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

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Summary

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 ≥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 ≥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 ≤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.

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Acknowledgments

The authors like to thank Ada van Eekelen for logistic support and Marijke Westerhout –Kersten and Kerstin van der Veen for assisting literature search. The work of Celina Alves and Bonnie Bakri was supported by a grant of Erasmus University MC

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Authors and Affiliations

  1. Department of Surgical Oncology, Erasmus University Medical Centre, Rotterdam, The Netherlands

    Madeleine M.A. Tilanus-Linthorst, Karina C.M. Bartels, Celina Alves & Bonnie Bakri

  2. Medical Oncology, Erasmus University Medical Centre, Rotterdam, The Netherlands

    Ellen Crepin, Jan G.M. Klijn & Cecile T.M. Brekelmans

  3. Clinical Genetics, Erasmus University Medical Centre, Rotterdam, The Netherlands

    Ans van den Ouweland & Hanne Meijers-Heijboer

  4. Department of Surgical Oncology, Erasmus University Medical Centre Rotterdam, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands

    Madeleine M.A. Tilanus-Linthorst

Authors
  1. Madeleine M.A. Tilanus-Linthorst
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  2. Karina C.M. Bartels
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  3. Celina Alves
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  4. Bonnie Bakri
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  5. Ellen Crepin
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  6. Ans van den Ouweland
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  7. Jan G.M. Klijn
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  8. Hanne Meijers-Heijboer
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  9. Cecile T.M. Brekelmans
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Corresponding author

Correspondence to Madeleine M.A. Tilanus-Linthorst.

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Tilanus-Linthorst, M.M., Bartels, K.C., Alves, C. et al. Selection bias influences reported contralateral breast cancer incidence and survival in high risk non-BRCA1/2 patients. Breast Cancer Res Treat 95, 117–123 (2006). https://doi.org/10.1007/s10549-005-9054-2

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  • DOI: https://doi.org/10.1007/s10549-005-9054-2

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