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No evidence of familial correlation in breast cancer metastasis

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Animal experiments support the hypothesis that the metastatic potential of breast cancer is a heritable trait of the host. Our objective was to evaluate correlations in metastasis occurrence in large families with multiple cases of breast cancer. We evaluated correlation among pairs of relatives in the occurrence and timing of distant metastasis using retrospective cohort data from 743 female breast cancer patients in 242 families. We adjusted for correlation in their age at diagnosis, year of diagnosis, educational level, lymph node involvement, and estrogen receptor status. Distant metastasis occurred in 255 patients (34.3%) during mean followup of 11.7 years. None of the correlation coefficients for metastasis in blood relatives differed significantly from zero. The estimated correlation coefficient in first-degree relatives was −0.03 (95% confidence interval −0.11 to 0.06). These findings suggest that a family history of metastatic breast cancer does not contribute substantially to risk of metastasis for breast cancer patients.

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References

  1. Crawford NP, Alsarraj J, Lukes L et al (2008) Bromodomain 4 activation predicts breast cancer survival. Proc Natl Acad Sci USA 105:6380–6385. doi:10.1073/pnas.0710331105

    Article  CAS  PubMed  Google Scholar 

  2. Hunter KW, Broman KW, Voyer TL et al (2001) Predisposition to efficient mammary tumor metastatic progression is linked to the breast cancer metastasis suppressor gene Brms1. Cancer Res 61:8866–8872

    CAS  PubMed  Google Scholar 

  3. Park YG, Zhao X, Lesueur F et al (2005) Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1. Nat Genet 37:1055–1062. doi:10.1038/ng1635

    Article  CAS  PubMed  Google Scholar 

  4. Eccles SA, Box G, Court W et al (1994) Preclinical models for the evaluation of targeted therapies of metastatic disease. Cell Biophys 24–25:279–291

    PubMed  Google Scholar 

  5. Heimann R, Lan F, McBride R et al (2000) Separating favorable from unfavorable prognostic markers in breast cancer: the role of E-cadherin. Cancer Res 60:298–304

    CAS  PubMed  Google Scholar 

  6. Quiet CA, Ferguson DJ, Weichselbaum RR et al (1995) Natural history of node-negative breast cancer: a study of 826 patients with long-term follow-up. J Clin Oncol 13:1144–1151

    CAS  PubMed  Google Scholar 

  7. Rosen PP, Groshen S, Saigo PE et al (1989) A long-term follow-up study of survival in stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma. J Clin Oncol 7:355–366

    CAS  PubMed  Google Scholar 

  8. Tan LK, Giri D, Hummer AJ et al (2008) Occult axillary node metastasis in breast cancer are prognostically significant: results in 368 node-negative patients with 20-year follow-up. J Clin Oncol 26:1803–1809. doi:10.1200/JCO.2007.12.6425

    Article  PubMed  Google Scholar 

  9. Wang Y, Klijn JGM, Zhang Y et al (2005) Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 365:671–679

    CAS  PubMed  Google Scholar 

  10. Clare SE, Sener SF, Wilkens W et al (1997) Prognostic significance of occult lymph node metastases in node-negative breast cancer. Ann Surg Oncol 4:447–451. doi:10.1007/BF02303667

    Article  CAS  PubMed  Google Scholar 

  11. Heimann R, Hellman S (2000) Clinical progression of breast cancer malignant behavior: what to expect and when to expect it. J Clin Oncol 18:591–599

    CAS  PubMed  Google Scholar 

  12. John EM, Hopper JL, Beck JC et al (2004) The breast cancer family registry: an infrastructure for cooperative multinational, interdisciplinary and translational studies of the genetic epidemiology of breast cancer. Breast Cancer Res 6:R375–R389. doi:10.1186/bcr801

    Article  PubMed  Google Scholar 

  13. Zhao LP, Prentice RL (1990) Correlated binary regression using a quadratic exponential model. Biometrika 77:642–648. doi:10.1093/biomet/77.3.642

    Article  Google Scholar 

  14. Prentice RL, Hsu L (1997) Regression on hazard ratios in multivariate failure analysis. Biometrika 84:349–363. doi:10.1093/biomet/84.2.349

    Article  Google Scholar 

  15. Clayton DG (1978) A model for association in bivariate life tables and its application in epidemiological studies of familial tendency in chronic disease incidence. Biometrika 65:141–151. doi:10.1093/biomet/65.1.141

    Article  Google Scholar 

  16. Hartman M, Lindström L, Dickman PW et al (2007) Is breast cancer prognosis inherited? Breast Cancer Res 9:R39. doi:10.1186/bcr1737

    Article  PubMed  Google Scholar 

  17. Hemminki K, Ji J, Försti A et al (2007) Survival in breast cancer is familial. Breast Cancer Res Treat 110:177–182. doi:10.1007/s10549-007-9692-7

