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!

AT A CHECK POINT IN CELL DIVISION 2 MAIN THINGS HAPPEN:

1. DNA is checked for mistakes and corrections are undertaken.2. Chromosome segregation to eventual daughter cells is checked to avoid uneven distribution of the chromosome. 
This last event seems to rely heavily on activity on unattached chinetochores where check point proteins (MAS 1 & 2, UB1 etc.) accumulate and block the APX (Anaphase promoting complex) until the checking is completed and Cyclin B and Securins are ubiquitinated and destroyed to release the check hold and allow mitosis to proceed.

The need for ubiquitination of Cyclin B elevate the role of Proteasome. That is why Antiproteasome appears very important in hematologic conditions where signal transduction and subsequent cyclin activity are the driving forces toward multiplictaion of cancer cells as we stated.

When all this is  going on, the cancer cell is at its weak point. That is why chemotherapy, particularly the Taxanes and the Vinca-alkaloids, is more effective. It not only disturbs the microtubule (inducing the 2nd law), but also breaks the actinic anchors to the cytoskeleton of membranes and cellular matrix causing the "Anoikis" like phenomenon within the cell. Lesion to actin like molecules (anchors) within the central nervous system could lead to neuropathy. As we know it has the side effect of these drugs (proof of concept to follow).