Abstract 52P
Background
The antibody-drug conjugate (ADC) trastuzumab deruxtecan is not only efficient in HER2 amplified breast cancers (BC), but also in BC with lower protein expression levels of HER2. These HER2 low tumors are well described for non-special type BC, but data on HER2 low in ILC is lacking. Here, we aim at reporting the prevalence of HER2 low and analyzing its association with clinicopathological features and survival in patients with early pure estrogen receptor-positive, HER2-negative (ER+/HER2-) ILC.
Methods
A multicentric retrospective study was performed including patients diagnosed with stage I-III ER+/HER2- pure ILC between 01/01/2000 and 12/31/2020. HER2- disease was categorized by immunohistochemistry (IHC) score into HER2 0, HER2 1+ and HER2 2+ (without amplification) following local guidelines prior to 2007 and ASCO/CAP guidelines from 2007 onwards. The association of HER2 low with clinicopathological variables was assessed using multinomial logistic regression. Univariable and multivariable survival analyses were performed to evaluate the association of HER2 low with disease-free (DFS), distant recurrence-free (DRFS) and overall survival (OS).
Results
Data from 2098 patients with ER+/HER2- ILC were collected of which 1103 (53%) had a HER2 low tumor. Of these, 716 (34%) had an IHC score of HER2 1+ and 387 (18%) of HER2 2+. A histological grade 3 (odds ratio (OR) 1.95, p-value 0.04) and a tumor size of ≥2cm (OR 1.85, p-value <0.01) was associated with HER2 2+ vs. HER2 0. This was not seen for HER2 1+ vs. HER2 0. In multivariable analyses, HER2 1+ was associated with worse DFS (hazard ratio (HR) 1.29, p-value 0.03) and OS (HR 1.41, p-value 0.01) as compared to HER2 0. HER2 2 was significantly associated with worse OS (HR 1.45, p-value 0.04), while a trend was seen for worse DFS. No significant results were seen when comparing the HER2 categories for DRFS.
Conclusions
In our cohort, HER2 low was present in more than half of the early ER+HER2- ILCs. Higher HER2 IHC scores were associated with unfavorable prognostic features (higher grade and tumor size) and worse survival outcomes (DFS and OS). Studies are needed to evaluate whether patients with HER2 low ER+ pure ILC would benefit from anti-HER2 ADCs.
Legal entity responsible for the study
Laboratory for Translational Breast Cancer Research, Department of Oncology, KU Leuven.
Funding
This study is supported by COST (European Cooperation in Science and Technology, www.cost.eu). The study was funded by the Luxembourg Cancer Foundation (grant FC/2018/07), besides personal funds by the KU Leuven Fund Nadine de Beauffort and a Conquer Cancer – Lobular Breast Cancer Alliance Young Investigator Award for Invasive Lobular Carcinoma Research, supported by Lobular Breast Cancer Alliance. Any opinions, findings, and conclusions expressed in this material are those of the author(s) and do not necessarily reflect those of the American Society of Clinical Oncology® or Conquer Cancer®, or Lobular Breast Cancer Alliance.
Disclosure
M.M. Karsten: Financial Interests, Personal, Invited Speaker: Roche, Gilead, Sysmex. G. Nader Marta: Financial Interests, Personal, Other, Travel: Roche, Bayer. H. Wildiers: Financial Interests, Institutional, Advisory Board: Roche, Lilly, AstraZeneca, Daiichi Sankyo, PSI Cro AG, KCE, MSD, MSD, E Squared Communications LLC; Financial Interests, Institutional, Invited Speaker: Eisai, AstraZeneca; Financial Interests, Institutional, Other, Consultancy fee: AbbVie, Immutep Pty; Financial Interests, Institutional, Expert Testimony: Daiichi Sankyo; Financial Interests, Institutional, Other, Consultancy: Daiichi Sankyo; Financial Interests, Institutional, Research Grant, Grant to the Leuven Breast Center to support the research database: Roche; Financial Interests, Institutional, Research Grant, Grant to institute to perform a multicentric national academic trial: Novartis; Other, Travel & accomodations: Pfizer; Other, Travel & accomodation: Roche; Other, Subscription fee: Gilead. C. Desmedt: Financial Interests, Personal, Invited Speaker: Lilly. All other authors have declared no conflicts of interest.