Endocrine Therapy Plus Anti-HER2 Therapy as Adjuvant Systemic Therapy for Luminal HER2-Positive Breast Cancer: An Analysis of the National Cancer Database.

Background: Guidelines regarding the usage of adjuvant systemic therapy in patients with small human epidermal growth factor receptor 2 (HER2)-positive and estrogen receptor/progesterone receptor-positive (luminal HER2 positive) tumors are nonspecific. Outcomes of chemotherapy followed by endocrine therapy (ET), with or without anti-HER2 therapy, vs ET alone (no chemotherapy) have not been widely studied in this disease subtype. We sought to examine the usage and outcomes of adjuvant systemic therapy (ET vs chemotherapy with or without trastuzumab) in stage I luminal HER2-positive breast cancer (BC), based on the large National Cancer Database.

Methods: We conducted a retrospective analysis of patients with luminal HER2-positive stage I BC, diagnosed between 2010 and 2015, in the United States, using univariable and multivariable logistic regression analyses. The Kaplan-Meier method estimated overall survival (OS).

Results: A total of 37 777 patients were included in the analysis; of these, n = 32 594 (86%) received adjuvant ET and n = 5183 (14%) received chemotherapy. Around 40% of all patients received anti-HER2 therapy (trastuzumab). Patients who received trastuzumab had a better 5-year OS (93.4% vs 92.0%, P = .0002) compared with those who did not. Patients who received anti-HER2 therapy plus ET had the best OS rate at 5 years (93.5%, confidence interval [CI]: 89.2%-98%, P < .0001) compared with those receiving anti-HER2 therapy plus chemotherapy (92.7%, CI: 89.4%-96.1%, P < .0001).

Conclusions: Most patients in the United States, with stage I luminal HER2 positive BC, received ET, not chemotherapy but most of them do not receive anti-HER2 therapy resulting in inferior outcome. Future trials exploring the de-escalation of systemic adjuvant therapy for early-stage luminal HER2-positive BC to ET plus anti-HER2 therapy would be desirable.