Independent Association of Lobular Involution and Mammographic Breast Density With Breast Cancer Risk

Abstract

BackgroundLobular 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.MethodsTo 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.ResultsAfter 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; Ptrend = .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; Ptrend = .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).ConclusionLobular involution and MBD are independently associated with breast cancer incidence; combined, they are associated with an even greater risk for breast cancer.

A case‐control study to assess the impact of mammographic density on breast cancer risk in women aged 40–49 at intermediate familial risk

“…After adjusting for absolute nondense area, every additional 10 cm 2 of dense tissue was associated with a 7% increase in odds of breast cancer in all women (n 5 292, actual age range [40][41][42][43][44][45][46][47][48][49][50], but with a 14% increase in premenopausal women (n 5 200, actual age range [40][41][42][43][44][45][46][47][48][49][50]. MD may therefore be an even more important risk factor in premenopausal compared to postmenopausal women among those at higher-thanaverage risk not currently within screening age range.…”

Breast Density and Breast Cancer Risk: Understanding of Biology and Risk

“…In support of this hypothesis, Ghosh et al reported an inverse association between mammographic density (defined by Wolfe's parenchymal patterns) and lobular involution among 2,667 women in the Mayo benign breast disease (BBD) cohort [5]. Compared with those with complete involution, women with no involution had an OR of 1.7 (95 % CI 1.2-2.3) of high density (DY pattern).…”

“…Involution was not, however, associated with the absolute dense area, but rather strongly positively associated with the absolute nondense area. Intriguingly, in a follow-up study based on the Mayo BBD cohort, Ghosh et al found that mammographic density and lobular involution are independent risk factors for breast cancer [5], arguing against the hypothesis that the association between mammographic density and breast cancer risk is explained to any large degree by involution. Ghosh et al also found that women with dense breasts and no lobular involution had the highest breast cancer risk and speculated that the stromal-rich environment in dense breasts results in a preponderance of growth factors that stimulate the epithelium in a non-involuted breast, which could lead to malignant transformation.…”

Apoptosis and Clearance of the Secretory Mammary Epithelium

“…Clinical studies show that completion of lobular involution may reduce future breast cancer incidence [163][164][165][166]. With aging, there is a gradual loss of breast epithelial tissue that typically begins in peri-menopause, which then accelerates during menopause.…”

“…Lobular involution, like post-lactational involution, may inversely correlate with breast cancer risk, since premenopausal women who underwent partial or complete lobular involution had a substantially decreased incidence of breast cancer, while postmenopausal women who showed delayed lobular involution were found to have a correspondingly elevated breast cancer incidence [164]. While much remains to be learned about how lobular involution is regulated, some clinical studies and animal models suggest that IGF-1 may inhibit involution of lobules in the breast [163].…”