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

M. Lambertini, C. Campbell, R.D. Gelber, G. Viale, A. McCullough, F. Hilbers, L.A. Korde, O. Werner, S. Chumsri, C. Jackisch, A.C. Wolff, I. Vaz-Luis, A.R. Ferreira, A. Prat, A. Moreno-Aspitia, M. Piccart, S. Loi, E. de Azambuja

Research output: Contribution to journalArticle

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. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Original languageEnglish
Pages (from-to)103-114
Number of pages12
JournalBreast Cancer Res. Treat.
Volume177
Issue number1
DOIs
Publication statusPublished - 2019

    Fingerprint

Keywords

  • Breast cancer
  • Estrogen receptor
  • HER2
  • Progesterone receptor
  • anthracycline
  • carboplatin
  • docetaxel
  • estrogen receptor
  • lapatinib
  • progesterone receptor
  • taxane derivative
  • trastuzumab
  • antineoplastic agent
  • epidermal growth factor receptor 2
  • adjuvant chemotherapy
  • adjuvant therapy
  • adult
  • aged
  • Article
  • bone metastasis
  • brain metastasis
  • cancer chemotherapy
  • cancer combination chemotherapy
  • cancer grading
  • cancer incidence
  • cancer patient
  • cancer prognosis
  • cancer recurrence
  • cancer risk
  • cancer survival
  • controlled study
  • disease association
  • disease free survival
  • distant disease free survival
  • drug efficacy
  • early cancer
  • ethnicity
  • exploratory factor analysis
  • false negative result
  • false positive result
  • follow up
  • human
  • human epidermal growth factor receptor 2 positive breast cancer
  • human tissue
  • liver metastasis
  • major clinical study
  • monotherapy
  • multicenter study (topic)
  • multiple cycle treatment
  • overall survival
  • phase 3 clinical trial (topic)
  • predictive value
  • priority journal
  • randomized controlled trial (topic)
  • survival rate
  • survival time
  • symptom
  • treatment duration
  • tumor volume
  • visceral metastasis
  • breast tumor
  • clinical trial
  • female
  • metabolism
  • molecularly targeted therapy
  • mortality
  • phase 3 clinical trial
  • proportional hazards model
  • randomized controlled trial
  • treatment outcome
  • Antineoplastic Combined Chemotherapy Protocols
  • Breast Neoplasms
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Female
  • Humans
  • Molecular Targeted Therapy
  • Proportional Hazards Models
  • Receptor, ErbB-2
  • Receptors, Progesterone
  • Treatment Outcome

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. Breast Cancer Res. Treat., 177(1), 103-114. https://doi.org/10.1007/s10549-019-05284-y