Molecular profile of atypical hyperplasia of the breast

Abstract

Purpose Atypical ductal and atypical lobular hyperplasia (AH) of the breast are important proliferative lesions which are associated with a significantly increased risk for breast cancer. The breast cancer which develops in association with AH may occur synchronously, representing local progression, or metachronously at a later date in either the ipsilateral or contralateral breast. These high-risk characteristics of AH suggest they contain significant genomic changes. Methods To define the genomic changes in AH, a comprehensive review of the literature was conducted to identify the numerical chromosomal and structural chromosomal changes, DNA methylation, and gene expression abnormalities in atypical ductal and atypical lobular hyperplasia. Results AHs are characterized by advanced genomic changes including aneuploidy, loss of heterozygosity, gross chromosomal rearrangements such as amplifications and large-scale deletions, DNA methylation of tumor suppressor and other genes, and gene expression differences between AH and surrounding normal breast tissue including significant estrogen receptor expression. Many of these changes are shared by an associated synchronous breast cancer, consistent with an important precursor role for AH. At the same time, many of the genomic changes of AHs are also shared by common sporadic breast cancer, consistent with a high risk for future development of metachronous breast cancer. Conclusions This molecular profile should help clarify the genomic characteristics and malignant predisposition of AH, and aid in the identification of new targets for the prevention of breast cancer

Molecular fingerprint of precancerous lesions in breast atypical hyperplasia

“…The occurrence and progression of breast cancer is generally believed to be a continuous process from normal epithelium to hyperplasia, AH, carcinoma in situ, and finally to invasive carcinoma. 1,16 AH is a major precancerous lesion, 17 and early treatment and monitoring during this important pathological stage can have significant impacts on the incidence of breast cancer. 5 However, the current large-scale epidemiological investigation showed that breast AH cannot be diagnosed and monitored accurately based on clinical features and risk factors.…”

Atypical Lesions of the Breast and Lobular Carcinoma in Situ in Pregnancy – Surgeons’ Practice

“…Rate of upgrade for biopsy-detected LN has been from 9% to 33% (8,21). For subsequent risk of cancer in AH, figures up to 3-to 4-fold increase in risk have been detected, mostly in same but also in opposite breasts, more frequent in younger ages, and more frequently invasive than in situ (9,(22)(23)(24). The risk of future cancer in ALH is around 4-to 5-fold, and 8-to 10-fold in LCIS.…”

Xihuang Pill inhibits the development of DMBA combined estrogen and progesterone induced breast precancerous lesions rats by PI3K/AKT/mTOR signaling pathway

“…Precancerous lesions are the necessary stage for the genesis and progression of breast cancer, and it includes simple hyperplasia, atypical hyperplasia and in situ carcinoma. So active intervention measures can block or even reverse the process of breast canceration [4]. Intervention of breast precancerous lesions and blocking its further development is the key to prevent and cure breast cancer.…”