Hormone Therapy in Breast and Prostate Cancer: Receptor Degraders Target Treatment Resistance
核心洞察
Hormone therapy remains a cornerstone treatment for breast and prostate cancer (搜索), the two major cancers driven by sex hormones, and can often be used curatively.
Oncologists at the University of Colorado Anschutz Cancer Center (搜索) describe two main strategies: blocking hormone production or blocking hormone binding to tumor receptors.
A newer drug class aims to degrade hormone receptors entirely, including mutated forms that keep receptors permanently active and drive treatment resistance.
Hormone therapy remains one of the most effective systemic approaches for breast and prostate cancer (搜索) — the two main cancers that depend on sex hormones to grow — and can often be used with curative intent, either alone or in combination with surgery, chemotherapy or radiation, according to oncologists at the University of Colorado Anschutz Cancer Center (搜索).
"Hormonally driven cancers express hormone receptors that then act as a growth stimulant for the cancer," said medical oncologist Laura Graham, MD, a CU Anschutz Cancer Center member and assistant professor of medical oncology in the CU Anschutz School of Medicine. Prostate cancer (搜索) expresses the androgen receptor (搜索), which binds testosterone, while breast cancer (搜索) often expresses the estrogen receptor (搜索) and the progesterone receptor (搜索).
Two Established Strategies: Blocking Production or Blocking Binding
One therapeutic approach blocks the body from producing the hormones that fuel these tumors. Drugs such as Lupron are used for both breast and prostate cancer (搜索), and Relugolix for prostate cancer, work by stopping the pituitary from signaling the testicles or ovaries to produce those hormones, Graham explained.
A second approach blocks the binding of the hormone to the receptor on the cancer cell. In prostate cancer (搜索), androgen receptor (搜索) pathway inhibitors include enzalutamide, apalutamide and darolutamide. In breast cancer (搜索), aromatase inhibitors such as anastrozole and letrozole reduce estrogen production and limit the growth of hormone receptor–positive breast cancer cells.
A New Class: Receptor Degraders
A newer class of drugs is designed to degrade the receptors so they can no longer act as growth stimulants, even when altered by cancer cells. In breast cancer (搜索), fulvestrant is an estrogen receptor (搜索) degrader already used clinically. In prostate cancer (搜索), newer agents are in development to degrade the androgen receptor (搜索), including altered forms of the receptor that 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," Graham said. "There are drugs being tested that essentially take the androgen receptor (搜索) and force it to bind to the proteasome system in the cell, which is like the cell's paper shredder."
Administration and Tolerability
Unlike many cancer drugs given by infusion, hormone therapies are typically administered as long-acting injections or as once-daily pills. Side effects vary by the cancer being treated. In men treated for prostate cancer (搜索), the abrupt loss of testosterone can be a difficult adjustment, Graham noted.
"Most men are not enthusiastic when we tell them that we're going to be taking away their testosterone," she said. "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."
Graham highlighted longer-term concerns: reduced bone density over time, possible increased risk of heart attack and stroke, and impaired glucose regulation. She advises patients to exercise five times a week for half an hour at an intensity that raises heart rate, plus resistance training at least twice a week.
Managing a "Second Menopause" in Breast Cancer
In women receiving hormone therapy for breast cancer (搜索), side effects similarly mirror menopause, according to breast cancer specialist Enrique Soto, MD, PhD, CU Anschutz Cancer associate director of global oncology and visiting associate professor of medical oncology in the CU Anschutz School of Medicine.
"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," Soto said. Patients may 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 added. "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." He encouraged patients to work with their care team to address symptoms rather than discontinuing treatment.
Role in Multidisciplinary Breast Cancer Care
In breast cancer (搜索), hormone therapy is often part of a multidisciplinary treatment plan and can be given after surgery or alongside radiation or chemotherapy when those treatments are needed, Soto said.
"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 said. "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 (搜索)."