Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2019 Jan 1;111(1):86-94.
doi: 10.1093/jnci/djy094.

Adjuvant Anti-HER2 Therapy, Treatment-Related Amenorrhea, and Survival in Premenopausal HER2-Positive Early Breast Cancer Patients

Matteo Lambertini  1 , Christine Campbell  2 , José Bines, Larissa A Korde  3 , Miguel Izquierdo  4 , Debora Fumagalli  5 , Lucia Del Mastro  6 , Michail Ignatiadis  1 , Kathleen Pritchard  7 , Antonio C Wolff  8 , Christian Jackisch  9 , Istvan Lang  10 , Michael Untch  11 , Ian Smith  12 , Frances Boyle  13 , Binghe Xu  14 , Carlos H Barrios  15 , José Baselga  16   17 , Alvaro Moreno-Aspitia  18 , Martine Piccart  1 , Richard D Gelber  19 , Evandro de Azambuja  1
Affiliations
Clinical Trial

Adjuvant Anti-HER2 Therapy, Treatment-Related Amenorrhea, and Survival in Premenopausal HER2-Positive Early Breast Cancer Patients

Matteo Lambertini et al. J Natl Cancer Inst. .

Erratum in

  • Corrigendum.
    [No authors listed] [No authors listed] J Natl Cancer Inst. 2019 Nov 1;111(11):1237. doi: 10.1093/jnci/djy197. J Natl Cancer Inst. 2019. PMID: 30329078 Free PMC article. No abstract available.

Abstract

Background: In premenopausal patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, the gonadotoxicity of trastuzumab and lapatinib remains largely uncertain, and the prognostic effect of treatment-related amenorrhea (TRA) is unknown.

Methods: In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (BIG 2-06) phase III trial, HER2-positive early breast cancer patients were randomized (1:1:1:1) to receive one year of trastuzumab, lapatinib, their sequence, or their combination. As per study protocol, menopausal status was collected in all patients at random assignment and at week 37 visit. We investigated TRA rates and whether TRA in patients with hormone receptor-positive and -negative tumors would impact disease-free survival (DFS) and overall survival (OS). Landmark and time-dependent modeling were used to account for guarantee-time bias. All statistical tests were two-sided.

Results: A total of 2862 premenopausal women were included, of whom 1679 (58.7%) had hormone receptor-positive disease. Median age was 43 (interquartile range = 38-47) years. Similar TRA rates were observed in the trastuzumab (72.6%), lapatinib (74.0%), trastuzumab→lapatinib (72.1%), and trastuzumab+lapatinib (74.8%) arms (P = .64). The association between TRA and survival outcomes differed according to hormone-receptor status (Pinteraction for DFS = .007; Pinteraction for OS = .003). For hormone receptor-positive patients, the TRA cohort had statistically significantly better DFS (adjusted hazard ratio [aHR] = 0.58, 95% confidence interval [CI] = 0.45 to 0.76) and OS (aHR = 0.63, 95% CI = 0.40 to 0.99) than the no TRA cohort. No difference was observed in hormone receptor-negative patients.

Conclusions: In this unplanned analysis, no association between TRA rate and type of anti-HER2 treatment was observed. TRA was associated with statistically significant survival benefits in premenopausal hormone receptor-positive/HER2-positive early breast cancer patients.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
CONSORT flow diagram. *Patients who underwent hysterectomy and/or bilateral oophorectomy before their week 37 visit. ALTTO = Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization; DFS = disease-free survival; GnRHa = gonadotropin releasing hormone agonist; ITT = intention-to-treat; OS = overall survival; TRA = treatment-related amenorrhea.
Figure 2.
Figure 2.
Disease-free survival in patients with hormone receptor–positive (A) and hormone receptor–negative (B) disease. Conditional landmark analysis (40-week landmark), Kaplan-Meier curves are shown; time (in years) is from randomization and the numbers of patients at risk in each group at various time points are shown below the graphs. CI = confidence interval; DFS = disease-free survival; HR = hazard ratio; TRA = treatment-related amenorrhea.
Figure 3.
Figure 3.
Overall survival in patients with hormone receptor–positive (A) and hormone receptor–negative (B) disease. Conditional landmark analysis (40-week landmark), Kaplan-Meier curves are shown; time (in years) is from randomization and the numbers of patients at risk in each group at various time points are shown below the graphs. CI = confidence interval; HR = hazard ratio; OS = overall survival; TRA = treatment-related amenorrhea.
See this image and copyright information in PMC

Comment in

References

    1. Siegel RL, Miller KD, Jemal A.. Cancer Statistics, 2018. CA Cancer J Clin. 2018;681:7–30. - PubMed
    1. Azim HA, Partridge AH.. Biology of breast cancer in young women. Breast Cancer Res. 2014;164:427. - PMC - PubMed
    1. Denduluri N, Somerfield MR, Eisen A, et al. Selection of optimal adjuvant chemotherapy regimens for human epidermal growth factor receptor 2 (HER2)-negative and adjuvant targeted therapy for HER2-positive breast cancers: An American Society of Clinical Oncology guideline adaptation of the Cancer Care Ontario Clinical Practice Guideline. J Clin Oncol. 2016;3420:2416–2427. - PubMed
    1. Curigliano G, Burstein HJ, Winer PE, et al. De-escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;288:1700–1712. - PMC - PubMed
    1. Ganz PA, Land SR, Geyer CE Jr, et al. Menstrual history and quality-of-life outcomes in women with node-positive breast cancer treated with adjuvant therapy on the NSABP B-30 trial. J Clin Oncol. 2011;299:1110–1116. - PMC - PubMed

Publication types

MeSH terms