Hormone Replacement Therapy and Breast Cancer

HORMONE REPLACEMENT THERAPY AND BREAST CANCER

Hormone replacement therapy (HRT) is the principal medical treatment available for troublesome menopausal symptoms and simply acts by replacing the hormones that are normally produced by the human ovary at physiological levels. Oestogen is the main hormone and is either given alone or in combination with a progestogen. A third hormone, testosterone, can also be given in conjunction with oestrogen.

Ever since the introduction of HRT in the 1960s there have been concerns that the prolongation of exposure to natural hormones may have an adverse effect on the breast and other oestrogen-sensitive tissues. Yet despite widespread use for several decades and numerous studies, there remains uncertainty and controversy about exactly what the risks are and how relevant they are to the majority of healthy post-menopausal women. What is clear is that HRT is an extremely effective treatment for menopausal symptoms and urogenital atrophy, is an effective treatment for osteoporosis and appears to have beneficial effects on cardiovascular system if started around time of menopause.

Controversy continues to surround the true effect of HRT on breast cancer risk. Part of the continuing uncertainty exists because most of the studies have been observational and such studies can only suggest an association with a factor (in this case HRT), they do not prove a true cause and effect. A large meta-analysis of observational study published in 1997 showed that there was no increased breast cancer risk when HRT was used for less than five years in early post-menopausal women. Thereafter, there does appear to be a small increase in risk of 1.35. In absolute numbers, this equates to 4 extra breast cancer cases per 1000 women who use HRT from the age of 50 for five years. The magnitude of the risk appears to be similar to that associated with late natural menopause (2.3% vs 2.8% per year, respectively) and increased with years of exposure. However, this effect is not seen in women who start HRT early for premature menopause, suggesting that it may be the lifetime sex hormone exposure that is relevant. More recently, a large randomized trial on HRT (the Women’s Health Initiative (WHI), reported a broadly similar risk to that seen in the epidermiological studies for combined oestrogen and progestogen treatment after 5 years but also found no increase in risk over 7 years with oestrogen-only treatment. Thus, the increase in risk seems to be more associated with the progestogen component.




In summary, otherwise healthy postmenopausal women in their late 40s and 50s wishing to take HRT should be reassured that the overall risk for developing breast cancer in the first few years as a result of their HRT is small. If they take oestrogen alone, that risk is probably even lower. Breast cancer is a multifactorial disease and overall other personal risk factors, such as family history, are likely to be more important predictive factors.