Journal of the National Cancer Institute Advance Access originally published online on March 25, 2008
JNCI Journal of the National Cancer Institute 2008 100(7):475-482; doi:10.1093/jnci/djn058
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© The Author 2008. Published by Oxford University Press.
ARTICLES |
Increased Risk of Recurrence After Hormone Replacement Therapy in Breast Cancer Survivors
On behalf of the HABITS Study Group
Affiliations of authors: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden (LH, M. Holmqvist); Regional Oncologic Center, Uppsala, Sweden (LH, M. Holmqvist); King’s College London, School of Medicine, Division of Cancer Studies, London, UK (LH); Department of Obstetrics and Gynecology, University Hospital and Institute of Clinical Medicine, Bergen University, Bergen, Norway (OEI); International Breast Cancer Study Group Coordination Center, Bern, Switzerland (CMR); Division of Obstetrics and Gynecology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping, Sweden (M. Hammar); Department of Oncology and Radiotherapy, Kuopio University Hospital, Kuopio, Finland (EK); Departments of Oncology and Radiotherapy (J. Jassem) and Plastic and Reconstruction Surgery (J. Jaskiewicz, DD), Medical University of Gdansk, Gdansk, Poland; Department of Surgery, St Olavs University Hospital, Trondheim, Norway (HEF); Chilean Oncology Research Cooperative Group, Santiago, Chile (OP, RA); Karolinska Institute, Stockholm, Sweden (RA); Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland (JM)
Correspondence to: Lars Holmberg, MD, PhD, King's College London, School of Medicine, Division of Cancer Studies, 3rd Floor, Bermondsey Wing, Guy's Hospital, London SE1 9RT, UK (e-mail: lars.holmberg{at}kcl.ac.uk).
Background: Hormone replacement therapy (HT) is known to increase the risk of breast cancer in healthy women, but its effect on breast cancer risk in breast cancer survivors is less clear. The randomized HABITS study, which compared HT for menopausal symptoms with best management without hormones among women with previously treated breast cancer, was stopped early due to suspicions of an increased risk of new breast cancer events following HT. We present results after extended follow-up.
Methods: HABITS was a randomized, non–placebo-controlled noninferiority trial that aimed to be at a power of 80% to detect a 36% increase in the hazard ratio (HR) for a new breast cancer event following HT. Cox models were used to estimate relative risks of a breast cancer event, the maximum likelihood method was used to calculate 95% confidence intervals (CIs), and 
2 tests were used to assess statistical significance, with all P values based on two-sided tests. The absolute risk of a new breast cancer event was estimated with the cumulative incidence function. Most patients who received HT were prescribed continuous combined or sequential estradiol hemihydrate and norethisterone.
Results: Of the 447 women randomly assigned, 442 could be followed for a median of 4 years. Thirty-nine of the 221 women in the HT arm and 17 of the 221 women in the control arm experienced a new breast cancer event (HR = 2.4, 95% CI = 1.3 to 4.2). Cumulative incidences at 5 years were 22.2% in the HT arm and 8.0% in the control arm. By the end of follow-up, six women in the HT arm had died of breast cancer and six were alive with distant metastases. In the control arm, five women had died of breast cancer and four had metastatic breast cancer (P = .51, log-rank test).
Conclusion: After extended follow-up, there was a clinically and statistically significant increased risk of a new breast cancer event in survivors who took HT.
| CONTEXT AND CAVEATS Prior knowledge The HABITS trial, on the effect of hormone replacement therapy (HT) on breast cancer risk among breast cancer survivors, was stopped in December 2003 after two large studies reported that HT increases risk of breast cancer among healthy women. In 2004, preliminary results from a median follow-up of 2 years were reported. Study design HABITS was a randomized, open-label noninferiority trial in which 447 Scandinavian women were randomly assigned to either HT (most often, to continuous combined or sequential estradiol hemihydrate and norethisterone) or to best symptomatic treatment without hormones. Contribution A total of 442 women could be followed for a median of 4 years. Women in the HT arm experienced new breast cancer events more than twice as often as women in the control arm (39 out of 221 vs 17 out of 221; hazard ratio = 2.4, 95% confidence interval = 1.3 to 4.2). The cumulative incidence of a new breast cancer event at 5 years was estimated at 22.2% for the HT arm and at 8.0% for the control arm. Implications Clinicians and their patients should weigh the benefits of use of HT for postmenopausal symptoms with the increased risk for new breast cancer events. Limitations The time at which the trial was terminated, certain characteristics of the patient population, and the types of HT used each could influence the degree to which use of HT increases breast cancer risk. The study was not placebo controlled, and some judgments about disease recurrence can be subjective.
|
Manuscript received September 19, 2007; revised January 25, 2008; accepted February 7, 2008.
Editorial about this Article
Related Article in JNCI
CiteULike 
Connotea 
Del.icio.us What's this?
J Natl Cancer Inst 2008 100: 451-452.
J Natl Cancer Inst 2008 100: 447.
This article has been cited by other articles:
|
|
 |
|
  M. Hickey, M. Peate, C.M. Saunders, and M. Friedlander Breast cancer in young women and its impact on reproductive function Hum. Reprod. Update, May 1, 2009; 15(3): 323 - 339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. T. Chlebowski and R. L. Prentice Menopausal Hormone Therapy in BRCA1 Mutation Carriers: Uncertainty and Caution J Natl Cancer Inst, October 1, 2008; 100(19): 1341 - 1343. [Full Text] [PDF]
|
|
|
|
|
|
N. S. Weiss Re: Should Observational Studies Be a Thing of the Past? J Natl Cancer Inst, August 6, 2008; 100(15): 1117 - 1117. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Brown HABITS trial results confirmed in two-year follow-up Menopause Int, June 1, 2008; 14(2): 48 - 51. [Full Text] [PDF]
|
|
|
|
 |
|
 Questions Remain About Hormone Therapy and Risk for Breast Cancer Recurrence Journal Watch Women's Health, May 8, 2008; 2008(508): 3 - 3. [Full Text]
|
|
|
|
 |
|
 Hormone Therapy in Breast Cancer Survivors Journal Watch (General), April 24, 2008; 2008(424): 2 - 2. [Full Text]
|
|
|
|
|
|
K. I. Pritchard Should Observational Studies Be a Thing of the Past? J Natl Cancer Inst, April 2, 2008; 100(7): 451 - 452. [Full Text] [PDF]
|
|