Findings from an observational study show type 2 diabetes increased the risk for an aggressive form of breast cancer in African-American women by more than 40 percent (Cancer Res 2017;77(22):6462-6469).
African-American women are disproportionately diagnosed with ER-negative breast cancer, with double the incidence of white women, according to researchers.
“Our results showed statistically significant evidence of an increased risk of ER-negative breast cancer in black women who had type 2 diabetes before they ever had breast cancer, primarily in the women who had diabetes for at least 5 years,” said Julie R. Palmer, ScD, Associate Director of Boston University's Slone Epidemiology Center, Professor of Epidemiology at Boston University School of Public Health, and Associate Director of Population Sciences at the BU-BMC Cancer Center.
“If these results are confirmed, type 2 diabetes would be a modifiable risk factor for ER-negative breast cancer.”
The study did not show diabetes increased incidence of estrogen receptor (ER)-positive breast cancer, which is the most common subtype (75%) and has a very high survival rate, Palmer noted.
Also garnering attention from oncologists and cancer researchers around the country is that the association Palmer and colleagues made between type 2 diabetes and ER-negative breast cancer was only observed in non-obese black women.
“This study's findings are both surprising and compelling,” commented Dennis Holmes, MD, Breast Cancer Surgeon and Researcher, and Interim Director of the Margie Petersen Breast Center, John Wayne Cancer Institute, at Providence Saint John's Health Center, Santa Monica, Calif.
“Obesity has long been recognized as a cause of both diabetes and breast cancer. However, this study demonstrates a convincing direct relationship between type 2 diabetes and ER-negative breast cancer, even among non-obese women. This insight is critically important, because [ER]-negative breast cancer is particularly challenging to treat,” Holmes told Oncology Times.
Although black women and white women get breast cancer at about the same rate, black women have a 40 percent higher mortality rate, according to the CDC. About 20 percent of white women in the U.S. are diagnosed with the ER-positive subtype, which is typically treated very successfully with hormone therapies (MMWR 2016;65(40):1093-1098).
The far more aggressive ER-negative breast cancer subtype typically is treated with chemotherapy, radiation, or surgery. It also is prone to returning, according to the CDC (MMWR 2016;65(40):1093-1098).
“A troubling aspect of breast cancer epidemiology is the higher risk of ER-negative breast cancer in African-Americans, which accounts significantly for the higher risk of breast cancer-related deaths among African-American women,” Holmes said.
Yet, little is known about associations by breast cancer subtype in African-American women, Palmer revealed. “We are still trying to understand the basic biological processes that lead to ER-negative breast cancer. One way to do this is to study factors that are more common in an African-American population.”
For the study, Palmer and colleagues analyzed data from the Black Women's Health Study (BWHS) to assess for an association between type 2 diabetes and breast cancer. The nationwide prospective cohort study utilizes questionnaires to collect self-reported medical histories from 59,000 enrollees on a biennial basis. Palmer was instrumental in creating the BWHS, which began in 1995.
From this massive dataset, the researchers identified 1,851 cases of invasive breast cancers, including 914 ER-positive diagnoses, and 468 women with ER-negative breast cancer. Among the latter group of women, the researchers found a 43 percent greater risk. Among non-obese black women, type 2 diabetes was associated with increased risk for ER-negative cancer 92 percent of the time.
“Our findings may account for some of the racial disparity in breast cancer, and could partly explain why mortality from breast cancer is so much higher in black women than white women,” Palmer stated.
African-American women also are twice as likely as white women to be diagnosed with diabetes, according to the CDC. The federal agency estimates more than 50 percent of black women will develop type 2 diabetes due to a high prevalence of obesity, high blood pressure, high cholesterol, and a lack of exercise.
“Researchers now believe triple-negative cancers have an inflammatory component, and patients with diabetes are in a perpetual inflammatory state,” noted Nisha Unni, MD, Assistant Professor and Breast Cancer Oncologist, University of Texas Southwestern Medical Center, Dallas.
