PATHOLOGY OF BREAST CANCER IN WOMEN CARRYING MUTATIONS IN BRCA1 AND BRCA2

Taken from The Breast Cancer Linkage Consortium (1997). Data from 118 breast tumors attributable to BRCA1, and 78 attributable to BRCA2. Five histopathologists, experts in breast disease, did the review. Every slide was seen by two pathologists. An age-matched group of 547 apparently sporadic female breast cancer cases served as control.
The overall grade of both BRCA1 and BRCA2 breast cancers was significantly higher than that of controls (p<0.0001 and p<0.04, resp.). For BRCA1 breast cancers this was due to higher scores for all three grade indices, whereas for BRCA2 breast cancers the grade was only significantly higher for tubule formation (table).
The histology of breast cancers in predisposed women also differs from that in sporadic cases, and there are differences between breast cancers in carriers of BRCA1 and BRCA2 mutations. The findings suggest that breast cancer due to BRCA1 has a different natural history compared to BRCA2 or apparently sporadic disease, which may have implications for screening and mangement.

Significance levels for the three grade indices
in BRCA1 and BRCA2 breast cancers

Multifactorial analysis of differences in BRCA1 and BRCA2 breast cancers.

The tumors in the collection were subjected to a more detailed examination of cytologic and architectural features. Specimens of tumor tissue (5-microm-thick sections) were examined independently by two pathologists, who were unaware of the case or control subject status, for the presence of cell mitosis, lymphocytic infiltration, continuous pushing margins, and solid sheets of cancer cells; cell nuclei, cell nucleoli, cell necrosis, and cell borders were also evaluated. The resulting data were combined with previously available information on tumor type and tumor grade and further evaluated by multifactorial analysis.

Feature	Effect	BRCA1	BRCA2
Mitoses	More	P=0.001	-
Mitoses	Less	-	P=0.003
Continuous pushing margin	Greater proportion of tumor	P<0.0001	P<0.0001
Lymphocytic infiltrate	More	P=0.002	NS
Tubule formation	Fewer	NS	P=0.0002

Taken from Lakhani et al. (1998).