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Selection bias influences reported contralateral breast cancer incidence and survival in high risk non-BRCA1/2 patients.

Abstract：

PURPOSE:The results of studies comparing survival in familial and sporadic breast cancer (BC) are inconsistent. A higher incidence of contralateral breast cancer (CBC) has been reported in familial BC. Ascertainment bias may influence both the reported familial CBC and survival. DESIGN:We assessed CBC incidence, distant disease free (DDFS) and overall survival (OS) in 327 BC patients who had > or =3 breast and/or ovarian cancers in the family but no BRCA1/2 gene mutation (non-BRCA1/2). They were matched to 327 sporadic controls for year and age at detection. To correct for ascertainment bias, we analyzed also separately the results (1) Of the 250 non-BRCA1/2 patients with DNA testing performed before diagnosis or within 2 years ('unselected') and (2) Of the 77 with testing > or =2 years after diagnosis (late-tested). RESULTS:Median follow-up of non-BRCA1/2 patients was 6.1 yrs. Ten years CBC incidence was 11% in non-BRCA1/2 versus 6% in sporadic patients (p = 0.002). At multivariate analysis CBC incidence was increased in late-tested non-BRCA1/2 (HR 4.6; p = 0.001) not in 'unselected' (HR 1.8; p = 0.1). Increased CBC occurred in non-BRCA1/2 patients mainly before genetic testing, suggesting ascertainment bias. Tumors were < or =T1 in 62% of non-BRCA1/2 versus 50% of sporadic patients (p = 0.003), node-negative in 55% versus 52% respectively (p = 0.5). After correction for stage and therapy, OS did not differ between 'unselected' non-BRCA1/2 and sporadic patients (HR 0.8; p = 0.3), but was improved in late-tested non-BRCA1/2. CONCLUSION:Overall survival and contralateral breast cancer incidence were similar in 'unselected' non-BRCA1/2- and sporadic patients. Reports of higher CBC incidence and better survival in non-BRCA1/2 patients may substantially be caused by DNA testing selection-bias.

journal_name

Breast Cancer Res Treat

journal_title

Breast cancer research and treatment

authors

Tilanus-Linthorst MM,Bartels KC,Alves C,Bakri B,Crepin E,van den Ouweland A,Klijn JG,Meijers-Heijboer H,Brekelmans CT

doi

10.1007/s10549-005-9054-2

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

117-23

issue

eissn

0167-6806

issn

1573-7217

journal_volume

pub_type

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Selection bias influences reported contralateral breast cancer incidence and survival in high risk non-BRCA1/2 patients.