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Precision Medicine in Breast Cancer: From Epidemiology to Cancer Prevention, Screening and Early Detection

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Epidemiology and Prevention".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 7400

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Dr. Anne Marie McCarthy

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Guest Editor

Department of Biostatistics, Epidemiology & Informatics, University of Pennsylvania, Philadelphia, PA 19104, USA
Interests: cancer epidemiology; cancer disparities; cancer prevention; screening and early detection; genetic testing; breast cancer; cancer genomics; precision medicine

Special Issue Information

Dear Colleagues,

A large body of literature heralds the potential benefits of precision medicine—a paradigm that uses individual variation in genes, environment, and lifestyle to improve disease prevention, diagnosis, and treatment. Breast cancer has been at the forefront of precision medicine. However, precision medicine approaches to breast cancer prevention have lagged behind advances in treatment. Expanding our ability to tailor and implement effective preventive interventions is necessary to fully realize the promise of precision medicine for public health. We are pleased to invite you to submit a manuscript for this Special Issue on breast cancer precision medicine as it relates to cancer prevention, screening, and early detection. This Special Issue aims to showcase epidemiological, clinical, and translational research that moves the field toward the precision prevention of breast cancer. Research areas may include (but are not limited to) the following: improved risk assessment tools, novel biomarkers of risk, chemoprevention, genetic susceptibility, impact of precision medicine on health disparities, relevant data integration and analytic methods, and the implementation of precision prevention strategies. In this Special Issue, original research articles and reviews are welcome. We look forward to receiving your contributions.

Dr. Anne Marie McCarthy
Guest Editor

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Keywords

breast cancer
precision medicine
precision prevention
personalized screening
screening
early detection
risk assessment
biomarkers
genetic susceptibility

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Published Papers (3 papers)

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Research

14 pages, 1801 KiB

Open AccessArticle

A Rare Variant in MDH2 (rs111879470) Is Associated with Predisposition to Recurrent Breast Cancer in an Extended High-Risk Pedigree

by Lisa A. Cannon-Albright, Jeff Stevens, Craig C. Teerlink, Julio C. Facelli, Kristina Allen-Brady and Alana L. Welm

Cancers 2023, 15(24), 5851; https://doi.org/10.3390/cancers15245851 - 15 Dec 2023

Cited by 2 | Viewed by 1785

Abstract

A significant fraction of breast cancer recurs, with lethal outcome, but specific genetic variants responsible have yet to be identified. Five cousin pairs with recurrent breast cancer from pedigrees with a statistical excess of recurrent breast cancer were sequenced to identify rare, shared candidate predisposition variants. The candidates were tested for association with breast cancer risk with UKBiobank data. Additional breast cancer cases were assayed for a subset of candidate variants to test for co-segregation. Three-dimensional protein structure prediction methods were used to investigate how the mutation under consideration is predicted to change structural and electrostatic properties in the mutated protein. One hundred and eighty-one rare candidate predisposition variants were shared in at least one cousin pair from a high-risk pedigree. A rare variant in MDH2 was found to segregate with breast-cancer-affected relatives in one extended pedigree. MDH2 is an estrogen-stimulated gene encoding the protein malate dehydrogenase, which catalyzes the reversible oxidation of malate to oxaloacetate. The molecular simulation results strongly suggest that the mutation changes the NAD⁺ binding pocket electrostatics of MDH2. This small sequencing study, using a powerful approach based on recurrent breast cancer cases from high-risk pedigrees, identified a set of strong candidate variants for inherited predisposition for breast cancer recurrence, including MDH2, which should be pursued in other resources. Full article

(This article belongs to the Special Issue Precision Medicine in Breast Cancer: From Epidemiology to Cancer Prevention, Screening and Early Detection)

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12 pages, 530 KiB

Open AccessArticle

Choice of Assessment and Subsequent Risk of Breast Cancer among Women with False-Positive Mammography Screening

by Bayan Sardini, Susanne Fogh Jørgensen, Lisbet Brønsro Larsen, Mohammad Talal Elhakim and Sisse Helle Njor

