Breast Cancer & Estrogen’s Link, Explained By Researchers

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Understanding breast cancer is important in part because the disease is so widespread. But even if no one in your life is affected by breast cancer, it's still important to stay informed about of the latest research in breast cancer. This is both because it's so common, but because there are a lot of myths around it.

"One in eight women will have breast cancer in their lifetime," Dr. Cesar Santa-Maria, Assistant Professor of oncology at Johns Hopkins Medicine, tells Bustle, and men can also get breast cancer diagnoses. 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 in the form of 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.

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, 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, and estrogen fuels their growth.

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"Estrogen receptor positive breast cancer cells are cells that are expressing estrogen receptor when they’re not supposed to," Dr. Marco Padilla-Rodriguez, 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.

Right now, people with these kinds of breast cancers will receive medication that blocks the action of estrogen to stop their primary tumors growing. These therapies, says Dr. Brown, "prevent estrogen production or block the estrogen receptor in cancer cells to prevent binding by estrogen, with the goal of starving the tumor of estrogen and interrupting cancer growth." However, research is also showing that estrogen has different roles in different stages of breast cancer — and it's changing the way we understand our hormones.

According to Dr. Padillo-Rodriguez's research, estrogen may cause ER-positive breast cancers to grow, but it can also have benefits. "In cancer in general, not just breast cancer, when the cancer begins to leave that primary tumor and spread into lymph nodes, blood, and elsewhere, it’s a clear sign that the cancer is advancing. It's called metastasis," he tells Bustle. In research published in Nature Communications in 2019, he and his co-authors discovered that when it comes to the spread of ER-positive breast cancers, estrogen actually stops them from spreading, even as it contributes to their development. "It promotes the growth of cancer cells, but it may also suppress their metastatic potential," he says. 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, particularly in the brain, but also lives in breast cells. When breast cancer cells were treated with estrogen, EVL changed their structure and caused a "decrease in motility and dissemination" (in other words, they stopped 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 has been shown to 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.

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It's one thing to talk about what estrogen does to breast cancer cells to help them grow or stop them shifting, but what about causing cancer in the first place? If you've ever taken hormonal birth control that includes synthetic estrogen, you may wonder if that might increase your risk of breast cancer. "There was a large study from Scandinavia recently that shows there’s 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. "But we know that these reproductive factors, like when women have their first period or their first child, do influence breast cancer risk." Increased estrogen levels over time do, in some studies, seem to show a relationship with increased breast cancer risk.

Dr. Brown is cautious, however, pointing out 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. Santa-Maria 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. "A patient should weigh the pros and cons with their doctor about going on oral contraceptive pills."

If you have a family history of ER-positive breast cancer, you may be concerned that oral contraceptives or hormone replacement therapy might increase your risk of breast cancer, but that isn't necessarily so. Inheriting BRCA gene mutations, says Dr. Santa-Maria, "can increase somebody's risk by 40 to 80%." If you have those mutations, taking oral contraceptives isn't immediately off the table. "The risk is mostly genetically driven rather than by the modest increases in oral contraceptives," he says. "This needs to be decided on an individual level with your doctor." Further, around 85% of people with breast cancer will not have a family history of the disease, according to the American Cancer Society, so it's important to understand your other potential risk factors.

The bigger picture when it comes to estrogen and breast cancer, researchers say, is still full of unanswered questions and exciting new research. The immune system, says Dr. Brown, might offer a new potential way to treat estrogen-driven cancers, but we're still a long way off from a potential drug — and we still don't know how to completely cure advanced metastatic ER-positive breast cancer, because estrogen-blocking therapies on their own aren't enough. However, 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

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, Professor, Medical Oncology, Harvard Dana-Farber Cancer Institute

Dr. Marco Padilla-Rodriguez, postdoctoral researcher, University of Arizona

Dr. Cesar Santa-Maria, Assistant Professor of Oncology, Johns Hopkins Medicine