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Metformin increased complete response rates in early-stage breast cancer
The rate of pathologic complete response was three time higher in women receiving neoadjuvant treatment for early-stage breast cancer plus metformin than in those women receiving neoadjuvant therapy without metformin.
Data from previously conducted studies has shown metformin decreased the incidence of cancer and cancer-related deaths in patients with diabetes. The current study was conducted to see if metformin increased the effectiveness of neoadjuvant chemotherapy.
“Given the tripling of the pathologic complete response rate in diabetic patients treated with metformin compared with those not receiving the drug in this study, additional work will be necessary to determine whether pathologic complete response is a relevant prognostic marker in this group of patients,” Pamela J. Goodwin, MD, MSc, FRCP, and colleagues, wrote in an accompanying editorial. Goodwin is professor of medicine at the University of Toronto, Mount Sinai Hospital, Ontario, Canada.
Researchers conducted a retrospective study of 2,529 patients who received neoadjuvant chemotherapy for early-stage breast cancer between 1990 and 2007. They analyzed data from 68 diabetic patients receiving metformin, 87 diabetic patients not receiving metformin and 2,374 patients without diabetes.
Response rate better with metformin
The pathologic complete response rate to treatment was 24% in the metformin group, 8.0% in the nonmetformin group and 16% in the group without diabetes (P=.02). A significant difference was found between the metformin and nonmetformin groups (P=.007) and the nonmetformin and nondiabetes groups (P=.04). Comparison between the metformin and nondiabetic groups showed a trend toward statistical significance (P=.10).
In multivariate analysis adjusted for diabetes status, BMI, age, stage, grade, ER/PR status, HER-2 status and neoadjuvant taxane use, use of metformin independently predicted pathologic complete response (OR=2.95; 95% CI, 1.07-8.17). Metformin was not, however, an independent predictor of relapse-free survival or OS.
Exploratory analysis of relapse-free survival and OS was performed at a median follow-up of 37 months. The estimated three-year relapse-free survival rates were not significantly different for the metformin, nonmetformin and nondiabetic groups (P=.66); however, the estimated three-year OS rates were statistically different for the three groups (P=.02).
Possible insulin effect?
In prior clinical studies elevated insulin levels were associated with poorer outcomes in patients with breast cancer; however, the use of metformin in women with early-stage breast cancer has been shown to reduce insulin levels, according to researchers.
Because almost twice as many women in the metformin group were using insulin, an exploratory analysis was performed to examine if insulin use affected the rate of complete response. The pathologic complete response rate was similar for insulin use vs. no insulin use in the metformin group; however, in the nonmetformin group, the rate of complete response was 0% for patients using insulin and 12% for those not using insulin (P=.05).
“These results suggest that part of the difference in pathologic complete response rates between the metformin and nonmetformin groups (and between the nonmetformin and nondiabetic groups) may be attributable to insulin use,” the researchers wrote. “However, insulin use is only one factor, because patients who were not receiving insulin also seemed to benefit from the addition of metformin.”
Goodwin and colleagues are currently involved in developing a large-scale, phase-3 trial to evaluate the effects of metformin on breast cancer outcomes.
“The totality of currently available evidence, including the results reported [in this trial], has reached a level sufficient to warrant action in initiating such a trial in the breast cancer adjuvant setting,” Goodwin and colleagues wrote.
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