Estrogens and Breast Cancer

16 years ago, a Women’s Health Institute (WHI) study was published.[1] This study proved revolutionary. It advised against the use of menopausal hormone therapy (MHT) and resulted in a media storm, causing confusion and a dramatic reduction in the number of prescriptions. Since then, reanalysis of the data and further research has suggested that in fact, for many women MHT is both effective and has a beneficial risk-benefit ratio.[2] As a result, the World Health Organisation have labelled MHT as a purveyor of benefit and not of risk.

Unfortunately, the lack of effective treatment following the WHI study left many women suffering. Speaking at COGI 2018, Prof. Fernand Labrie indicated that treatment of postmenopausal symptoms became a major unmet need. This, he suggested, was mainly due to the fear of estrogens.

 

Do estrogens promote breast cancer?

Dr. Christian Singer explained that exposure to estrogens is a determinant of breast cancer risk. He discussed that estrogens can induce and promote breast cancer, with mechanisms relating to oxidative metabolism in the Catechol pathway and e2 receptor binding leading to altered gene expression. However, recent data has suggested that estrogens alone do not have a significant effect and may even have a positive effect on breast cancer risk or cancer-related mortality.[3]

Further supporting this research, Dr. Herjan Bennink shared fascinating data on lifetime breast cancer risk in females, males and male-to-female transgender persons. Females have a lifetime breast cancer risk of 1 in 8, while males have a risk of 1 in 1000. In order to develop breast tissue, male-female transgender persons must undergo high dose of estrogen treatment for many years. However, risk of breast cancer in these persons remains 1 in 1000. This suggests that alternative factors must play a significant role in the development of breast cancer. Dr. Bennick suggested that these could include an array of considerations including number of menstrual cycles and lifestyle factors.

 

Could estrogens help to prevent breast cancer?

In a special countercurrent lecture, Dr. Bennink argued that while estrogens have a mechanism to promote breast cancer, they may also have some protective effect. As an example, he explained that pregnancy can result in a significant reduction in risk of estrogen-receptor positive breast cancer. We know that pregnancy is associated with a large increase in estrogens. One could hypothesise that this could be protective. However, the specific mechanism of action is not clear and more research is required to fully understand if estrogens could have some protective effects on breast cancer risk.  


Sources:

[1] Writing Group for the Women's Health Initiative Investigators. Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal WomenPrincipal Results From the Women's Health Initiative Randomized Controlled Trial. JAMA. 2002;288(3):321–333. doi:10.1001/jama.288.3.321

[2] Roger A. Lobo; Where Are We 10 Years After the Women's Health Initiative?, The Journal of Clinical Endocrinology & Metabolism, Volume 98, Issue 5, 1 May 2013, Pages 1771–1780, https://doi.org/10.1210/jc.2012-4070

[3] Marjoribanks J, Farquhar C, Roberts H, Lethaby A, Lee J. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database of Systematic Reviews 2017, Issue 1. Art. No.: CD004143. DOI: 10.1002/14651858.CD004143.pub5