The study by Kesler and Blayney1 in this issue of JAMA Oncology investigated the impact of anthracycline-based chemotherapy regimens (ANTHR) on cognitive performance and resting state functional magnetic resonance imaging (fMRI) brain connectivity within the default mode network (DMN) in female breast cancer survivors. Brain connectivity has become a major focus in neuroscience that is rapidly translating to the clinical realm where brain disorders are viewed from a system or network perspective rather than as a set of affected regions. The DMN is of particular interest as a measure of the brain’s resting state of spontaneous cognition, or thought processes when not task-focused. Disruptions of the DMN have been associated with neurodegenerative disease as well as systemic chemotherapy.2 Kesler and Blayney1 found that, compared with breast cancer survivors treated with non–ANTHR-based regimens or breast cancer survivors not treated with chemotherapy (NC), ANTHR was associated with poorer verbal memory, as well as with altered connectivity of the left precuneus region, which is part of the superior parietal lobule involved in episodic memory, visuospatial processing, and aspects of consciousness. Although the finding of lower connectivity of the left precuneus to other brain regions was not specific to the ANTHR group, it was more pervasive. The non-ANTHR group also displayed lower connectivity of this brain region to a frontal region compared with NC. This finding suggests that different chemotherapy regimens may affect DMN connectivity through a similar mechanism, with ANTHR-based regimens having a greater impact, perhaps through an oxidative stress-linked metabolic pathway, as posited by the authors.1
Nudelman KNH, McDonald BC, Saykin AJ. Imaging Brain Networks After Cancer and Chemotherapy: Advances Toward Etiology and Unanswered Questions. JAMA Oncol. 2016;2(2):174–176. doi:10.1001/jamaoncol.2015.4551
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