Neil Osterweil

December 08, 2011

December 8, 2011 (San Antonio, Texas) — Every medical student knows that correlation is not causality, but there is further damning evidence of an association between diabetes and risk for breast cancer, reported Swedish investigators here at the 34th Annual San Antonio Breast Cancer Symposium (SABCS).

A case-control study drawing on data from Sweden's extensive birth-to-death population registry and a national prescription registry showed that diabetes was associated with a nearly 40% increase in risk for breast cancer, reported Hakan Olsson, MD, a professor in the departments of oncology and cancer epidemiology at Lund University in Lund, Sweden.

"There is a link between diabetes and breast cancer even after adjusting for obesity and abnormal blood lipids, especially seen within 4 years of a cancer diagnosis," Dr. Olsson said.

The authors also found a significant association between overall cancer risk among patients with diabetes who used the long-acting insulin analogue insulin glargine (Lantus, Sanofi Diabetes).

The oral antidiabetic agent metformin, in contrast, was associated with a trend toward lower cancer risk among people with diabetes, but this finding was not statistically significant.

The insulin findings, however, seem to contradict those of a meta-analysis also presented December 7 at the International Diabetes Federation (IDF) World Diabetes Congress 2011 in Dubai, United Arab Emirates. That study, which included data from observational studies and randomized, controlled trials, found no additional cancer associated with the use of long-acting insulin, according to a Sanofi spokesperson.

The evidence for a link between diabetes and breast cancer risk, on the other hand, appears to be strong, commented Jennifer A. Ligibel, from the Division of Breast Oncology at the Dana Farber Cancer Institute in Boston, Massachusetts.

"I think this work is very important as we try to better understand the relationship between obesity, which is unfortunately a growing health problem here in the US and around the world, and its link to cancer," Dr. Ligibel said.

She noted that the MA 32 study, a phase 3 randomized trial of metformin vs placebo in early-stage breast cancer, is recruiting patients in the United States and Canada. Investigators will examine whether metformin may interfere with the growth of early breast cancer and whether it could be combined with other therapies to reduce the incidence of recurrence.

Dr. Olsson and colleagues looked at data on 2724 case-patients with cancer and 20,542 controls (matched for age, sex, and residence) from outpatient and inpatient population-based registries to explore the relationship between cancer, diabetes, obesity, and/or abnormal blood lipids.

They also drew information on insulin glargine and metformin use from the Swedish pharmacy prescription registry. In all, 202 case-patients and 1297 controls had used glargine, and 1036 case-patients and 7039 controls had used metformin.

They found in a univariate analysis that for the time interval of 90 to 1460 days before a breast cancer diagnosis, diabetes was associated with an odds ratio (OR) for breast cancer of 1.18 (95% confidence interval [CI], 0.99 - 1.40). Neither obesity nor lipid abnormality was significantly associated with breast cancer risk over the same period.

In a multivariate analysis controlling for obesity and lipids, diabetes was associated with an OR of 1.37 (95% CI, 1.10 - 1.71). But in an analysis looking at breast cancer diagnosed 5 to 10 years after a diabetes diagnosis, the association fell apart (OR, 1.11; 95% CI, 0.88 - 1.40).

Although their follow-up method did not allow them to look at specific cancer types, they analyzed overall cancer risk among glargine and metformin users and found that glargine was associated with an OR of 2.88 (95% CI, 1.15 - 6.64), whereas metformin was associated with a nonsignificant trend toward lower risk (0.92; 95% CI, 0.82 - 1.09).

But those findings were called into question by Robert Cuddihy, MD, from the Medical Diabetes Division of Sanofi, headquartered in Bridgewater, New Jersey.

He pointed to a 2009 study (Diabetologia. 2009;52:1745-1754) looking at registry data from 114,841 Swedish residents who had a prescription for insulin, which found that in 2006 and 2007, insulin glargine use was associated with a relative risk for breast cancer of 1.99 (95% CI, 1.31 - 3.03).

But with additional follow-up, the investigators did not find an increased risk for breast cancer among insulin glargine users during 2008.

"We need data for additional years before we can state with reasonable certainty that the increase in breast cancer incidence that we observed in Sweden in 2006 and 2007 was due to a random fluctuation or whether there is an association with the use of insulin glargine," they wrote in a second study (Acta Oncol. 2011;50:685-693).

Dr. Cuddihy noted that much larger international studies underway or on the drawing board will better answer the question of whether an actual or only phantom risk for breast cancer or other types of cancer is associated with insulin glargine use.

The study was funded by Sweden's Southern Health Care Region. Dr. Olsson and Dr. Ligibel have disclosed no relevant financial relationships. Dr. Cuddihy is an employee of Sanofi, manufacturer of insulin glargine.

34th Annual San Antonio Breast Cancer Symposium (SABCS): Abstract P1-08-06. Presented December 8, 2011.


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