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Does Hormone Replacement Therapy Increase Risk of Breast Cancer?

 A plethora of studies suggest that estrogen levels in the body and the use of estrogen replacement therapy after menopause increases risk of breast cancer. As reviewed by G. Colditz (J.Natl. Cancer Inst., June 3, 1998), the combined reanalysis of original data from 51 epidemiological studies that included more than 52,000 patients with breast cancer and more that 100,000 women without breast cancer indicates that, for each year a woman uses postmenopausal hormones her risk of breast cancer increases by 2.3%, and the findings do not vary significantly between studies.

 

In this report they found evidence of a causal relationship between these hormones and breast cancer, based on strict scientific criteria.

 

Since the 1970's, strong evidence has been in place to show that early menopause is associated with a reduced risk of breast cancer. For every one-year increase in age at menopause, the risk of breast cancer increases by approximately 3%. This evidence plus additional factors indicate that a woman's lifetime exposure to estrogen is related to breast cancer risk, the greater the exposure the greater the risk.

 

Estrogen is thought to increase risk of breast cancer due to its influence of increasing the rate of breast cell growth and cell division, and the accumulation of genetic damage. The accumulation of genetic (DNA) damage leads to the development of cancer cells.

 

Further support is provided by the fact that obesity is related to higher levels of estrogen and increased risk of breast cancer. Lean, postmenopausal women have both lower estrogen levels and lower age-specific incidence of postmenopausal breast cancer.

 

Estrogen is known to facilitate the growth of tumors among women already diagnosed with breast cancer, hence the use of drugs (i.e. tamoxifen) and procedures (oophorectomy – removal of ovaries) to block the effects of estrogen on breast cancer cells.

 

Taken together, these data indicate that higher levels of estrogen among postmenopausal women are associated with increased incidence of breast cancer and that higher levels after diagnosis lead to poorer survival.

 

Use of postmenopausal hormones increases the level of estrogens in postmenopausal women. A positive relationship between the duration of use of hormones and the risk of breast cancer has been reported by many investigators who have conducted meta-analyses (combined studies evaluation) of the published epidemiological studies.

 

Steinberg et al. noted that among the U.S. case control studies published from 1977 to 1991, a positive relationship was observed between the duration of hormone use and the risk of breast cancer in 11 of the12 studies with community control subjects. Among prospective studies, an increased risk with increasing duration of hormone use was reported in all four studies.

 

Oxford investigators revealed an increased risk of breast cancer associated with the duration of use of hormone replacement therapy was 2.3% per year when full statistical control was implemented.

 

This means that for every year a woman remains on hormone replacement therapy, her risk of breast cancer increases another 2.3%. Thus a woman on hormone replacement therapy from ages 50 to 65 has increased her risk of breast cancer by 37.5% compared to a woman having not used hormone replacement for the same time period. By age 70 her risk would be 46% greater than the non-user.

 

A redeeming factor is that estrogen replacement therapy may induce a less malignant form of breast cancer as these patients tend to have improved survival compared to women who develop breast cancer and did not previously use estrogen replacement therapy.

 

Currently many postmenopausal women employ the use of hormone replacement therapy for a number of reasons. Estrogen replacement is known to reduce the risk of osteoporosis, heart disease, ovarian cancer and possibly Alzheimer disease.

 

In the American Cancer Society study 43.7% of the women who took hormones did so to relieve menopausal symptoms, 39.5% after a hysterectomy, and 7% for other reasons.

 

As pointed out by Colditz, up to age 70 cancer is a more serious threat to women than is heart disease and the average years lost per death is 11.8 for heart disease and 19.5 for breast cancer. Thus, the increased risk of breast cancer induced by hormone replacement therapy is not justified in the case of using it to prevent heart disease. As well, new drugs and better lifestyle practices can successfully reduce risk of osteoporosis. For heart disease and osteoporosis there is a wide range of lifestyle or clinical options that can reduce risk, many with fewer potential side effects than the increase in the risk of breast cancer caused by the use of postmenopausal hormones.

 

The good news is that the use of lower doses of estrogen (.33 mg vs. 0.62 mg or 1.25 mg) appears to relieve menopausal symptoms, lower risk of heart disease, and osteoporosis (in conjunction with calcium supplementation) without increasing risk of breast cancer.  As well, more naturally derived estrogens appear to be much safer than the estrogen derived from mare's urine.

