Radisky Derek C, Visscher Daniel W, Frank Ryan D, Vierkant Robert A, Winham Stacey, Stallings-Mann Melody, Hoskin Tanya L, Nassar Aziza, Vachon Celine M, Denison Lori A, Hartmann Lynn C, Frost Marlene H, Degnim Amy C
Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, 32224, USA.
Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
Breast Cancer Res Treat. 2016 Feb;155(3):423-30. doi: 10.1007/s10549-016-3691-5. Epub 2016 Feb 4.
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.
年龄相关的小叶退化(LI)是一种生理过程,随着女性年龄增长,乳腺的终末导管小叶单位会发生退化。对患有良性乳腺疾病(BBD)的女性进行的乳腺活检分析发现,LI的程度与随后患乳腺癌的风险呈负相关。在此,我们评估个体女性LI的自然病程,以及LI进展对乳腺癌风险的影响。梅奥诊所BBD队列由1967年至2001年期间的13455名患有BBD的女性组成。BBD队列包括1115名进行过多次良性活检的女性,其中106名已患乳腺癌。在这个多次活检队列中,通过首次活检时的年龄和活检之间的时间来检查LI过程的进展。使用标准化发病率比和Cox比例风险分析评估LI进展与乳腺癌风险之间的关系。与整个BBD队列相比,进行多次活检的女性年龄更小,乳腺癌家族史略高。随着活检之间时间的增加以及首次活检时年龄在55岁及以上的女性,后续活检时LI的程度更大。在进行多次活检的女性中,与有退化进展的女性相比,有退化停滞(缺乏进展,HR 1.63)的女性患乳腺癌的风险显著更高,p = 0.036。多次活检的BBD队列允许对LI的自然进展进行纵向研究。多次活检队列中的大多数女性在良性活检之间显示出LI状态的进展,对于首次活检时处于围绝经期年龄范围的女性,进展程度最高。首次活检和后续活检之间LI状态的进展与降低的乳腺癌风险相关。