A127: Standardized measures of lobular involution and subsequent breast cancer risk among women with benign breast disease

Jonine Figueroa1,2,Ruth Pfeiffer1,Louise Brinton1,Maya Palakal1,Amy Degnim3,Derek Radisky3,Lynn Hartmann3,Marlene Frost3,Melody Stallings3,Daphne Papathomas1,Stephen Hewitt1,Daniel Visscher3,Mark Sherman1

1National Cancer Institute, Bethesda, MD, USA,2University of Edinburgh, Edinburgh, Scotland, UK,3Mayo Clinic Cancer Center, Rochester, MN, USA

Presenting date: Monday 2 November
Presenting time: 12.20-13.10

Background

 

Lesser degrees of terminal duct lobular unit (TDLU) involution, indicating elevated quantities of epithelium in the breast, predict higher breast cancer risk; however, standardized measures to quantitate levels of TDLU involution have only recently been developed. We assessed the performance of three measures of TDLU involution, with high intra/inter pathologist reproducibility, in predicting subsequent breast cancer risk among women in the Mayo benign breast disease (BBD) cohort.

Method

 

We performed a masked evaluation of biopsies from 99 women with BBD who subsequently developed breast cancer (cases) after a median of 16.9 years and 145 age-matched controls.  We assessed three metrics inversely related to TDLU involution: TDLU count/cm2, median TDLU span (microns) and median acini count/TDLU (categories 0-10; 11-20; 21-30; 31-50; >50). Associations with subsequent breast cancer risk for quartiles (or categories of acini counts) of each of these measures were assessed with multivariable conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CI).

Results

 

In multivariable models, TDLU counts (quartile4 vs. quartile1, OR=2.44, 95%CI=0.96-6.19, ptrend=0.02) and TDLU spans (quartile4 vs. quartile1, OR=2.83, 95%CI=1.13-7.06, ptrend=0.03) were associated with subsequent breast cancer diagnoses. Women with TDLU spans and TDLU count measures above the median were at increased risk: OR=3.75 (95%CI= 1.40-10.00, ptrend=0.008), compared with women below the median for both metrics.

Conclusion

Reproducible metrics of TDLU involution were associated with breast cancer risk among women with BBD, suggesting that future research on clinical translation of these measures for risk prediction are potentially important.