Novel breast tissue feature strongly associated with risk of breast cancer

Abstract

Purpose: Accurate, individualized risk prediction for breast cancer is lacking. Tissue-based features may help to stratify women into different risk levels. Breast lobules are the anatomic sites of origin of breast cancer. As women age, these lobular structures should regress, which results in reduced breast cancer risk. However, this does not occur in all women.

Methods: We have quantified the extent of lobule regression on a benign breast biopsy in 85 patients who developed breast cancer and 142 age-matched controls from the Mayo Benign Breast Disease Cohort, by determining number of acini per lobule and lobular area. We also calculated Gail model 5-year predicted risks for these women.

Results: There is a step-wise increase in breast cancer risk with increasing numbers of acini per lobule (P = .0004). Adjusting for Gail model score, parity, histology, and family history did not attenuate this association. Lobular area was similarly associated with risk. The Gail model estimates were associated with risk of breast cancer (P = .03). We examined the individual accuracy of these measures using the concordance (c) statistic. The Gail model c statistic was 0.60 (95% CI, 0.50 to 0.70); the acinar count c statistic was 0.65 (95% CI, 0.54 to 0.75). Combining acinar count and lobular area, the c statistic was 0.68 (95% CI, 0.58 to 0.78). Adding the Gail model to these measures did not improve the c statistic.

Conclusion: Novel, tissue-based features that reflect the status of a woman's normal breast lobules are associated with breast cancer risk. These features may offer a novel strategy for risk prediction.

Fig 1.

(A) Shown is a field of normal lobules (terminal duct lobular units), each composed of multiple acini. (B) Complete regression (involution) of these lobules has occurred, leaving small residual structures largely depleted of acini. Reprinted with permission.

Fig 2.

(A) We subdivided an intact lobule to facilitate counting of individual acini. (B) Delineation of the circumference of the lobule for calculation of lobule area by the computer software is demonstrated.

Fig 3.

Whole-breast mounts from (A) preinvolutional and (B) postinvolutional women. Reprinted with permission.