Structural Brain Differences in Breast Cancer Patients Compared to Matched Controls Prior to Chemotherapy

Abstract

Understanding the relationship between chemotherapy and cognitive impairment requires information on pre-treatment variability between cancer patients and well-matched controls. The purpose of this study was to investigate neuroanatomical differences between breast cancer (BC) patients and controls, prior to chemotherapy,controllingfor possible confounding variables. Twenty-three female early-stage BC patients underwent MRI scanning after surgery but before chemotherapy and were sex-, age-and education-matched to non-cancer controls. Whole brain and region of interest (ROI) group comparisons of grey (GM) and white matter (WM) were performed using voxel-based morphometry.Significant ROI structural differences between BC patients and controls were found depending on the type of analysis used and the covariates entered. This is one of the first imaging studies to focus on pre-chemotherapy neuroanatomical differences between BC patients and well-matched controls, considering demographic, psychological and biological factors in the analyses. Results highlight the importance of better understanding the whole patient prior to chemotherapy, stressing the importance of rigorous methodological procedures. Keywords:Cognitive impairment, Magnetic resonance imaging (MRI), Voxel-based morphometry (VBM), Pre-treatment effects, Chemotherapy, Surgery, Neuropsychology, Anatomy IntroductionRecent medical advances have greatly improved the odds of achieving long term survival in cancer patients. This has led to increased attention for improving post-treatment quality of life. One factor of particular interest is related to patient self-reports of cognitive impairments following chemotherapy treatment, most often revealed in breast cancer (BC) populations. Patients have coined terms like "chemo fog" and "chemo brain" to refer to these changes that can manifest both during and after treatment. The incidence of chemotherapy-related impairments is www.ccsenet.org/ijb International Journal of Biology Vol. 4, No. 2; April 2012 ISSN 1916-9671 E-ISSN 1916 4 highly variable with a range of 17-75% reported across neuropsychological studies (Correa & Ahles, 1997). Despite this variability, these assessments, along with both structural and functional neuroimaging investigations, support the existence of the self-reported deficits (Abraham et al., 2008; Ahles et al., 2002; Ahles, Tope, Furstenberg, Hann, & Mills, 1996; Bender et al., 2006; Berglund, Bolund, Fornander, Rutqvist, & Sjoden,1991; Brezden, Phillips, Bunston, & Tannock, 2000; Brown et al., 1998;Castellon et al., 2004; Deprezet al., 2003; de Ruiter et al., 2010; Ferguson, McDonald, Saykin, & Ahles, 2007; Gottschalk, Holcombe, Jackson, & Bechtel, 2003; Hurria et al., 2006; Inagaki et al., 2007; Jenkins et al., 2006; Kesler et al., 2009;Kreukels et al., 2005;Kreukels et al., 2006; Kreukels et al., 2008;Mar Fan et al., 2005;McDonald, Conroy, Ahles, West, & Saykin, 2010;Saykin et al., 2006;Saykin, Ahles, & Schoenfeld, 2003; Schagen et al., 1999;Scherwath et al., 2006; Serva...

Brain cortical structural differences between non-central nervous system cancer patients treated with and without chemotherapy compared to non-cancer controls: a cross-sectional pilot MRI study using clinically indicated scans

“…Structural [15, 19, 34] and functional MRI [23, 24, 35] studies have found that abnormalities may already exist in the absence of chemotherapy for breast cancer patients. More recent neuroimaging studies of other types of cancer including lung [26] and testicular cancer [27] also suggest that structural abnormalities exist without chemotherapy.…”

A systemic literature review of neuroimaging studies in women with breast cancer treated with adjuvant chemotherapy

“…In one study semi-automatic segmentation procedure was used [34] and in three automatic seqmentation procedure were used [10, 13, 39]. Most of the studies were conducted in cross-sectional design: 10 in breast cancer survivors treated with CTx [4, 6, 10, 13, 34, 35, 38–40, 43] and 2 in breast cancer patients prior to CTx [41, 58]; 5 studies were conducted with longitudinal design [11, 36, 37, 61, 62]. The results obtained from breast cancer patients treated with CTx were compared to breast cancer patient without CTx [34, 38, 55], healthy controls [4, 10, 13, 35, 40, 41, 62], non-cancer reference subjects [39, 43], or breast cancer patients without CTx and healthy controls [6, 36, 37, 58, 61].…”

“…Most of the studies were conducted in cross-sectional design: 10 in breast cancer survivors treated with CTx [4, 6, 10, 13, 34, 35, 38–40, 43] and 2 in breast cancer patients prior to CTx [41, 58]; 5 studies were conducted with longitudinal design [11, 36, 37, 61, 62]. The results obtained from breast cancer patients treated with CTx were compared to breast cancer patient without CTx [34, 38, 55], healthy controls [4, 10, 13, 35, 40, 41, 62], non-cancer reference subjects [39, 43], or breast cancer patients without CTx and healthy controls [6, 36, 37, 58, 61]. In four studies breast cancer patients were treated with the same schema of CTx [38, 39, 43, 58] and in the other studies different schemas were applied [4, 6, 10–13, 34–37, 40, 42].…”

“…During fMRI cognitive processes were assessed using verbal and visual working memory tasks [4, 8, 18, 46, 48, 49, 52–54], visual memory task [5, 57], verbal memory task [9, 14–16], attention [53] and executive functioning [5, 7, 41, 55, 57]. Most studies were conducted in cross-sectional design: 14 in breast cancer survivors treated with CTx [3–5, 7, 9, 14, 16, 17, 44–46, 51, 57, 65] and 4 in breast cancer patient prior to CTx [48–50, 58]; 8 studies were conducted in longitudinal design [8, 15, 18, 52–56].…”

Opening up the Window into “Chemobrain”: A Neuroimaging Review

“…Such variability makes it difficult to convince those outside the patient population of the reality of cognitive impairments found in cancer patients undergoing or having completed chemotherapy. The considerable variability in results from one study to the next are due to differences in key study design factors including: (1) sample size (many studies use only a small number of patients), (2) differences in the nature of the neuropsychological battery used (e.g., targeted tests or complete battery) resulting in differential sensitivity to subtle cognitive changes, (3) increased sensitivity of computerized testing in conjunction with pencil and paper assessments, (4) nature of the control group (example: healthy controls vs. non-chemotherapy patient group), (5) definition and/or criteria of cognitive impairment adopted, (6) effects of anesthesia on cognition for patients who also underwent surgery [27], (7) stress of cancer diagnosis and treatment, (8) existence of pre-treatment differences in cognition between BC patients and controls [28–31], (9) possible negative effects of endocrine treatment on cognition [23], and (10) data analysis methods used, in particular, whether impairment is defined at the group or individual level and, in the case of longitudinal studies, whether or not the analyses control for practice effects associated with repeated testing. These factors must be systematically controlled in future studies if progress is to be made in understanding the effects of cancer treatments on cognition.…”