Pre-Operative Hormone Therapy May Improve Surgical Options for Women Mastectomy for Breast Cancer

Many women with larger breast cancer opt for mastectomy due to concern over their surgeon’s ability to completely remove the tumor with smaller, breast-preserving operations. But research co-led by a University of Maryland Marlene and Stewart Greenebaum Cancer Center investigator has shown that significant numbers of post-menopausal women with large, estrogen-rich cancers may be able to opt for breast-conserving surgery instead with pre-operative aromatase inhibitor (AI) therapy. John A. Olson Jr., M.D., Ph.D., professor and vice chairman of the department of surgery at the University of Maryland and chief of general and oncologic surgery at University of Maryland Medical Center, was co-principal investigator of the phase II national clinical trial, which found that more than half of the postmenopausal women who initially faced mastectomy were able to have a lumpectomy after taking AIs for four months. The principal investigator of the research, conducted by the American College of Surgeons Oncology Group (ACOSOG) and recently presented at the Society of Surgical Oncology’s national meeting, was Matthew Ellis, M.D., Ph.D., of Washington University in St. Louis.

Less toxic more targeted drugs

AIs, which inhibit the production of estrogen in postmenopausal women, are a form of endocrine therapy that is a lower-toxicity option than chemotherapy. For many years, chemotherapy was thought to be the more effective approach, but growing evidence that a breast tumor’s behavior is determined by the genes it expresses rather than its size alone has helped renew interest in estrogen receptor-positive cancers and targeted drug therapies for them, Dr. Olson explains.

“Now, there’s more awareness that the biology of the tumor should drive the specific therapy,” he says. “The first targeted therapy in breast cancer was tamoxifen ... and I think we’re coming around now to oral, non-toxic therapies, so I think the time is right for this type of neoadjuvant therapy.”

The ACOSOG study analyzed results from 374 patients with stage II and III estrogen receptor-positive tumors, 45.7% of whom were considered candidates for mastectomy and 53.2% for lumpectomy (1.1% were considered inoperable). Patients received one of three FDA-approved oral AIs, including anastrozole, letrozole or exemestane. After 16 weeks, 352 women had surgery: 241 underwent lumpectomy and 111 had a mastectomy, but the group having breast-conserving surgery included 84 of 163 (51%) women who had been initially deemed by their surgeons to require mastectomy.

Pioneering leadership, multiple reasons for success

University of Maryland’s Angela H. Brodie, Ph.D., a professor of pharmacology and experimental therapeutics, pioneered the development of AIs, which have also shown effectiveness at helping prevent breast cancer in some high-risk patients. It is thought that about 80% of breast cancer in postmenopausal women expresses hormone receptors, including estrogen receptors.

One drawback of the ACOSOG trial was that it wasn’t randomized as far as the timing of the drug in relation to surgery, Dr. Olson notes, so it couldn’t prove that AIs alone caused the tumors to become more appropriate for breast-sparing surgery over the four-month span. Multiple factors may have accounted for the change, “but the data show that the response to endocrine therapy, as well as what the surgeon thought up front, was really driving this,” he says.

Patients took a small risk in opting for AI therapy while awaiting surgery, with about one in 12 tumors continuing to grow during the study period. But participants were monitored at “careful frequency,” Dr. Olson says. Importantly, Dr. Ellis designed an add-on to the trial that allowed those patients whose tumors didn’t respond to endocrine therapy to switch to chemotherapy instead, which was “a very clever way of assessing a tumor’s response.” Others opted for immediate surgery. 

Compelling benefits for patients

Postmenopausal women with estrogen-rich tumors who are struggling with the prospect of a mastectomy have much to gain from the idea of a carefully supervised regimen of endocrine therapy, according to Dr. Olson. Not only might they be able to avoid a larger surgery — with its attendant longer recovery time and potential complications — but there are many other advantages to lumpectomy.

“I think the greatest benefit is the preservation of body image for those women who feel it’s an important part of their life,” he says. “It empowers patients. They’re getting what should be very effective treatment, and then it’s giving them the time to understand their disease and their surgical options.

“The women who participated in this trial did a great service to the public,” Dr. Olson adds. “Their participation helped advance the field.”

This page was last updated: November 7, 2013

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