Background: Cognitive complaints are common among patients (pts) receiving adjuvant therapy (Rx) for early stage BC. Longitudinal prospective data is needed to help understand the relationship between measured cog fcn, patient reported cognitive changes, and patient reported depression and fatigue. We conducted a prospective trial to evaluate the effects of chemo- (CTX) and hormone therapy (HRx) on brain and cog fcn in pts with early stage BC using multiple objective and subjective tests as well as MRI/PET imaging. Here we report relationships between objective measures and patient reported outcomes (PRO). Methods: Eligibility included female pts planning to receive adjuvant Rx for ESBC. Pts were enrolled in 3 Rx groups (grps): CTX, CTX and HRx, and HRx, with a 4^thno Rx age/education matched control group. All pts underwent a battery of objective and subjective cog tests before start of rx, 1 mo after CTX or 5 mo after start of HRx (FU1), then 9 mo (FU2) and 18 mo (FU3) after CTX. Brain MRI, PET and serum estradiol were performed at baseline, FU1 and FU2. Results: 81 pts were enrolled as follows: 14 CTX, 33 CTX and HRx, 22 HRx, and 12 control. 90% completed FU1, 72% FU2, and 62% FU3, with 29 pts waiting to complete testing. Demographics were similar between grps, median age was 54 (range 34-71), 78% were Caucasian. At FUP1, depression (BDI-II) and fatigue predicted poorer overall perceived cog fcn (FACT-Cog); decline in letter fluency (FAS) on cog testing also predicted poorer overall perceived cog fcn (FACT-Cog). Decline in verbal memory (CVLT-II) predicted perceived memory deficits (FACT-Cog Memory), even after controlling for depression and fatigue. Conclusions: In pts receiving adjuvant Rx for early stage BC, depression, fatigue, and decline in letter fluency predicted poorer perceived cog fcn. Decline in verbal memory independently predicted perceived memory deficits, demonstrating that PRO are related to actual deficits in cog fcn. Future intervention studies should focus on these factors. Funding: NIH R01 1AG025303-01A2. Clinical trial information: 00755313.