Abstract P2-14-09: Prospective Evaluation of Change in 2-Point Discrimination of Index Finger as a Potential Early Predictive Marker for Carpal Tunnel Syndrome among Women Receiving Adjuvant Aromatase Inhibitor Therapy for Postmenospausal Breast Cancer in the Exemestane and Letrozole Pharmacogenomics (ELPh) Trial
Authors: Bardia A , Rosson G , Giles J , Cornblath D , Flockhart D , Hayes DF , Jeter S , Hayden J , Lemler S , Nguyen A , Storniolo AM , Tarpinian K , Zhang Z , Henry NL , Stearns V. 
Published: April 2011

Introduction: Third generation aromatase inhibitors (AIs) represent an integral part of hormonal therapy in postmenopausal women with hormone receptor (HR)-positive breast cancer. AIs are associated with musculoskeletal symptoms in up to 50% of women. Post-hoc analyses of adjuvant AI trials (ATAC and IES) have suggested that AIs might be associated with carpal tunnel syndrome (CTS), a pressure-induced neuropathy disorder caused by compression on the median nerve. The clinical diagnosis of CTS is made with typical symptoms of pain, weakness, and paresthesias in affected arm. A variety of tests, including change in 2-point discrimination (2PD) can be used to aid in diagnosis. However, the actual incidence of CTS and clinical utility of diagnostic tests such as 2PD have not been prospectively examined among women receiving AIs. Methods: Postmenopausal women with stage 0-III HR-positive breast cancer, who had completed local therapy and, if indicated, adjuvant chemotherapy, and who were enrolled in the multi-center Exemestane and Letrozole Pharmacogenetics (ELPh) trial underwent prospective evaluation of 2PD with the Disc-criminator™ (sliding aesthesiometer) at baseline, and 3 months, following initiation of the AI. The end of the Disc-criminator™ was applied at the two points at same time to the skin on the volar tip pulp of the index fingers, and the threshold value (in mm) was determined as the shortest distance between the two points a woman was able to differentiate. The exercise was repeated thrice at each point. Abnormal 2PD thresholds were defined using standard criteria (outside 95 percentile for age). The differences in mean 2PD from baseline to 3 months were analyzed using a multivariate mixed effects model where the correlations from repeated measures were accounted for by assuming an unstructured covariance structure. A p value &lt; 0.05 was considered statistically significant.

Results: A total of 104 women underwent baseline 2PD testing. The mean age was 59 years, 55.8% had stage I disease, and 42.3% received adjuvant chemotherapy. We observed abnormal 2PD thresholds in 1.9% and 3.5% of women at baseline and 3 months respectively. There was a significant worsening in the adjusted mean 2PD from baseline (3.4 mm) to 3 months (4 mm, p=0.01). The increase in mean 2PD following 3 months of AI therapy was higher among women with age &gt; 55 (p=0.02), BMI &gt; 25 (p=0.002), African Americans (p=0.02), and those who received adjuvant chemotherapy (p=0.05), as compared to their counterparts. Conclusion: Adjuvant AI therapy was associated with a significant worsening of 2PD at 3 months, particularly among older women, overweight women, and those receiving adjuvant chemotherapy. Correlation with CTS symptoms and need for surgical release will be presented at the meeting. Our results suggest that 2PD is a non-invasive method that may potentially allow for early detection of CTS. If confirmed, change in 2PD could serve as an objective early predictor for subsequent CTS in postmenopausal women with breast cancer initiating AI therapy.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-14-09.