Adding Anti-HER2 Therapy to Neoadjuvant Endocrine Therapy Seems Effective in Hormone Receptor and HER2 Positive Breast Cancer Patients Unfit for Chemotherapy: A Nationwide Population-Based Cohort Study

Introduction: Data are lacking on the optimal neoadjuvant systemic treatment (NST) for women with hormone receptor-positive (HR+) human epidermal growth factor receptor 2-positive (HER2+) breast cancer if they are unfit to receive the combination of chemotherapy and anti-HER2 therapy. The aim of this study was to determine whether the rates of ypT0 and ypN0 differ between patients treated with neoadjuvant endocrine therapy (NET) versus NET combined with anti-HER2 therapy (NET+aHER2). Materials and Methods: Data from the Netherlands Cancer Registry were analysed to identify women diagnosed with primary HR+/HER2+ breast cancer between 2008 and 2019, treated with either NET or NET+aHER2. The ypT0 and ypN0 rates were analysed (using uni- and multivariable logistic regression analyses, as applicable) in relation to the characteristics of the patient, the tumour, and the treatment. Results: Of the 190 patients identified (median age 77), 150 had been treated with NET and 40 with NET+aHER2. Patients with clinically node-positive disease (cN+) were significantly more likely to have been treated with NET+aHER2 (p = 0.029). The ypT0 rate was significantly higher after NET+aHER2, with 10.0% (4/40) versus 1.3% (2/150) following NET (p = 0.019). The ypN0 rate was significantly higher after NET+aHER2, with 25.0% (6/24) versus 5.5% (3/55) following NET in the cN+ patients (p = 0.020) and 81.3% (13/16) versus 55.8% (53/95) after NET in the cN- patients (p = 0.047). In the cN- patients, the ypN0 status was independently associated with age (p = 0.008) and the administration of NET+aHER2 (p = 0.016). Conclusions: The rates of ypT0 and ypN0 in women with HR+/HER2+ breast cancer treated with NST was significantly higher following NET+aHER2 than after NET.