Role of Ovarian Function Suppression Still Unclear in Breast Cancer

Ruth O'Regan, MD

Breast cancer in younger women needs a different adjuvant treatment strategy from that used in post-menopausal women, but it may not have to include suppressing ovarian function, according to Ruth O'Regan, MD, at the 2017 Lynn Sage Breast Cancer Symposium.

Patients have a hard time with artificially induced menopause and some research suggests it may have a negligible effect on the success of their treatment, said O'Regan, division chief of hematology and medical oncology at the University of Wisconsin. She spoke Friday at the symposium, which is sponsored by Northwestern University's Robert H. Lurie Comprehensive Cancer Center.

"We need to hone in on getting a biomarker for who needs ovarian suppression," she said, noting that among women under 35, 20% stop taking the associated endocrine therapy because the side effects are too onerous. However, as long as they continue to take tamoxifen as prescribed, some studies show equivalent survival and recurrence rates.

Only about 1 in 5 new cases of breast cancer between 2009 and 2013 were in women under 50, according to SEER data, but while relapse-free survival rates are virtually identical for all age groups over 40, rates are significantly lower for women younger than 40 (Azim, Clin Ca Res 2012;18:1341-51).

There is some sentiment that breast cancer in younger women is a different disease, O'Regan said, but the difference is primarily that premenopausal women are more likely to have triple-negative breast cancer and less luminal A cancer. The overall adjuvant regimen recommendations are currently the same for both age groups, except that for the younger group, they include ways to preserve fertility and minimize side effects from longer-term use of tamoxifen or other agents.

O'Regan reviewed research for several adjuvant regimens, including tamoxifen alone, tamoxifen with ovarian function suppression (through oophorectomy, radiation, or use of LHRH agonists), and exemestane with ovarian function suppression. Results of the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT) showed that the regimens were similar in effectiveness among women who had not had chemotherapy, but they differed significantly in the number of side effects. Exemestane was associated with more musculoskeletal problems and osteoporosis—2 side effects that O'Regan said are particularly problematic for younger women who may be on these treatment regimens much longer.

The SOFT study specifically compared tamoxifen with and without ovarian suppression. The 5-year freedom from breast cancer rate was 95.8% for those treated with tamoxifen alone versus 95.1% and 97.1% for tamoxifen or exemestane plus ovarian suppression. In the 3 groups, respectively, there were 6, 7, and 3 distant recurrences at 5 years.

While there was almost no difference in freedom from breast cancer or freedom from distant recurrence among women who not received chemotherapy, ovarian function suppression significantly increased the risk of hot flashes, sweating, insomnia, osteoporosis, and hypertension, among other symptoms. O'Regan noted that patients might be at risk of developing premature coronary artery disease as well.

However, for women who had had chemotherapy, both studies showed clear improvement in recurrence rates from including ovarian function suppression as part of the adjuvant regimen.

Those treated with tamoxifen alone had a 78.0% 5-year freedom from breast cancer rate compared with 82.5% and 85.7% for those treated with ovarian suppression and tamoxifen or exemestane, respectively. The freedom from distant recurrence rate was 83.6% for tamoxifen alone and 84.8% and 87.8% for those treated with ovarian suppression and tamoxifen or exemestane, respectively. When compared with tamoxifen alone, these were statistically significant.

"Given the added toxicities [of ovarian function suppression], we need a better way of working out which patients need this approach," O'Regan said.

Several areas still require additional research, O’Regan pointed out. Specifically as it comes to biomarkers for selecting ovarian function suppression. Right now the progesterone receptor and the Ki-67 protein have both shown some promise as biomarkers, but more work is needed.