Abstract CT109: Adjuvant ovarian suppression in high risk premenopausal breast cancer: ten-year follow-up of a phase I-II study

Abstract

Abstract Background: Two randomized studies have shown the benefit of ovarian suppression in the adjuvant treatment of high risk premenopausal breast cancer, both with estrogen receptor positive (ER+) (Pagani et al. N Engl J Med 2014) and estrogen receptor negative (ER-) (Moore et al. N Engl J Med 2015). Nevertheless the median follow-up of these studies was limited to 68 and 49 months, respectively. Here we present the results of a large, phase I-II study, of adjuvant ovarian suppression in ER+ and in ER- patients, after a median follow-up of 123 months (range 93-223). Two hundred patients were enrolled between 06-1997 and 06-2007. The primary end point of the study was to find the best dose and schedule of a luteinizing hormone releasing hormone (LH-RH) analogue given to prevent ovarian failure in premenopausal patients treated with adjuvant chemotherapy. Secondary end points were disease free survival (DFS) and overall survival (OS). Methods: One week before chemotherapy, a LH-RH analogue was administered, 3.75 mg every 28 days for 1 year to the first cohort of 64 patients. The same monthly dose was given, for 2 years, to the second cohort of 36 patients. Because we had observed a decrease of 31% in the recurrence rate for the longer administration of LH-RH analogue, the 11.25 mg dose every 84 days, for 5 years, was chosen for the remaining 100 patients. The treatment consisted of: a- LH-RH analogue; b- Breast conserving (74%) and radical surgery (26%); c- Tailored systemic therapy concurrent with radiation therapy; d- Aromatase inhibitor in ER+ patients. Results: The median age was 43 years (range 26-45), the mean number of positive axillary nodes was 3.2 (range 1-25), including 20 patients with >10 positive nodes. 71% of patients were ER+ and/or progesterone receptor positive (PGR+), 29% were ER - and PGR-, 21% of patients were c-ErbB-2 positive. The median KI-67 was 30% (range 15% -100%). Ovarian failure rate was 10% in patients younger than 40 years and 44% in patients older than 40 years. The 15-year DFS and OS rate were 64% and 73%, respectively. 15-year DFS rate of ER+ and ER- patients were 74% and 44% respectively (P<0.005), while the 15-year OS rate were 74% and 75%, respectively (P>0.005). The usual pattern of toxicity of chemotherapy was observed. Hot flashes and G1 osteopenia occurring after LH-RH analogue administration were temporary and receded after the cessation of therapy. Conclusions: LH-RH administration, concurrent with chemotherapy is tolerable and useful. Five full term pregnancies were observed. The long-term recurrence and survival rate for ER+ and ER-patients were similar, with different patterns: ER+ patients had disease recurrences even after 13 years, while ER- patients had late new primaries, but no recurrence after 5 years. Citation Format: Francesco Recchia, Giampiero Candeloro, Massimo Bratta, Michele Rosselli, Silvio Rea. Adjuvant ovarian suppression in high risk premenopausal breast cancer: ten-year follow-up of a phase I-II study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT109.