 

As an alternative, the standardized grade of black cohosh, soy isoflavones and gamma oryzanol have been shown collectively to reduce menopausal symptoms, lower cholesterol and support bone health. These natural agents have been used successfully by postmenopausal women as a substitute for hormone replacement or in concert with hormone replacement therapy.

 

 Dr. James Meschino D.C., M.S., N.D.

 

References:

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16. Huang Z, Hankinson ES, Colditz GA, Stampfer MJ, Hunter DJ, Manson JE, et al. Dual effects of weight and weight gain on breast cancer risk. JAMA 1997;278:1407-11

 

17. Systemic treatment of early beast cancer by hormonal, cytotoxic, or immune therapy. 133 randomised trials involving 31,000 recurrences and 24,000 deaths among 75,000 women. Early Breast Cancer Trialists' Collaborative Group. Lancet 1992;339:1-15

 

18. Toniolo PG, Levitz M, Zeleniuch-Jacquotte A, Banerjee S, Koenig KL, Shore RE, et al. A prospective study of endogenous estrogens and breast cancer in postmenopausal women. J Natl Cancer Inst 1995;87:190-7

 

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Black Cohosh References

1  Stolze, H: An alternative to treat menopausal complaints. Gyne 3:1416,1982

2  Warnecke, G: Influencing menopausal symptoms with a phytotherapeutic agent. Med Welt. 36:871-4,1985

3  Stoll,W: Phytopharmacon influences atrophic vaginal epithelium. Double-blind study — Cimicifuga vs. estrogenic substances. Therapeuticum 1:23-31,1987

4  Schildge,E: Essay on the treatment of premenstrual and menopausal mood swings and depressive states. Rigelh Biol Umsch 18 (2):18-22,1964

5  Bruker,A: Essay on the phytotherapy of hormonal disorders in women. Med Welt.44:2331-3,1960

6  Murray,M: Remifemin:Answers to some common questions. AM J Natural Med. Vol.4 (3), April 1997

7  Gorlich,N: Treatment of ovarian disorders in general practice. Arztl Prax. 14:1742-3,1962

 

Gamma-Oryzanol References

1  Murase,Y et al: Clinical studies of oral administration of gamma-oryzanol on climacteric complaints and its syndrome. Obstet Gynecol Prac (12) 147-149,1963

2  Ishihara,M: Effect of gamma-oryzanol on serum lipid peroxide levels and climacteric disturbances. Asia Oceania J Obstet Gynecol (10), 317, 1984

3  Yoshino,G et al: Effects of gamma-oryzanol on hyperlipidemic subjects. Curr Ther Res (45), 543-552,1989

4  Yoshino,G et al: Effects of gamma-oryzanol and probucol on hyperlipidemia. Curr Ther Res (45), 975-982,1989

Soy References

1  Murkies,A L et al: Dietary flour supplementation decreases post-menopausal hot flashes: effect of soy and wheat. Maturitas (21), 189-195,1995

2  Albertzazzi,P et al: The effect of dietary soy supplementation on hot flashes. Obstet Gynecol (91), 6-11,1998

3  Cassidy,A et al: Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of pre-menopausal women. Am J Clin Nutr (60), 333-340,1994

4  Valente,M et al: Effects of 1-year treatment with ipriflavone on bone in postmenopausal women with low bone mass. Calcif Tissue Int 1994; 54:377-80

5  Tsuda,M et al: The effect of ipriflavone on bone resorption in tissue culture. J Bone Miner Res 1986:1:207-11

6  Patter,S M et al: Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 1998:68 (suppl) 137-9

7  Dalais,F S et al: Dietary soy supplementation increases vaginal cytology maturation index and bone mineral content in post menopausal women Am J Clin Nutr 1998;68 (suppl) 1519 (abstr)

8  Anderson J W et al: Meta-analysis of the effects of soy protein intake on serum lipids. N Engl J Med 1995;333:276-82

9  Messina,M: Legumes and Soybeans:overview of their nutritional profiles and health effects. Am J Clin Nutr 1999 Vol 70 (suppl); 439-50

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