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HABITS (Hormonal Replacement Therapy After Breast Cancer - is It Safe?), a Randomized Comparison: Trial Stopped

Posted on: Thursday, 17 February 2005, 03:00 CST

Objective:

To determine in a non-blinded, randomized clinical trial with prospective follow-up, whether breast cancer survivors develop significantly more breast cancer events on hormone replacement therapy (HRT) compared with patients who try the best non-HRT therapy.

Introduction:

Following breast cancer treatment, menopausal symptoms can reduce quality of life significantly. Anecdotal evidence, case-control studies and other non-randomized reports have suggested that HRT does not adversely affect breast cancer prognosis.

Methods:

From May 1997 through to September 2003, breast cancer survivors (Stage 0-II) with menopausal symptoms deemed to require treatment, as assessed by both the patient and her physician, were randomized to 2 years of HRT (n= 219) or the best symptomatic treatment without HRT (n = 215). All subjects were free from disease as well as significant cardiovascular or other co-morbidities. No specific HRT was preferred for the 2-year period; clinical judgment and 'local practice' guided physician choice of HRT.

Results:

* All analyzes were performed by intention-to-treat.

* The mean age of enrolled patients in each arm was 55 years.

* Twenty-one per cent of patients in each group were on adjuvant tamoxifen.

* At a median follow-up of 2.1 years, for all women, the relative hazards (RH) risk for a new breast cancer event in the HRT group was 3.5 compared to the non-HRT group.

* Among hormone receptor-positive and receptor-negative patients, the RH was 4.8 and 1.8, respectively.

* A total of 11 women in the HRT group (vs. two women in the non- HRT group) developed local recurrences, Ave (vs. one) developed contralateral cancers, and 10 (vs. five) developed distant metastasis.

* There were five deaths in the HRT group (three were due to breast cancer) and four breast cancer deaths in the non-HRT group.

* In 2002, a similar clinical trial, the Stockholm trial, agreed to pool safety and data analyzes with the HABITS trial. At this time the HABITS trial was stopped, RH for the Stockholm trial was 0.82. No other data for the latter trial were reported.

Conclusions:

The steering committee of the HABITS trial terminated the study because the data demonstrated a high-risk of adverse events attributable to HRT for menopausal symptom relief among breast cancer survivors. Continued 5-year follow-up results are forthcoming. Women being treated for breast cancer that are on HRT should not continue with the HRT.

Commentary:

The pendulum with regard to the risk-benefit profile of HRT is swinging.

Contrary to the conventional wisdom of the 199Os, the Women's Health Initiative Trial definitively demonstrated that, among postmenopausal women, the risks of HRT (increased risk of breast cancer, coronary artery disease, dementia and stroke) outweighed the benefits (relief of climateric symptoms, improved bone density). Limitations to this thought-provoking study include the non-blinded nature of the study design, lack of long-term time frame, lack of difference in overall survival data, lack of quality of life data and lack of sufficient power to perform meaningful subset analyzes (e.g. nodal status and stage of breast cancer). Nonetheless, the results of the HABITS trial represent the highest level of evidence- based data on the subject of HRT for breast cancer survivors. The results are congruent with experimental evidence that hormonal therapy enhances breast cancer cell growth and contributes to a growing body of evidence that helps guide our clinical decision- making.

Selected references:

Col NF, Hirota LK, Orr RK, et al. Hormone replacement therapy after breast cancer: a systematic review and quantitative assessment of risk. J Clin Oncol 2001;19:2357-63

O'Meara ES, Rossing MA, Daling JR, et al. Hormone replacement therapy after a diagnosis of breast cancer in relation to recurrence and mortality. J Nad Cancer Inst 2001;93:754-62

Chlebowski Hendrix SL, Langer RD, et al, for the WHI investigators. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women. JAMA 2003;289:2343- 53

Peters GN, Fodera T, Sabol et al. Estrogen replacement therapy after breast cancer: a 12-year follow-up. Ann Surg Oncoi 2001;8:828- 32

Loprinzi CL, Barton DL, Rhodes Management of hot flashes in breast cancer survivors. Lancet Oncoi 2001;2:199-204

Holmberg L, Anderson H, for the HABITS steering and data monitoring committees. Lancet 2004;363:453-5

Commentary by: Celia Chao, MD, Norton Healthcare Pavilion, Louisville, KY, USA

Copyright CRC Press Sep 2004

Source: Women's Oncology Review

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