It has long been known that ovarian production of the sex steroid hormone, estrogen, affects growth, differentiation, and function of the mammary gland. By interacting with estrogen-response elements contained in the promoter region of specific genes, modulation of gene expression ultimately results in the biological effects of estrogen.
Despite the clear understanding of the genomic mechanism of estrogen action, it is also postulated that estradiol can exert nongenomic effects on cell biology by interacting with other proteins, including a putative membrane estrogen receptor, growth factor receptors, and intermediate cell signaling molecules [ 2 — 4 ]. Paradoxically, they discovered that estradiol inhibited, rather than stimulated, cell proliferation. In spite of these findings, both the action of an estrogen-responsive reporter construct and the expression of an endogenous estrogen-responsive gene could be stimulated by estrogen.
In the same year, Garcia et al. Oesterreich and her colleagues report the creation of a MCF7 cell line that is unresponsive to estrogen [ 11 ].
Compared to other studies, Oesterreich et al. What are the genes regulated by estradiol in this system? Intriguingly, Oesterreich et al. Considerable crosstalk has already been documented between the signaling pathways of estrogen and the IGFs [ 12 ].
Breast cancer types: What your type means
It has also been suggested that signaling components of the IGF-I system are regulated by estrogen [ 14 ]. For example, estrogen treatment failed to induce expression of a key endogenous estrogen-responsive gene, the progesterone receptor gene. Since the cells were derived from MCF7 cells that have been shown to induce progesterone receptor expression following estrogen treatment, one would hypothesize that the cells would express the proper combination of coregulatory factors required for induction of the progesterone receptor gene.
While Oesterreich et al. Although it is possible that low concentrations of estrogen in the media were responsible for the restored gene expression, it seems unlikely because the cells were maintained in serum stripped of endogenous steroids. Oesterreich et al. These results provide the clearest demonstration of the crosstalk between estrogen and the IGF-I pathway. Indeed, the idea that estrogen functions to cancel growth inhibitory signals has also been suggested by another recent study [ 19 ].
The results of Oesterreich et al. Cancer Res. J Biol Chem. The longer EPT is used, the higher the risk. The risk returns to that of a woman who never used EPT the usual risk within 3 years of stopping the hormones. Breast cancers in women taking EPT are more likely to be found when they are bigger and have spread beyond the breast.
To put the risk into numbers, if 10, women took EPT for a year, it would result in up to about 8 more cases of breast cancer per year than if they had not taken hormone therapy HT. Taking EPT is also linked to increased breast density as seen on a mammogram. Increased breast density can make it harder to find breast cancer on a mammogram.
Risk factors for ovarian cancer are harder to study because it is a less common cancer.
Even when something increases the risk of developing ovarian cancer, the risk of actually getting this cancer is still likely to be low. Although there were more cases of ovarian cancer in the women on EPT, this may have been due to chance because of the small number of women who were affected with this cancer. However, a recent analysis combined the results of more than 50 studies, including randomized controlled trials and observational studies.
This analysis found that women who took estrogen and progestin progesterone after menopause did have an increased risk of getting ovarian cancer. The risk was highest for women taking hormones, and decreased over time after the hormones were stopped. To put the risk into numbers, if 1, women who were 50 years old took hormones for menopause for 5 years, one extra ovarian cancer would be expected to develop.
Women who took EPT had a lower risk of getting colorectal cancer at all, but the cancers they got were more advanced more likely to have spread to lymph nodes or distant sites than the cancers in the women not taking hormones. Some observational studies have found a lower risk of colorectal cancer in women taking EPT, but some did not. So far, though, observational studies have not linked EPT with a higher risk of colorectal cancer.
EPT is not linked to a higher risk of getting lung cancer , but it is linked to a higher risk of dying from lung cancer. EPT is not linked to a higher risk of any type of skin cancer including both melanoma and other types of skin cancer. In women who still have a uterus, using systemic ET has been shown to increase the risk of endometrial cancer cancer of the lining of the uterus. The risk remains higher than average even after ET is no longer used. Although most studies that showed an increased risk were of women taking estrogen as a pill, women using a patch or high-dose vaginal ring can also expect to have an increased risk of endometrial cancer.
