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!

BRCA 1,2  
BR=Breast   CA=cancer
Tumor suppressor gene which encodes a protein regulator of transcription gene involved with cell proliferation (once again it is a regulator that is involved!)

1. Prophylactic Bilateral mastectomy reduces the short term risk of Breast cancer, and overall risk by 90%
2.Adding Bilateral Salpingo-Oophorectomy decreases risk of Breast and Ovarian cancer.
3.BRCA1 high grade and Hormone Receptor Negative, majority are basal like subtype  (but also more Atypia and Medullary histology found here!
4.whereas BRCA2 are more likely receptor positive and of luminal subtype
5. Risk of contralateral breast cancer in those with the disease 50-60%
6.BRCA 2 increases risk of Gastric,bilary,gallbladderand pancreatic cancer also.
7. The 2 HITS Theory assumes that the first hit is to have the abnormality but with the protecting presence of the normal BRCA gene.  The second (environment factor) Hit knock out the normal BRCA to unleash the effect of the abormal BRCA1-100
IF YOU HAVE IT
1-Abide by strict surveillance protocol
2-Bilateral protective Mastectomy
3. Bilateral protective Oophorectomy
4. participation in preventive research drug (Tamoxifen,Raloxifen)

and know about possibility of insurance issues that may arise
SEE A GENETIC COUNSELOR PRIOR TO TESTING!