Breast cancer hormone replacement

There is much interest in the possible hormonal effects of phytoestrogens in both men and women. The majority of studies conducted in women have examined the ability of phytoestrogens to alleviate menopausal symptoms. Whilst hormone replacement therapy is recommended for women experiencing menopausal symptoms, there remains some uncertainty as to whether HRT can increase the risk of breast cancer. As a result of these concerns, investigations into natural alternatives such as phytoestrogens have received considerable attention. 

Long-term use of hormone-replacement therapy and concurrent use of progestins appear to contribute to breast cancer risk.7 The use of postmenopausal estrogen-replacement therapy in women with a history of breast cancer generally is considered contraindicated. However, most experts believe that the safety and benefits of low-dose oral contraceptives currently outweigh the potential risks and that changes in the prescribing practice for the use of oral contraceptives are not warranted. Oral contraceptives are known to reduce the risk of ovarian cancer by about 40% and the risk of endometrial cancer by about 60%. 

In a reanalysis of 51 studies, less than 5 years of therapy with combined estrogen and progestogen was associated with a 15% increase in risk for breast cancer, and the risk increased with greater duration of treatment. Five years after discontinuation of hormone replacement therapy, the risk of breast cancer was no longer increased. 

Diamanti-Kandarakis E, Sykiotis GP, Papavassiliou AG (2003) Selective modulation of postmenopausal women cutting the Gordian knot of hormone replacement therapy with breast carcinoma. Cancer 97 12... 

Million Women Study Collaborators (2003) Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 362 419-427... 

Collaborative Group on Hormonal Factors in Breast Cancer (1997) Breast cancer and hormone replacement therapy collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet 350 1047-1059... 

Holli K, Isola J, Cuzick J (1997) Hormone replacement therapy and biological aggressiveness of breast cancer. Lancet 350 1704-1705... 

Santen RJ, Pinkerton J, McCartney C (2001) Clinical review 121 Risk of breast cancer with progestins in combination with estrogen as hormone replacement therapy. J Clin Endocrinol Metab 86(l) 16-23... 

Hormone therapy has proven highly effective in controlling the menopausal syndrome, especially severe hot flushes (MacLennan et al. 2004), even at doses significantly lower than those used until now (Speroff et al. 2000 Utian et al. 2001). Women s Health Initiative studies found that hormone replacement therapy, when administered as a primary prevention intervention for CVD in older women, increases the risk of heart disease and breast cancer. Even if a protective effect on fracture and colon cancer was observed, the risk-benefit ratio led to a recommendation of this treatment only for the short-term relief of menopausal symptoms (Rossouw et al. 2002 Anderson et al. 2004). The role of early administration of ovarian hormones to young postmenopausal women in the prevention of cardiovascular disease or late dementia remains... 

The clinical problems that arise in the menopause are hot flushes, sweating, depression, decreased libido, increased risk of cardiovascular disease and osteoporosis. The latter results in increased incidence of hip, radial and vertebral fractures. Oestrogen is one factor controlling synthesis of active vitamin D and osteoporosis is in part due to a deficiency of vitamin D. Not surprisingly, to reduce these problems, administration of oestrogen is recommended (known as hormone replacement therapy or HRT). HRT reduces some of the risk factors for coronary artery disease since it reduces blood pressure and decreases the blood level of LDL-cholesterol and increases that of HDL-cholesterol. However, there is considerable debate about whether HRT increases the risk of breast or endometrial cancer. 

Estrogens are most commonly used as a component of combination contraceptives or as hormone replacement therapy in postmenopausal women. Benefits in postmenopausal women include relief of moderate to severe vasomotor symptoms and decreased risk of osteoporosis. Hormone replacement therapy also may be used in vaginal and vulvar atrophy and in hypoestrogenism caused by hypogonadism, castration, or primary ovarian failure. Less commonly, select breast or prostate cancer... 

Hormones regulate many important bodily functions and are also associated with cancer. One of the first hints of the relationship of hormones to cancers was the observation that nuns had a greater incidence of breast cancer. This was naturally related to the nuns not having children and now we know that breast cancer may be hormone related. Since then there have been numerous studies on the use of birth control with cancer, childbirth, and most recently hormone replacement association with cancer. In males there is ongoing study of the hormones and prostate cancer. While it is clear that hormones and cancer are related, the exact characterization of this relationship is still unclear. 

Ross RK, Paganini-Hill A, Wan PC, Pike MC. Effect of hormone replacement therapy on breast cancer risk estrogen versus estrogen plus progestin. J Natl Cancer Inst 2000 92(4) 328-32. 

The chief therapeutic uses of estrogens and progestins are as oral contraceptives and hormone replacement therapy. Progestins and SERMs are also important agents in the treatment of osteoporosis, breast cancer, endometrial cancer, and infertility. 

The FDA requires Wyeth to add a new warning to its hormone-replacement drug Prempro about risks of heart attacks, sttokes, breast cancer, and blood clots associated with its use. 

February 19 The judge on a successful suit brought by three women with breast cancer against Wyeth for its hormone replacement drug Prempro sets final damages at 58 million— 23 million to compensate the women and 35 million in punitive damages. 

There is today no reasonable doubt that hormone replacement therapy increases the risk of breast cancer. As always, however, the devil is in the detail, and argument... 

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