Metformin may affect breast cancer proliferation
depending on a woman’s insulin resistance, with decreased proliferation
occurring in women with an increased homeostasis model assessment index,
according to phase 2 study results.
Researchers evaluated women with stage I to stage IIa
breast cancer who were candidates for elective surgery. Researchers measured
Ki-67 levels in a pretreatment biopsy and then again in a post-treatment
surgical specimen. Ki-67 is used as a marker because of its postulated role in
predicting drug efficacy.
Patients were randomly assigned to treatment with
metformin 850-mg tablets (n=100) or placebo (n=100). The primary endpoint of
the study was the change in Ki-67 at 4 weeks.
The study failed to meet its primary endpoint. Metformin
had a nonsignificant effect on Ki-67 compared with placebo.
In a subgroup analysis, the researchers measured the
effect of metformin on Ki-67 according to insulin resistance status (P
for interaction =.045). They found a nonsignificant 10.5% decrease of
proliferation in women with elevated homeostasis model assessment (HOMA) index
(>2.8), and a nonsignificant 11.1% increase in proliferation in women with
no insulin resistance (HOMA ≤2.8).
The researchers also discovered that metformin did have
a significant effect on Ki-67 in a subgroup of 119 women with luminal B tumors
(P for interaction =.05).
Although researchers said the effect of metformin
according to HOMA index had only a nominal statistical significance of
P=.045, “the qualitative interaction between metformin and insulin
resistance may have important clinical implications and warrants confirmation
in independent studies.”
In an accompanying editorial, Matthew Martin,
PhD, a postdoctoral fellow at The Institute of Cancer Research, and
Richard Marais, PhD, director of the Paterson Institute for Cancer
Research, both in the United Kingdom, noted recent studies in mice demonstrated
that metformin and doxorubicin cooperate to suppress breast cancer growth, and
that a combination of metformin and VEGF receptor signaling inhibitors help
suppress the growth of some types of melanoma.
“As we move into the era of personalized medicine,
it is not difficult to imagine how novel targeted agents could be combined with
metformin to inhibit tumor-cell growth directly and simultaneously normalize
the pathologic microenvironment that induces and maintains tumor growth,”
- Bonanni B. J Clin Oncol. 2012;doi:10.1200/JCO.2011.39.3769.