Breast Cancer Incidence and HRT in Canada

Abstract and Introduction

Abstract

Background In 2002, results of the Women's Health Initiative clinical trial indicated that the long-term risks of combined estrogen and progestin hormone replacement therapy outweighed the health benefits for postmenopausal women. The resulting decline in use of hormone replacement therapy was followed by concurrent decreases in breast cancer incidence in several countries. The aim of the current study was to determine whether similar declines occurred in Canada.
Methods Data on prescriptions for hormone therapy were obtained from a national registry of pharmacy-filled prescriptions to confirm the reported trend in use of hormone replacement therapy among approximately 1200 women aged 50–69 years who participated in the National Population Health Survey between 1996 and 2006 and whose data were extrapolated to the Canadian female population. Age-standardized incidence rates for breast cancer were obtained from the population-based Canadian Cancer Registry for the same period, and mammography rates were obtained from the Canadian Community Health Survey. Joinpoint regression was used to examine changes in trends in the use of hormone replacement therapy and breast cancer incidence.
Results A reduced frequency of use of hormone replacement therapy was reflected in the decrease in dispensed hormone therapy prescriptions after 2002. The largest drop in use of combined hormone replacement therapy (from 12.7%, 95% confidence interval [CI] = 10.1% to 14.2%, to 4.9%, 95% CI = 3.4% to 6.8%, of all women) occurred between January 1, 2002, and December 31, 2004, among women aged 50–69 years. This drop occurred concurrently with a 9.6% decline in the incidence rate of breast cancer (from 296.3 per 100 000 women, 95% CI = 290.8 to 300.5 per 100 000 women, in 2002 to 268.0 per 100 000 women, 95% CI = 263.3 to 273.5 per 100 000 women, in 2004). Mammography rates were stable at 72% over the same period.
Conclusion During the period 2002–2004, there was a link between the declines in the use of hormone replacement therapy and breast cancer incidence among Canadian women aged 50–69 years, in the absence of any change in mammography rates.

Introduction

Results from the Women's Health Initiative^[1] clinical trial in July 2002 indicated that the risks of long-term use of combined estrogen and progestin hormone replacement therapy outweigh the health benefits. The Women's Health Initiative trial of more than 16 600 postmenopausal women in the United States identified an increased risk of stroke, myocardial infarction, and breast cancer in users of hormone replacement therapy compared with women who used a placebo, especially among women aged 50–69 years, who are the predominant users of hormone replacement therapy.^[2] Concerns about hormone replacement therapy triggered a drop in the use of hormone replacement therapy in several countries after 2002.^[3,4] The fallout from the Women's Health Initiative trial was reminiscent of earlier investigations in the 1970s that linked estrogen therapy to endometrial cancer risk^[5–7] and that led to a dramatic decline in prescriptions for estrogen shortly thereafter.^[8]

A potential link between a decline in the use of hormone replacement therapy and a decline in invasive breast cancer has now been reported in numerous countries.^[9–20] Data from the US Surveillance, Epidemiology, and End Results Program showed an 11.8% decline in the incidence of invasive breast cancer between 2001 and 2004.^[21] Most of the decline was of small early-stage tumors in women aged 50–69 years. A 14.7% decline was observed in estrogen receptor–positive breast cancer among women aged 50–69 years but was not observed in younger women. A concomitant decline in the number of filled prescriptions for combined hormone replacement therapy was reported over the same time period.^[22] The decline in hormone replacement therapy helped explain the drop in estrogen receptor–positive (ie, hormone-sensitive) tumors, which are the predominant type in users of combined hormone replacement therapy. Another study^[23] reported a 13% annual decline between 2001 and 2003 in the rate of estrogen receptor–positive breast cancer among postmenopausal women aged 50–69 years who were undergoing routine mammography.

If the observed declines in breast cancer are indeed related to a decline in the use of hormone replacement therapy, then the trends in breast cancer incidence before 2002 should follow earlier trends in the use of hormone replacement therapy. Thus, the temporality, biological plausibility, and consistency in two time periods should add further support to the role of hormone replacement therapy in breast cancer incidence. In this study, we aimed to determine whether changes in breast cancer incidence in postmenopausal women were linked to changes in the use of hormone replacement therapy in Canada.

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