Cancers 2023, 15(6), 1867; https://doi.org/10.3390/cancers15061867 - 20 Mar 2023

Cited by 1 | Viewed by 2213

Abstract

Women with false-positive mammography screening results have a two- to four-fold higher risk of breast cancer. This study aimed to investigate if the subsequent risk of breast cancer after a false-positive mammography screening is associated with the received diagnostic assessment. The study population consisted of women who underwent false-positive mammography screening from January 2010 to June 2019. They were categorised into seven groups depending on the elements in the assessment (standard care: additional mammography, ultrasound, and if they had a relevant biopsy). Risks of interval cancer, next-round screen-detected cancer, and long-term breast cancer for non-standard care assessments were compared to standard care assessments using Binomial and Cox regression models. We included 44,279 women with a false-positive result. Invasive assessments that lacked an ultrasound or additional mammography were not more associated with an increased risk of subsequent cancers compared to that of ‘all three elements’. The few assessments that included ‘only ultrasound’ or ‘only mammography’ resulted in higher relative risks of next-round screen-detected cancer of 1.52 (95% CI: 0.93–2.47) and 1.67 (95% CI: 0.54–5.16), respectively, compared to that of standard care. The increased subsequent risk of breast cancer among women with a previous false-positive result was not found to be correlated with the choice of elements in the assessment process. Full article

(This article belongs to the Special Issue Precision Medicine in Breast Cancer: From Epidemiology to Cancer Prevention, Screening and Early Detection)

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18 pages, 2082 KiB

Open AccessArticle

Factors Influencing Residual Glandular Breast Tissue after Risk-Reducing Mastectomy in Genetically Predisposed Individuals Detected by MRI Mammography

by Frederic Dietzel, Leoni Kolberg, Anne Sophie Vesper, Jürgen Hoffmann, Carolin Nestle-Krämling, Karin Zwiefel, Verena Friebe, Lino M. Sawicki, Nils Martin Bruckmann, Kai Jannusch, Janna Morawitz, Gerald Antoch, Tanja Natascha Fehm, Julian Kirchner and Svjetlana Mohrmann

Cancers 2023, 15(3), 829; https://doi.org/10.3390/cancers15030829 - 29 Jan 2023

Cited by 6 | Viewed by 2640

Abstract

Purpose: This study seeks to evaluate MR imaging morphological factors and other covariates that influence the presence of residual glandular tissue after risk-reducing mastectomy in patients with a familial predisposition. Methods: We analyzed women of a high-risk collective with pathogenic mutation (BRCA1 (n = 49), BRCA2 (n = 24), or further mutation (n = 9)). A total of 117 breasts were analyzed, 63 left and 54 right, from a cohort of 81 patients, who were on average 40 years old. The mean follow-up was 63 months (range 12–180 months, SD = 39.67). Retrospective analysis of MR imaging data from 2006–2022 of patients of a high-risk collective (all carriers of a pathogenic mutation) with contralateral (RRCM) or bilateral risk-reducing mastectomy (RRBM) was performed. In the image data the remaining skin flap thickness by distance measurements at eight equally distributed, clockwise points and the retromamillary area, as well as by volumetry of each breast, was elected. Residual glandular tissue was also volumetrized. In addition, patient-related covariates were recorded and their influence on postoperative residual glandular tissue and skin flap thickness was analyzed by uni- and multivariate regressions. Results: A significant association with postoperative residual glandular tissue was shown in multivariate analysis for the independent variables breast density, skin flap mean, and surgical method (all p-values < 0.01). A negatively significant association could be seen for the variables preoperative breast volume (p-values < 0.01) and surgeon experience (most p-values < 0.05–<0.1). Conclusion: Postoperative residual glandular tissue is an important tool for quantifying the risk of developing breast cancer after risk-reducing mastectomy. Different effects on residual glandular tissue were shown for the independent variables breast density, skin flap, surgical method, preoperative breast volume, and surgeon experience, so these should be considered in future surgical procedures preoperatively as well as postoperatively. Breast MRI has proven to be a suitable method to analyze the skin flap as well as the RGT. Full article

(This article belongs to the Special Issue Precision Medicine in Breast Cancer: From Epidemiology to Cancer Prevention, Screening and Early Detection)

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