Study of Erlotinib and Metformin in Triple Negative Breast Cancer

Breast cancer has several different subtypes based upon measurement of expression of proteins found on the surface of the cancer cells. Cancers that lack expression of three of these proteins, namely the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), are termed triple negative. By studying the molecular attributes of breast cancer cells from a large group of breast cancer patients, a profile of markers enriched in triple negative breast cancers (TNBC) was discovered. This profile includes loss of expression of the protein, Phosphatase and Tensin homolog (PTEN), increased expression of the protein, epidermal growth factor receptor (EGFR), and disruption of the cells ability to repair DNA. These alterations also allow the tumor to thrive and likely evade treatment. Observation has been made that the drug combination of metformin and erlotinib can inhibit triple negative cells with these alterations. A clinical trial will be conducted to test the ability of patients to tolerate the treatment (Phase I trial). This trial will be available to triple negative breast cancer patients with metastatic disease. Other goals of the study will be to confirm that the drugs are working properly and whether or not there are enough responses to the treatment to warrant additional studies. If the treatment proves to be effective, even if only in a subset of triple negative patients, future studies will focus on validating biomarkers that can identify patients that will respond to the drug combination, as well as discovering how cells become resistant to the treatment. The research has the potential to advance a new effective treatment for a highly lethal disease and thus could prolong patient survivals while maintaining a high quality of life.