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HRT and breast cancer

One of Bandolier's GP readers has picked up on the thoughtful BMJ editorial by Klim McPherson [1] on the use of hormonal supplements in postmenopausal woman, and their effects on the risk of breast cancer. Bandolier is not in a position to produce a full risk assessment balancing all the arguments, but is able to lay out some of the issues.

Balance of risk

The thrust of this editorial, and the arguments about the use of HRT are, roughly, these:-
  1. A 50 year old woman has a baseline lifetime risk of coronary heart disease of about 45%, of hip fracture of about 15% and of breast cancer about 8%.
  2. HRT can suppress menopausal symptoms and prevent osteoporosis.
  3. HRT may be protective against coronary heart disease.
  4. HRT may be associated with increased risk of breast cancer.
Clearly there is a balance between likely benefit and harm which may be measured in length and quality of life depending upon how large are the effects of HRT on osteoporosis, heart disease and breast cancer.

Nurses' Health Study

This is a US study involving nearly 122,000 female nurses aged 30 to 55 years in 1976. They have been followed every two years since then, with detailed questionnaire which included items about known or suspected risk factors for cancer and cardiovascular diseases.

Breast cancer diagnosis (or death) was one outcome, and details about newly diagnosed cancers were obtained, with permission, from hospital records and reviewed for over 93% of cases identified. Data from women with carcinoma in situ, who reported breast cancer in 1976, or who were premenopausal were omitted [2].

This left some 24,000 women who were postmenopausal in 1976, rising to nearly 70,000 by 1990. Follow up of index cases was over 95% for breast cancer diagnosis and 98% for fatal breast cancer.

Risk assessment

The relative risk was defined as the incidence of breast cancer among women who had taken hormones after the menopause divided by the incidence in women who had never taken such therapy. Various statistical methods were used to avoid bias from different sources.

Results

There were 725,000 women-years of follow up, with 1935 cases of breast cancer among postmenopausal women.
  • Use of any type of hormone or combination increased the risk of breast cancer for conjugated oestrogens alone, for oestrogen plus progestins and for progestins alone.
  • For current users of postmenopausal hormones the increased risk of breast cancer became significant when hormones had been used for more than five years.
  • Women who had formerly used postmenopausal hormones had no significantly increased risk compared with women who had never used hormones, and this was true even for women who had taken hormones for five or more years in the past.
The magnitudes of the increased risks are shown in the figures. For women currently taking postmenopausal hormones for more than five years, the increased risk of breast cancer was about 50%. A somewhat greater increased risk of about 70% was found with women aged 60-64. The increased risks probably lasted for about two years after women stopped taking the hormones.

What's the answer?

This is a multifaceted problem, and without all the facts it is probably not possible to be definite. McPherson [1] expands on how finely balanced the arguments may be. Crucially important is the length of the protective effect of hormone supplements after administration stops.

Bandolier 3 reviewed the Effective Health Care bulletin on hormones and osteoporosis. Bandolier 18 examined the genetics of breast cancer, and Bandolier 20 looked at measures that might reduce falls in the elderly.

Hormones are not the only answer. What we can be sure of is that postmenopausal women using hormone replacement are at relatively little increased danger of breast cancer for the first five years of their use.

What are the other questions?

One of the major issues is osteoporosis, which has been called "a silent epidemic". The burden of osteoporosis to the many, and increasing, numbers of elderly women (and men) is important on a personal basis; the NHS performs some 60,000 operations for hip fractures every year, and there may be 40 premature deaths every day. It may cost the NHS over £700 million a year.

Coronary heart disease is the major cause of death in women; prevention may be better than treatment. Its importance was one reason why it was chosen for the second Bandolier conference. A useful, general, review of prevention of both osteoporosis and coronary heart disease in primary care has recently been published [3] and is a thoughtful, if gentle, way in to these important subjects.

References:

  1. K McPherson. Breast cancer and hormonal supplements in postmenopausal women. British Medical Journal 1995 311: 699-70.
  2. GA Colditz, SE Hankinson, DJ Hunter et al. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. New England Journal of Medicine 1995 332: 1589-93.
  3. C Waine. Prevention of both osteoporosis and coronary heart disease in primary care. British Journal of Clinical Practice 1996 50: 44-6.



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