title: Natural history of age-related lobular involution and impact on breast cancer risk.
abstract: Age-related lobular involution (LI) is a physiological process in which the terminal duct lobular units of the breast regress as a woman ages. Analyses of breast biopsies from women with benign breast disease (BBD) have found that extent of LI is negatively associated with subsequent breast cancer development. Here we assess the natural course of LI within individual women, and the impact of progressive LI on breast cancer risk. The Mayo Clinic BBD cohort consists of 13,455 women with BBD from 1967 to 2001. The BBD cohort includes 1115 women who had multiple benign biopsies, 106 of whom had developed breast cancer. Within this multiple biopsy cohort, the progression of the LI process was examined by age at initial biopsy and time between biopsies. The relationship between LI progression and breast cancer risk was assessed using standardized incidence ratios and by Cox proportional hazards analysis. Women who had multiple biopsies were younger age and had a slightly higher family history of breast cancer as compared with the overall BBD cohort. Extent of LI at subsequent biopsy was greater with increasing time between biopsies and for women age 55 + at initial biopsy. Among women with multiple biopsies, there was a significant association of higher breast cancer risk among those with involution stasis (lack of progression, HR 1.63) as compared with those with involution progression, p = 0.036. The multiple biopsy BBD cohort allows for a longitudinal study of the natural progression of LI. The majority of women in the multiple biopsy cohort showed progression of LI status between benign biopsies, and extent of progression was highest for women who were in the perimenopausal age range at initial biopsy. Progression of LI status between initial and subsequent biopsy was associated with decreased breast cancer risk.
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, 32224, USA. radisky.derek@mayo.edu.
authors: Derek C
authors: DC
authors: Radisky
authors: Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
authors: Daniel W
authors: DW
authors: Visscher
authors: Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA.
authors: Ryan D
authors: RD
authors: Frank
authors: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors: Robert A
authors: RA
authors: Vierkant
authors: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors: Stacey
authors: S
authors: Winham
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, 32224, USA.
authors: Melody
authors: M
authors: Stallings-Mann
authors: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors: Tanya L
authors: TL
authors: Hoskin
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL, USA.
authors: Aziza
authors: A
authors: Nassar
authors: Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
authors: Celine M
authors: CM
authors: Vachon
authors: Department of Information Technology, Mayo Clinic, Rochester, MN, USA.
authors: Lori A
authors: LA
authors: Denison
authors: Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
authors: Lynn C
authors: LC
authors: Hartmann
authors: Division of Oncology Research, Mayo Clinic, Rochester, MN, USA.
authors: Marlene H
authors: MH
authors: Frost
authors: Department of Surgery, Mayo Clinic, Rochester, MN, USA.
authors: Amy C
authors: AC
authors: Degnim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D001706:Biopsy; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000473:pathology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008327:Mammography; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000473:pathology*; D016016:Proportional Hazards Models; D012307:Risk Factors
keywords: Benign breast disease; Breast cancer risk; Lobular involution