Abstract
BackgroundPrevious findings indicated that polymorphism in gene catechol-O-methyltransferase (COMT) had been linked to chemotherapy-related cognitive impairment (CRCI). Nevertheless, the motivation of COMT polymorphisms in regulating cognitive impairment in breast cancer survivors with disparate status of human epidermal growth factor receptor 2 (HER2) was still vague.ObjectiveThe current research aimed to evaluate the regulation of the risk by COMT genotype on CRCI in breast cancer survivors with disparate status of HER2.MethodsBreast cancer survivors (103 with HER2− and 118 with HER2+) underwent neuropsychological tests before and after chemotherapy, containing event- and time-based prospective memory (EBPM and TBPM). Three single-nucleotide polymorphisms (SNPs) were estimated by providing peripheral blood, containing COMT (rs165599, rs737865, and rs4680).ResultsThe EBPM and TBPM performances was lower as compared with these before chemotherapy (z = −7.712, z = −2.403, respectively, p < 0.01). Furthermore, the EBPM and TBPM performances of HER2− group survivors were lower than those of HER2+ group survivors after chemotherapy (z = −7.181, p < 0.01; z = −2.205 p < 0.05, respectively). The survivors with COMT (rs165599) A/A genotype carriers had a meaningfully poorer chance of memory descend [dominant model: adjusted, OR = 2.21, CI (95%) = 1.156–4.225, p = 0.016] and showed better on TBPM test, relative to G/G genotype. Patients with the COMT (rs737865) A/G and G/G genotype showed protective function than the patients with the A/A and performed better on MMSE and TBPM tests.ConclusionThe types of HER2 may be correlated to chemotherapy-related prospective memory impairments in breast cancer survivors. Furthermore, the COMT (rs165599, rs737865) polymorphisms were correlated to the risk of TBPM decline scores and possibly be a potential genetic identifying for increasing risk of CRCI in breast cancer patients with disparate status of HER2.
Highlights
Breast cancer is the most familiar malignancy in Chinese women and the sixth main cause of cancer-related death [1]
Inclusion criteria were as follows: [1] breast cancer was defined by immunohistochemical and pathological diagnosis and that positive of Her-2 was recorded as standard immunohistochemistry 3+ or ISH positive; [2] adriamycin, paclitaxel, cyclophosphamide, and fluorouracil were applied by standard chemotherapy regimen or combined with Herceptintargeted therapy, based on chemotherapy, but no hormone therapy; [3] age and pathological type were not limited; [4] the participant could carry out normal daily activities, with Karnofsky performance status scale (KPS) scores ≥80; and [5] there are no communication barriers and could proceed with normal language communication
In the human epidermal growth factor receptor 2 (HER2)− group, 95 breast cancer patients were discriminated as non-special-type invasive ductal carcinoma (IDO-NOS), 3 breast cancer patients were discriminated as special-type invasive ductal carcinoma (IDO-S), and 5 patients were discriminated as microinvasive carcinoma (MIC)
Summary
Breast cancer is the most familiar malignancy in Chinese women and the sixth main cause of cancer-related death [1]. By the end of 2008, 169,452 new breast cancer cases were reported in China; 44,908 cases were related deaths [2]. A large body of evidence have reported that breast cancer patients experience a moderate to severe degree of cognitive impairment during or after chemotherapy [7,8,9]. These cognitive function deficits involved memory, attention, information processing speed, executive function, and visual space function. This phenomenon is referred to as chemotherapy-related cognitive impairment (CRCI) [10]. The motivation of COMT polymorphisms in regulating cognitive impairment in breast cancer survivors with disparate status of human epidermal growth factor receptor 2 (HER2) was still vague
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