No abstract

Low-grade precursor lesions, such flat epithelial atypia (FEA), low-grade ductal carcinoma in situ (lg-DCIS), and lobular neoplasia (LN) often coexist with invasive tubular carcinomas (TCs) of the breast. To evaluate a possible clonal relationship, we have examined a series of 27 TC and the surrounding putative precursor lesions using loss of heterozygosity analysis and mitochondrial DNA sequencing. In these lesions (22 FEA, 10 lg-DCIS, 3 LN), loss of heterozygosity was most frequently observed on the long arm of chromosome 16 as well as at chromosome 8p21, 3p14, 1p36 and 11q14 with a high degree of homology of allelic losses between FEA, lg-DCIS and tubular carcinomas. In the adjacent invasive tubular carcinomas, mitochondrial DNA sequencing revealed identical mutation patterns in 50% of the lg-DCIS and in 12 of 21 (57%) informative cases of FEA. No direct association was seen between TC and LN or columnar cell lesions without nuclear atypia. Our data indicate, that in the majority of cases lg-DCIS and FEA are directly related to tubular breast cancer with a possible precursor role.

Triple-negative breast cancer (TNBC) is characterized by the lack of estrogen and progesterone receptors and the lack of HER2 expression or amplification. Much interest has recently been focused on these triple-negative (TN) subtypes because they may be aggressive and are more likely to recur and metastasize than other subtypes of breast cancer. TNBC accounts for approximately 10–24% of all breast cancer cases, and typically it occurs in younger patients and in patients with BRCA1 mutation. There is a substantial heterogeneity of TNBCs both at the morphological and the molecular level, but there are also common features, such as low tumor grade and accelerated tumor proliferation. Morphologically, TNBC may present as invasive ductal, metaplastic, medullary, apocrine, or other types. Molecularly, they are most frequently associated with a basal phenotype, but there is a distinct subgroup of cancers that are not of basal type and belong to the claudin-low or molecular-apocrine type. The basal phenotype is frequently associated with the loss of BRCA1.