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Metformin Seems to Lower Risk of Estrogen-Receptor-Positive Breast Cancer in Women With Type 2 Diabetes

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Women with type 2 diabetes who take metformin to control their blood sugar appear to have a lower risk of estrogen-receptor-positive breast cancer, the most common type of breast cancer, according to a study.

The research was published online on Jan. 28, 2021, by the Annals of Oncology. Read “A prospective study of type 2 diabetes, metformin use, and risk of breast cancer.”

Metformin, diabetes, and breast cancer risk
About the study
What this means for you

Metformin, diabetes, and breast cancer risk

In type 2 diabetes, a person’s blood glucose, or blood sugar, levels are too high because the body does not make or use insulin well. Insulin is a hormone that helps glucose get into cells to give the cells energy. Without enough insulin, glucose stays in the blood. Over time, this can cause damage to the eyes, kidneys, and nerves and cause heart disease and stroke.

Metformin (brand names: Fortamet, Glucophage, Glumetza, Riomet) reduces blood sugar levels by lowering the amount of glucose produced by the liver.

A number of earlier studies have suggested that women with type 2 diabetes have a higher-than-average risk of breast cancer. Other studies have suggested that women taking metformin to treat type 2 diabetes have a lower-than-average risk of breast cancer.

Still, the earlier studies looked only at women with type 2 diabetes, and they also didn’t take into account how long the women took metformin. Either of these factors could have affected the results.

The researchers who did the study reviewed here wanted to overcome these limitations, so they decided to do a new study.

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About the study

The researchers looked at information from 44,541 women age 35 to 74 who were part of the Sister Study.

The Sister Study, being conducted by the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, enrolled more than 50,000 women from the United States and Puerto Rico from 2003 to 2009. All the women in the study had a sister or half-sister who had been diagnosed with breast cancer. Because the sisters have shared genes, environments, and experiences, the researchers hope to identify breast cancer risk factors and ways to prevent the disease.

When the women joined the Sister Study, they had an in-person exam, gave blood samples, and completed questionnaires on their medical history, lifestyle, and demographics. The women complete annual health updates and fill out detailed questionnaires every 3 years.

Women with type 1 diabetes were not included in this study.

Of the women in the study:

  • 38,960 did not have type 2 diabetes
  • 5,581 had type 2 diabetes

Among the women with type 2 diabetes, 61% were treated at some point with metformin.

Women with type 2 diabetes:

  • were older
  • had a higher body mass index (BMI)
  • were less active
  • had poorer diet quality
  • breastfed for shorter periods of time
  • were more likely to be part of a racial/ethnic minority group
  • were younger when they started menstruating

Half the women were followed for less than 8.6 years and half were followed for longer periods of time.

During follow-up, 2,678 cases of invasive breast cancer and DCIS were diagnosed:

  • 277 women with type 2 diabetes were diagnosed with breast cancer
    • 184 cancers were estrogen-receptor-positive
    • 36 cancers were estrogen-receptor-negative
    • 25 cancers were triple-negative (estrogen- and progesterone-receptor-negative and HER2-negative)
  • 2,401 women without type 2 diabetes were diagnosed with breast cancer
    • 1,800 cancers were estrogen-receptor-positive
    • 303 cancers were estrogen-receptor-negative
    • 155 cancers were triple-negative

The researchers’ analysis showed no overall link between type 2 diabetes and breast cancer risk. But when the researchers looked at specific subtypes of breast cancer, they found that type 2 diabetes was linked to a higher risk of triple-negative breast cancer.

The results also showed that compared to women who didn’t have type 2 diabetes, women who had type 2 diabetes and took metformin:

  • had a lower risk of estrogen-receptor-positive breast cancer, especially if a woman took metformin for 10 years or longer
  • had a higher risk of estrogen-receptor-negative breast cancer
  • had a higher risk of triple-negative breast cancer

“Taken together, these findings suggest that having type 2 diabetes may increase the risk of developing breast cancer, but that taking metformin may protect against developing [estrogen-receptor]-positive breast cancer, the most common type of breast cancer,” Dale Sandler, Ph.D., chief of the Epidemiology Branch of NIEHS and lead researcher, said in a statement. “Metformin did not appear to protect against [estrogen-receptor]-negative or triple-negative breast cancer. We can't say for sure if the increased risk of triple-negative breast cancer is because metformin doesn't protect women against the negative effects of having type 2 diabetes or because metformin use can cause triple-negative breast cancer. Since there are no mechanistic data supporting a causal effect of metformin, the former interpretation seems more likely.”

“It's important to note that some of our findings, especially for triple-negative breast cancer, were based on a small number of cases and those results need replication,” added Yong-Moon Mark Park, postdoctoral fellow at NIEHS and lead author of this study. “Further studies are needed to discover whether the apparent increased risk of triple-negative breast cancer is caused by metformin or is due to the absence of protection from metformin.”

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What this means for you

The results of this study are very interesting, but more research is needed to better understand any links between breast cancer risk, type 2 diabetes, and metformin treatment.

This study does not mean that women who don’t have type 2 diabetes should take metformin to reduce breast cancer risk.

The researchers who did the study said that women with type 2 diabetes and their doctors should discuss whether having type 2 diabetes should affect how frequently the women are screened for breast cancer.

If you do have type 2 diabetes and you have a choice of the type of medicine you take to manage it, you may want to ask your doctor if metformin would be a good option for you.

Together, you and your doctor can figure out the best way to manage the type 2 diabetes and keep your risk of breast cancer as low as it can be.

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Written by: Jamie DePolo, senior editor

Reviewed by: Brian Wojciechowski, M.D., medical adviser

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