Thursday, January 17, 2013

PUTTING THINGS TOGETHER IN TRIPLE NEGATIVE BREAST CANCER BRCA TESTING AND THE MTOR UNVEIL NEW PARADIGM SHIFT AT CRBCM

Now that we know that up to 85% of triple negative Breast cancers could have the BRCA Mutation in some cohort,  it is becoming a guideline shift that this test be performed not only for prognosis, but also for therapeutic information.  The presence of BRCA positivity generally imparts worse prognosis of this disease.
But knowing if it is BRCA1 positive will give it an atypical morphology as per  the article from Stanford suggests:

"The luminal A subtype of breast cancer had the highest frequency of PIK3CA mutation (45%), and the basal subtype had the lowest (9%). These data are consistent with the results of prior studies, as luminal A and basal-like subtypes roughly correspond to ER-positive and triple-negative breast cancer by immunohistochemistry (IHC), respectively. Even though PIK3CA mutations are oncogenic, they are a good prognostic factor and are associated with improved survival.[12] This is important to consider when assessing patient survival in trials in patients with PIK3CA mutations."

BRCA 2 is mostly of Luminal histology and therefore will be more susceptible to PIK3CA/MTOR blockade which will explain their better prognosis.  We still believe that as we move forward, the role of interferon and Mtor is still to be explored.  As that in Luminal triple negative BRAC2 positive hormone manipulation with MTOR could still be tried. We still believe that EGFR inhibitor in combination to MTOR inhibitor and inhibitor of NK-kB or antiproteasome are all potential add-ons!

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