Letters

Hormone replacement therapy and the breast

Studies must determine the evidence

Women still want to have hormone replacement therapy

Author's reply

Studies must determine the evidence

EDITORAs active members of the Australasian Menopause Society, we are disappointed at the conclusions that Dixon drew in his editorial on hormone replacement therapy and the breast.¹ Although it may be true that hormone replacement therapy makes mammograms harder to interpret, it is far from clear that it causes breast cancer.

A recent overview by Bush et al emphasises the weakness of Dixon's argument, based, as it is, almost entirely on level three observational studies.² Unlike Dixon's selection of studies with the highest odds ratio, Bush et al's review was of 45 studies assessing the association between use of hormone replacement therapy and risk of breast cancer. It found that risk was reduced (relative risk<0.9) in 20% of the studies, did not change in 47% (0.9-1.1), and increased in 33% (1.1-2.0). In no study did relative risk increase above 2.0, and in the 20 studies where the relation between risk of breast cancer and combined oestrogen and progestin therapy was studied only four reported a significant difference in relative risk, with two showing an increased and two a decreased risk.

The heterogeneity of these data is in stark contrast to the homogeneity of the data on mortality from breast cancer in users of hormone replacement therapy that were reviewed: all 11 of the studies reported a reduction in risk. Unlike Dixon, the authors concluded that the likelihood of an adverse effect of hormone replacement therapy on breast cancer must be small.

The Australasian Menopause Society is a sponsor of the women's international study of long duration oestrogen use after the menopause (the WISDOM trial), a large prospective 15 year randomised placebo controlled trial. The results of this trial, together with those of the women's health initiative in the United States, will be needed to answer the question of whether hormone replacement therapy has any effect (beneficial or adverse) on breast cancer.

Until then strong opinions will continue to be held about hormone replacement therapy and its relation to risk of breast cancer, often derived from selective quoting of the available literature. These opinions heighten the anxiety of women who have valid reasons for taking hormone replacement therapy and do not afford them the opportunity of informed choice.

Alastair H MacLennan, professor of obstetrics and gynaecology. 
Women's and Children's Hospital, University of Adelaide, Adelaide, South Australia, Australia

Beverley Lawton, principal investigator. 
WISDOM New Zealand, Wellington School of Medicine and Health Sciences, University of Otago, New Zealand

Rodney J Baber, clinical senior lecturer in obstetrics and gynaecology. 
University of Sydney, Royal North Shore Hospital, Sydney 2065, New South Wales, Australia rbaber{at}mail.usyd.edu.au

Competing interests: AHM is editor in chief of Climacteric, the journal of the International Menopause Society. He has received research grants to conduct phase 1 and phase 3 trials of various products for managing the menopause and its sequelae and is the principal investigator of WISDOM, Australia. BL is involved in three clinical trials of hormone replacement therapy in postmenopausal women and receives funding from the Medical Research Council in the United Kingdom for the WISDOM trial. RJB has received research grants to conduct phase 2 and phase 3 clinical trials on the effects of various types of hormone replacement therapy, selective oestrogen receptor modulators, and phytoestrogens in postmenopausal women. The WISDOM trial in Australia is sponsored by the UK Medical Research Council, Australian National Health and Medical Research Council, Australian Heart Foundation, South Australian Anti Cancer Foundation, Australasian Menopause Society, and Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Women still want to have hormone replacement therapy

EDITORI was dismayed to read Dixon's editorial about hormone replacement therapy and its effect on the breast¹ and have been provoked to respond by the anguished cries for help by both patients and colleagues. Dixon, in the words of Bernard Levin, has become a single issue fanatic. There's more to women's health concerns than breast cancer.

Frightening women off hormone replacement therapy could have many unpredicted consequences. The lifetime risk for women of dying of breast cancer is only 1 in 26, with between three and 10 times that risk of dying from heart disease, depending on whether they are smokers or non-smokers.² For all we know, hormone replacement therapy could protect more women from death due to cardiovascular disease and osteoporotic fractures than the worst estimates for the increased incidence of breast cancer. Furthermore, as Dixon concedes, many of these cancers in women receiving hormone replacement therapy are of a favourable phenotype. It is therefore altogether perverse to criticise hormone replacement therapy for making screening mammograms uninterpretable.

Surely, given an informed choice, most women would be glad of the excuse to opt out of the national screening programme, which is of questionable value,³ in favour of an intervention that improves short term and long term quality of life. Of course many women taking hormone replacement therapy have mastalgia and nodularity, but most of my patients are happy to live with this in exchange for the sense of wellbeing that they get from taking the therapy. Hormone replacement therapy also improves skin elasticity, mood, sexuality, and cognitive function.⁴

Are we really asking women to give all this up so as to make the life of our screening radiologists more comfortable?

Michael Baum, emeritus professor of surgery. 
University College London, CRC/UCL Cancer Trials Centre, London NW1 2ND m.baum{at}ctc.ucl.ac.uk

Author's reply

Truth or tact? You have to choose, most times they are not compatible

Eddie Cantor

EDITORThe recent qualitative review by Bush et al is the basis of the objections of Baber et al to the conclusions I drew on the effects of hormone replacement therapy on the breast of postmenopausal women.¹

This review took no account of the quality of studies included, it did not consider type of hormone replacement therapy used, its mode of delivery, or the age at which women started taking it. Figure 2 in their publication did, however, confirm that four of the five most recently published studies have shown an excess risk of breast cancer for combined regimens in postmenopausal women. Bush et al doubt whether oestrogen is important in breast cancer development and propose that some additional, as yet unidentified, factor is secreted from the ovary.

New data from over 9300 women with early breast cancer randomised to receive five years of treatment with adjuvant tamoxifen alone, anastrozole alone, or tamoxifen and anastrozole combined were presented last year by Baum. They show that after 33 months, there were five new invasive contralateral breast cancers in the 3112 patients taking anastrozole compared with 30 in 3116 women receiving tamoxifen and 23 in 3125 in the combination arma significant reduction in contralateral breast cancers with anastrozole compared with tamoxifen (hazard ratio 0.42 (0.22-0.79), P=0.0054). These data explode the myth of an unknown factor proposed by Bush et al and confirm the importance of oestrogen in the development of breast cancer.

It was not my intention to try to frighten women off taking hormone replacement therapy. The US Food and Drug Administration removed the treatment of osteoporosis as an indication for oestrogen replacement therapy in 1999 because of lack of evidence from randomised trials. There are new specific and better drugs for this condition.² "Hormone replacement therapy should not be prescribed for the express purpose of preventing cardiovascular disease."³ In the heart and oestrogen/progestin replacement study women over 65 taking hormone replacement therapy had worsening urinary incontinence and an increased risk of fatal stroke.⁴

Baum is inconsistent. He believes that women should be provided with all available data on screening so that they can make an informed choice yet he would deny them all available information on hormone replacement therapy. There is no doubt that oestrogen significantly improves the quality of many women's lives. The challenge for women and their clinicians remains to control menopausal symptoms and to deliver the benefits of oestrogen while minimizing the problems that continue to be reported with these preparations. ^{4 5}

J M Dixon, consultant surgeon and senior lecturer. 
Academic Office, Edinburgh Breast Unit, Western General Hospital, Edinburgh EH4 2XU jmd{at}wght.demon.co.uk

Competing interests: None declared.