Effects of estrogen alone vs. estrogen plus progestin on breast cancer risk
In the past decade, results from large prospective cohort studies and the Women’s Health Initiative (WHI) randomized placebo-controlled hormone therapy trials have substantially changed thoughts about how estrogen alone and estrogen plus progestin influence the risk of breast cancer, according to a review published TK in the Journal of The National Cancer Institute.
Although hormone therapy is currently used by millions of women for menopausal symptoms, there is still concern about hormone therapy–induced breast cancer risk. In addition, the effects of estrogen plus progestin versus estrogen alone on breast cancer are not completely understood.
To compare the effects of estrogen alone versus those of estrogen plus progestin on breast cancer risk, Rowan T. Chlebowski, M.D., Ph.D., of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and Garnet Anderson, Ph.D., at Fred Hutchinson Cancer Research Center, looked at data from two randomized, placebo-controlled full scale clinical trials conducted in the WHI. One trial evaluated estrogen plus progestin in postmenopausal women with an intact uterus, and the other evaluated estrogen alone in postmenopausal women with prior hysterectomy. Estrogen plus progestin statistically significantly increased the risk of breast cancer. In contrast, estrogen alone use in postmenopausal women with a previous hysterectomy, statistically significantly decreased the risk of breast cancer.
The randomized clinical trial findings differ from the predominance of observational studies, which suggested that both estrogen alone and estrogen plus progestin increase breast cancer incidence. Dr. Chlebowksi explains that “an imbalance in the use of mammography with greater screening for hormone users could explain some of the increase in breast cancer incidence with estrogen alone seen in cohort studies because screened populations have more cancers detected than unscreened populations.”
Breast cancer is the second most common cancer in women world-wide with 1.05 million new cases being estimated in the year 2001. In developed countries, it is the most common cancer in women. Populations from countries of North America are at high risk of breast cancer, with incidence rates in US white women going up to 103.7 per 100,000. High rates are also reported from Europe and Australia. In the United Kingdom, nearly 30,000 new cases of breast cancer are diagnosed every year with nearly 15,000 deaths reported from this disease.
The incidence rate of breast cancer has been rising both in the developed and developing countries and it is becoming frequent in some developing countries like Egypt and Tunisia. Carcinoma breast is the second most common cancer among Indian women, and an increasing trend in its incidence has been observed in most of the metropolis with Mumbai toping the list.
Sex-hormones have been implicated in various human cancers such as endometrial cancer, breast and prostatic cancer (among sex-organ related neoplasm) or colon cancer, gall-bladder cancer, kidney cancer, etc. ( non sex-organ related neoplasm).
However, the association between estrogen and breast cancer assumes special significance since breast cancer represents an enormous public health problem. Breast cancer risk is enhanced by increasing the duration of exposure to endogenous ovarian hormones, so early menarche or late menopause increases the risk. Further, the risk of breast cancer is directly related to the age at which women bear first child. An early first, full-term pregnancy seems to have a protective effect. Women whose first pregnancy is delayed to their late 30s are at a higher risk than multiparous women. Unmarried women tend to be at a higher risk than married women. Further, nulliparity increases and high parity decreases the risk of breast cancer, at least after the age of 50. Nevertheless, the endocrine mechanisms concerning pregnancy and risk of breast cancer are poorly understood. Exogenous hormonal factors such as estrogen replacement therapy and combined oral contraceptive use may cause a small increase in the risk for breast cancer.
While the mechanisms underlying the different effects of estrogen alone and estrogen plus progestin are not completely understood, the authors state that preclinical and other clinical evidence suggests “the findings in the clinic, taken together with preclinical evidence, indicate that many breast cancers in post-menopausal women can survive only a limited range of estrogen exposures.”
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Breast cancer is appearing to represent an enormous public health problem. The etiology of breast cancer is thought to involve a complex interplay of genetic, hormonal and environmental factors that influence the physiological status of the host. However, there are substantial experimental, epidemiological and clinical evidences, which show that breast cancer risk is influenced by endogenous sex-steroid hormones.
Physiologically, estradiol is the most active estrogen, whereas testosterone is the most potent androgen in women. Besides, the major and specific binding protein for testosterone and estradiol in blood is SHBG. In peripheral tissues, particularly in adipose tissue, aromatase enzyme converts androgens to estrogens.
After menopause, these extraovarian sources of estrogen play an important role in the body. More adipose tissues or obesity are related to dietary fat, specifically the intake of saturated fats of animal origin.
Also, the degree of obesity is a major determinant of blood cholesterol and triglycerides. All these factors affect the metabolism of sex-steroid hormones.
Recently, several studies have demonstrated a close relationship between sex-steroid hormones and immune system. Further, it has been demonstrated that tumour-infiltrating lymphocytes and macrophages could play a significant role in steroidogenesis.
About LA BioMed
Founded in 1952, LA BioMed is one of the country’s leading nonprofit independent biomedical research institutes. It has approximately 100 principal researchers conducting studies into improved treatments and cures for cancer, inherited diseases, infectious diseases, illnesses caused by environmental factors and more. It also educates young scientists and provides community services, including prenatal counseling and childhood nutrition programs. LA BioMed is academically affiliated with the David Geffen School of Medicine at UCLA and located on the campus of Harbor-UCLA Medical Center.
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Diana Soltesz
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Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed)