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Women taking combination HRT are at greater risk of breast cancer

BMJ 2000; 320 doi: https://doi.org/10.1136/bmj.320.7231.333/a (Published 05 February 2000) Cite this as: BMJ 2000;320:333
  1. Deborah Josefson
  1. San Francisco

    Women who use combination hormone replacement therapy (HRT) with oestrogen and progesterone face a greater breast cancer risk than those taking oestrogen alone, according to a new report (JAMA 2000; 283:485-91, 534-5).

    The study, led by Dr Catherine Schairer, an epidemiologist at the US National Cancer Institute, analysed data on 46355 postmenopausal women. The researchers sought to determine whether commonly prescribed combination hormone replacement therapy placed women at increased risk of breast cancer compared with oestrogen alone.

    Postmenopausal oestrogen replacement helps to mitigate menopausal symptoms such as hot flushes, vaginal dryness, and mood swings, and additionally has been found to protect against osteoporotic fractures, Alzheimer's disease, and coronary artery disease. The downside of oestrogen replacement is an increased risk of breast and endometrial cancers and of developing deep vein thromboses.

    Progesterone is usually added to oestrogen replacement to reduce the risk of endometrial cancer in women receiving unopposed oestrogen therapy, but the effect of these added hormones on the risk of breast cancer has been largely unknown.

    In this study, a retrospective cohort analysis, the researchers examined follow up data on menopausal women collected between 1980 and 1995 in subjects enrolled in the breast cancer detection demonstration project, which was initially conducted from 1973 to 1980. The average age at the start of follow up was 58 years, and the mean duration of follow up was 10.2 years.

    Overall, 473687 person years of data were accumulated; 42%of person years were associated with no hormonal use, 38%with oestrogen only, 4%with oestrogen plus progesterone, and 6%with both combined and oestrogen only regimens at different times. Additionally, 1% of person years involved progesterone alone.

    The most common oestrogen taken was conjugated oestrogen, such as Premarin; medroxyprogesterone acetate, or Provera, was the commonly taken progesterone. Information on breast cancer risks, breast surgery (or consultations for it), height and weight, and educational level were obtained and controlled for.

    Of the initial 46355 subjects, 33004 completed all questionnaires and were included in the study. In all, 2082 cases of breast cancer were identified in the study subjects, some through self reporting and others through reports of deaths from breast cancer. Pathology reports obtained for 1713 of these cancers showed that 255 of the cancers were in situ and 1456 (85%) were invasive.

    The researchers found that women taking combination hormone replacement therapy experienced a 40%greater risk of breast cancer than those taking no therapy; women taking oestrogen alone had a 20%greater risk. Moreover, the relative risk increased with duration of therapy, increasing by 0.01 for each year of oestrogen only use and by 0.08 a year for those taking oestrogen plus progesterone.

    The results were found to be significant only in lean women, those with a body mass index (weight(kg)/(height(m)2)) of 24.2 or less, and those who were either currently taking hormone replacement or had taken it within four years.

    Commenting on the report, Dr Schairer said that the research suggests that combination replacement may increase the risk of breast cancer but admitted that the mode of replacement—continuous versus cyclic—was not controlled for and that further studies will need to be done.

    Although this and some other studies, such as the nurses' health study, show increased risk, the data are still murky.

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