Variable All cases Sporadic BRCA - BRCA1+ stage > 1 Estrogen receptor positive Progesterone receptor positive Chemotherapy, yes Age ≤ 35 Grading III Sporadic BRCA- BRCA1+ Stage > I Estrogen receptor positive Progesterone receptor positive Age ≤ 35 years Grading III Model without chemotherapy Sporadic BRCA- BRCA1+ stage > I Estrogen receptor positive Progesterone receptor positive Age ≤ 35 Grading III N° (%) HR 5012 (85) 4172 (83) 1.00 785 (16) 0.76 55 (1) 0.29 4090 (82) 0.82 3138 (64) 0.79 2372 (47) 3.49 < .0001 2213 (44) 0.68 < .0001 199 (4) 1.12 .42 1778 (35) 1.39 < .0001 1780 (36) 1.00 404 (8) 0.97 29 (2) 0.38 1571 (71) 0.81 1492 (67) 0.76 128 (6) 1.15 1689 (76) 3.55 < .0001 1116 (50) 1.38 < .0001 2799 (56) 2392 (85) 1.00 - 381 (14) 0.56 < .0001 26 (1) 0.23 .056 951 (34) 3.43 < .0001 2519 (90) 0.82 2298 (82) 0.82 71 (3) 0.95 662 (24) 1.39 < .0001 p - < .001 .002 .03 .004 - 0.79 .05 .083 .021 .44 .17 .08 .85 [95% CI] 0.64 to 0.89 0.13 to 0.62 3.01 to 4.04 0.69 to 0.98 0.67 to 0.93 0.59 to 0.77 0.84 to 1.49 1.22 to 1.58 0.78 to 1.20 0.14 to 0.99 2.65 to 4.76 0.65 to 1.02 0.61 to 0.96 0.81 to 1.62 1.15 to 1.64 - - - 0.43 to 0.73 0.14 to 1.02 2.89 to 4.09 0.63 to 1.08 0.65 to 1.03 0.56 to 1.60 1.15 to 1.68 Model with chemotherapy 2213 (44) Abbreviations: HR, hazard ratio; CI, confidence interval involved. Patients who know they are at high risk of developing breast cancer may be more likely to partici- pate in surveillance programs and start at a younger age, receive an earlier diagnosis, and subsequently, experience a better outcome. One of the most important findings of our study was that the survival difference was attributable, in a multi- variate analysis, to the patient’s BRCA1 status and was observed in patients treated with chemotherapy. This finding is important when, as happens in a family cancer centre like in ours, we are faced with a patient or a healthy woman who has a family history of breast Cortesi et al. BMC Cancer 2010, 10:90 http://www.biomedcentral.com/1471-2407/10/90 Table 2 Cox’s proportional hazard regression models for overall survival Page 7 of 9 Figure 4 A comparison of the group of BRCA1 patients who received or did not receive chemotherapy did not show any difference in overall survival (log-rank test, p = .69). cancer. By collecting all the information about indivi- duals affected by breast cancer, very long-term survivors can be identified by predicting a predisposition for being a BRCA1-mutation carrier in the descendants. Further- more, BRCA1 carriers may be more likely to be found among women who have a high probability of hereditary breast cancer and who have a long term survival. If BRCA1 carriers could be identified through these char- acteristics, the use of expensive tests could be avoided and the rate of positive analyses increased. Our study involves a very large number of Caucasian patients with breast cancer (N = 5923) who were first evaluated for their family history of breast cancer and subsequently for BRCA1 status. The most common weakness of previous studies includes the small number of patients or selection bias, such as a retrospective ana- lysis for BRCA1 status. Owing to the large number of subjects, we could calculate OS differences between risk groups, and even in subgroup analyses. Unexpectedly, the survival difference according to H risk and BRCA1 status was not related to the DFS. This finding shows that the H risk and BRCA1 patients have the same DFS as the other two groups, but seem to respond better to chemotherapeutic agents. This finding is in contrast with the results of Rennert et al. [8] who showed an insignificant difference in OS between BRCA carriers and non carriers and between BRCA1 carriers and BRCA-negative patients treated with chemotherapy. Our argument is that, in BRCA1 patients, 41% of relapses were local recurrences, whereas in patients with sporadic BC the local recurrence rate was 25%, and dis- tant metastases accounted for 75%. Consequently, it is