Premalignant and In Situ Breast Disease: Biology and Clinical Implications

Abstract

Most types of invasive breast cancer are thought to evolve over long periods from specific preexisting benign lesions. Of the many types of benign entities found in the human breast, only a few have clinically significant premalignant potential. Currently, the best-characterized premalignant lesions are atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ. Ductal carcinoma in situ is considered to be a preinvasive malignant lesion. Two additional lesions, unfolded lobules and usual ductal hyperplasia, are sometimes considered to be very early premalignant epithelial abnormalities. Premalignant lesions are currently defined by their histologic features, and not all necessarily progress to invasive cancer. This suggests that although lesions within specific categories look alike, they must possess underlying genetic differences that cause some to remain stable and others to advance. The development of modern molecular genetic techniques has allowed breast cancer researchers to clarify the multistep model of breast carcinogenesis. Recent studies indicate that cancer evolves by highly diverse genetic mechanisms, and research into these altered pathways may identify specific early defects that might be targeted to prevent progression of premalignant lesions to invasive cancer. Current clinical management is heterogeneous and depends on histologic examination and individual patient factors. Options for breast cancer risk reduction and prevention are available.

High prevalence of PIK3CA/AKT pathway mutations in papillary neoplasms of the breast

“…Because precursors of infiltrating breast carcinoma, such as ductal carcinoma in situ, and even atypical ductal hyperplasia, have been shown to exhibit key genetic changes in common with carcinoma, 20,[33][34][35][36][37][38] we sought to investigate the relationship of papillary lesions to the spectrum of breast premalignant lesions by analyzing kinase mutations. Point mutations in PIK3CA and AKT1 are relatively common in breast carcinoma (average 25 and 4%, respectively), [10][11][12][13][14][15][16][17][18][19][20][21][22][23] and are located in a small number of 'hotspots', many of which have transforming capabilities in vitro.…”

“…On the basis of molecular data, primarily loss of heterozygosity and comparative genomic hybridization studies, a number of authors have shown clonal chromosomal aberrations in usual ductal hyperplasia, though they occur at lower frequency, with fewer alterations per lesion, as compared with atypical ductal hyperplasia, ductal carcinoma in situ, and invasive carcinomas; other studies have shown identical chromosomal changes in usual ductal hyperplasia and accompanying invasive carcinoma. 37,[42][43][44][45][46][47][48] Investigation of activating point mutations in PIK3CA, AKT and other cell signaling pathways in usual ductal hyperplasia, and other breast precursor lesions such as atypical ductal hyperplasia and columnar cell change, should be instructive in further characterizing the divergent molecular and histologic pathways of breast cancer evolution.…”

Columnar cell lesions associated with breast calcifications on vacuum-assisted core biopsies: clinical, radiographic, and histological correlations

“…[3][4][5][6][7] According to Schnitt and Vincent-Salomon, 1 columnar cell lesions have been grouped into the categories of columnar cell change and columnar cell hyperplasia without or with atypia. Other authors 8 have proposed a subcategorization of columnar cell lesions depending on the presence of architectural and/or cytological atypia.…”

Women at High Risk for Breast Cancer--What the Primary Care Provider Needs to Know

“…The literature review by Arpino et al 11 suggests a 4-to 5-fold increased risk of invasive breast cancer in women with ADH at a median follow-up of 17 years, which is doubled if the woman has an associated family history of breast cancer.…”