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Breast cancer, early stage

4827 - Adjuvant anti-HER2 therapy, treatment-induced amenorrhea (TIA) and survival in premenopausal patients (pts) with HER2-positive (HER2+) early breast cancer (EBC): analysis from the ALTTO trial (BIG 2-06)


09 Sep 2017


Breast cancer, early stage


Cytotoxic Therapy;  Breast Cancer


Matteo Lambertini


Annals of Oncology (2017) 28 (suppl_5): v43-v67. 10.1093/annonc/mdx362


M. Lambertini1, C. Campbell2, J. Bines3, L. Korde4, M.A. Izquierdo Delso5, D. Fumagalli6, K. Pritchard7, A. Wolff8, C. Jackisch9, I. Lang10, M. Untch11, I. Smith12, F.M. Boyle13, B. Xu14, C.H. Barrios15, J. Baselga16, A. Moreno-Aspitia17, M. Piccart18, R. Gelber19, E. De Azambuja20

Author affiliations

  • 1 Breast Cancer Translational Research Laboratory, Institute Jules Bordet, 1000 - Brussels/BE
  • 2 Statistics, Frontier Science, Kingussie/GB
  • 3 Oncology, INCA - Instituto Nacional de Cancer, 20231-050 - Rio de Janeiro/BR
  • 4 Breast Cancer Therapeutics, National Cancer Institute, Bethesda/US
  • 5 Oncology, Novartis, 4002 - Basel/CH
  • 6 Breast International Group, Breast International Group, Brussels/BE
  • 7 Ncic Clinical Trials Group, Sunnybrook Odette Cancer Center, Sunnybrook HSC, M4N 3M5 - Toronto/CA
  • 8 Johns Hopkins School Of Medicine, Johns Hopkins University, 21231 - Baltimore/US
  • 9 Obstetrics And Gynecology, Sana Clinic Offenbach, Offenbach/DE
  • 10 Oncology, National Institute of Oncology Hungary, 1122 - Budapest/HU
  • 11 Multidisciplinary Breast Cancer Center, Helios Klinikum Berlin Buch, 13125 - Berlin/DE
  • 12 Breast Unit, Royal Marsden Hospital NHS Foundation Trust, SW3 6JJ - London/GB
  • 13 Medicine, University of Sydney, Sydney/AU
  • 14 Chinese Academy Of Medical Sciences, Cancer Hospital, 100021 - Beijing/CN
  • 15 Department Of Medicine, PUCRS School of Medicine, Porto Alegre/BR
  • 16 Oncology, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 17 Oncology, Mayo Clinic, Jacksonville/US
  • 18 Medical Oncology, Institute Jules Bordet, 1000 - Brussels/BE
  • 19 Biostatistics And Computational Biology, Dana-Farber Cancer Institute, 2215 - Boston/US
  • 20 Department Of Medicine, Institute Jules Bordet, 1000 - Brussels/BE


Abstract 4827


In premenopausal pts with HER2+ EBC, the prognostic effect of TIA is unknown and the gonadotoxicity of trastuzumab (T) and lapatinib (L) remains largely uncertain. We aimed to assess the prognostic effect of TIA and the impact of T and/or L on the risk of developing TIA in premenopausal pts with HER2+ EBC.


ALTTO was an international, open-label, randomised phase 3 trial in pts with HER2+ EBC. Pts were randomised in 4 adjuvant anti-HER2 arms: T alone, L alone, a sequence of the 2 agents (T->L) and their combination (T+L). As per study protocol, menopausal status was collected in all pts at randomisation and at week 37. By selecting only premenopausal pts at randomisation, we investigated whether TIA in pts with hormone receptor-positive (HR+) and negative (HR-) EBC would impact on disease-free (DFS) and overall survival (OS), and the risk factors for developing TIA. Landmark and time-dependent modeling were used to account for guaranteed time bias.


Out of 8381 pts randomised in ALTTO, 2862 were included in this analysis. Median age was 43 years (range 38-47); 1679 (59%) pts had HR+ EBC. Pts with HR+/HER2+ EBC who experienced TIA had significant better DFS (hazard ratio [HR] 0.64; 95% confidence intervals [CI] 0.52-0.79) and OS (HR 0.53; 95% CI 0.38-0.74) than those who did not have TIA. By contrast, pts with HR-/HER2+ EBC had similar DFS (HR 0.85; 95% CI 0.68-1.07) and OS (HR 0.89; 95% CI 0.64-1.25) regardless of whether they had TIA (interaction P for DFS=0.009 and for OS = 0.002). A similar TIA rate was observed in the T (72.6%), L (74.0%), T->L (72.1%) and 74.8% (T+L) arms (p = 0.644). Older age (p 


In premenopausal pts with HR+/HER2+ EBC, TIA was associated with significant survival benefits. Anti-HER2 agents did not impact the likelihood of developing TIA. These data are of great importance in oncofertility counseling and support the use of ovarian suppression as part of adjuvant endocrine therapy in premenopausal HR+/HER2+ EBC pts.

Clinical trial identification

The trial is registered with the clinicaltrial.gov identifier, number NCT00490139.

Legal entity responsible for the study

Novartis Pharma AG, Basel, Switzerland


Novartis Pharma AG and the National Cancer Institut of the National Institutes of Health.


E. De Azambuja: Honoraria from Roche. Travel grants from Roche and GlaxoSmithKline outside the submitted work.


All other authors have declared no conflicts of interest.


E. De Azambuja: Honoraria from Roche. Travel grants from Roche and GlaxoSmithKline outside the submitted work.

All other authors have declared no conflicts of interest.

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