Abstract 242P
Background
We and others reported that HER2-low expression is unstable during disease evolution. The availability of anti-HER2 antibody-drug conjugates (ADCs) for HER2-low metastatic BC (MBC) patients (pts) commands attention to the identification of those with HER2-0 primary BC who may acquire HER2-low phenotype at relapse. Driven by the urgency of maximizing treatment access, we developed an AI-based model to predict this phenomenon.
Methods
We included a large multicentric retrospective cohort of pts with matched HER2 status on primary and MBC samples. All the variables in the dataset were used to build the model, including, among others: primary and MBC phenotype, timing and site of relapse and of relapse biopsy, treatments for primary BC. The dataset underwent preprocessing to address missingness: we applied Multiple Imputation by Chained Equations algorithm to observations without missing values in key relapse-related features. Features were tested for collinearity through the calculation of the Variance Inflation Factor, and one-hot-encoded due to the high representation of categorical variables. In the final dataset, pts were randomly assigned to training and test set. The training set (n=561) was subjected to random under-sampling to mitigate the target class imbalance. To prevent lack of explainability, a Generalized Linear Model was then fitted (10-fold repeated cross-validation to prevent overfitting).
Results
Among 749 pts (final dataset), 296 had HER2-0 primary BC, of which 109 (37%) gained HER2-low expression at relapse. The model was able to predict this switch with a 74% accuracy. Sensitivity and specificity were 74%. Hormone receptor expression and timing of relapse biopsy (≤ vs >2 years from relapse) were the variables associated with the highest importance for the AI model (p<0.05).
Conclusions
Our AI model, based on clinicopathological features, showed promising accuracy in predicting the conversion from HER2-0 primary BC to HER2-low phenotype at relapse. This model may help identifying pts with HER2-0 primary BC for whom a relapse biopsy should be prioritized to maximize treatment access to anti-HER2 ADCs for HER2-low BC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
F. Miglietta: Financial Interests, Personal, Invited Speaker: Roche, Novartis, Seagen, Pfizer, Lilly, Menarini; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD. T. Giarratano: Financial Interests, Personal, Invited Speaker, outside the submitted work: Roche, Novartis, Seagen, Eli Lilly, Gliead, Daiichi Sankyo, Istituto Gentili. C.A. Giorgi: Financial Interests, Personal, Invited Speaker, outside the submitted work: Eli Lilly, Novartis, Seagen, AstraZeneca. F. Girardi: Financial Interests, Personal, Other, travel support; outside the submitted work: Eli Lilly, Gilead; Financial Interests, Personal, Invited Speaker, outside the submitted work: AstraZeneca, Eli Lilly, Gilead. D. Massa: Financial Interests, Personal, Other, travel support; outside the submitted work: Eli Lilly. M. Fassan: Financial Interests, Institutional, Research Grant, outside the submitted work: Astellas Pharma, QED therapeutics, Macrophage pharma, Diaceutics; Financial Interests, Personal, Invited Speaker, outside the submitted work: Astellas Pharma, AstraZeneca, Pierre Fabre, GSK, Roche, Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker, outside the: Johnson & Johnson, Bristol Myers Squibb, Amgen, Eli Lilly, Novartis, Incyte. M.V. Dieci: Financial Interests, Personal, Invited Speaker: Eli Lilly, Exact sciences, Gilead, Seagen, Daiichi Sankyo, Novartis; Financial Interests, Personal, Advisory Board: Novartis, Eli Lilly, Seagen, Exact Science, Daiichi Sankyo, Gilead; Financial Interests, Personal, Other, Consultancy: Pfizer; Financial Interests, Personal, Other, Consultancy on educational project: Roche. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, GSK, AstraZeneca, Gilead, Exact Sciences; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Merck, Exact Sciences, Eisai, Olema Oncology, AstraZeneca, Daiichi Sankyo, Pfizer; Financial Interests, Personal, Expert Testimony: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, GSK, Daiichi Sankyo, Nerviano, Pfizer; Non-Financial Interests, Member: ASCO. All other authors have declared no conflicts of interest.