Ovarian Suppression for Young Women with Breast Cancer

Summary and Comment |
January 20, 2015

Ovarian Suppression for Young Women with Breast Cancer

  1. William J. Gradishar, MD

Adding ovarian suppression to adjuvant tamoxifen or exemestane was effective in patients who received prior chemotherapy.

  1. William J. Gradishar, MD

Adjuvant endocrine therapy for premenopausal patients with breast cancer has been limited to tamoxifen because functioning ovaries negate the effects of aromatase inhibitors. Small studies have shown that ovarian suppression (OFS) alone reduces the risk for breast cancer recurrence, but an appropriately sized, rigorously conducted trial to evaluate the effect of OFS in young patients has been lacking.

Now, investigators have conducted a prospective, randomized, phase III trial (the Suppression of Ovarian Function Trial [SOFT]), in which more than 3000 premenopausal women were randomized to 5 years of adjuvant tamoxifen therapy alone, 5 years of tamoxifen plus OFS, or 5 years of exemestane plus OFS. OFS was achieved with the gonadotropin-releasing–hormone agonist triptorelin, bilateral oophorectomy, or bilateral ovarian radiation. Patients were stratified by receipt or nonreceipt of prior adjuvant chemotherapy.

At median follow-up of 5.6 years, results were as follows:

  • For all patients, 5-year disease-free survival (DFS; the primary endpoint) was similar with tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS (86.4%, 88.4%, 90.9%, respectively).

  • Patients who did not receive prior chemotherapy (90% were ≥40 years of age) tended to have favorable clinical features: 91% had node-negative status, 85% had tumors ≤2 cm in size, and 41% had low-grade tumors. For these patients, DFS was >95% across all three treatment groups.

  • Patients who did receive prior chemotherapy tended to have more worrisome clinical features. For these patients, DFS was clearly improved with the addition of OFS: DFS with tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS was 78.0%, 82.5%, and 85.7%, respectively.

  • In the youngest patients (age, ≤35), of whom 94% received chemotherapy, DFS with tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS was 67.7%, 78.9%, and 83.4%, respectively.

  • Postmenopausal symptoms were more common with the addition of OFS.

Comment

The SOFT trial demonstrates that there is a group of premenopausal women with favorable clinical features who have an exceptionally good prognosis and that the type of adjuvant endocrine therapy they receive does not seem to matter. It also shows that for patients with more worrisome clinical features who are likely to receive a recommendation for adjuvant chemotherapy, particularly those younger than 35, ovarian suppression with an aromatase inhibitor offers the best strategy for reducing the risk for breast cancer recurrence.

Editor Disclosures at Time of Publication

  • Disclosures for William J. Gradishar, MD at time of publication Consultant / Advisory board Biologics, Inc. Editorial boards Clinical Breast Cancer; Journal of Clinical Oncology; Oncology Leadership positions in professional societies American Society of Clinical Oncology (Nominating Committee Chair)

Citation(s):

Reader Comments (1)

DARA KOPER Physician, Other, Regulatory Agency

The word "effective" in the title of a NEJM JW summary will be misleading, because adding OFS did not provide a significant benefit in this study. Only in a subgroup, young women with undesirable clinical findings.

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