Researchers Explain How Breast Cancer & Estrogen Are Linked

Understanding breast cancer is important in part because the disease is so widespread, affecting around one in eight women. But even if no one in your life is affected by the disease, it's still important to stay informed about of the latest research in breast cancer — according to the World Health Organization, about half of breast cancer diagnoses occur in women with no risk factor for the disease other than their gender and age (40 and older). Research around breast cancer and estrogen, in particular, is an important field of study, since there are so many misconceptions about estrogen in general.

Estrogen is a hormone produced naturally in the body, and many people also take it synthetically as hormonal birth control. Experts tell Bustle that science right now indicates that estrogen has a very complicated relationship with breast cancer, and that it's not easy to make generalizations.

How Does Estrogen Affect Breast Cancer?

The most obvious link between estrogen and breast cancer is found in breast cancers that depend on estrogen to survive. "About two-thirds to three-quarters of breast cancers require estrogen for their growth," Dr. Myles Brown M.D., a professor of medicine at the Dana-Farber Cancer Institute, tells Bustle. These cancers are known as estrogen-receptor positive cancers, or ER positive cancers.

"Estrogen receptor positive breast cancer cells are cells that are expressing estrogen receptor when they’re not supposed to," Marco Padilla-Rodriguez Ph.D., a postdoctoral researcher at the University of Arizona who studies cellular and molecular medicine, tells Bustle. In bodies without cancer, estrogen tells these cells to grow at particular times, like during pregnancy to prepare for breastfeeding, but when they become cancerous, they start to grow all the time, and that causes tumors. People with these kinds of breast cancers will receive medication that blocks estrogen to stop their primary tumors growing.

But while estrogen may cause ER-positive breast cancers to grow, it can also stop it from metastasizing, or spreading to other areas of the body. "It promotes the growth of cancer cells, but it may also suppress their metastatic potential," says Padillo-Rodriguez, who authored a 2019 paper published in Nature Communications on this finding. Metastatic breast cancer currently has no cure, so this is a crucial discovery.

The culprit is a protein called EVL, which is found throughout the body. When breast cancer cells were treated with estrogen, EVL changed their structure and stopped them from spreading to other parts of the body. So estrogen isn't just a growth trigger for breast cancer; it may, in the future, help targeted therapies to prevent ER-positive cancers spreading. At the same time, research published in Nature in 2019 shows that in breast cancers that don't involve estrogen, the hormone can help cells spread to the brain, opposite to how it works in ER-positive breast cancer. So estrogen's relationship with breast cancers is a very complex one.

Can Estrogen Cause Cancer?

It's one thing to talk about what estrogen does to breast cancer cells, but what about before a cancer grows in the first place? Myriad factors influence whether you might develop breast cancer, like family history, age you first menstruated, and more, but increased estrogen levels over time do seem to have a relationship with breast cancer risk. In 2017, a Scandinavian study published in the New England Journal of Medicine showed there was a small increase in breast cancer risk in people who take oral contraceptives or take hormones. "It’s a very small increased risk," Dr. Brown tells Bustle. Transgender women who use hormones also have a higher rate of breast cancer than cisgender men. A study of 2,260 transgender women in the Netherlands published in the British Medical Journal in 2019 found that 15 of them had developed breast cancer. The process of undergoing estrogen hormone therapy appeared to increase the risk by up to 47 times, the researchers said.

Dr. Brown stresses that estrogen isn't the only factor that influences cancer growth — progesterone and other hormones do, too. The relationship between estrogen levels and the risk of breast cancers, he says, is "complicated," and depends heavily on factors like whether you've gone through menopause. Dr. Cesar Santa-Maria M.D., assistant professor of oncology at Johns Hopkins Medicine, agrees. "Oral contraceptive pills can modestly increase the risk of breast cancer, but what we're talking about is incremental increases of risk," he tells Bustle, noting that there are plenty of pros to birth control and it's a decision to make with your doctor. "The risk is mostly genetically driven rather than by the modest increases in oral contraceptives," he adds.

The bigger picture when it comes to estrogen and breast cancer, researchers say, is still full of unanswered questions and exciting new research. A lot of new approaches are being studied — and every new breakthrough means potential lives saved.

Studies referenced:

Collaborative Group on Hormonal Factors in Breast Cancer. (2012) Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. Lancet Oncology. 13(11), 141–1151. doi: 10.1016/S1470-2045(12)70425-4

Contreras-Zárate, MJ, Day, NL, Ormond, DR, Borges, VF, Tobet, S, Gril, B, Steeg, PS & Cittelly DM (2019). Estradiol induces BDNF/TrkB signaling in triple-negative breast cancer to promote brain metastases. Oncogene. 38, 4685–4699. https://www.nature.com/articles/s41388-019-0756-z

de Blok, C., Wiepjes, C. M., Nota, N. M., van Engelen, K., Adank, M. A., Dreijerink, K., Barbé, E., Konings, I., & den Heijer, M. (2019). Breast cancer risk in transgender people receiving hormone treatment: nationwide cohort study in the Netherlands. BMJ (Clinical research ed.), 365, l1652. https://doi.org/10.1136/bmj.l1652

Mørch, LS, Skovlund, CW, Hannaford, PC, Iversen, L, Fielding, S, Lidegaard Ø. (2019) Contemporary Hormonal Contraception and the Risk of Breast Cancer. N Engl J Med. 377, 2228-2239. doi: 10.1056/NEJMoa1700732

Padilla-Rodriguez, M, Parker, SS, ADams, DG, Westerling, T, Puleo, JI, Watson, AW, Hill, SM, Noon, M, Gaudin, R, Aaron, J, Tong, D, Roe, DJ, Knudsen, B, Mouneimne, G. The actin cytoskeletal architecture of estrogen receptor positive breast cancer cells suppresses invasion. Nature Communications 9, 2980. https://www.nature.com/articles/s41467-018-05367-2#article-info

Experts:

Dr. Myles Brown, M.D.

Marco Padilla-Rodriguez Ph.D.

Dr. Cesar Santa-Maria M.D.