Abstract P1-12-06: Co-SOFT: The cognitive function substudy of the suppression of ovarian function trial (SOFT)
Authors: Phillips Kelly-Anne , Feng Yang , Ribi Karin , Bernhard Jürg , Puglisi Fabio , Bellet Meritxell , Spazzapan Simon , Karlsson Per , Budman Daniel R , Zaman Khalil , Abdi Ehtesham A , Domchek Susan M , Regan Meredith M , Coates Alan S , Gelber Richard D , Maruff Paul , Boyle Frances , Forbes John F , Fleming Gini F , Francis Prudence A 
Published: May 2015

Abstract
Background: Cognitive impairment is a potential side-effect of breast cancer (BC) treatment. Estrogen is an important neuromodulator that affects cognition. Estrogen depletion by oophorectomy or GnRH agonists may adversely affect cognition in non-oncological settings, but there are few data regarding the cognitive effects of ovarian function suppression (OFS) in women with breast cancer.
Patients and Methods: Between November 2003 and January 2011, 3066 premenopausal women with hormone receptor-positive BC were randomised on the SOFT trial to 5 years of adjuvant endocrine therapy with tamoxifen alone, tamoxifen+OFS or exemestane+OFS. OFS was achieved by the GnRH agonist triptorelin, oophorectomy or ovarian irradiation. Prior chemotherapy was allowed, provided women had premenopausal estradiol levels at enrolment. Women eligible for Co-SOFT must not have received any prior adjuvant endocrine therapy. At study entry (t1), and approximately 1 year after SOFT randomisation (t2), objective cognitive function was assessed with a brief computerized test battery comprising 7 tasks (CogState Ltd: cogstate.com). Subjective cognitive function, psychological distress, fatigue, insomnia and quality of life were also assessed. Co-SOFT recruited 86 of a planned 321 patients from 27 of 426 SOFT centres between November 2007 and January 2011, when Co-SOFT was closed as the SOFT trial completed accrual. The protocol-specified primary comparison was the change in the composite score of the CogState tasks over 1 year for women randomised to tamoxifen versus tamoxifen+OFS. However, due to low accrual this was modified, prior to any analysis, to compare the tamoxifen versus the pooled tamoxifen+OFS and exemestane+OFS groups. Cognitive test scores were standardized according to age-specific norms, averaged to compute the composite score and then change between t1 and t2 calculated; a negative change in composite score indicates deterioration in cognitive function. Change in composite score was compared using Wilcoxon rank sum test.
Results: Of 86 Co-SOFT enrolled patients, 74 underwent both t1 and t2 CogState testing and were included in the primary analysis (7 withdrew consent/declined assessment, 5 missed testing due to scheduling). Of these 74 women, 20 were randomised to tamoxifen and 54 to OFS+tamoxifen (28) or OFS+exemestane (26). Baseline characteristics were well balanced between the 2 groups. During the first year 49 women utilised GnRH alone for OFS, 4 had GnRH followed by oophorectomy and 1 had oophorectomy alone. There was no significant difference in the changes in the CogState composite scores from t1 and t2 for patients randomised to tamoxifen alone compared with OFS+oral endocrine therapy (median, -0.057 versus -0.146 respectively, p=0.51). There were no significant between-group differences in the changes from t1 and t2 for any of the 7 individual cognitive tasks comprising the composite score.
Conclusions: The results of this 1-year longitudinal substudy suggest that the addition of OFS to oral endocrine therapy does not significantly affect cognitive function in the setting of adjuvant BC treatment. Co-SOFT was limited by small sample size, so further investigation of the impact of OFS on cognitive function in BC patients is warranted.
Citation Format: Kelly-Anne Phillips, Yang Feng, Karin Ribi, Jürg Bernhard, Fabio Puglisi, Meritxell Bellet, Simon Spazzapan, Per Karlsson, Daniel R Budman, Khalil Zaman, Ehtesham A Abdi, Susan M Domchek, Meredith M Regan, Alan S Coates, Richard D Gelber, Paul Maruff, Frances Boyle, John F Forbes, Gini F Fleming, Prudence A Francis. Co-SOFT: The cognitive function substudy of the suppression of ovarian function trial (SOFT) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-06.