Pregnancy Hormone Research May Lead to New Methods of Breast Cancer Prevention

Researchers in Finland are learning more about how hormones influence the risk of developing breast cancer, which may lead to a hormone-based treatment to reduce the risk of developing cancer later in life.

In a nested case-control study published in the journal Cancer Research on October 3, 2014, Fortner and colleagues studied the relationship between circulating steroid hormone levels and cancer.¹

Broadly speaking, the relationship between hormones and cancer has been known since the 16th century, when Italian physician Bernadino Ramazzini noted incidence of breast cancers were higher than normal among celibate nuns than in the general population. The fact that the nuns never became pregnant proved to be responsible for the increased risk.²

Later researchers, such as Scottish physician George Beatson, discovered that removing a woman's ovaries induced remissions of some breast cancers in premenopausal women. It was later discovered that sex hormones were the common thread between these discoveries.²

In the early to mid-1990s, researchers noted associations between breast cancers and early puberty, late menopause, pregnancy, obesity, and use of estrogen and estrogen-like drugs.²

Building on this research, Fortner and colleagues analyzed levels of circulating steroid hormones during pregnancy and the later risk of breast cancer. Researchers examined data from 1199 patients who had developed breast cancer and 2281 patients who were demographically similar but had not developed breast cancer, and then analyzed the levels of patients' sex hormones (estradiol, estrone, progesterone, and testosterone) previously recorded during early pregnancy.¹

High levels of estradiol were associated with an increased risk of developing breast cancer before the age of 40 years (P = .01), whereas low levels of estradiol were associated with a higher rate of breast cancer at age 40 years or later (P = .02).¹

In addition, high levels of steroid hormones in early pregnancy predicted a higher risk of developing more aggressive breast cancers lacking estrogen receptors and progesterone receptors at a younger age (ie, younger than 40 years). However, high steroid hormone levels in early pregnancy were also associated with a lower overall risk of developing breast cancer after the age of 40 years.¹

Current knowledge about the use of estrogens and the risk of developing breast cancer suggests that sex hormones, including progesterone and estrogen, act as accelerators of breast cancer growth but do not directly cause cancer.³

Given that high levels of sex hormones are believed to accelerate breast cancer growth, and that high levels of sex hormones exhibited during pregnancy may offer a protective benefit, it is clear that the relationship between hormones and breast cancer is complex.³

Administering pulsed doses of hormones in women who do not plan to have children or women who cannot have children may be a future method of breast cancer prevention. Researchers have already conducted this experiment in rats. Early results of animal data suggest that administering a combination of estrogen and progesterone to simulate the hormonal levels observed in pregnancy may be of some value.³

Understanding more about the way sex hormones affect women's later risk of developing breast cancer may help scientists understand more about how to reduce that risk using pulsed hormone treatments as a method of preventing the disease. Armed with this data, researchers may be able to turn the cancer-accelerating effects of sex hormones⁴ into a cancer-preventing effect through cyclic administration of sex hormones that simulates the hormonal patterns of pregnancy. More research will be necessary to determine if this is a useful strategy of chemoprevention in humans.

References:

• Fortner RT, Schock H, Kaaks R, et al. Early Pregnancy Sex Steroids and Maternal Breast Cancer: A nested case-control study. Cancer Res. 2014.
• Clarke R, Liu MC, Bouker KB, et al. Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling. Oncogene. 2003;22(47):7316-7339.
• Tsubura A, Uehara N, Matsuoka Y, Yoshizawa K, Yuri T. Estrogen and progesterone treatment mimicking pregnancy for protection from breast cancer. In Vivo. 2008;22(2):191-201.
• Davidson BA, Moorman PG. Risk-benefit assessment of the combined oral contraceptive pill in women with a family history of female cancer. Expert Opin Drug Saf. 2014;13(10):1375-1382.