Adjuvant Endocrine Therapy for Premenopausal Breast Cancer

Published - Written by Karen Sokal-Gutierrez, MD, MPH, FAAP

A 42-year-old woman visited her oncologist to discuss follow-up treatment after completing surgery, radiation, and chemotherapy for premenopausal, estrogen-receptor–positive breast cancer that involved axillary lymph nodes. The patient said, “I’m still young, and I want to do everything possible to stay healthy and survive to see my young children graduate from college. What is the best treatment for me now?”

Successful treatment for women with premenopausal breast cancer must consider the fact that many tumors are stimulated to grow and spread by premenopausal hormones. After initial surgery, radiation therapy and/or chemotherapy, adjuvant tamoxifen for 5 or 10 years has been shown to reduce the risk of recurrence of premenopausal estrogen-receptor–positive breast cancer, with increasing survival benefits during 5–15 years of follow-up. However, the effect of adding ovarian suppression is less certain.

Two large, multicenter, randomized, double-blind studies examined different 5-year adjuvant endocrine treatment regimens in over 5700 premenopausal women with estrogen or progesterone-receptor–positive breast cancer. The Suppression of Ovarian Function Trial (SOFT) assessed the value of adding ovarian suppression to tamoxifen and the role of the aromatase-inhibitor exemestane plus ovarian suppression (3 treatment arms: tamoxifen alone, tamoxifen plus ovarian suppression, and exemestane plus ovarian suppression). The Tamoxifen and Exemestane Trial (TEXT) compared exemestane versus tamoxifen in women treated with ovarian suppression (2 treatment arms: tamoxifen plus ovarian suppression and exemestane plus ovarian suppression).  In both trials, ovarian suppression was achieved with  intramuscular triptorelin every 28 days, bilateral oophorectomy, or ovarian irradiation.

This week, NEJM published the 8-year follow-up results for the two trials. In the SOFT trial, for the tamoxifen-alone group, 8-year disease-free survival was 78.9% and overall survival was 91.5%. In combined analysis of the two trials, 8-year disease-free survival was 82.8% in the tamoxifen-plus-ovarian suppression group and 86.8% in the exemestane-plus-ovarian suppression group (P<0.001), and 8-year overall survival was 93.3% and 93.4%, respectively. Overall survival was approximately 4 to 5 percentage points lower in women who remained premenopausal after chemotherapy. In women with HER2-negative disease, exemestane plus ovarian suppression improved 8-year freedom-from-distant recurrence rates compared to tamoxifen plus ovarian suppression.

Adverse events, primarily related to hormone suppression, were common and included hot flashes, osteoporosis, vaginal dryness and dyspareunia, musculoskeletal symptoms, and hypertension. Grade 3 or greater adverse events were experienced by 24.6% of patients in the tamoxifen group, 31.0% in the tamoxifen-ovarian suppression group, and 32.3% in exemestane-ovarian suppression group.

The authors concluded that adding ovarian suppression to 5-year tamoxifen treatment improved disease-free and overall survival and that exemestane plus ovarian suppression further reduced recurrence, especially in women with HER2-negative disease. However, patients should be informed about possible side effects and receive treatment to palliate symptoms, if needed.

Returning to the case above, the oncologist can reassure the patient that adjuvant endocrine therapy to suppress the production of ovarian hormones and block hormonal action on tissues can help prevent breast cancer recurrence and improve survival. The physician can affirm a commitment to work together to tailor the patient’s endocrine treatment to try to ensure that she will see her children graduate from college.

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Karen is a 2017-2018 NEJM Editorial Fellow, Clinical Professor at UC Berkeley-UCSF Joint Medical Program and UC Berkeley School of Public Health, researcher on children’s nutrition and oral health, and member of American Academy of Pediatrics.