Long-term hazard of recurrence in HER2+ breast cancer patients untreated with anti-HER2 therapy

Kathrin Strasser-Weippl, Nora Horick, Ian E Smith, Joyce O’Shaughnessy, Bent Ejlertsen, Frances Boyle, Aman U Buzdar, Pierre Fumoleau, William Gradishar, Miguel Martin, Beverly Moy, Martine Piccart-Gebhart, Kathleen I Pritchard, Deborah Lindquist, Erica Rappold, Dianne M Finkelstein, Paul E Goss

Worldwide, many patients with HER2+ (human epidermal growth factor receptor 2) early breast cancer (BC) do not receive adjuvant trastuzumab. Hazards of recurrence of these patients with respect to hormone receptor status of the primary tumor have not been described. Using data from 1,260 patients randomized to placebo in the adjuvant TEACH trial, we report 10-year annual hazards of recurrence in HER2+ patients not treated with anti-HER2 therapy. Disease-free survival (DFS) was 75% after 5 and 61% after 10 years, respectively. Patients with HER2+ hormone receptor positive (HR+ (hormone receptor positive); ER+ (estrogen receptor positive) or PR+ (progesterone receptor positive)) disease had a significantly better DFS than patients with HER2 + HR- (ER-/PR-) disease (hazard ratio 0.72, P = 0.02). This difference was explainable by a significantly higher hazard of recurrence in years 1-5 in HER2 + HR- compared to HER2 + HR+ patients, with a mean risk of recurrence of 9%/year for HR- versus 5%/years in HR+ patients (hazard ratio 0.59, P = 0.002 for years 1-5). The high early risk of recurrence of HER2 + HR- patients declined sharply over time, so that it was similar to that seen in HER2 + HR+ patients in years 6-10 (hazard ratio 0.97, P = 0.92 for years 6-10). Our results show that outcomes in HER2+ patients with early BC not receiving anti-HER2 therapy strongly depend on HR expression. The very high early risk of relapse seen in HER2 + HR- patients is particularly relevant in health care settings with limited access to adjuvant anti-HER2 treatment. The event rates shown for subpopulations of HER2+ BC patients suggest that in resource-constrained environments patients with HER2 + HR- early BC should be prioritized for consideration of adjuvant anti-HER2 therapy.