Association Between Tumor Size and Nodal Positivity for HER2+ and Triple-Negative Early-Stage Breast Cancer: A Population-Based Study.

[BACKGROUND] The 2021 American Society of Clinical Oncology (ASCO) guidelines recommend neoadjuvant systemic therapy (NST) over upfront surgery for human epidermal growth factor receptor 2-positive (HER2+) and triple-negative breast cancers if node-positive or at least T1c. In practice, many clinicians use a 2-cm (T2) or node-positive threshold for NST, leaving controversy regarding management of clinically node-negative T1c HER2+ and triple-negative tumors. Accurate estimation of nodal status is therefore essential to guide management. This study evaluated the association between tumor size and nodal involvement in T1-T2 HER2+ and triple-negative tumors and assessed predictors of nodal positivity in T1c tumors.

[METHODS] A population-based retrospective cohort study was conducted using Institute for Clinical Evaluative Sciences (ICES) Ontario administrative data (2000-2019). The primary outcome was regional nodal positivity (N1-N3) stratified by tumor size (T1a-T2) and receptor subtype. Multivariable logistic regression identified independent predictors of nodal positivity in T1c tumors.

[RESULTS] The study analyzed 11,007 T1a-T2 cases including 1923 hormone receptor-negative (HR-)-HER2+ cases, 4542 HR+HER2+ cases, and 4542 triple-negative cases. Among T1a/b tumors, the nodal positivity rates ranged from 11 to 22% for HR-HER2+, 11-14% for HR+HER2+, and 7-11% for triple-negative tumors. Among T1c tumors, the rates were 32% for HR-HER2+, 26% for HR+HER2+, and 19% for triple-negative tumors. Among T2 tumors, the rates were 38% for HR-HER2+, 42% for HR+HER2+, and 30% for triple-negative tumors. Among T1c tumors, HR-HER2+ subtype and patient age younger than 50 years were independently associated with increased odds of nodal positivity.

[CONCLUSIONS] Nodal positivity rates are substantial for T1-T2 HER2+ and triple-negative tumors, even for T1a/b tumors. Among T1c tumors, HR-HER2+ subtype and age of 50 years or younger independently predicted increased nodal positivity, supporting NST especially for these patients.