The honest headline should have been. Metformin fails to benefit metabolically normal breast cancer patients.
“Patients with ERBB2+ breast cancer in the metformin group vs the placebo group had longer invasive disease–free survival (metformin, 1.93 events per 100 patient-years vs placebo, 3.05 events per 100 patient-years; HR, 0.64; 95% CI, 0.43-0.95; P = .03) and had longer overall survival (metformin, 0.78 deaths per 100 patient-years vs placebo, 1.43 deaths per 100 patient-years; HR, 0.54; 95% CI, 0.30- 0.98; P = .04”
Patients who are not metabolically normal are the ones who are most likely to benefit from metformin therapy in breast cancer.
“Metabolic syndrome (MetS) is a cluster of medical conditions that is associated with an increased risk for cardiovascular disease, T2D, and cancer.3 The clinical diagnosis is made when any 3 of the following 5 conditions are present: abdominal obesity, hypertension, low high-density lipoprotein cholesterol, elevated triglycerides, and high fasting blood glucose levels. Although each of the individual elements of MetS has long-term health implications, it is the combination of these elements that is most concerning as MetS is a precursor of insulin resistance, the driving factor for T2D. Metformin is primarily used in the management of T2D. In patients with breast cancer, the development of insulin resistance has been associated with worse breast cancer outcomes.”
Metformin cut the number of patients who died in half if they were ERBB2 positive. ERBB2 is also called HER2 and EGFR2. (Epidermal Growth Factor Receptor 2) These are different names for the same growth factor receptor. Look at the diagram above. This represents the core signaling pathway that is involved in cardiovascular disease. EGFR2 goes in the purple growth factor box in the middle of the diagram. The molecules in the red boxes—angiotensin II, HMG CoA reductase, and aldosterone— are all activated by fast food, processed food, and increased abdominal fat to increase oxidant production which directly activates EGFR. These factors activate the components of the metabolic syndrome. Oxidants also caused gene mutations. Growth factor signaling from EGFR subsequently switches on mTOR and switches off AMPK-key factors in cancer metabolism. Metformin switches off mTOR and switches on AMPK which directly interferes with this core mechanism of disease.
The criteria used in this study are more stringent than those used to approve much more expensive chemotherapy drugs. Here we looked at disease-free survival and overall survival. Chemotherapy drugs often have no evidence that they prolong disease free survival or prolong life. They are approved on the basis of surrogate markers like tumor shrinkage. Some of them do nothing to improve the length or quality of life. Now we have evidence from a controlled clinical trial that metformin is effective in the 20% of breast cancer patients who are EGFR2 positive.
Blocking the red box factors in the diagram in patients with high-risk type 2 diabetes prolongs life by 8 years compared with usual care. This is a great example of how multiple chronic illnesses are tied together and offers the promise of much more precise treatments in primary care. Is is essential for primary care providers to know more about this core molecular biology.
Excellent analysis by you. I am in complete agreement with you. Frankly I do not agree with the study's data interpretation/duration for data extraction.incidentally, it is either my insight or mistake at the breast and prostate are "comparable" and that metformin would be of benefit and prostate cancer. H Robert Silverstein MD FACC
Not surprised! The entire industry is corrupt to its core. They go by their preordained narratives then cherry-picking the data to fit it somehow to the point of absurdity!