Date of Award

January 2012

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Meena S. Moran

Second Advisor

Brenda Cartmel

Subject Area(s)

Medicine

Abstract

Purpose/Objectives: This study was conducted to assess whether a relationship exists between breast cancer molecular subtype and extent of regional lymph node involvement at disease presentation in a cohort of early-stage breast cancer patients treated with breast conservation therapy (BCT). Furthermore, clinical-pathologic features and disease outcomes were correlated with tumor molecular subtype. Materials/Methods: Eligible cases were stage I/II disease who had undergone BCT and had available slides for a central pathological review and tissue microarray analysis (TMA). After staining and categorization of each case by ER, PR, and HER-2 status, the constituents of the cohort were classified as luminal A and B, HER-2 or triple negative (TN). Data regarding extent of nodal disease was abstracted from pathology reports, and correlated to the four tumor molecular subtypes. Additional clinical-pathologic features were also analyzed to assess if any association between tumor molecular subtype and other patient/tumor characteristics exist. Outcomes were evaluated via Kaplan-Meier Survival Analysis (KMSA). Results: The median follow-up time for this cohort of 453 patients was 7 years. Assessment of N stage as a function of molecular subtype did not reveal any statistically significant difference (p = 0.54). There was no statistically significant difference in the percentage of patients who presented with nodal positive disease (p = 0.70) or in the number of positive nodes at the time of presentation (p = 0.66) across the four subtypes. However, there was a statistically significant difference in the pathologic T stage at the time of presentation in which on subgroup analysis, the TN subtype was more likely to present with T Stage II/III disease as compared to the remaining subtypes (44.4% vs. 23.5%) (p < 0.01). There were statistically significant differences in the KMSA for distant metastasis-free survival time (p < 0.01) and disease-free survival observed in this cohort (p = 0.02). Conclusions: Although a significant association between tumor molecular subtype and extent of regional lymph node involvement was not demonstrated, a significant association between tumor molecular subtype and primary tumor size was identified. These hypothesis-generating findings will need to be confirmed through future investigations.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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