Reproductive factors and the expression of stromal markers in benign breast biopsy samples.

Abstract

Background: We examined the associations of several reproductive factors with expression of stromal fibroblast markers αSMA, TNC, FAP, S100A6, and MMP14.

Methods: We included 694 cancer-free women with biopsy-confirmed incident benign breast disease within the Nurses' Health Study II. Breast cancer risk factor data were obtained from biennial questionnaires. Immunofluorescence of stromal markers was completed on tissue microarrays. For each core, % positivity was quantified with inForm v2.6.0. Generalized linear regression was used to examine the associations of reproductive factors with log-transformed positivity for each marker.

Results: In multivariate analysis, nulliparous status showed a suggestive positive association with TNC expression (β = 0.79, 95% CI -0.10, 1.68, p = 0.08) but was not associated with the other stromal markers (all p > 0.10). No associations were seen for number of children, age at 1st birth, breastfeeding, continuous age at menarche, time between menarche and age at first birth, and time since last birth with any of the markers' expression. Categorical age at menarche showed a suggestive positive association with MMP14 (p-trend = 0.07).

Conclusion: Our findings suggest that nulliparous status and age at menarche may be associated with the expression of stromal fibroblast activation markers TNC and MMP14, respectively. Further studies are needed to confirm these findings.