The role of hormonal replacement therapy is controversial in the development of breast cancer. What does seem clear is that combined estrogen with progesterone taken orally either continually or sequentially does raise the risk by a quarter to a third if taken over a decade. Looking more closely into this group of women, it appears that C-19 progestins have a lower risk than C-21 progestins and the mechanism of action may be the potentiation of the proliferative effect of estrogens in breast tissue.
In contrast, taking estrogens alone or the delivery of estrogens with progesterone transdermally does not increase the risk of breast cancer (Opatrny et al BJOG 2008;115:169-75). The authors carried out a large observational case-control study on UK women with a mean age of 61 years that takes into account the hormone therapy women took at all stages of their post-menopausal lives as the Women's Health Initiative (WHI) study caused many to swap preparations. This new data confirms the estrogen-only arm of findings of the WHI study which showed no increased risk of breast cancer.
It is interesting that transdermal preparations were not associated with increased risk either. They provide constant low hormone levels in the blood which avoids hepatic protein synthesis which does occur with the oral route, causing peaks and troughs from one dose to the next. Transdermal estrogens alone or with progesterone did not raise the risk of breast cancer.
Tibolone is a selective tissue estrogen activity regulator which has estrogenic activity on the vagina and bone without similar effects on breast and endometrial tissue. The study summarised here showed that women using tibolone alone were not at increased risk of breast cancer but the numbers were small.
Information continues to become available showing that selected prescriptions of replacement hormones should be tailored to each woman's requirements in terms of the type of medication, the dosage, the route of administration and the duration of use if unwanted side-effects are to be avoided.