Because of this increased cancer risk, women who have gone through menopause and who still have a uterus are given a progestin along with estrogen.
Studies have shown that EPT does not increase the risk for endometrial cancer. Long-term use of vaginal creams, rings, or tablets containing topical estrogen doses may also increase the levels of estrogen in the body. ET is not linked to a higher risk of breast cancer. In fact, certain groups of women taking ET, such as women who had no family history of breast cancer and those who had no history of benign breast disease, had a slightly lower risk of breast cancer. This analysis found that women who took estrogen after menopause did have an increased risk of getting ovarian cancer.
The risk was highest for women currently taking estrogen, and decreased over time after estrogen was stopped. To put the risk into numbers, if 1, women who were 50 years old took estrogen for menopause for 5 years, one extra ovarian cancer would be expected to develop. Observational studies have shown that women who take ET have a higher risk for ovarian cancer compared with women who take no hormones after menopause.
The overall risk remains low, but it does increase the longer a woman uses ET. The risk of ovarian cancer goes down after a woman stops taking the hormone. Observational studies have found a lower risk of colorectal cancer in women who have used ET for many years.
Estrogen Dependent Cancers
ET does not seem to have any effect on the risk of lung cancer. ET is not linked to a higher risk of any type of skin cancer including both melanoma and other types of skin cancer. The decision to use estrogen, alone ET or with a progestin therapy EPT , after menopause should be made by each woman and her doctor after weighing the possible risks and benefits. Things to think about include:. And just as you would if you were taking another type of medicine, you need to see your doctor regularly. Your doctor can see how well the treatment is working, monitor you for side effects, and let you know what other treatments are available for your symptoms.
All women should report any vaginal bleeding that happens after menopause to their doctors right away — it may be a symptom of endometrial cancer. A woman who takes EPT does not have a higher risk of endometrial cancer, but she can still get it. Women using vaginal cream, rings, or tablets containing only estrogen should talk to their doctors about follow-up and the possible need for progestin treatment.
11 Foods High in Estrogen
Adding a progestin does raise the risk of breast cancer, so ET is a better option for women without a uterus. Women should follow the American Cancer Society guidelines for cancer early detection, especially those for breast cancer. These include vitamins and soy-based and herbal products like black cohosh and red clover. There are also endless arrays of special blends of herbs and vitamins that claim to reduce the discomforts of menopause. These products are considered dietary supplements not drugs.
They have not been evaluated by the Food and Drug Administration FDA to be sure that they work or even that they are safe.
You should discuss herbs or supplements with your doctor before taking them. Well-controlled scientific studies are needed to help find out if these products work and if they are any safer than the hormone therapy drugs now in use. The American Cancer Society medical and editorial content team. Provides accurate, up-to-date cancer information to patients, their families, and the general public.
No matter who you are, we can help. Contact us anytime, day or night, for information and support. Lancet Oncol. Breast cancer and hormone-replacement therapy in the Million Women Study. Ovarian cancer and hormone-replacement therapy in the Million Women Study. Postmenopausal hormone use and breast cancer associations differ by hormone regimen and histologic subtype. J Natl Cancer Inst. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women.
Breast cancer after use of estrogen plus progestin in postmenopausal women. N Engl J Med. Estrogen plus progestin and colorectal cancer in postmenopausal women.
About the Author
Colditz GA. Relationship between estrogen levels, use of hormone replacement therapy, and breast cancer. Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies. A prospective study of postmenopausal hormone use and ovarian cancer risk. Cyclic hormone replacement therapy using quarterly progestin.
Obstet Gynecol. Failure of estrogen plus progestin therapy for prevention. Geller, SE, Studee L. Botanical and dietary supplements for menopausal symptoms: What works, what does not. Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis. Am J Med.
Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. Postmenopausal hormone use and incident ovarian cancer: Associations differ by regimen.