BCL2 positivity predicts favorable breast cancer outcome
MedWire News: The antiapoptotic protein B-cell lymphoma 2 (BCL2) is a favorable prognostic marker for all types of early-stage breast cancer, independent of tumor size, grade, and stage, study findings indicate.
"Previous studies had identified that expression of BCL2 was associated with improved survival from breast cancer, but this was attributed to its correlation with estrogen receptor (ER) status," note Carlos Caldas (University of Cambridge, UK) and colleagues.
To test the clinical validity of BCL2 as an independent prognostic marker, Caldas and team examined 11,212 patients with early-stage breast cancer. The study took into account other predictive markers such as tumor size and grade, lymph node status and ER, progesterone receptor (PR), and human epidermal growth factor receptor (HER)2 status.
The researchers found that ER, PR, and BCL2 positivity were associated with improved survival while HER2 positivity was associated with inferior survival. For ER and PR this effect was time dependent and only persisted in the short term, whereas for BCL2 and HER2, the effect persisted over time.
Multivariate analyses that included tumor size, grade, lymph node status, ER, PR, HER2, and BCL2 status revealed that BCL2 positivity retained independent prognostic significance and was associated with a 24% reduced risk for death, compared with BCL2 negative status.
Furthermore, BCL2 positivity was a powerful prognostic marker in ER-negative, ER-positive, HER2-negative, and HER2-positive disease, where it was associated with a 37%, 44%, 45%, and 30% reduced risk for death, respectively. The prognostic impact of BCL2 remained irrespective of whether women had received adjuvant chemotherapy or adjuvant endocrine therapy.
Caldas and team also found that adding BCL2 to the Adjuvant! Online prognostic model significantly improved the survival prediction for a subset of cases with a 10-year follow-up, giving an area under the receiver operating characteristic curve of 0.684, versus 0.677 without BCL2.
"Novel markers that could be used to save women from unnecessary cytotoxic adjuvant therapy are urgently needed and BCL2 provides valuable additional prognostic information to guide clinical decision making in this setting," write Caldas and co-authors in the British Journal of Cancer.
"Further work is now needed to ascertain the exact way to apply BCL2 testing for risk stratification and to standardize BCL2 immunohistochemistry for this application," they conclude.
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By Laura Dean