Why early treatment of obesity matters:  pAkt/mTor and glycolysis is activated in obese women during the initiation of triple-negative breast cancers and can be targeted by metformin chemoprevention — ASN Events
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  3. Why early treatment of obesity matters:  pAkt/mTor and glycolysis is activated in obese women during the initiation of triple-negative breast cancers and can be targeted by metformin chemoprevention

Why early treatment of obesity matters:  pAkt/mTor and glycolysis is activated in obese women during the initiation of triple-negative breast cancers and can be targeted by metformin chemoprevention (#232)

Victoria Seewaldt 1 , Catherine Ibarra 1 , Patricia Keely 2 , Chistopher Sistrunk 1 , Adrian Ambrose 1 , Amira Carter 1
  1. Duke University, Durham, NC, USA
  2. University of Wisconsin, Madison, WI, USA
Background: Obesity is one of the most important preventable causes of cancer, accounting for >20% of cancer deaths. Obesity increases insulin and activates Akt/mTor, glycolysis, and glucose-uptake. AMPK counters these signals and is activated by metformin. 

Hypothesis: pAkt/mTor and glycolysis are elevated in obese women prior to development of TNBC and are targeted by metformin-chemoprevention.

Methods/Results: Using proteomic-profiling and metabolic-imaging, we tested pAkt/mTor and metabolism in TNBC and matched normal breast tissue from lean (BMI<25) and obese (BMI>30) women. In obese women, pAkt/mTor and metabolism was activated in TNBC and normal tissue. In lean women only TNBC exhibited pAkt/mTor/metabolic-activation. We tested sequential biopsies from women who had normal biopsy and did or did not progress to TNBC within 12 months. In women that progressed, we observed activation of Akt/mTor/glycolysis/glucose-uptake in the "normal" biopsy.

Conclusions: pAkt/mTor/metabolic-signaling is activated in normal tissue prior to development of TNBC. Enrollment in our ALLIANCE-prevention trial is ongoing and will test the ability of metformin to target pAkt/mTor and metabolism.

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