Background: High-risk breast cancer screening for BRCA1/2 mutations carriers with clinical breast exam, mammography and MRI have sensitivities approaching 100%. Even with intensive screening BRCA mutation carriers can present with self-detected interval cancers. We investigate screening practices and presentation among a cohort of Irish BRCA1/2 mutation carriers. Methods: Females with breast cancer belonging to kindreds now known to harbour BRCA1/2 mutations were retrospectively identified. Records were reviewed for BRCA mutation, demographics, breast cancer diagnosis, stage, histology and screening. We assessed screening modalities and whether breast cancers were diagnosed at screening or as interval cancers. Results: 53 cases of breast cancer were diagnosed from 1968-2010 among 53 Irish hereditary breast ovarian cancer kindreds. BRCA mutation status was unknown at time of diagnosis but subsequently confirmed. Detection method was identified in 50% of patients: 84% by clinical breast exam (CBE), 4% mammography, 4% MRI and 8% by a combination of CBE and mammography. Fifteen women (28%) developed second breast cancer; 9(60%) were undergoing screening, 2 were not and 27% were unknown. 22% were detected by CBE alone; 34% mammography; 22% a combination of mammography and CBE and 22% by MRI. In 41%, histology changed between first and second diagnosis. Two women developed a third breast cancer. In one, her second was an interval cancer despite being in a screening programme. Her third was radiologically detected. Conclusions: In this cohort of Irish BRCA1/2 mutation carriers almost 25% of second breast cancers were not detected by screening. 4% of cases were phenocopies and in 41% histology changed between first and second diagnosis.

Characteristic	No.	%
	63
1st Breast Cancer	53	84
Median Age Range	42 24-73
BRCA1	25	40
BRCA2	27	42
Stage
I	14	27
II	25	48
III	4	8
Unknown	9	17
Histology
Ductal	30	57
Other	10	19
Unknown	13	24
2nd Breast Cancer	15	28
Median Age Range	48 36-71
BRCA1	5	33
BRCA2	8	53
Stage
I	8	53
II	3	20
III	3	20
Histology
Ductal	12	80
Other	2	13
3rd Breast Cancer	2	4
Median Age Range	54 53-55
BRCA2	2	100
Stage
I	1	50
III	1	50
Histology
Ductal	2	100