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Results from a large international study co-led by a VCU Massey Cancer Center physician-scientist concluded that adding ovarian suppression to adjuvant therapy (post surgery) with tamoxifen substantially reduced breast cancer recurrence in young, premenopausal women with hormone-sensitive early breast cancer who received chemotherapy because of a high risk for recurrence of their cancer. The practice-changing study was co-led by medical oncologist Charles Geyer, M.D., who serves as associate director for clinical research at Massey, and its results were recently presented at the 2014 San Antonio Breast Cancer Symposium and published online in the New England Journal of Medicine.

The main goal of the phase 3 clinical trial known as SOFT (Suppression of Ovarian Function Trial) was to determine whether blocking estrogen production through ovarian suppression therapy combined with standard adjuvant hormone therapy with tamoxifen would reduce breast cancer recurrence. The researchers found that ovarian suppression reduced breast cancer recurrence in high-risk patients who remained premenopausal after adjuvant chemotherapy, particularly in women under the age of 35. In addition, combining ovarian suppression with exemestane instead of tamoxifen further reduced recurrence rates in this population. The benefits of exemestane over tamoxifen were previously reported in the summer of 2014 in another publication in the New England Journal of Medicine that analyzed the results of another trial known as TEXT (Tamoxifen and Exemestane Trial) in combination with some of the patients from SOFT.

“This study will change clinical practice because it demonstrates that younger patients who maintain or regain ovarian function following chemotherapy for their hormone-receptor positive breast cancer obtain substantial benefits from the addition of ovarian suppression to adjuvant hormone therapy,” says Geyer, who is also Harrigan, Haw, Luck Families Chair in Cancer Research and member of the Developmental Therapeutics research program at Massey as well as professor in the Division of Hematology, Oncology and Palliative Care at the VCU School of Medicine. Geyer oversaw the National Surgical Breast and Bowel Project’s (NSABP) involvement in SOFT when he served as its director of medical affairs from 2004 to 2011.

Ovarian suppression was achieved by one of three ways: either monthly injections of a drug known as triptorelin (most common), surgical removal of the ovaries or radiation of the ovaries. In comparison to adjuvant hormone treatment with tamoxifen alone, treatment with tamoxifen plus ovarian suppression reduced the risk of breast cancer recurrence by 22 percent in women who did not remain in menopause following chemotherapy. Early or temporary menopause is a common side effect of chemotherapy, which can suppress estrogen production and cause menopausal symptoms. In women who receive chemotherapy, the menopause is often permanent. In younger women under the age of 35, menopausal symptoms are often temporary because ovarian function and estrogen production recovers after completion of the chemotherapy. The most important finding of the study was that women under the age of 35, an age group at particularly high risk of recurrence, benefitted most from the addition of ovarian suppression. After five years, only one in five women under age 35 receiving ovarian suppression plus tamoxifen experienced breast cancer recurrence, compared to one in three receiving tamoxifen alone. Among women under age 35 receiving exemestane plus ovarian suppression, only one in six experienced breast cancer recurrence.

SOFT also evaluated low risk women who did not require chemotherapy and whose adjuvant treatment consisted only of tamoxifen. Ovarian suppression was not beneficial for this group of women.

In addition to recurrence rates, the researchers also assessed patient-reported quality of life throughout the trial. Women treated with tamoxifen plus ovarian suppression initially reported worse hormone-related symptoms and sexual functioning than those receiving tamoxifen alone. However, after two years, differences in side effects between both groups were no longer apparent. Those who received exemestane plus ovarian suppression reported effects on sexual functioning throughout treatment.

“While ovarian suppression does not benefit everyone, clinicians and patients can use this data and the related information about the treatment’s side effects to tailor therapy for premenopausal women with hormone receptor-positive breast cancer,” says Geyer. “We believe the results of this study can improve the outcomes of cancer treatment for many young breast cancer patients.”

SOFT enrolled more than 3,000 premenopausal women with hormone receptor-positive early-stage breast cancer between December 2003 and April 2011. Trial treatment lasted five years; the women continue to be followed for life to assess long-term prognosis and side effects. The trial was led by the International Breast Cancer Study Group (IBCSG), in partnership with the Breast International Group (BIG), the National Surgical Breast and Bowel Project (NSABP) and other North American Breast Cancer Groups, and supported by IBSCG, Pfizer, Ipsen and the U.S. National Cancer Institute (NCI).

Written by: John Wallace