HMGA2 and its role in clinical response to treatment in patients with locally advanced breast cancer

B74

Objective: Close to 40,000 women still die from breast cancer annually. The number of African-American women who die from breast cancer remains disproportionate to the incidence of breast cancer in this population. For this subgroup, more research is warranted to aggressively improve survival. Traditional methods to diagnose breast cancer include the assessment of histological appearance, the identification of specific tumor subtypes, tumor grading, lymph node status and the presence of metastases. These techniques are useful for the initial evaluation of breast cancer but do not predict the clinical outcome of patients following specific treatments. Recent studies have identified a molecular marker for breast cancer, HMGA2, which has not been identified in healthy patients, that appears to have a role in tumor progression and metastasis. Further studies have shown that HMGA2 mRNA expression in the peripheral circulation of breast cancer patients correlates with a poor clinical outcome and can be a better predictor of clinical outcome than even lymph node metastasis. We hypothesize that in patients with locally advanced breast cancer, HMGA2 expression could be an important predictor of clinical response in African-American women.
 Methods: 34 patients diagnosed with locally advanced breast cancer were included in this study. All patients were treated with adriamycin/ cytoxan or AC/Zarnesta. The patients had to have either a partial or complete response resulting in surgery. Pre-and post-chemo specimens were immunostained for HMGA2 expression.
 Results: Eight patients have been examined thus far. Two (25%) patients were African-American (AA), 4 (50%) were Hispanic, and two (25%) were white. Mortality appeared to correlate with HMGA2 expression post-chemotherapy. The mortalities were in one AA patient with stage I disease (ER-/PR-/HER2-) and the other was a Hispanic patient, stage III (ER/PR+, HER2-). HMGA2 expression did not appear to correlate with stage or ER/PR status. All the patients with one exception were HER2 negative.
 Conclusions: In these preliminary studies, the HMGA2 status of the primary tumor post-chemotherapy appeared to be a greater predictor of survival than pre-chemotherapy. HMGA2 potentially plays a role in poor clinical outcome tumor progression and metastasis.