About 20-25 percent of all breast cancers are the so-called “triple-negative” subtypes, which include ER-negative, progesterone-negative, and HER2-negative breast cancers; hence, the name (MMWR 2016;65(40):1093-1098).
But while the observational study led by Palmer showed incidence of ER-negative breast cancer is higher in black women with type 2 diabetes, “it does not prove a causal association, which means it does not prove that diabetes led to the development of breast cancer,” Unni pointed out. “Since the prevalence of both triple-negative breast cancer, as well as type 2 diabetes, is higher in African-American women, the association could just be a reflection of that,” she told Oncology Times.
Jack Jacoub, MD, Medical Oncologist and Medical Director, MemorialCare Cancer Institute at Orange Coast Medical Center, Fountain Valley, Calif., agreed the study by Palmer, et al. “is a hypothesis-generating dataset, as we have long known African-American women have worse prognostic breast cancer, higher mortality rates from breast cancer, and high rates of triple-negative breast cancer than their white counterparts.”
However, the study's findings helped reinforce Jacoub's position that women at risk “be counseled about metabolic health, diabetic control, and the possible link to increased breast cancer risk due to chronic inflammation.
“Cancer-screening should be emphasized,” Jacoub told Oncology Times. “Frankly, I also look for reasons to put female patients at risk on metformin, given the recently accumulating data on its efficacy (Curr Oncol 2017;24(2):e85-e91).”
The study by Palmer, et al. “also informs physicians that diabetic and metabolic derangement control should be emphasized, and perhaps that more metformin and other hypoglycemic agents should be used in treating this patient population,” he commented.
Targeted Clinical Strategies
Several studies have suggested diabetes is a risk factor for breast cancer. One recent study also found an association between type 2 diabetes and breast cancer in African-American women, for example; however, the researchers did not report results separately for ER-negative and ER-positive disease.
Tomi Akinyemiju, PhD, MS, Associate Professor of Epidemiology and Assistant Dean for Inclusive Excellence, College of Public Health and Markey Cancer Center, University of Kentucky, Lexington, said the findings in the Palmer-led study “are in line with recently published work by our group (Obesity 2017; doi:10.1002/oby.22067).”
The research led by Akinyemiju showed a significant association between lack of metabolic health—defined as a patient with any combination of the following three conditions: high blood pressure, dyslipidemia, high triglycerides, diabetes or high fasting blood glucose, high waist circumference and cancer mortality—but only among normal-weight individuals, she explained.
Speaking to the clinical implications of the results from the Palmer-led study, Akinyemiju told Oncology Times: “If type 2 diabetes is found to increase the risk of the more aggressive ER-negative breast cancer subtype, then targeted interventions focused on patients with diabetes may help reduce breast cancer incidence among African-American women, and reduce racial disparity in breast cancer outcomes that have remained intractable over the past few decades.”
Akinyemiju further noted the study led by Palmer also shows women with diabetes and using medication to treat it had a 30 percent increased risk of ER-negative breast cancer, compared with more than a two-fold increased risk among those not using medications.
“This suggests strongly that clinical strategies to ensure that type 2 diabetes is well-controlled using either medication, or lifestyle changes, such as weight loss and exercise, may be a promising approach to reducing the risk and mortality of breast cancer in African-American women,” she concluded.
If borne out with additional research, the findings of Palmer, et al. could lead to new treatment approaches “to reduce risk or even prevent triple-negative breast cancer in a population that is at higher risk,” said Melissa D. Fana, MD, FACS, Chief of Breast Surgery, Southside Hospital at Northwell Health System, Bay Shore, N.Y.
The results of the study “also support the recent understanding that it is the biology of breast cancer which is key in understanding how to better treat patients with individualized treatment regimens, and perhaps one day soon prevent breast cancer with targeted strategies,” she concluded.
Chuck Holt is a contributing writer.