Relationship Between Age and Axillary Lymph Node Involvement in Women With BC

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Abstract:http://jco.ascopubs.org/cgi/content/abstract/27/18/2931

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Supplementary editorial provided by OncologySTAT
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Axillary lymph node involvement in breast cancer decreases with age but increases after age 70 years. Because axillary node involvement is associated with smaller tumors among older women, decreased immunity may be involved.
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While some studies show that lymph node (LN) involvement in breast cancer increases with age, other studies suggest decreased LN involvement. The aim of this retrospective analysis by Wildiers et al was to shed some light on conflicting results regarding the association between age and LN-positive breast cancer. The results showed a piecewise effect of age and nodal status, with a reversal at approximately 70 years. Before age 70 years, increasing age at diagnosis was associated with decreasing risk of node involvement. However, in older women (>70 years), an increased risk of node involvement was observed, which was also correlated with smaller tumor size. In older women, the prognostic effect of larger tumor size for LN involvement became weaker with increased age. The study included data from 2568 women with invasive breast cancer who were treated at the University Hospitals Leuven in Belgium between 2000 and 2005. A logistic regression model that adjusted for other clinicopathologic factors was used to predict LN involvement. The results were then validated in a second cohort of 2155 women enrolled in the Eindhoven Cancer Registry (ECR). These women had similar characteristics to those in the University Hospitals Leuven dataset and were diagnosed with breast cancer between 2005 and 2006.
Age was categorized as <50 years, 50 to 69 years, 70 to 79 years, and >80 years. Age was negatively related to LN involvement for women up to 70 years and was positively related for women >70 years at diagnosis. In the univariate analysis, factors associated with LN involvement included tumor size, tumor grade, and HER-2/neu receptor status. Hormone-receptor status had no association with outcome.
In multivariate analysis, age demonstrated a piecewise effect on LN involvement, which decreased by 13% per 10-year increase in age (odds ratio [OR], 0.87; 95% CI, 0.78-0.96; P = .0048). LN involvement increased by 60% per centimeter increase in tumor size (OR, 1.60; 95% CI, 1.50-1.70). After age 70 years, a reversal occurred whereby increasing age was associated with an increased risk of LN involvement (OR, 2.93; 95% CI, 1.60-5.35; P = .0008). In the older women, the effect was more evident in smaller tumors. For larger tumors, LN involvement decreased as age at diagnosis increased. Conversely, for smaller tumors, LN involvement increased with age. The results were replicated in the ECR dataset.
The study showed a nonlinear association between age at breast cancer diagnosis and LN involvement that contradicts the hypothesis that the increased LN involvement in older women is associated with larger tumors. The authors postulate that the ability of smaller, earlier stage tumors to metastasize in older women may stem from an age-related decline in immunologic function, which leads to lower defense against tumor invasion and metastasis.

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