Effect of HER2 status on distant recurrence in early stage breast cancer

Abstract

It has long been recognized in breast cancer that the effect of hormone receptor (HR) status on recurrence rates varies over time and with the site of recurrence. However, there is relatively little in the literature on the effect of human epidermal growth factor receptor 2 (HER2) on recurrence patterns. We wanted to assess whether the effect of HER2 status on the risk of distant recurrence changed over time and/or with HR status and whether these relationships varied with site of recurrence. We retrospectively studied 11,011 women diagnosed with stage I, II, or III breast cancer after 1997 who had data on HR status and HER2 status. 20 % were HR negative and HER2 negative (so-called "triple-negatives"), 7 % were HR negative and HER2 positive, 64 % were HR positive and HER2 negative, and 10 % were HR positive and HER2 positive. The estimated overall cumulative incidence of developing distant metastases is 20 % at 4 years, 30 % at 8 years, and 36 % at 12 years. The 12-year cumulative incidence was 23 % for bone, 16 % for liver, 14 % for lung, 13 % for distant lymph node, 10 % for brain, and 8 % for pleura. After adjusting for potential confounding factors, the nature of the effect of HER2 on recurrence rates was found to differ markedly across the sites of recurrence. For brain and pleura recurrences, the effect of HER2 depended on HR status in ways that significantly changed over time. For bone recurrences, the effect of HER2 did not depend on HR status, but did change significantly over time. For liver and distant lymph node recurrences, there was a significant effect of HER2 status that did not change with time or HR status. For lung recurrences, rates did not significantly vary with HER2 status.

Figure 1

Cumulative incidence curve estimates by HR/HER2 subgroup and site of recurrence

Figure 2

Adjusted competing risk model log hazard ratio function (LHRF) estimates for HER2 status (positive vs. negative) according to HR status, year since diagnosis, and site of recurrence. Red curves are for HR negative patients and green curves are for HR positive patients. Solid lines are point estimates and dashed lines are corresponding 95% confidence intervals.