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. 2015 Apr 16;17(1):56.
doi: 10.1186/s13058-015-0568-1.

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

Kathrin Strasser-Weippl  1 , Nora Horick  2 , Ian E Smith  3 , Joyce O'Shaughnessy  4 , Bent Ejlertsen  5 , Frances Boyle  6 , Aman U Buzdar  7 , Pierre Fumoleau  8 , William Gradishar  9 , Miguel Martin  10 , Beverly Moy  11 , Martine Piccart-Gebhart  12 , Kathleen I Pritchard  13 , Deborah Lindquist  14 , Erica Rappold  15 , Dianne M Finkelstein  16 , Paul E Goss  17
Affiliations

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

Kathrin Strasser-Weippl et al. Breast Cancer Res. .

Abstract

Introduction: Worldwide, many patients with HER2+ (human epidermal growth factor receptor 2-positive) 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.

Methods: 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.

Results: 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 to 5 in HER2+ HR- compared to HER2+ HR+ patients, with a mean risk of recurrence of 9%/year for HR- versus 5%/year in HR+ patients (hazard ratio 0.59, P=0.002 for years 1 to 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 to 10 (hazard ratio 0.97, P=0.92 for years 6 to 10).

Conclusions: 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.

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Figures

Figure 1
Figure 1
Annual hazard of disease recurrence in centrally confirmed HER2+ placebo patients in TEACH. HER2+, human epidermal growth factor receptor 2 positive; TEACH, Tykerb evaluation after chemotherapy.
Figure 2
Figure 2
Annual hazards and time-dependent hazard ratio for disease recurrence in centrally confirmed HER2+ patients by HR status. (a) Annual hazard of disease recurrence in centrally confirmed HER2+ placebo patients in TEACH, according to HR status (95% confidence limits at 2-year intervals). (HR+ = ER+ and/or PR+; HR- = ER- and PR-). (b) Hazard ratio for disease recurrence in centrally confirmed HER2+ placebo patients in TEACH, comparing HR+ versus HR-. (HR+ = ER+ and/or PR+; HR- = ER- and PR-). ER-, estrogen receptor negative; ER+, estrogen receptor positive; HER2+, human epidermal growth factor receptor 2 positive; HR-, hormone receptor negative; HR+, hormone receptor positive; PR-, progesterone receptor negative; PR+, progesterone receptor positive; TEACH, Tykerb evaluation after chemotherapy.
Figure 3
Figure 3
Univariable hazard ratios for risk of disease recurrence by prognostic factors in centrally confirmed HER2+ placebo patients in TEACH. HER2+, human epidermal growth factor receptor 2 positive; TEACH, Tykerb evaluation after chemotherapy.
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