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


Histological type and subtype diagnosis according to familial predisposition

Histological (sub)type Controls
(%)
BRCA1 cases BRCA2 cases
(%)Odds ratio (%)Odds ratio
Invasive ductal NOS 74 74 1.00 76 1.00
Invasive lobular 10 8 0.36 (0.15-0.86) 10 1.04 (0.50-2.13)
Tubular 5 2 0.50 (0.16-1.50) 0 ...
Mucoid 0 1 ... 1 ...
Medullar/atypical medullary 2 13 5.16 (2.42-11.03) 3 1.60 (0.49-5.29)
Ductal lobular 3 1 0.32 (0.07-1.34) 3 0.81 (0.28-2.32)
Others 6 6 0.92 (0.41-2.03) 7 1.08 (0.44-2.65)

In situ carcinoma according to familial predisposition

Characteristics Controls
(%)
BRCA1 cases BRCA2 cases
(%)Odds ratio (%)Odds ratio
Ductal carcinoma in situ absent 44 59 1.00 48 1.00
Ductal carcinoma in situ present 56 41 0.51 (0.35-0.75) 52 0.81 (0.52-1.26)
Lobular carcinoma in situ absent 94 98 1.00 97 1.00
Lobular carcinoma in situ present 6 2 0.31 (0.09-1.09) 3 0.38 (0.12-1.26)

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.
There were no differences in the major histological types (invasive ductal and lobular) between BRCA1, BRCA2, and control breast cancers. Of the subtypes, more carcinomas were registered as medullary or atypical medullary in BRCA1 cases than in controls (p<0.0001), but not in BRCA2 cases. No BRCA2 mutation carriers had tubular carcinomas (p=0.001). Ductal carcinoma in situ was seen in fewer BRCA1 cases than in controls (p=0.001), but the rate in BRCA2 cases was similar to that in controls. The differences in the rates of LCIS, lower in both BRCA1 and BRCA2 cases relative to controls, were not significant.
The pathology of breast cancers in predisposed women also differs from that in sporadic cases, in that the overall grade of both BRCA1 and BRCA2 breast cancers was significantly higher than that of controls. 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.