Adjuvant Hormonal Therapy in Premenopausal Women

Neha Vapiwala, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 13, 2003

Faculty Disclosure: Gini F. Fleming, MD
In this presentation Dr. Fleming discusses the use of triptorelin for the treatment of breast cancer which is an off label use.

Presenter: Gini F. Fleming, MD
Affiliation: University of Chicago

Long-term follow-up of node-negative breast cancer patients treated with mastectomy alone has shown significantly worse outcome in premenopausal estrogen receptor-positive (ER +)patients. Although this data represents over 20 years of follow-up and stems from a time when receptor status was not routinely measured, the suggestion that receptor positivity conferred a negative prognosis in premenopausal patients prompted further study. Historically, four trials have been conducted in premenopausal patients using CMF chemotherapy without tamoxifen by the International Breast Cancer Study Group. Combining the data, both 10-year disease-free (DFS) and overall survivals (OS) were better in patients > 35 yrs old, compared to those < 35 years old. While outcome in the former subset did not differ significantly based on ER status, it did in those < 35 yrs old (10-yr OS in ER+ = 39% vs ER- = 56%). It has been demonstrated that ovarian ablation without chemotherapy provides an absolute survival benefit of 12.5% in patients < 50 yrs old. Additionally, the NSABP B-14 trial has shown risk reduction in ER+, N- patients. A smaller study of metastatic breast cancer in ER + premenopausal women has shown superior overall and median survival in those receiving both a leutinizing-hormone releasing hormone (LHRH) agonist and tamoxifen, compared to either agent alone. Finally, ECOG 5188 has reported improved outcome in premenopausal patients treated with the combination of CAF chemotherapy, goserelin and tamoxifen compared to chemotherapy alone or with goserelin. Based on the very leading results above, many questions can be raised. Can the use of ovarian suppression add to the benefit seen with tamoxifen in premenopausal patients? Are there patients in whom chemotherapy can be omitted altogether? Finally, how should the ever-emerging aromatose inhibitors be incorporated into this regimen? Three important trials seeking to answer some of these questions are currently open. The first, SOFT (Suppression of Ovarian Function Trial) will randomize ER/PR + patients who either never received chemotherapy or remained premenopausal after completing chemotherapy to one of 3 arms: tamoxifen x 5 yrs; ovarian function suppression (OFS) + tamoxifen x 5 yrs; or OFS + exemestane. A second trial, TEXT (Tamoxifen and Exemestane Trial) has an accrual goal of 1,845 premenopausal patients, all of whom will receive OFS with triptorelin. They will then be randomized to either exemestane x 5 yrs or tamoxifen x 5 yrs. The third study, PERCHE (Italian for "why?", as in "why chemotherapy?") hopes to enroll 1,750 patients, all of whom will receive OFS with triptorelin. They will then be randomized to either 1) any chemotherapy + tamoxifen or exemestane or 2) no chemotherapy + tamoxifen or exemstane. With a large international collaboration and vigorous efforts by physicians to enroll patients, these three studies should provide some much needed insight into the management of ER+ premenopausal breast cancer patients.