Association between mammographic density and age-related lobular involution of the breast

Abstract

Purpose: Mammographic density and lobular involution are both significant risk factors for breast cancer, but whether these reflect the same biology is unknown. We examined the involution and density association in a large benign breast disease (BBD) cohort.

Patients and methods: Women in the Mayo Clinic BBD cohort who had a mammogram within 6 months of BBD diagnosis were eligible. The proportion of normal lobules that were involuted was categorized by an expert pathologist as no (0%), partial (1% to 74%), or complete involution (>or= 75%). Mammographic density was estimated as the four-category parenchymal pattern. Statistical analyses adjusted for potential confounders and evaluated modification by parity and age. We corroborated findings in a sample of women with BBD from the Mayo Mammography Health Study (MMHS) with quantitative percent density (PD) and absolute dense and nondense area estimates.

Results: Women in the Mayo BBD cohort (n = 2,667) with no (odds ratio, 1.7; 95% CI, 1.2 to 2.3) or partial (odds ratio, 1.3; 95% CI, 1.0 to 1.6) involution had greater odds of high density (DY pattern) than those with complete involution (P trend < .01). There was no evidence for effect modification by age or parity. Among 317 women with BBD in the MMHS study, there was an inverse association between involution and PD (mean PD, 22.4%, 21.6%, 17.2%, for no, partial, and complete, respectively; P trend = .04) and a strong positive association of involution with nondense area (P trend < .01). No association was seen between involution and dense area (P trend = .56).

Conclusion: We present evidence of an inverse association between involution and mammographic density.

Fig 1.

Distribution of involution and parenchymal pattern in the Mayo Clinic benign breast disease cohort. N1, nondense; P1, prominent ductal pattern occupying less than a fourth of the breast; P2, prominent ductal pattern occupying more than a fourth of the breast; DY, homogenously dense.

Fig 2.

Involution and parenchymal pattern by age at diagnosis of benign breast disease in the benign breast disease cohort. Solid line indicates proportion of women in each age group with homogenously dense pattern (DY).

Fig 3.

Hypothesized association between mammographic density, lobular involution, and breast tissue composition. Mammographically dense tissue represents higher proportions of epithelium and stroma, and less fat. Our results indicate a positive association of percent mammographic density with lack of lobular involution. However, the association between stroma and lobular involution in regards to mammographic density is yet unclear. Potentially, women with lobular involution but higher percent density have a strong stromal, rather than fat component.