Koleck Theresa A, Bender Catherine M, Sereika Susan M, Ryan Christopher M, Ghotkar Puja, Brufsky Adam M, Jankowitz Rachel C, McAuliffe Priscilla F, Clark Beth Z, Conley Yvette P
University of Pittsburgh School of Nursing, Pittsburgh, Pennsylvania.
Columbia University School of Nursing, New York, New York.
Cancer Med. 2017 Feb;6(2):339-348. doi: 10.1002/cam4.964. Epub 2017 Jan 13.
Intertumor heterogeneity has been proposed as a potential mechanism to account for variability in cognitive performance in women diagnosed with breast cancer. The purpose of this study was to explore associations between variation in pathologic tumor features (PTFs) and variability in preadjuvant therapy cognitive performance in postmenopausal women newly diagnosed with early-stage breast cancer. Participants (N = 329) completed a comprehensive battery of neuropsychological tests to evaluate cognitive performance after primary surgery but prior to initiation of adjuvant anastrozole±chemotherapy. PTF data were abstracted from medical records. Robust multiple linear regression models were fit to estimate associations between individual PTFs and the cognitive function composite domain scores. All models controlled for age, estimated intelligence, and levels of depressive symptoms, anxiety, fatigue, and pain. Diagnosis of a HER2-positive tumor contributed to poorer verbal (b = -0.287, P = 0.018), visual (b = -0.270, P = 0.001), and visual working (b = -0.490, P < 0.001) memory performance compared to diagnosis of a HER2-negative tumor. Similarly, as HER2 immunohistochemistry classification score increased, verbal (b = -0.072, P = 0.093), visual (b = -0.081, P = 0.003), and visual working (b = -0.170, P < 0.001) memory performance score decreased. Associations with performance were also noted between location, focality/centricity, hormone receptor expression, cellular proliferation (i.e., Ki67), and Oncotype DX Breast Cancer Assay Recurrence Score .) Our results suggest that certain PTFs related to more aggressive tumor phenotypes or inferior breast cancer prognosis may be implicated in poorer preadjuvant therapy cognitive performance. Follow-up studies that include a cognitive assessment before primary surgery should be conducted to further delineate the role of intertumor heterogeneity on cognitive performance.
肿瘤间异质性被认为是解释乳腺癌女性认知功能差异的一种潜在机制。本研究的目的是探讨绝经后新诊断为早期乳腺癌的女性患者病理肿瘤特征（PTF）的差异与辅助治疗前认知功能差异之间的关联。参与者（N = 329）完成了一系列全面的神经心理学测试，以评估初次手术后但在开始辅助阿那曲唑±化疗之前的认知功能。PTF数据从病历中提取。采用稳健多元线性回归模型来估计个体PTF与认知功能综合领域得分之间的关联。所有模型均对年龄、估计智力以及抑郁症状、焦虑、疲劳和疼痛水平进行了控制。与HER2阴性肿瘤诊断相比，HER2阳性肿瘤的诊断导致言语记忆（b = -0.287，P = 0.018）、视觉记忆（b = -0.270，P = 0.001）和视觉工作记忆（b = -0.490，P < 0.001）表现较差。同样，随着HER2免疫组化分类评分的增加，言语记忆（b = -0.072，P = 0.093）、视觉记忆（b = -0.081，P = 0.003）和视觉工作记忆（b = -0.170，P < 0.001）表现得分下降。在肿瘤位置、局灶性/中心性、激素受体表达、细胞增殖（即Ki67）和Oncotype DX乳腺癌检测复发评分与认知表现之间也发现了关联。我们的结果表明，某些与更具侵袭性的肿瘤表型或较差的乳腺癌预后相关的PTF可能与辅助治疗前较差的认知功能有关。应进行包括初次手术前认知评估的随访研究，以进一步阐明肿瘤间异质性对认知功能的作用。
