Independent association of lobular involution and mammographic breast density with breast cancer risk

J Natl Cancer Inst. 2010 Nov 17;102(22):1716-23. doi: 10.1093/jnci/djq414. Epub 2010 Oct 29.

Abstract

Background: Lobular involution, or age-related atrophy of breast lobules, is inversely associated with breast cancer risk, and mammographic breast density (MBD) is positively associated with breast cancer risk.

Methods: To evaluate whether lobular involution and MBD are independently associated with breast cancer risk in women with benign breast disease, we performed a nested cohort study among women (n = 2666) with benign breast disease diagnosed at Mayo Clinic between January 1, 1985, and December 31, 1991 and a mammogram available within 6 months of the diagnosis. Women were followed up for an average of 13.3 years to document any breast cancer incidence. Lobular involution was categorized as none, partial, or complete; parenchymal pattern was classified using the Wolfe classification as N1 (nondense), P1, P2 (ductal prominence occupying <25%, or >25% of the breast, respectively), or DY (extremely dense). Hazard ratios (HRs) and 95% confidence intervals (CIs) to assess associations of lobular involution and MBD with breast cancer risk were estimated using adjusted Cox proportional hazards model. All tests of statistical significance were two-sided.

Results: After adjustment for MBD, having no or partial lobular involution was associated with a higher risk of breast cancer than having complete involution (none: HR of breast cancer incidence = 2.62, 95% CI = 1.39 to 4.94; partial: HR of breast cancer incidence = 1.61, 95% CI = 1.03 to 2.53; P(trend) = .002). Similarly, after adjustment for involution, having dense breasts was associated with higher risk of breast cancer than having nondense breasts (for DY: HR of breast cancer incidence = 1.67, 95% CI = 1.03 to 2.73; for P2: HR of breast cancer incidence = 1.96, 95% CI = 1.20 to 3.21; for P1: HR of breast cancer incidence = 1.23, 95% CI = 0.67 to 2.26; P(trend) = .02). Having a combination of no involution and dense breasts was associated with higher risk of breast cancer than having complete involution and nondense breasts (HR of breast cancer incidence = 4.08, 95% CI = 1.72 to 9.68; P = .006).

Conclusion: Lobular involution and MBD are independently associated with breast cancer incidence; combined, they are associated with an even greater risk for breast cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging*
  • Biopsy
  • Breast / pathology*
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Carcinoma, Lobular / diagnostic imaging
  • Carcinoma, Lobular / epidemiology*
  • Carcinoma, Lobular / pathology
  • Carcinoma, Lobular / surgery
  • Female
  • Humans
  • Incidence
  • Mammography*
  • Middle Aged
  • Minnesota / epidemiology
  • Risk Assessment
  • Risk Factors