Primarily used to treat breast cancer and prostate cancer — the two main cancers that depend on sex hormones to grow — hormone therapy is an effective treatment method that can often be used curatively, either alone or in conjunction with surgery, chemotherapy, or radiation.
“Hormonally driven cancers express hormone receptors that then act as a growth stimulant for the cancer,” says medical oncologist and University of Colorado Anschutz Cancer Center member Laura Graham, MD. “Prostate cancer expresses the androgen receptor, which binds to testosterone, and breast cancer often expresses the estrogen receptor and the progesterone receptor. You can block the body from producing those hormones by using drugs that stop the pituitary from telling the testicles or ovaries to produce those hormones — drugs like Lupron for breast and prostate cancer or Relugolix for prostate cancer.”
Other types of hormonal therapies block the binding of the hormone to the receptor on the cancer cell. In prostate cancer, androgen receptor pathway inhibitors include enzalutamide, apalutamide, and darolutamide; in breast cancer, aromatase inhibitors like anastrozole and letrozole are used to reduce estrogen production and limit the growth of hormone receptor–positive breast cancer cells.
A new class of drugs is aimed at degrading the receptors so they can no longer act as growth stimulants even when altered by the cancer cells. In breast cancer, fulvestrant is an estrogen receptor degrader that is already used clinically. In prostate cancer, newer drugs are being developed to degrade the androgen receptor, including altered forms of the receptor that can contribute to treatment resistance.
“One of the ways that the cancers become resistant to the treatments is by mutating the hormone receptor so it's always on,” says Graham, assistant professor of medical oncology in the CU Anschutz School of Medicine. “There are drugs being tested that essentially take the androgen receptor and force it to bind to the proteasome system in the cell, which is like the cell's paper shredder.”
Unlike many other cancer drugs that are administered by infusion, hormone therapy drugs are typically either long-acting injections or pills taken once a day. Side effects vary by the type of cancer being treated — in men being treated for prostate cancer, the sudden loss of testosterone can be a difficult adjustment, Graham says.
“Most men are not enthusiastic when we tell them that we're going to be taking away their testosterone,” she says. “I tell them to expect things that we typically associate with menopause for women — hot flashes, fatigue, mood changes, being more tearful or more irritable than they're used to. The thing I really worry about is that over time, it can lower bone density, it may increase your risk of heart attack and stroke, it can impair some of your glucose regulation. I tell people that they have to exercise five times a week, half an hour, something that gets their heart rate up, and then at least twice a week they should do some kind of resistance training.”
In women taking hormone therapy for breast cancer, side effects also are similar to those of menopause, says breast cancer specialist and CU Anschutz Cancer associate director of global oncology Enrique Soto, MD, PhD.
“What I always tell my patients is that the side effects of hormone therapy are very similar to the side effects of menopause, because what we are causing is kind of a second menopause,” says Soto, visiting associate professor of medical oncology in the CU Anschutz School of Medicine. “They can experience hot flashes, joint or muscle aches, vaginal dryness, and changes in bone health.
“The good news is that we have very good strategies to manage side effects,” he adds. “For almost all the side effects that people get, we have interventions we can do so they feel better. In some scenarios, we can switch medications so that we find the right one for each patient. We encourage people to talk to their care team and work with their care team to try to solve these symptoms or improve them, rather than just stopping treatment.”
In breast cancer, Soto says, hormone therapy is often part of a multidisciplinary treatment. It can be given after surgery or in conjunction with radiation or chemotherapy, if those treatments are needed.
“Hormone therapy can be used alone in some cases, and in other cases it can be combined with other medications such as targeted therapies,” he says. “One of the advantages of hormonal therapy is that if tumors express hormone receptors, it can often control cancer very effectively and for a very long period without needing to use chemotherapy. Even though these pills have been around for a long time, they are still, I believe, the best treatment we have against breast cancer.”