    Article  PubMed  Google Scholar 

  18. Lindstrom LS, Hall P, Hartman M et al (2007) Familial concordance in cancer survival: a Swedish population-based study. Lancet Oncol 8:1001–1006. doi:10.1016/S1470-2045(07)70282-6

    Article  PubMed  Google Scholar 

  19. Bradley CJ, Given CW, Roberts C (2002) Race, socioeconomic status, and breast cancer treatment and survival. J Natl Cancer Inst 94:490–496

    PubMed  Google Scholar 

  20. Dalton SO, Ross L, Düring M et al (2007) Influence of socioeconomic factors on survival after breast cancer–a nationwide cohort study of women diagnosed with breast cancer in Denmark 1983–1999. Int J Cancer 121:2524–2531. doi:10.1002/ijc.22979

    Article  CAS  PubMed  Google Scholar 

  21. Lifsted T, Le Voyer T, Williams M et al (1998) Identification of inbred mouse strains harboring genetic modifiers of mammary tumor age of onset and metastatic progression. Int J Cancer 77:640–644. doi:10.1002/(SICI)1097-0215(19980812)77:4<640::AID-IJC26>3.0.CO;2-8

    Article  CAS  PubMed  Google Scholar 

  22. Crawford NP, Ziogas A, Peel DJ et al (2006) Germline polymorphisms in SIPA1 are associated with metastasis and other indicators of poor prognosis in breast cancer. Breast Cancer Res 8:R16

    Article  PubMed  CAS  Google Scholar 

  23. Costa S, Pinto D, Pereira D et al (2008) Importance of TP53 codon 72 and intron 3 duplication 16 bp polymorphisms in prediction of susceptibility on breast cancer. BMC Cancer 8:32. doi:10.1186/1471-2407-8-32

    Article  PubMed  CAS  Google Scholar 

  24. Hoyal CR, Kammerer S, Roth RB et al (2005) Genetic polymorphisms in DPF3 associated with risk of breast cancer and lymph node metastases. J Carcinog 4:13–21. doi:10.1186/1477-3163-4-13

    Article  PubMed  CAS  Google Scholar 

  25. Nordgard SH, Ritchie MD, Jensrud SD et al (2007) ABCB1 and GST polymorphisms associated with TP53 status in breast cancer. Pharmacogenet Genomics 17:127–136

    Article  CAS  PubMed  Google Scholar 

  26. Goode EL, Dunning AM, Kuschel B, Healey CS, Day NE, Ponder BAJ, Easton DF, Pharoah PPD et al (2002) Effect of germ-line genetic variation on breast cancer survival in a population-based study. Cancer Res 62:3052–3057

    CAS  PubMed  Google Scholar 

  27. Schmidt MK, Tollenaar RAEM, de Kemp SR et al (2007) Breast cancer survival and tumor characteristics in premenopausal women carrying the CHEK2*1100delC germline mutation. J Clin Oncol 25:64–69. doi:10.1200/JCO.2006.06.3024

    Article  CAS  PubMed  Google Scholar 

  28. Udler M, Maia AT, Cebrian A et al (2007) Common germline genetic variation in antioxidant defense genes and survival after diagnosis of breast cancer. J Clin Oncol 25:3015–3023. doi:10.1200/JCO.2006.10.0099

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This research was supported by grant number 12IB-0167 from the California Breast Cancer Research Program, and used data from the Breast Cancer Family Registry, which is supported by RFA #CA-95-011 of the US National Cancer Institute, National Institutes of Health. The authors thank Li Hsu for a computer program to estimate correlations in censored survival data, and John Malick for data processing support at the Fox Chase Cancer Center.

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Authors and Affiliations

  1. Department of Health Research and Policy, Stanford University School of Medicine, Redwood Building, Room T204, Stanford, CA, 94305-5405, USA

    Alice S. Whittemore, Jerry Halpern, Anna Felberg & Valerie McGuire

  2. Fox Chase Cancer Center, Philadelphia, PA, USA

    Beth Stearman & Mary Daly

  3. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    Vickie Venne & Saundra S. Buys

Authors
  1. Alice S. Whittemore
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  2. Beth Stearman
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  3. Vickie Venne
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  4. Jerry Halpern
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  5. Anna Felberg
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  6. Valerie McGuire
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  7. Mary Daly
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  8. Saundra S. Buys
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Correspondence to Alice S. Whittemore.

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Whittemore, A.S., Stearman, B., Venne, V. et al. No evidence of familial correlation in breast cancer metastasis. Breast Cancer Res Treat 118, 575–581 (2009). https://doi.org/10.1007/s10549-009-0368-3

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  • DOI: https://doi.org/10.1007/s10549-009-0368-3

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