A new approach to breast cancer terminology based on the anatomic site of tumour origin: The importance of radiologic imaging biomarkers

Tabár, Làszló; Dean, Peter B.; Tucker, F. Lee; Yen, Amy Ming‐Fang; Chen, Sam Li Sheng; Jen, Hsiao-Hsuan; Wang, Jackson Wei-Chun; Smith, Robert A.; Duffy, Stephen W.; Chen, Chien-Jen

doi:10.1016/j.ejrad.2022.110189

Cited by 20 publications

(26 citation statements)

References 39 publications

(42 reference statements)

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“…In addition, the radiomic analysis of screening images could allow better in vivo characterization to more accurately determine which findings require biopsy [ 42 , 43 ] or are indicative of aggressive disease. For example, Tabar et al have created subclassifications of mammographic findings previously generically referred to as “DCIS” to distinguish acinar findings, which tend to be lower risk from the more ominous presentations accompanied by linear calcifications in the major lactiferous ducts, likely indicating that neoductgenesis is already occurring [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Overdetection of Breast Cancer

Yaffe

Mainprize

2022

Current Oncology

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Overdetection (often referred to as overdiagnosis) of cancer is the detection of disease, such as through a screening program, that would otherwise remain occult through an individual’s life. In the context of screening, this could occur for cancers that were slow growing or indolent, or simply because an unscreened individual would have died from some other cause before the cancer had surfaced clinically. The main harm associated with overdetection is the subsequent overdiagnosis and overtreatment of disease. In this article, the phenomenon is reviewed, the methods of estimation of overdetection are discussed and reasons for variability in such estimates are given, with emphasis on an analysis using Canadian data. Microsimulation modeling is used to illustrate the expected time course of cancer detection that gives rise to overdetection. While overdetection exists, the actual amount is likely to be much lower than the estimate used by the Canadian Task Force on Preventive Health Care. Furthermore, the issue is of greater significance in older rather than younger women due to competing causes of death. The particular challenge associated with in situ breast cancer is considered and possible approaches to avoiding overtreatment are suggested.

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Section: Discussionmentioning

confidence: 99%

Overdetection of Breast Cancer

Yaffe

Mainprize

2022

Current Oncology

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“…These and other studies have provided compelling evidence for the site-specific presence of distinct progenitors in ducts and TDLUs 3 , 12 – 14 . This observation is potentially much more far-reaching if viewed in context with data of distinct disease-free survival rates exclusively determined by cell of origin in ducts and lobules as determined by mammography and histology 15 , 16 . That duct-derived tumors may exhibit the worst prognosis 15 , 16 emphasizes the importance of establishing further evidence for a relationship between normal double-positive progenitors in ducts and basal-like breast cancer.…”

Section: Introductionmentioning

confidence: 91%

Ductal keratin 15+ luminal progenitors in normal breast exhibit a basal-like breast cancer transcriptomic signature

et al. 2022

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Normal breast luminal epithelial progenitors have been implicated as cell of origin in basal-like breast cancer, but their anatomical localization remains understudied. Here, we combine collection under the microscope of organoids from reduction mammoplasties and single-cell mRNA sequencing (scRNA-seq) of FACS-sorted luminal epithelial cells with multicolor imaging to profile ducts and terminal duct lobular units (TDLUs) and compare them with breast cancer subtypes. Unsupervised clustering reveals eleven distinct clusters and a differentiation trajectory starting with keratin 15+ (K15+) progenitors enriched in ducts. Spatial mapping of luminal progenitors is confirmed at the protein level by staining with critical duct markers. Comparison of the gene expression profiles of normal luminal cells with those of breast cancer subtypes suggests a strong correlation between normal breast ductal progenitors and basal-like breast cancer. We propose that K15+ basal-like breast cancers originate in ductal progenitors, which emphasizes the importance of not only lineages but also cellular position within the ductal-lobular tree.

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“…Pathologists apply the cytologic resemblance of malignant cells to cells within normal ducts or TDLUs in order to subtype breast cancers into "ductal" versus "lobular" cancers, but the resulting nomenclature is inconsistent with the anatomic site of origin. Unfortunately, the use of cellular criteria to define the site of origin became the accepted diagnostic standard, causing considerable confusion, since the cancer subtypes originating within the TDLU are described by the current terminology as if some were originating from the ducts (ductal carcinoma in situ and invasive ductal carcinoma) and others were originating from the lobules (lobular carcinoma in situ and invasive lobular carcinoma) [4]. The immunohistochemical biomarker, E-cadherin, is used in cases with borderline morphology to differentiate between subtypes of supposedly ductal or lobular origin.…”

Section: The Terminal Ductal Lobular Unit (Tdlu) Is the Site Of Origi...mentioning

confidence: 99%

“…Physicians caring for breast cancer patients have an obligation to understand the basic anatomic details of the breast and use a consistently accurate terminology, because breast diseases arise from specific anatomic locations [1][2][3][4] and long-term patient outcomes appear to be largely determined by the ductal versus acinar origin of breast cancers [5,6]. Azzopardi has expressed these obligations as follows: "All pathologists accept that it is essential to have a thorough knowledge of the normal structure of, say, the kidney or the liver before studying and reporting on the pathology of that organ.…”

Section: Introductionmentioning

confidence: 99%