Is Metformin really effective in treating breast cancer?

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Is Metformin really effective in treating breast cancer?

Is Metformin really effective in treating breast cancer? JAMA’s latest clinical study finds different results.

Type 2 diabetes is one of the most common chronic diseases worldwide, and breast cancer is the most common cancer in women.

Scientific evidence links diabetes to higher rates of different cancers, accelerated progression and higher aggression.

As the “cornerstone” of type 2 diabetes, Metformin has been used clinically for half a century, and its safety and efficacy have been extensively verified.

In recent years, basic and clinical research has found that in addition to being the most widely used oral hypoglycemic drug, Metformin also has effects such as weight loss, cardiovascular protection, intestinal flora improvement, hair loss treatment, anti-inflammatory, anti-aging and anti-tumor effects.

At present, more and more attention has been paid to the research on the anti-tumor aspects of Metformin as an “old drug with new use”.

Previous observational and preclinical studies have shown that Metformin can reduce the risk of developing some cancers, including breast cancer, and improve survival. In theory, the drug could reduce the growth rate of cancer cells by improving a patient’s metabolism, particularly insulin levels, or possibly directly affect the cancer cells.

Metformin once held great promise in treating breast cancer, but the latest randomized, double-blind trial recruited non-diabetic breast cancer patients who took a placebo or metformin twice a day.

The researchers found that adding metformin to standard breast cancer treatment did not improve outcomes for the two most common types of breast cancer, but there was a therapeutic benefit for HER2-positive breast cancer.

The study, titled: Effect of Metformin vs Placebo on Invasive Disease Free Survival in Patients With Breast Cancer , was published in the top international medical journal JAMA on May 24, 2022 .

The landmark clinical trials, led by Dr. Pamela Goodwin of Cedars-Sinai Medical Center in the United States , tracked more than 3,600 breast cancer patients from Canada, the United States, Switzerland and the United Kingdom, and is the largest study of its kind to date.

The researchers analyzed ER/PgR+ and ER/ PgR- (regardless of HER2 status) breast cancer patients and found that the addition of Metformin to standard treatment was associated with improved invasive survival (IDFS) , overall survival There was no improvement in OS or other outcomes .

Effects of Metformin versus placebo on invasive disease-free survival and overall survival

While the study found Metformin to be ineffective in treating the most common type of breast cancer, the trial found a potentially important result for a less common but more aggressive type of breast cancer, HER2-positive breast cancer .

For this subtype of breast cancer, the researchers found that 5 years of Metformin use may reduce mortality, and HER2-positive cancers account for about 20 percent of all breast cancers.

Exploratory analysis of the effect of Metformin versus placebo on invasive disease-free survival and overall survival in patients with HER2-positive breast cancer

In conclusion, Metformin has no benefit in most common breast cancers, but in cases of HER2-positive breast cancer, the findings suggest that it may be beneficial.

A potential next step will be to test the effects of Metformin in patients with HER2-positive breast cancer in a randomized clinical trial.

Before Metformin can be used as a breast cancer treatment, these results need to be replicated in future studies to demonstrate that it could provide an additional treatment option for HER2-positive breast cancer.

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Previous studies have explored the effect of Metformin on the treatment of breast cancer in patients with type 2 diabetes.

In March 2021, a study published in the journal Annals of Oncology showed that taking Metformin in women with type 2 diabetes may help reduce the risk of developing ER-positive breast cancer.

The study followed 44,541 women who had never had breast cancer (these patients’ sisters or half-sisters were diagnosed with breast cancer) for about 8 years, and 2,678 participants were eventually diagnosed with breast cancer, 3227 with type 2 diabetes and 2389 with new-onset type 2 diabetes.

Results of the study showed that women with type 2 diabetes taking Metformin had a 14% lower risk of ER+ breast cancer, and long-term Metformin use (≥ 10 years) had a 38% lower risk of ER+ breast cancer, compared with patients without type 2 diabetes.

However, the risk of ER- breast cancer was increased by 25% and the risk of triple-negative breast cancer was increased by 74%.

In Chinese patients with invasive breast cancer and type 2 diabetes, the researchers also conducted a study of the effect of Metformin on survival outcomes. The results were published in the journal Scientific Reports on May 11, 2021 .

This study retrospectively analyzed 3757 patients with primary breast cancer who underwent surgery in Hebei Cancer Hospital from January 2010 to December 2013, and finally included 3553 patients. 312 cases, 79 cases in the diabetes insulin group, and 23 cases in the diabetes diet and exercise group.

Survival curve analysis and log-rank test were performed on follow-up data for disease-free survival and overall survival.

The results of the study showed that the survival rates of the non-diabetic group, the Metformin group, and the insulin group were significantly different.

The 5-year disease-free survival rates were 85.8%, 96.1%, and 73.0%, respectively, and the 5-year overall survival rates were 87.3% and 97.1%, respectively. %, 73.3% .

The results of this study suggest that Metformin may have a favorable effect on the survival outcomes of Chinese patients with invasive breast cancer and type 2 diabetes , and further multi-center large-sample prospective studies are needed to verify.

For decades, scientists have been exploring the relationship between Metformin and breast cancer.

Its effect is different between different breast cancer subtypes. Its clinical effect still needs to be confirmed by more experiments, and the mechanism behind it is also waiting for further exploration. .

References :
[1] Goodwin PJ, Chen BE, Gelmon KA, et al. Effect of Metformin vs Placebo on Invasive Disease-Free Survival in Patients With Breast Cancer: The MA.32 Randomized Clinical Trial. JAMA. 2022 May 24;327(20) :1963-1973. doi: 10.1001/jama.2022.6147. PMID: 35608580.
[2] Lohmann AE, Goodwin PJ. Diabetes, Metformin and breast cancer: a tangled web. Ann Oncol. 2021 Mar;32(3):285-286. doi: 10.1016/j.annonc.2020.12.014.
[3] Hui T, Shang C, Yang L, et al. Metformin improves the outcomes in Chinese invasive breast cancer patients with type 2 diabetes mellitus. Sci Rep. 2021 May 11;11(1):10034. doi: 10.1038/s41598 -021-89475-y. PMID: 33976288; PMCID: PMC8113316.