Host, reproductive, and lifestyle factors in relation to quantitative histologic metrics of the normal breast

Breast Cancer Research

Research

Jill E. Henry¹  Maire A. Duggan²  Shaoqi Fan³  Alyssa Klein³  Mustapha Abubakar³  Ruth M. Pfeiffer³  Gretchen L. Gierach³  Scott Lawrence⁴  Karun Mutreja⁴ 

[1]Biospecimen Collection and Banking Core, Susan G. Komen Tissue Bank at the IU Simon Comprehensive Cancer Center, Indianapolis, IN, USA

[2]Department of Pathology and Laboratory Medicine, University of Calgary, T2N2Y9, Calgary, AB, Canada

[3]Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Shady Grove, 20850, Bethesda, MD, USA

[4]Molecular and Digital Pathology Laboratory, Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., 21702, Frederick, MD, USA

关键词: Breast cancer;    Etiology;    Risk factors;    Parity;    Body mass index;    Race;    Ethnicity;    Family history;    Breast tissue composition;    Normal breast;    Epithelium;    Stroma;    Epithelium-to-stroma proportion;   

DOI  :  10.1186/s13058-023-01692-7

 received in 2023-05-01, accepted in 2023-07-29,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundEmerging data indicate that variations in quantitative epithelial and stromal tissue composition and their relative abundance in benign breast biopsies independently impact risk of future invasive breast cancer. To gain further insights into breast cancer etiopathogenesis, we investigated associations between epidemiological factors and quantitative tissue composition metrics of the normal breast.MethodsThe study participants were 4108 healthy women ages 18–75 years who voluntarily donated breast tissue to the US-based Susan G. Komen Tissue Bank (KTB; 2008–2019). Using high-accuracy machine learning algorithms, we quantified the percentage of epithelial, stromal, adipose, and fibroglandular tissue, as well as the proportion of fibroglandular tissue that is epithelium relative to stroma (i.e., epithelium-to-stroma proportion, ESP) on digitized hematoxylin and eosin (H&E)-stained normal breast biopsy specimens. Data on epidemiological factors were obtained from participants using a detailed questionnaire administered at the time of tissue donation. Associations between epidemiological factors and square root transformed tissue metrics were investigated using multivariable linear regression models.ResultsWith increasing age, the amount of stromal, epithelial, and fibroglandular tissue declined and adipose tissue increased, while that of ESP demonstrated a bimodal pattern. Several epidemiological factors were associated with individual tissue composition metrics, impacting ESP as a result. Compared with premenopausal women, postmenopausal women had lower ESP [β (95% Confidence Interval (CI)) = −0.28 (− 0.43, − 0.13); P < 0.001] with ESP peaks at 30–40 years and 60–70 years among pre- and postmenopausal women, respectively. Pregnancy [β (95%CI) vs nulligravid = 0.19 (0.08, 0.30); P < 0.001] and increasing number of live births (P-trend < 0.001) were positively associated with ESP, while breastfeeding was inversely associated with ESP [β (95%CI) vs no breastfeeding = −0.15 (− 0.29, − 0.01); P = 0.036]. A positive family history of breast cancer (FHBC) [β (95%CI) vs no FHBC = 0.14 (0.02–0.26); P = 0.02], being overweight or obese [β (95%CI) vs normal weight = 0.18 (0.06–0.30); P = 0.004 and 0.32 (0.21–0.44); P < 0.001, respectively], and Black race [β (95%CI) vs White = 0.12 (− 0.005, 0.25); P = 0.06] were positively associated with ESP.ConclusionOur findings revealed that cumulative exposure to etiological factors over the lifespan impacts normal breast tissue composition metrics, individually or jointly, to alter their dynamic equilibrium, with potential implications for breast cancer susceptibility and tumor etiologic heterogeneity.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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