Matrix metalloproteinase 2 (MMP2) is an
enzyme with important functions in
breast cancer invasion and
metastasis. However, it is unclear whether circulating MMP2 levels may predict
breast cancer risk. We conducted a prospective nested case-control analysis in the Nurses' Health Study among 1136 cases who were diagnosed with invasive
breast cancer between 1992 and 2004 and 1136 matched controls. All participants provided blood samples in 1989-1990, and a subset (170 cases, 170 controls) contributed an additional sample in 2000-2002. Pre-diagnostic plasma MMP2 levels were measured via immunoassay, and conditional logistic regression was performed to calculate odds ratios (
ORs) and 95% confidence intervals (95% CIs), adjusted for
breast cancer risk factors. No association was observed between plasma MMP2 levels and risk of total invasive
breast cancer (top vs. bottom quartile, OR=1.0; 95% CI: 0.7, 1.2; p-trend=0.89). Findings did not vary significantly by time since blood draw, body mass index, postmenopausal
hormone use, or menopausal status at either blood draw or
breast cancer diagnosis. MMP2 was associated with a greater risk of nodal
metastases at diagnosis (top vs. bottom quartile, OR=1.5; 95% CI: 1.0, 2.2; p-heterogeneity, any vs. no lymph nodes=0.002), but no significant associations were observed with other
tumor characteristics or with recurrent or fatal
cancers. Plasma MMP2 levels do not appear to be predictive of total invasive
breast cancer risk, although associations with aggressive disease warrant further study.