What Is the Risk of Recurrence in HER2-Positive Breast Cancer?

Two trials and 3000 patients with HER2-positive breast cancer were analyzed for recurrence risk 5 to 10 years after diagnosis.

A combined analysis of 2 trials totaling more than 3000 patients found a generally low risk of recurrence (RoR) in years 5 to 10 after HER2-positive breast cancer diagnosis. Hormone receptor (HR)-positive disease was associated with improved recurrence-free survival (RFS).

“Unlike HR-positive HER2-negative breast cancer, the risk of late relapses in patients with HR-positive, HER2-positive disease remains unknown,” wrote study authors led by Saranya Chumsri, MD, of the Mayo Clinic in Jacksonville, Florida. “Currently, there are limited data available regarding the risk of late recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab-based chemotherapy.”

The authors analyzed results from 3177 patients with HER2-positive breast cancer treated with adjuvant chemotherapy with or without trastuzumab (Herceptin); they were included in the North Central Cancer Treatment Group N9831 and National Surgical Adjuvant Breast and Bowel Project B-31 trials. Results were published online ahead of print on October 17 in the Journal of Clinical Oncology.

The mean age in the cohort was 49.5 years, and the median time to recurrence or death was 2.5 years; for patients without an event, the median follow-up time was 8.0 years. A total of 54.5% of patients had HR-positive disease, and 48.0% of all patients were treated with adjuvant trastuzumab-based chemotherapy.

Patients who had HR-positive disease significantly better recurrence-free survival at 10 years, at 73.84% compared with 69.22% in HR-negative patients (P < 0.001). A similar benefit of trastuzumab was observed in HR-positive and negative patients, however.

Among those treated with trastuzumab, the cumulative hazard for RFS among HR-positive patients during the first five years was 10.96%, compared with 17.48% for HR-negative patients, for a hazard ratio (HR) of 0.60 (95% CI, 0.45-0.79; P < 0.001). The difference based on HR status disappeared, however, in years 5 to 10, with an HR of 1.32 (95% CI, 0.93-1.88; P = 0.12).   

The overall RoR was low in years 5 to 10. Among patients with no lymph node involvement, the RoR in those years was 3.23%; among those with involvement of 1 to 3 lymph nodes, the RoR was 6.39%.

“Overall, our analysis demonstrated persistent benefit of adjuvant trastuzumab in the long term,” the authors wrote. They noted that the lack of longer follow-up does limit the results’ interpretation. “Given concerning adverse effects and potentially less benefit of extended adjuvant endocrine therapy, particularly in patients with N0 or N1 disease, our findings highlight the need to develop better risk-prediction models and biomarkers to identify which patients have sufficient risk for late relapse to warrant the use of extended endocrine therapy in HER2-positive breast cancer.”


Incidence of Late Relapses in Patients With HER2-Positive Breast Cancer Receiving Adjuvant Trastuzumab: Combined Analysis of NCCTG N9831 (Alliance) and NRG Oncology/NSABP B-31 | Journal of Clinical Oncology. https://ascopubs.org/doi/full/10.1200/JCO.19.00443