Cancer
Oral contraceptive use and the expression of stromal markers in benign breast tissue Maisey Ratcliffe* Maisey Ratcliffe Ratcliffe Ratcliffe Ratcliffe Ratcliffe Ratcliffe University of Florida
Purpose:
Oral contraceptives (OC) have been shown to influence breast cancer (BCa) risk, particularly among current and recent users. Breast stroma, particularly fibroblasts, may play an important role in breast carcinogenesis. It is unclear whether OCs can influence stromal fibroblasts. We investigated, for the first time, the association of OCs with the expression of stromal fibroblast markers alpha-smooth muscle actin (αSMA), tenascin-C (TNC), fibroblast activation protein (FAP), calcyclin (s100A6), and matrix metallo-peptidase (MMP14).
Methods:
This study included cancer-free women with biopsy-confirmed benign breast disease (BBD) from an incident BBD study within the Nurses’ Health Study II cohort. OC use and BCa risk factor data were obtained from biennial questionnaires. Immunofluorescence (IF) of stromal markers was performed on tissue microarrays. The % positivity for each core was quantified using inForm v2.6.0. Generalized linear regression was used to examine the associations of OCs (use status, total duration, age at 1st and last use, and time since last use) with log-transformed marker expression, adjusted for relevant BCa risk factors.
Results:
Among 693 cancer-free women, OC use status at biopsy was positively associated with FAP expression (current vs. never β=0.99, 95% Confidence Interval [CI] 0.08, 1.90; past vs. never β=0.59, 95% CI 0.06, 1.12; p-trend=0.01). Total duration of use was positively associated with TNC (β per 1-year=0.08, 95% CI 0.02, 0.15; β for ≥10 vs. ≤1-year=1.24, 95% CI 0.06, 2.41; p-trend=0.03). No associations were found for αSMA, s100A6, and MMP14. Age at 1st use, years since last use, age at last use, and use before 1st pregnancy were not associated with any of the markers.
Conclusion:
Our findings suggest increased breast stromal fibroblast activity (as captured by higher FAP and TNC expression) in current and past OC users, and those with longer total duration of OC use. Further studies are needed to confirm these findings.