Treatment Helps Preserve Fertility for Some Women with Breast Cancer
, by NCI Staff
Results from an NCI-sponsored clinical trial show that giving some younger women with early-stage breast cancer a hormone-suppressing drug in addition to chemotherapy helps to preserve ovarian function and improves their ability to get pregnant after treatment.
The findings were published March 5 in the New England Journal of Medicine.
The POEMS trial tested whether administering injections of the drug goserelin (Zoladex) prior to and during standard pre- or post-operative chemotherapy could help to prevent long-term failure of ovarian function—a common side effect of chemotherapy that can leave women infertile. The trial enrolled women between the ages of 18 and 49 who had estrogen-receptor (ER) negative, early-stage breast cancer. By blunting production of hormones that regulate ovarian activity, goserelin temporarily causes the ovaries to become dormant—a form of chemical menopause-- protecting them from chemotherapy, which seeks out actively reproducing cells.
Overall, only 8 percent of women who received monthly injections of goserelin beginning 1 week prior to chemotherapy experienced ovarian failure (as measured by the loss of menstruation and postmenopausal levels of the hormone FSH), compared with 22 percent of women who received chemotherapy alone. Also, 21 percent of women in the goserelin group had at least one pregnancy, compared with just 11 percent in the chemotherapy-alone group.
The trial randomized a smaller population of eligible patients—218 in total—than had originally been planned, explained study co-author Lori Minasian, M.D., of NCI’s Division of Cancer Prevention. However, detailed statistical analyses showed a consistent positive benefit of goserelin across multiple different endpoints, she continued, findings that were convincing even with a smaller than planned study sample.
A trial like POEMS was difficult to conduct, Dr. Minasian explained, because it needed to enroll not just younger women, among whom breast cancer is relatively rare, but also women whose cancer was not responsive to hormones. In ER-positive breast cancers, which are much more common than ER-negative breast cancers, extended treatment with hormone-blocking drugs such as tamoxifen are an essential part of therapy and improve survival.
So limiting the trial to ER-negative, premenopausal patients, although challenging, was essential to do the trial, explained its lead investigator Halle Moore, M.D., of the Cleveland Clinic Taussig Cancer Institute.
“We wanted to measure ovarian function at 2 years,” Dr. Moore said, “and the extended hormonal treatments [used in hormone receptor-positive patients] would interfere with our ability to measure menopausal hormones [such as FSH] and whether women were having menstrual periods, which were included in our ovarian failure definition.”
“An important feature of this trial is that we not only had a biologic correlate—menstruation and hormone levels—but we also had actual pregnancy outcomes,” Dr. Minasian said. “That really is the value of this trial.”
The investigators also found that patients who received both goserelin and chemotherapy lived longer, both overall and without their disease returning. Given the small number of patients and the excellent prognosis of women with early-stage disease, the observed survival differences are by no means definitive, Dr. Minasian stressed.
“At the very least, we can say that this approach doesn’t appear to be detrimental in these patients,” she said. “But no patient should have this treatment solely because they think it will provide a survival advantage.”
By preventing some of the menopausal symptoms caused by chemotherapy-induced ovarian failure, adding goserelin to chemotherapy treatment may also improve patients’ quality of life, Dr. Moore added.
The trial findings received substantial attention when they were initially presented last June at the 2014 American Society of Clinical Oncology annual meeting, and they appear to be influencing care for women with breast cancer, Dr. Moore said.
“I think oncologists are beginning to use goserelin routinely, and publication of the results will only increase awareness,” she said.
At the Cleveland Clinic, premenopausal women with breast cancer are routinely offered the treatment. Some patients who plan on having children, she continued, have opted to use goserelin and also undergo embryo or egg cryopreservation to optimize their chances of getting pregnant after their cancer treatment.
Dr. Moore described a younger patient with early-stage breast cancer she saw recently who had almost backed out of having chemotherapy because of fertility concerns.
“I discussed [the goserelin] option with her,” she said. “Even though she doesn’t know for sure if she wants children, just that feeling of being able to improve those prospects was comforting to her, and she went ahead with the treatment.”