67). Among pts with stage III and IV IBC, 54% and 39% had HER2-low tumors, respectively, whereas the remaining had HER2-0 tumors. ER-expressing tumors were more common in pts with HER2-low vs HER2-0 stage III IBC (65% vs 38%, p<0.01) (Table). Among stage III pts undergoing surgery (n=182), pathologic complete response (pCR) rates were higher for pts with HER2-0 compared to HER2-low IBC (11% vs 6%, OR 1.8, 95% CI:0.6-5.3), but only small differences in pCR rates persisted when separately analyzing ER+ and ER- IBC. With a median follow up of 56 months, similar disease-free survival (DFS) was observed among ER+ HER2-0 vs HER2-low IBC (48-month DFS, 63% vs 63%, HR 1.10, 95% CI: 0.57-2.13) and ER- HER2-0 vs HER2-low IBC (48-month DFS 28% vs 25%, HR 1.19, 95% CI: 0.69-2.04). Differences in overall survival (OS) were also small, both among ER+ HER2-0 vs HER2-low IBC (48-month OS: 80% vs 81%, HR 0.82, 95% CI: 0.39-1.73) and ER- HER2-0 vs HER2-low IBC (48-month OS: 34% vs 47%, HR 1.34, 95% CI: 0.74-2.41). ER- IBC consistently had worse DFS and OS compared to ER+ IBC, regardless of HER2-low status. Table: 206P
Distribution of HER2-low tumors depending on ER expression and stage
| HER2-low | HER2-0 | Total | p-value | |
| STAGE III DISEASE | 112 | 97 | 209 | |
| - ER-negative | 39 (34.8%) | 60 (61.9%) | 99 | p<0.01 |
| - ER-Low (1-9%) | 7 (6.3%) | 9 (9.3%) | 16 | |
| - ER-positive (≥10%) | 66 (58.9%) | 28 (28.9%) | 94 | |
| STAGE IV DISEASE | 26 | 41 | 67 | |
| - ER-negative | 12 (46.2%) | 19 (46.3%) | 31 | p=1.00 |
| - ER-Low (1-9%) | 1 (3.8%) | 1 (2.4%) | 2 | |
| - ER-positive (≥10%) | 13 (50%) | 21 (51.2%) | 34 |
Conclusions
Among pts with stage III IBC, HER2-low tumors are more likely than HER2-0 tumors to be ER-positive. Only marginal differences in outcomes were observed in HER2-low compared with HER2-0 IBC when controlling for ER status, not supporting the definition of a distinct subtype.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
P. Tarantino: Financial Interests, Personal, Invited Speaker: AstraZeneca. T.A. King: Financial Interests, Personal, Invited Speaker: Exact Sciences, Berins Healthcare. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Pfizer; Financial Interests, Personal, Advisory Board: Ellipsis, Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences; Financial Interests, Personal, Advisory Board, Advisory Board: Exact Science, Celcuity; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Invited Speaker, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Invited Speaker, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Officer, Member of the Advisory Council: EUSOMA. M.M. Regan: Financial Interests, Personal, Advisory Board, Also invited speaker: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board, Includes consulting: Tolmar Pharmaceuticals; Financial Interests, Personal, Invited Speaker: WebMD; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb, Bayer; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trial supported by company: Novartis; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trials supported by company: Pfizer, Ipsen, TerSera; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trial drug supply from company: Roche; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trials supported or drug supply from company: AstraZeneca; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trials with funding from company: Debiopharm; Non-Financial Interests, Advisory Role: Bristol-Myers Squibb. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Novartis, Gilead, Genentech/Roche, Eisai, Sanofi, SeaGen, Daichii Sankyo, 4D Pharma, Puma, ARC Therapeutics; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Other, Consultant: Nektar, Nanostring, Athenex, Blueprint Medicines; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol-Myers Squibb, OncoPep, OncoSec, Certara, Mersana Therapeutics, Ellipses Pharma; Financial Interests, Personal, Advisory Board, Ad board participant/consultant/DSMC: Odonate; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Invited Speaker, Invited speaker for pharma supported educational activity: Chugai Pharmaceuticals; Financial Interests, Personal, Advisory Board, Advisory board participant: G1 Therapeutics; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Personal, Advisory Board, Advisory Board participation: Zentalis, OncXerna; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; 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, Invited Speaker: CytomX. All other authors have declared no conflicts of interest.