Breast cancer histologic subtypes show excess familial clustering

Abstract

BACKGROUND:The inherited predisposition to developing specific histologic subtypes of invasive breast carcinoma has been incompletely investigated. By using a large, population-based database, the authors sought to investigate familial clustering of breast cancer by histologic subtype. METHODS: By using the Utah Population Database, which links genealogy records to the National Cancer Institute's statewide Surveillance, Epidemiology, and End Results cancer registry, the authors identified patients with breast cancer by histology and tested for evidence of shared genetic predisposition to histologic specific subtypes by examining pairwise relatedness and estimating the relative risk (RR) among first-degree, second-degree, and third-degree relatives. RESULTS: The authors identified 23,629 individuals in the Utah Population Database who had at least 3 generations of genealogy and at least 1 primary breast cancer, 2883 (12.2%) of which were specific histologic subtypes other than invasive ductal carcinoma (including inflammatory [n = 178], lobular [n = 1688], and mucinous [n = 542]). Statistically significant excess distant relatedness was identified for the mucinous subtype (P = .011) as well as for inflammatory breast cancers (P = .024). The RR for breast cancer of any histology in second-degree relatives was significantly increased for patients with inflammatory (RR, 1.32; 95% CI, 1.02-1.68; P = .03), lobular (RR, 1.36; 95% CI, 1.25-1.47; P < .001), and mucinous (RR, 1.27; 95% CI, 1.12-1.44; P = .00021) subtypes. CONCLUSIONS: These findings provide evidence for significant familial clustering within histological subtypes for lobular, mucinous, and inflammatory breast carcinomas. Further research is required to identify the underlying genetic variants responsible for the increased risk. Studies of high-risk pedigrees segregating a specific histologic subtype could be a powerful design for predisposition gene identification.

Histological and molecular classification of breast cancer: what do we know?

“…However, in histopathological practice, cell type characteristics, number of cells, type and location of secretion, immunohistochemical profile and architectural characteristics determine if the tumor is ductal or lobular, in addition to its sub-classifications, rather than its precise location in the mammary tissue 7,8 . About 50% to 80% of newly diagnosed breast cancer cases are called invasive ductal carcinoma (IDC); the rest of the cases are classified as invasive lobular carcinoma (ILC) 9 . IDCs can be classified as "no specific type" because these tumors do not present sufficient morphological characteristics to be determined as a characteristic histological type; they can also be recognized as a "special type" if they present sufficient distinctive characteristics, and particular cellular and molecular behavior 9,10 .…”

“…About 50% to 80% of newly diagnosed breast cancer cases are called invasive ductal carcinoma (IDC); the rest of the cases are classified as invasive lobular carcinoma (ILC) 9 . IDCs can be classified as "no specific type" because these tumors do not present sufficient morphological characteristics to be determined as a characteristic histological type; they can also be recognized as a "special type" if they present sufficient distinctive characteristics, and particular cellular and molecular behavior 9,10 . The most common special types of breast cancer include: medullary carcinoma, metaplastic carcinoma, apocrine carcinoma, mucinous carcinoma, cribriform carcinoma, tubular carcinoma, neuroendocrine carcinoma, classic lobular carcinoma, and pleomorphic lobular carcinoma 10 .…”

Breast lumps: Types, biomarkers and prognosis

“…Since the cell type characteristics, cells numbers, type and location of secretion in addition to immunohistochemical profiles which determined the tumor ductal or lobular [37]. About 50-80% of breast cancers newly diagnosed are invasive ductal carcinoma (IDC), while the rest are invasive lobular carcinoma (ILC) [38]. IDCs sometime classified into "no specific type" if there is no sufficient morphological characteristic to be classified as a distinct histological type, or it recognized as "special type" if there is special cellular characteristic and special molecular behavior [39], the most common special types of IDCs are: medullary carcinoma, apocrine carcinoma, metablastic carcinoma, mucinous carcinoma, tubular carcinoma, classical lobular carcinoma, pleomorphic lobular carcinoma, neuroendocrine carcinoma, mucinous carcinoma, cribriform carcinoma [38].…”

“…The most common type constitutes about 40-75% of IDCs, it usually has high range of morphological and behavioral variation [38], the characteristic features of the cells are pleomorphic with protruding nucleoli with active mitosis, an area of calcification and necrosis can be seen in more 50% of the cases [37].…”

“…Special type of breast carcinoma and account for 5% of all special subtypes, associated with better clinical outcome and minimal involvement of the axillary lymph nodes [41]. Usually affect female in a third or fourth decade of life and associated with mutation in breast cancer gene 1 (BRCA1) [38]. Microscopically this tumor characterized by wellcircumscribed cancer, constitute of large pleomorphic cells and syncytial growth fashion with multiple mitotic activity in addition to lymphoplasmacystic infiltration, also it may associate with spindle cells metaplasia and giant tumor cells [42,43].…”