ArticleBreast cancer research : BCR2018
The origins of breast cancer associated with mammographic density: a testable biological hypothesis.
Article in Breast cancer research : BCR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03920098 (The Chilean Maternal and Infant Nutrition Cohort Study II), which is not on this map. Cited by 26 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Chilean Maternal and Infant Nutrition Cohort Study II
Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Supplemental Screening as an Adjunct to Mammography for Breast Cancer Screening in People With Dense Breasts: A Health Technology Assessment.Ontario health technology assessment series · 2023Pooled it
- The impact of patient characteristics and lifestyle factors on the risk of an ipsilateral event after a primary DCIS: A systematic review.Breast (Edinburgh, Scotland) · 2020Pooled it
- Effect of a Randomized Trial of a Web-Based Intervention on Patient-Provider Communication About Breast Density.Journal of women's health (2002) · 2021Trial
- Stiff stroma increases breast cancer risk by inducing the oncogene ZNF217.The Journal of clinical investigation · 2020Trial
- Body mass index-associated gut microbial taxa and functional pathways in women with benign and malignant breast disease.Breast cancer research and treatment · 2026Article
- The DeepJoint Algorithm: An Innovative Approach for Studying the Longitudinal Evolution of Quantitative Mammographic Density and Its Association With Screen-Detected Breast Cancer Risk.Biometrical journal. Biometrische Zeitschrift · 2026Article
- Studying the association between longitudinal nondense breast tissue measurements and the risk of breast cancer: a joint modeling approach.American journal of epidemiology · 2025Article
- Relationship between breast tissue involution and breast cancer.Frontiers in oncology · 2025Review
- [Examination of breast density in breast cancer discordant twin pairs].Magyar onkologia · 2024Article
- Temporal changes in mammographic breast density and breast cancer risk among women with benign breast disease.Breast cancer research : BCR · 2024Article
- Breast cancer risk factors and mammographic density among 12518 average-risk women in rural China.BMC cancer · 2023Article
- Ultrasound as a Method for Early Diagnosis of Breast Pathology.Journal of personalized medicine · 2023Article
- Studying the association between longitudinal mammographic density measurements and breast cancer risk: a joint modelling approach.Breast cancer research : BCR · 2023Article
- Association of polycystic ovary syndrome with mammographic density in Turkish women: a population-based case-control study.Revista da Associacao Medica Brasileira (1992) · 2023Article
- Mammographic density in relation to breast cancer recurrence and survival in women receiving neoadjuvant chemotherapy.Frontiers in oncology · 2023Article
- Chest CT for Breast Cancer Diagnosis.Life (Basel, Switzerland) · 2022Article
- Deep learning identification of stiffness markers in breast cancer.Biomaterials · 2022Article
- Article
- Mammographic Density Changes over Time and Breast Cancer Risk: A Systematic Review and Meta-Analysis.Cancers · 2021Review
- Association of Breast Density With Breast Cancer Risk Among Women Aged 65 Years or Older by Age Group and Body Mass Index.JAMA network open · 2021Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundOur purpose is to develop a testable biological hypothesis to explain the known increased risk of breast cancer associated with extensive percent mammographic density (PMD), and to reconcile the apparent paradox that although PMD decreases with increasing age, breast cancer incidence increases.
methodsWe used the Moolgavkar model of carcinogenesis as a framework to examine the known biological properties of the breast tissue components associated with PMD that includes epithelium and stroma, in relation to the development of breast cancer. In this model, normal epithelial cells undergo a mutation to become intermediate cells, which, after further mutation, become malignant cells. A clone of such cells grows to become a tumor. The model also incorporates changes with age in the number of susceptible epithelial cells associated with menarche, parity, and menopause. We used measurements of the radiological properties of breast tissue in 4454 healthy subjects aged from 15 to 80+ years to estimate cumulative exposure to PMD (CBD) in the population, and we examined the association of CBD with the age-incidence curve of breast cancer in the population.
resultsExtensive PMD is associated with a greater number of breast epithelial cells, lobules, and fibroblasts, and greater amounts of collagen and extracellular matrix. The known biological properties of these tissue components may, singly or in combination, promote the acquisition of mutations by breast epithelial cells specified by the Moolgavkar model, and the subsequent growth of a clone of malignant cells to form a tumor. We also show that estimated CBD in the population from ages 15 to 80+ years is closely associated with the age-incidence curve of breast cancer in the population.
conclusionsThese findings are consistent with the hypothesis that the biological properties of the breast tissue components associated with PMD increase the probability of the transition of normal epithelium to malignant cells, and that the accumulation of mutations with CBD may influence the age-incidence curve of breast cancer. This hypothesis gives rise to several testable predictions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.