Although the importance of family history as a risk factor for breast cancer is widely recognized, there is disagreement on its impact upon prognosis, with conflicting results reported in several series [3
]. The discovery of the breast cancer susceptibility genes BRCA1-2 has allowed a clearer identification of genetically related cases.
Some studies suggest that mutations of the BRCA gene may be related, besides their impact on the susceptibility to breast and ovarian cancer, to distinctive biological characteristics and clinical course.
In general, the histopathologic features of BRCA associated cases are reported as being more unfavourable as compared to sporadic cases, with more high-grade, oestrogen receptor negative and rapidly proliferating tumours [5
]. In a recent study, nodal status was found to be correlated with tumour size in BRCA-1 negative but not in BRCA-1 positive patients [6
]. In some relatively small studies, the prognosis of patients with BRCA mutations was worse [7
] or comparable [10
] to that of sporadic cases. In these series, prognostic factors were generally worse than in sporadic cases. In a Finnish study [12
], it was noted that BRCA1 breast cancer patients had a lower survival rate than sporadic cases, BRCA2 patients or patients with non BRCA1/2 related familial breast cancer. However, the difference was not statistically significant. It should be noted that the BRCA positive patient populations studied varied much, including Ashkenazi Jewish patients with node negative disease [7
], early-onset disease [8
], or familial breast cancer [11
]. Also control groups were different, varying from BRCA negative cases in the same population to large population based registries. The clinical implications of these findings appear not to be fully understood and more data on the issue are necessary before conclusions can be drawn. In particular, the impact of BRCA alterations upon survival is unclear [13
In the present series, we analyzed the clinical characteristics, treatment and outcome in a group of patients with familial breast cancer according to their BRCA status.
The first finding to be mentioned is that, even in a group of breast cancer with a family history, the incidence of BRCA mutations is relatively low (about 25%) in our population of Italian women. This further stresses the need for stringent selection criteria before offering the test to the individual women. Besides, as a consequence, the study population was not large enough to detect small differences between BRCA positive and negative case..
The characteristics of patients differed in the two groups, in that features linked to an aggressive course (premenopausal status, poorly differentiated tumours, ER negative, node positive) were or tended to be more frequent in BRCA (predominantly BRCA2) positive patients. Treatment was similar.
The first event was more frequently distant metastases in BRCA-WT patients and contralateral breast cancer in BRCA positive patients. Time to progression was superimposable.
When survival curves are examined, one should take into account that the mechanism of the study caused long survivors to be overrepresented, which translates into very high long term survival rates (median survival has not been reached at 20 years). It appears that, while event free survival is superimposable, the percentage of long term survivors is higher among BRCA positive patients. This would be in accordance with a protective effect of BRCA, which counteracts the unfavourable prognostic factors associated with BRCA positivity. No difference emerged in our series between BRCA1 and BRCA2 positive patients, but the small number of BRCA1 cases in this predominantly BRCA2 series precludes conclusions. These findings are not entirely comparable with most data reported so far, in that in our series all patients had a family history of breast cancer and patients with BRCA-WT were probably positive for other unknown mutated genes. This is in agreement with a possible protective effect of BRCA positivity even within otherwise genetically related breast cancer.