Cortesi et al. BMC Cancer 2010, 10:90 http://www.biomedcentral.com/1471-2407/10/90 breast cancer (log-rank p = .12; Fig. 1C). After the genetic analysis, 80 patients were classified as BRCA1 carriers and 931 were considered BRCA negative. In the BRCA1 carrier group, 8 deaths (5 caused by a second tumour arising after breast cancer) and 13 relapses (6 local recurrences and 7 distant recurrences) were reported, whereas in the BRCA negative group 220 deaths and 240 relapses occurred. The 10-year overall survival rate was 77% for BRCA1 carriers, 77% for BRCA-negative patients, and 73% for sporadic breast cancer (log-rank p < .001; Fig. 1B). The 10-year DFS was 75% in sporadic breast cancer, 70% in the BRCA- negative patients, and 70% in the BRCA1 group (log- rank p = .45; Fig. 1D). The study group of 80 BRCA1 cases was compared with 320 matched sporadic cases from the Modena can- cer registry which were the same age, and had the same tumour grade and stage. Results are shown in Fig. 2. A statistically significant difference in OS was seen for BRCA1 patients compared with sporadic BC (85% vs. 73%, respectively, p = .05). According to the hormone receptor status, the hor- mone receptor-negative patients in the H risk group and the BRCA1 patients had a better OS (Fig. 3A, B) while a hormone receptor-positive advantage was only seen in the H risk group, but not in the BRCA1 group (Fig. 3C, D). Figure 2 Probability of survival in 80 BRCA1 breast cancer cases and 320 sporadic breast cancer controls matched for age and tumour grade and stage, using Kaplan-Meier analysis. There was a statistically significant difference between the two groups (log-rank test, p = .05). Page 5 of 9 Multivariate survival analysis according to prognostic factors and chemotherapy Of the 5923 patients, 5012 were included in multivariate analyses, which included BRCA1 status, disease stage, ER status, PgR status, grading, age, and chemotherapy. The BRCA1 positive and negative status was a signifi- cant independent factor for improved OS (HR = 0.29; p = .002 and HR = 0.76; p = < .001, respectively) com- pared with the sporadic breast cancer cases. Positive ER and PgR status was associated with a better OS (HR = 0.82; p = .03 and HR = 0.79; p = .004, respectively). Also, chemotherapy was an important factor in reducing the mortality rate (HR = 0.68; p < .0001). Stage > I (HR = 3.49; p < .0001) and grading III (HR = 1.39; p < .0001) were significant factors for poorer OS. Younger age (≤ 35 years) represented a risk factor for a shorter OS, but the trend was not statistically significant. In a model that included 2213 patients receiving chemother- apy, BRCA1-positive status (HR = 0.38; p = .05) but not BRCA1-negative status (HR = 0.97; p = .79) reduced the mortality rate. Positive PgR status (HR = 0.76; p = .021) was a favourable factor as was positive ER status (HR = 0.76; p = .083), but did not reach statistical significance. Stage > I (HR = 3.55; p < .0001) and grading III (HR = 1.38; p < .0001) were factors statistically associated with an increased risk of death. There was a similar but non significant trend in age ≤ 35 years (HR = 1.15; p = .44). Conversely, in a model without chemotherapy, the BRCA1-positive status lost statistical significance in reducing mortality (HR = 0.23; p = 0.056), whereas the BRCA1-negative status maintained its favourable impact (HR = 0.56; p < .0001). Also, positive ER (HR = 0.82, p = .17) and PgR status (HR = 0.82; p = .08) and age less than 35 years (HR = 0.95;p = .85) did not affect OS. Finally, stage > 1 (HR = 3.43; p < .0001) and grading III (HR = 1.39; p < .0001) were statistically associated with an increased risk of death. Detailed results for multivari- ate analysis are shown in Table 2. In comparing BRCA1 patients who did or did not receive chemotherapy, no difference was seen in terms of OS (see Fig. 4), even if all the death events in the treated group of patients were derived from second tumours (4 cases). Discussion The results of this large analysis show that patients con- sidered at H risk of being BRCA1 carriers had a better OS than patients considered at IS increased risk or to have sporadic breast cancer. This difference was also maintained in BRCA1 carriers with respect to BRCA1- negative and sporadic breast cancer patients. Notably, 91.2% (73/80) of BRCA1 carriers were identified in the H risk group, and may explain the survival advantage in this group of patients, even if other reasons may be