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Introduction: - A defective apoptotic mechanism contributes to the origin and progression of breast cancer. With the current classification of breast carcinoma into molecular subtypes with distinct prognosis and response to therapy, we sort to analyze the expression levels of p53 and Bcl-2 in molecular breast cancer subtypes of Pre-menopausal African-American women.

Methods: - A retrospective analysis of data on the expression levels of p53 and Bcl-2 performed by IHC. Results were correlated to molecular breast cancer subtypes (luminal A, Luminal B, Basal like, HER-2), ER/PR, HER-2 receptor status and clinicopathologic variables. Our study population included all pre-menopausal African-American women < 50yrs, stratified into two groups <35yrs, > 35yrs, diagnosed with breast cancer from 1998-2005 who had assessable data (n=130).

Results:-

An inverse correlation between p53 and Bcl-2 protein expression was noted but was only statistically significant for the cohort of patients > 35yrs (rho = -0.217; P= .04).

p53 positivity correlated inversely with expression of both ER and PR receptors, (rho=-0.332, p=.000; rho=-0.223, p=.018), and directly to HER-2 receptors, (rho=0.218, p=.020). However when stratified by age this inverse relationship only held for p53/ER, for the cohort > 35yrs, (rho-0.307, p=.003), for p53/HER-2 correlation, the direct correlation was maintained in the > 35yrs, however an inverse correlation was noted in the < 35yrs (rho-0.452, p=.04).

Bcl-2 positivity correlated directly with expression of both ER and PR receptors, (rho=0.384, p=.000; rho=.303, p=.002), and inversely to HER-2 receptors, (rho=-0.264, p=.007). When stratified by age only the >35 yrs cohort maintained the direct correlation between Bcl-2 and ER/PR, and the inverse correlation between Bcl-2/HER-2.

There was an association between Bcl-2 positivity and Luminal A subtype, (p<.000). Bcl-2 showed no statistical significant association to Basal like or Luminal B subtype, however when stratified by age patients < 35yrs with basal like subtype were more likely to show Bcl-2 positivity compared to those >35yrs. Bcl-2 negativity was significantly associated with the HER-2 subtype, ( p<.001).

p53 positivity showed an association to Basal like and HER-2 subtype, (p<.02), (p<.05). p53 negativity showed an association to Luminal A subtype (< .000). p53 showed no statistically significant association to luminal B subtype.

Bcl-2 positivity directly correlated with high tumor stage (rho = 0.256; P=0.019), Bcl-2 positivity showed no correlation with tumor size, however p53 expression was significantly associated to tumor size (p<.04).

Conclusion: - Overexpression of p53 and Bcl-2 in the young < 35yrs pre-menopausal African-American women may be associated with biologic aggressiveness of breast cancer seen in this cohort of patients

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

American Association for Cancer Research
2007