Dissecting the effect of hormone receptor status in patients with HER2-positive early breast cancer: exploratory analysis from the ALTTO (BIG 2-06) randomized clinical trial

Matteo Lambertini, Christine Campbell, Richard D. Gelber, Giuseppe Viale, Ann McCullough, Florentine Hilbers, Larissa A. Korde, Olena Werner, Saranya Chumsri, Christian Jackisch, Antonio C Wolff, Ines Vaz-Luis, Arlindo R. Ferreira, Aleix Prat, Alvaro Moreno-Aspitia, Martine Piccart, Sherene Loi, Evandro de Azambuja

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Abstract

Purpose: Limited evidence exists on the impact of hormone receptor (HR) status to counsel HER2-positive early breast cancer patients receiving adjuvant anti-HER2 therapy. Methods: ALTTO (BIG 2-06) was an international, intergroup, open-label, randomized phase III trial in HER2-positive early breast cancer patients randomized to receive 1 year of trastuzumab and/or lapatinib. HER2, estrogen and progesterone receptors were centrally tested for all patients. We investigated the impact of HR status on prognosis, risk of disease-free survival (DFS) events over time, patterns of first DFS events, and factors associated with risk of DFS events overall, in years 0–5 and 6–8. Results: Out of 6273 patients included in this analysis, 3603 (57.4%) had HR-positive tumors. Median follow-up was 6.93 years. Five-year and 8-year DFS were 86% and 80% in patients with HR-positive disease, and 83% and 79% in those with HR-negative tumors, respectively. Mean annual hazards of recurrence in years 0–5 were 3% in patients with HR-positive disease and 4% in those with HR-negative tumors, while in years 6–8 they were 3% and 2%, respectively. Distribution of first DFS event in years 6–8 (P = 0.005) and type of first distant recurrence (P < 0.001) were significantly different between the two groups. Risk factors for DFS events overall, in years 0–5, and 6–8 were different in patients with HR-positive and HR-negative tumors. Conclusions: HER2-positive early breast cancer is characterized by the presence of two diseases with distinct natural history based on HR status requiring the development of different follow-up strategies and future de-escalation and escalation clinical trials.

Original languageEnglish (US)
Pages (from-to)103-114
Number of pages12
JournalBreast Cancer Research and Treatment
Volume177
Issue number1
DOIs
StatePublished - Aug 30 2019

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Keywords

  • Breast cancer
  • Estrogen receptor
  • HER2
  • Progesterone receptor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Lambertini, M., Campbell, C., Gelber, R. D., Viale, G., McCullough, A., Hilbers, F., Korde, L. A., Werner, O., Chumsri, S., Jackisch, C., Wolff, A. C., Vaz-Luis, I., Ferreira, A. R., Prat, A., Moreno-Aspitia, A., Piccart, M., Loi, S., & de Azambuja, E. (2019). Dissecting the effect of hormone receptor status in patients with HER2-positive early breast cancer: exploratory analysis from the ALTTO (BIG 2-06) randomized clinical trial. Breast Cancer Research and Treatment, 177(1), 103-114. https://doi.org/10.1007/s10549-019-05284-y