HISTOPATHOLOGY OF BREAST CANCER AND ITS RELATIONSHIP TO GENETICS
Breast cancers arising in BRCA1 mutation carriers can often be distinguished from cancers occurring in BRCA2 or non-BRCA1/2 carriers on morphological (Lakhani et al. 1998), immunopathological (Lakhani et al. 2002), cytogenetic (Wessels et al. 2002), gene expression (Hedenfalk et al. 2001; Van’t Veer et al. 2002; Sorlie et al. 2003), and mutational grounds (Nik-Zainal et al. 2012). BRCA1-related breast cancers are usually infiltrating ductal carcinomas of high grade. Although the term is seldom used now, studies have shown that an atypical medullary phenotype is more common in BRCA1-related breast cancer than in matched controls (Lakhani et al. 1998). BRCA1-related breast cancers are much more likely to be triple negative (TN) (ER, PR, and HER2 negative) than are other types of breast cancer (Schneider et al. 2008).
Notably, some studies of PALB2 mutation carriers have also noticed an excess of TN breast cancer, but comprehensive studies are required (Tischkowitz and Xia 2010). BRCA2-related cancers are usually ER positive, and unlike sporadic breast cancer, the percentage of Tumours that are ER positive does not increase with age (Foulkes et al. 2004). It has been noted that HER2 positivity is commonly found in breast cancers arising in women with germline TP53 mutations (Wilson et al. 2010; O’Shaughnessy et al. 2011), which could aid in selecting who to offer germline TP53 testing.
Ductal carcinoma in situ (DCIS) and lobular carcinoma are underrepresented in BRCA1 mutation carriers. Sequencing studies of women with DCIS have revealed a small percentage of BRCA1 and BRCA2 mutations (~1 and 2.5 %, respectively) (Claus et al. 2005).