Abstract PD6-11: Altered regional cerebral blood flow in adjuvant-treated breast cancer survivors after chemo- and endocrine therapy

Abstract

Abstract Objectives: In the first published observation of altered brain metabolism in patients exposed to chemotherapy (Breast Cancer Res Treat. 2007; 103:303-311), we described diminished metabolism in prefrontal cortex in proportion to magnitude of diminishment of short-term memory performance, 5-10 years following patients’ last chemotherapy dose. Subsequently, at least 7 other groups of investigators have independently demonstrated altered cerebral metabolism of frontal cortex as assessed by FDG-PET (J Nucl Med. 2019; 60:16821690). We now offer the first report of regional cerebral blood flow (rCBF) changes assessed by [O-15]water PET in prospectively recruited subjects with newly diagnosed breast cancer, longitudinally followed from time of initial therapy for one year. Methods: A total of 204 brain [O-15]water PET scans were obtained of 17 right-handed female subjects newly diagnosed with breast cancer, with near-equal portions of 10 chemo-exposed (C) and 7 unexposed (U) subjects undergoing endocrine therapy in the ensuing year (5/10, 3/7). For each subject, 12 scans were obtained – 6 during short-term memory, long-term memory, and control tasks presented in counterbalanced order soon after completion of any adjuvant chemotherapy but prior to initiation of any endocrine therapy (baseline), and repeating one year later. PET data were assessed through paired t statistical tests at the voxel level, after Family Wise Error (FWE)-based corrections for multiple comparisons. Results: Across all subjects, scans at baseline during short-term recall revealed most marked activation of bilateral temporal-occipital cortex (peak voxel t=7.20; size 4,649 voxels, p<.0005 FWEcorr.) and similar activation occurred during long-term recall (t=6.48; 6,446 voxels, p<.0005 FWEcorr.). One year later, left prefrontal cortex, including Broca’s area, activated during short-term recall (t=5.74; 227 voxels, p=.02 FWEcorr), as did bilateral medial occipital cortex (t=5.45; 908 voxels, p<.0005 FWEcorr.); during long-term recall, prefrontal cortex activated with greater bilaterality, but with an extent in left frontal lobe (1031 voxels, p=.008 FWEcorr.) about double the size of right (452 voxels), and with less occipital activation. In therapy-stratified analyses, baseline short-term recall of left prefrontal cortex, including Broca’s area, activated more extensively (3253 voxels, p<.0005 FWEcorr.) in U, while C showed more extensive activation in medial occipital cortex (5670 voxels, p<.0005 FWEcorr.vs. 423 voxels, p=.001). One year later, short-term recall in U continued to activate left prefrontal cortex including Broca’s area (4035 voxels, p<.0005 FWEcorr.), while C still primarily activated medial occipital cortex (976 voxels, p=.008 FWEcorr.), though demonstrating a shift of activation away from this region relative to one year prior, with more voxels of activation tending to appear in left prefrontal cortex over that interval. Similar, though less striking, differences were observed during long-term recall. Conclusions: Activation of rCBF during recall of verbal associative memories was diminished in left prefrontal brain areas critical to verbal memory performance in C relative to U. Concomitantly, C demonstrated apparent compensatory activation of primary visual cortex, involved in perceiving the visually presented verbal memory cues, in lieu of specific activation of the prefrontal cortical regions in the dominant hemisphere involved in processing language information. The strengths of these therapy-associated differences were generally diminished one year later, consistent with partial interim recovery in C of cerebral processing by language-specialized areas. Citation Format: Claire L Vandenberg, Patricia A Ganz, Stephen S Liu, Daniel HS Silverman. Altered regional cerebral blood flow in adjuvant-treated breast cancer survivors after chemo- and endocrine therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD6-11.