Epidemiology: Lesions Conferring Increased Risk of Breast Carcinoma

Epidemiology: Lesions Conferring Increased Risk of Breast Carcinoma

Epithelial hyperplasia image is associated with an increased bilateral risk of invasive cancer. Genetic studies suggest that this lesion is not a direct precursor but rather an indicator of risk.

Columnar cell change image is often found in proximity to tubular carcinomas image, and both share similar genetic changes. Therefore, columnar cell change is thought to be a predictor of risk and a potential precursor.



  • Benign breast disease (BBD)


  • BBD can be classified according to subsequent risk of developing invasive breast cancer


Study of Benign Breast Lesions

  • Widespread use of mammographic screening has led to increased detection of BBD

  • Studies have identified 2 main classes of benign lesions

    • Risk indicators for development of invasive breast cancer

      • Predict generalized increased risk to both breasts

      • May be associated with other risk factors such as those related to hormone exposure

    • Precursor lesions for invasive carcinoma

      • Cells or lesions that may accumulate additional changes to eventually evolve into carcinoma

      • Lesions are nonobligate precursors; majority do not progress during patient’s lifetime

  • Some lesions are both risk indicators and precursors

    • For example, 60% of cancers developing after atypical hyperplasia (AH) are ipsilateral, and 40% are contralateral

      • Suggests that AH not only is an indicator of bilateral risk but can also act as a precursor in same breast

Morphologic Studies

  • BBD was originally classified according to histologic appearance

  • Association with carcinoma was postulated based on appearance and location

    • Some BBD resembles carcinoma

      • Hyperplasia resembles atypical ductal hyperplasia (ADH), which resembles DCIS

      • Atypical lobular hyperplasia (ALH) and LCIS are cytologically identical to invasive lobular carcinoma

      • Radial sclerosing lesions are similar in appearance to tubular carcinoma

  • BBD is frequently seen adjacent to invasive carcinomas

    • ALH and LCIS near invasive lobular carcinoma

    • ADH and DCIS near invasive ductal carcinoma

    • Columnar cell change (± flat epithelial atypia), ALH/LCIS, and tubular carcinoma (“Rosen triad”)

Epidemiologic Studies

  • In 3 large studies, BBD in breast biopsies from women without cancer were categorized

    • Nashville Study

    • Nurses’ Health Study

    • Mayo Clinic Study

  • Women were followed over time to determine groups most likely to develop invasive carcinoma

  • Each study confirmed importance of classification of BBD to predict risk of subsequent carcinoma

  • Estimates of risk associated with each group of lesions were similar

Biologic Studies

  • Attempt to separate markers of risk from true precursors of invasive carcinoma

    • Loss of heterozygosity (LOH) for selected markers

    • Gene expression profiling

    • Comparative genomic hybridization

  • Most common recognized precursors are similar to ER-positive cancers

    • “Low-grade neoplasia” family includes columnar cell lesions, flat epithelial atypia, ADH, ALH, LCIS, and low-grade DCIS

      • Show strong diffuse positivity for ER

      • In normal breast, only ER-negative cells undergo division

      • Therefore, there must be a change in regulation of cell proliferation

    • Often associated with invasive tubular carcinoma, invasive cribriform carcinoma, grade 1 and 2 lobular carcinomas, and grade 1 invasive ductal carcinomas

      • All share deletions of 16q and gains of 1p

    • Radial sclerosing lesions are sometimes associated with tubular carcinomas or lobular carcinomas

      • Some are associated with loss of 16q

      • In some cases, it may be difficult to distinguish radial sclerosing lesion from low-grade invasive carcinoma

    • High-grade ER-positive cancers also show 16q deletions and are likely etiologically related to low-grade ER-positive cancers

  • Precursors for ER-negative cancer have not been established

Jul 6, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Epidemiology: Lesions Conferring Increased Risk of Breast Carcinoma

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