In the first large trial of its kind in the United States, researchers have shown that estrogen-lowering drugs can shrink tumors and reduce mastectomy rates for patients with stage 2 or 3 breast cancer.
Patients with these larger breast tumors have two options, Matthew J. Ellis, MD, PhD, of Washington University School of Medicine in St. Louis and principal investigator of the trial conducted by the American College of Surgeons Oncology Group, stated in a press release.
“One option is to undergo mastectomy. The second is to receive medication before surgery to reduce the size of the tumor so that breast-conserving surgery becomes possible,” he stated.
Those who choose the second option usually receive chemotherapy. But now, Ellis and colleagues have shown that post-menopausal women with estrogen-receptor positive breast cancer can benefit from a class of drugs called aromatase inhibitors that lower the amount of estrogen in the body. Since estrogen-receptor positive breast cancers feed off estrogen, aromatase inhibitors can slow or stop the growth of these tumors in women who have undergone menopause.
Though estrogen no longer comes from the ovaries in post-menopausal women, they still make small amounts of estrogen with the enzyme aromatase. Aromatase inhibitors block this enzyme, eliminating the body’s remaining estrogen. Because aromatase inhibitors don’t stop the ovaries from making estrogen, they only work in post-menopausal women.
The results appeared online in the Journal of Clinical Oncology.
Of the 159 women in the trial who were originally told they required mastectomy, 81 or slightly more than half saw sufficient tumor shrinkage after 16 weeks of aromatase inhibitor treatment to undergo breast-conserving surgery instead.
“At the beginning, all of these patients were going to get mastectomy and at the end of the trial only half got mastectomy,” Ellis, also an oncologist who treats patients at the Alvin J. Siteman Cancer Center at Washington University and Barnes-Jewish Hospital, stated. “That’s a very substantial improvement in surgical outcomes.”
In addition, of the 189 women originally considered “marginal” for breast conservation — because it would likely be disfiguring — 83% saw enough tumor regression to undergo breast conserving-surgery rather than mastectomy. Of the four patients originally classified as inoperable, because mastectomy would not remove all the cancer, three saw enough tumor regression to undergo breast-conserving surgery and only one received mastectomy.
Beyond these benefits, aromatase inhibitors do not have the toxic side effects of traditional chemotherapy. For this particular group of patients, Ellis stated it is well established that aromatase inhibitors are more active in preventing relapses than chemotherapy.
Despite the improved surgical outcomes for some patients in this trial, Ellis pointed out that many women still required mastectomy because their tumors did not respond adequately to the aromatase inhibitor treatment.
“The biggest question in my mind is how best to treat the aromatase inhibitor-resistant patients,” he stated. “These patients have poor outcomes and currently there is no known targeted therapy for them. The question of aromatase inhibitor resistance is a critical issue to understand and address therapeutically.”
In an effort to find out why certain tumors are resistant to these drugs, Ellis and colleagues at Washington University’s Genome Institute just reported the complete tumor and healthy DNA sequences of 50 breast cancer patients enrolled in this trial. Twenty-six of the 50 tumors responded to treatment and 24 tumors did not.
“The patients gifted a sample of their tumor to the study and, because we know whether a tumor is responsive or resistant, we can start doing really profound studies to understand the molecular basis for variation in response,” he stated. “Ultimately, we hope the genomics instruct which new drugs to use to develop more effective treatment strategies.”