Ovarian Suppression Improves Prevention of HR-Positive Breast Cancer Recurrence

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Adding OFS to adjuvant postsurgical tamoxifen therapy can reduce breast cancer recurrence.
Adding OFS to adjuvant postsurgical tamoxifen therapy can reduce breast cancer recurrence.

SAN ANTONIO—Adding ovarian function suppression (OFS) to adjuvant postsurgical tamoxifen therapy can reduce breast cancer recurrence in premenopausal women with early-stage hormone receptor–positive (HR-positive) breast cancer who have undergone chemotherapy without reaching menopause, according to findings from the randomized, phase 3 suppression of ovarian function trial (SOFT). The findings were presented at the 2014 San Antonio Breast Cancer Symposium.

A secondary analysis showed that additional reductions in recurrence are associated with exemestane plus OFS, reducing relative risk of breast cancer recurrence by 35%. That translates to seven to eight fewer breast cancer recurrences per 100 patients in 5 years, according to lead study author Prudence Francis, MD, head of breast medical oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia.

“We found that that adding ovarian suppression to tamoxifen was somewhat beneficial for those women with early-stage, HR-positive breast cancer who remained premenopausal after chemotherapy,” Dr. Francis reported. “However, we found a greater reduction in recurrence in this same patient group with the use of ovarian suppression plus the aromatase inhibitor exemestane.”

The researchers enrolled 3,047 women with early-stage, HR-positive breast cancer in the study. The mean age of all study participants was 43 years. Participants were randomly assigned to receive 5 years of tamoxifen (n=1,018), tamoxifen and ovarian suppression (n=1,015), or exemestane and ovarian suppression (n=1,014). In most patients, ovarian suppression was achieved using monthly triptorelin injections; others chose to undergo permanent ovarian oblation.

At a median follow-up of 5.6 years, study participants with a chemotherapy history and who were assigned to receive tamoxifen with ovarian suppression had an overall statistically nonsignificant 22% reduction in breast cancer recurrence compared to those who received tamoxifen without ovarian suppression, Dr. Francis reported.

In other words, adding ovarian suppression to tamoxifen did not significantly improve disease-free survival (DFS) overall (P = 0.10, not significant), Dr. Francis reported. Nineteen percent of participants ceased tamoxifen therapy early, she noted.

However, breast cancer recurrence rates were decreased by 35% among premenopausal women who underwent chemotherapy for early-stage HR-positive breast cancer and who received exemestane with ovarian suppression.

Benefits from OFS were “most striking” in women younger than age 35 years, she said.

“For women who have not reached menopause and have HR-positive breast cancer that carries sufficient risk of recurrence that they receive chemotherapy, physicians are likely to discuss the option of treatment with ovarian suppression plus an aromatase inhibitor,” she said.

However, OFS comes with risks of its own, she cautioned: it was associated with increased menopausal symptoms and rates of depression, hypertension, diabetes, and osteoporosis.

“Long-term followup in SOFT is crucial to assess overall survival and late toxicities,” she added. “Future analyses are planned.”

The International Breast Cancer Study Group (IBCSG), National Cancer Institute, and Pfizer funded the study.


  1. Francis PA, Regan MM, Fleming GF et al. S3-08. Presented at: San Antonio Breast Cancer Symposium 2014. Dec. 9-13, 2014; San Antonio, TX.

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