New approaches to treating women with advanced estrogen receptor-positive (ER+) breast cancer are in development, which includes both hormone therapy and combinations with targeted agents. The continuing goal is to understand disease biology and individualize treatment regimens to increase survival, while reducing toxicities that lessen quality of life for patients.
First-Line Hormonal Therapy
Hormonal therapies that block estrogen signaling are still the most important element of therapy regimens for both pre- and postmenopausal women with advanced ER+ breast cancer. Premenopausal women are generally treated with tamoxifen, a drug that severs the tumor’s source of growth stimulation, estrogen. Tamoxifen is a selective estrogen receptor modulator (SERM) that prevents the binding of estrogen to the estrogen receptor in breast tissue. Women diagnosed prior to menopause are also given drugs that temporarily stop the ovaries from producing estrogen. An oophorectomy is also an option. Because most women are diagnosed with early-stage disease, they will have likely already been treated with adjuvant tamoxifen at the time of progression. These patients are typically treated with an aromatase inhibitor (AI) and an ovarian function suppressant.
Matthew Goetz, MD
AIs are the standard of care for postmenopausal, ER+ metastatic breast cancer based on studies showing treatment with AIs results in longer survival compared with treatment with tamoxifen.1
AIs inhibit the enzyme aromatase, which helps produce estrogen outside of the ovaries. Response rates for postmenopausal women to first-line hormone therapy are approximately 21% to 32%.2,3
Another hormonal agent, fulvestrant, is an anti-estrogen therapy that, unlike SERMs, has no estrogen agonist activity. Fulvestrant is not approved in the first-line metastatic setting, but follow-up data from phase II trials recently showed that treatment of postmenopausal women with ER+ breast cancer with 500 mg of fulvestrant may result in better outcomes compared with treatment with anastrozole (median time to progression, 23.4 months vs 13.1 months, respectively; P
Further studies are needed to confirm this result.
Patients with metastatic ER+ breast cancer can generally be divided into those who present with de novo metastatic disease and those who have already received hormone therapy in the adjuvant setting. Postmenopausal patients with early-stage disease are most commonly started on a nonsteroidal AI, either anastrozole or letrozole, said Matthew Goetz, MD, associate professor of Oncology and Pharmacology at the Mayo Clinic, Rochester, Minnesota. Exemestane, a steroidal AI, is also an option in the adjuvant setting. Exemestane was compared with anastrozole and letrozole in 7576 women with postmenopausal, early-stage ER+ breast cancer. The adjuvant phase III trial, MA.27, showed that the distant disease-free survival for women taking either the steroidal or nonsteroidal AIs for 5 years was the same.5