The results of the highly anticipated Suppression of Ovarian Function Trial (SOFT) were presented at the 2014 San Antonio Breast Cancer Symposium (SABCS), held December 9–13 in San Antonio, Texas. Early-stage premenopausal estrogen receptor (ER)-positive breast cancer patients who had received prior chemotherapy benefited from the combination of ovarian suppression with standard-of-care tamoxifen. But, a greater reduction in recurrence occurred in high-risk women, 35 years of age or younger, who did not reach menopause after receiving initial chemotherapy, and were then given ovarian suppression in combination with the aromatase inhibitor exemestane.

Older premenopausal women who received no prior chemotherapy before starting the trial did well with tamoxifen alone, demonstrating that the addition of ovarian suppression is not necessary in this lower-risk patient group with a median age of 46.

“We see no advantage of adding ovarian suppression for this group,” said study author Prudence Francis, MD, head of breast medical oncology at the Peter MacCallum Cancer Centre in Melbourne, who presented the results at a press conference.

The results were also published in the New England Journal of Medicine. The trial was led by the International Breast Cancer Study Group. In the United States, the trial was funded by the National Cancer Institute.

Results from another portion of the SOFT trial were presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.

Tamoxifen is the standard hormonal therapy following surgery for premenopausal hormone receptor–positive breast cancer. Previous trials showed that women who enter menopause following chemotherapy have a lower risk of breast cancer recurrence.

It has been unclear whether ovarian suppression on top of tamoxifen results in better outcomes. Prior trials did not address the role of ovarian suppression on disease recurrence, as these trials did not wait long enough after initial chemotherapy to assess whether the chemotherapy would cause the patient to enter menopause. Therefore, Francis explained, these trials masked any potential role of ovarian suppression.

The SOFT trial overcame this issue by waiting 8 months after chemotherapy to assess whether the patient entered menopause due to chemotherapy or remained premenopausal and could benefit from ovarian suppression.

The trial enrolled 3,047 patients who had early-stage hormone receptor–positive disease into two cohorts: 1) a no chemotherapy group that remained premenopausal 12 weeks after surgery, and 2) a prior chemotherapy group that remained premenopausal after 8 months of chemotherapy. Patients were randomized to one of three treatment arms for 5 years: tamoxifen (1,018 patients), tamoxifen and ovarian suppression (1,015 patients), or exemestane and ovarian suppression (1,014 patients). Ovarian suppression was in the form of monthly triptorelin injections. All patients received therapy for 5 years.

Women in the group that did not receive chemotherapy had lower-risk disease on average, while those who received prior chemotherapy were younger and had higher-risk disease. Slightly more than 50% of patients had received prior chemotherapy before enrolling in the trial.

Overall, women who received tamoxifen with ovarian suppression had an improvement in disease-free survival compared with those treated with tamoxifen alone, although the difference was not statistically significant.

Women who received prior chemotherapy benefited the most from the addition of ovarian suppression. The relative risk of breast cancer recurrence decreased by 22% in those women who received both ovarian suppression and tamoxifen and who had prior chemotherapy, compared with those who were just treated with tamoxifen. This decrease was not statistically significant. Out of every 100 patients, the addition of ovarian suppression to tamoxifen resulted in 4 to 5 fewer patients having a recurrence within 5 years in this cohort.

Women who received prior chemotherapy and were treated with exemestane with ovarian suppression had a 35% decrease in the risk of breast cancer recurrence compared with the women who were treated with tamoxifen-a statistically significant result. This translated to 7 or 8 fewer women out of 100 having a recurrence within 5 years.

According to Francis, the study investigators found that the most striking effect of the advantage in adding ovarian suppression to treatment was among women 35 years old or younger who received prior chemotherapy. One in three women who received tamoxifen alone had a recurrence within 5 years compared with one in six women who received exemestane plus ovarian suppression.

For this patient population, Francis feels this is a “practice-changing trial.”

Overall quality of life was not reduced, although ovarian suppression increased menopausal symptoms, particularly in the first 2 years. Additionally, exemestane with ovarian suppression affected sexual functioning. The quality-of-life details are part of a separate presentation at the meeting.

According to Francis, patients continue to be followed for cancer recurrence and any potential late-onset side effects, as well as overall survival.

Reference

1. Francis PA, Regan MM, Fleming GF, et al. Randomized comparison of adjuvant tamoxifen (T) plus ovarian function suppression (OFS) versus tamoxifen in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): Analysis of the SOFT trial. Presented at 2014 San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, Texas. Abstract S3-08.