Skip to main content

Advertisement

SpringerLink
Log in

Family history of breast cancer in first-degree relatives and triple-negative breast cancer risk

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

Abstract

Triple-negative breast cancer accounts for less than 20% of breast cancers overall, but is the predominant subtype among carriers of mutations in BRCA1. However, few studies have assessed the association between breast cancer family history and risk of triple-negative breast cancer. We examined the relationship between having a family history of breast cancer in first-degree relatives and risk of triple-negative breast cancer, and risk of two other breast cancer subtypes defined by tumor marker expression. We evaluated data collected by the Breast Cancer Surveillance Consortium from 2,599,946 mammograms on 1,054,466 women, among whom 15% reported a first-degree family history of breast cancer. Using Cox regression in this cohort, we evaluated subtype-specific associations between family history and risk of triple-negative (N = 705), estrogen receptor-positive (ER+, N = 10,026), and hormone receptor-negative/HER2-expressing (ER−/PR−/HER2+, N = 308) breast cancer among women aged 40–84 years. First-degree family history was similarly and significantly associated with an increased risk of all the subtypes [hazard ratio (HR) = 1.73, 95% confidence interval (CI): 1.43–2.09, HR = 1.62, 95% CI: 1.54–1.70, and HR = 1.56, 95% CI: 1.15–2.13, for triple-negative, ER+, and ER−/PR−/HER2+, respectively]. Risk of all the subtypes was most pronounced among women with at least two affected first-degree relatives (versus women with no affected first-degree relatives, HRtriple-negative = 2.66, 95% CI: 1.66–4.27, HRER+ = 2.05, 95% CI: 1.79–2.36, HRER−/PR−/HER2+ = 2.25, 95% CI: 0.99–5.08). Having a first-degree family history of breast cancer was associated with an increased risk of triple-negative breast cancer with a magnitude of association similar to that for the predominant ER+ subtype and ER−/PR−/HER2+ breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ER:

estrogen receptor

PR:

progesterone receptor

HR:

hazard ratio

CI:

confidence interval

BCSC:

Breast Cancer Surveillance Consortium

IHC:

immunohistochemistry

FISH:

fluorescence in situ hybridization

References

  1. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406:747–752

    Article  PubMed  CAS  Google Scholar 

  2. Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, Deming SL, Geradts J, Cheang MC, Nielsen TO, Moorman PG, Earp HS, Millikan RC (2006) Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295:2492–2502

    Article  PubMed  CAS  Google Scholar 

  3. Onitilo AA, Engel JM, Greenlee RT, Mukesh BN (2009) Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res 7:4–13. doi:7/1-2/4[pii]10.3121/cmr.2009.825

    Article  PubMed  CAS  Google Scholar 

  4. Kim MJ, Ro JY, Ahn SH, Kim HH, Kim SB, Gong G (2006) Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes. Hum Pathol 37:1217–1226

    Article  PubMed  CAS  Google Scholar 

  5. Del Casar JM, Martin A, Garcia C, Corte MD, Alvarez A, Junquera S, Gonzalez LO, Bongera M, Garcia-Muniz JL, Allende MT, Vizoso F (2008) Characterization of breast cancer subtypes by quantitative assessment of biological parameters: relationship with clinicopathological characteristics, biological features and prognosis. Eur J Obstet Gynecol Reprod Biol 141(2):147–152

    Article  PubMed  Google Scholar 

  6. Foulkes WD, Stefansson IM, Chappuis PO, Begin LR, Goffin JR, Wong N, Trudel M, Akslen LA (2003) Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst 95:1482–1485

    PubMed  CAS  Google Scholar 

  7. Haffty BG, Yang Q, Reiss M, Kearney T, Higgins SA, Weidhaas J, Harris L, Hait W, Toppmeyer D (2006) Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol 24:5652–5657

    Article  PubMed  Google Scholar 

  8. Parise CA, Bauer KR, Brown MM, Caggiano V (2009) Breast cancer subtypes as defined by the estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) among women with invasive breast cancer in California, 1999–2004. Breast J 15:593–602. doi:TBJ822[pii]10.1111/j.1524-4741.2009.00822.x

    Article  PubMed  Google Scholar 

  9. Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V (2007) Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer 109:1721–1728

    Article  PubMed  Google Scholar 

  10. Yang XR, Sherman ME, Rimm DL, Lissowska J, Brinton LA, Peplonska B, Hewitt SM, Anderson WF, Szeszenia-Dabrowska N, Bardin-Mikolajczak A, Zatonski W, Cartun R, Mandich D, Rymkiewicz G, Ligaj M, Lukaszek S, Kordek R, Garcia-Closas M (2007) Differences in risk factors for breast cancer molecular subtypes in a population-based study. Cancer Epidemiol Biomarkers Prev 16:439–443

    Article  PubMed  CAS  Google Scholar 

  11. Millikan RC, Newman B, Tse CK, Moorman PG, Conway K, Smith LV, Labbok MH, Geradts J, Bensen JT, Jackson S, Nyante S, Livasy C, Carey L, Earp HS, Perou CM (2008) Epidemiology of basal-like breast cancer. Breast Cancer Res Treat 109:123–139

    Article  PubMed  Google Scholar 

  12. Ballard-Barbash R, Taplin SH, Yankaskas BC, Ernster VL, Rosenberg RD, Carney PA, Barlow WE, Geller BM, Kerlikowske K, Edwards BK, Lynch CF, Urban N, Chrvala CA, Key CR, Poplack SP, Worden JK, Kessler LG (1997) Breast Cancer Surveillance Consortium: a national mammography screening and outcomes database. AJR Am J Roentgenol 169:1001–1008

    PubMed  CAS  Google Scholar 

  13. Collaborative Group on Hormonal Factors in Breast Cancer (2001) Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet 358:1389–1399

    Article  Google Scholar 

  14. Pharoah PD, Day NE, Duffy S, Easton DF, Ponder BA (1997) Family history and the risk of breast cancer: a systematic review and meta-analysis. Int J Cancer 71:800–809

    Article  PubMed  CAS  Google Scholar 

  15. Kalbfleisch JD, Prentice RL (2002) The statistical analysis of failure time data. Wiley, New York

    Google Scholar 

  16. Raghunathan TE, Lepkowski JM, Van Hoewyk J, Solenberger P (2001) A multivariate technique for multiply imputing missing values using a sequence of regression models. Surv Methodol 27:85–95

    Google Scholar 

  17. Negri E, Braga C, La Vecchia C, Franceschi S, Parazzini F (1997) Family history of cancer and risk of breast cancer. Int J Cancer 72:735–738

    Article  PubMed  CAS  Google Scholar 

  18. Anderson H, Bladstrom A, Olsson H, Moller TR (2000) Familial breast and ovarian cancer: a Swedish population-based register study. Am J Epidemiol 152:1154–1163

    Article  PubMed  CAS  Google Scholar 

  19. Li CI, Daling JR, Malone KE, Bernstein L, Marchbanks PA, Liff JM, Strom BL, Simon MS, Press MF, McDonald JA, Ursin G, Burkman RT, Deapen D, Spirtas R (2006) Relationship between established breast cancer risk factors and risk of seven different histologic types of invasive breast cancer. Cancer Epidemiol Biomarkers Prev 15:946–954. doi:15/5/946[pii]10.1158/1055-9965.EPI-05-0881

    Article  PubMed  Google Scholar 

  20. Carpenter CL, Ross RK, Paganini-Hill A, Bernstein L (2003) Effect of family history, obesity and exercise on breast cancer risk among postmenopausal women. Int J Cancer 106:96–102. doi:10.1002/ijc.11186

    Article  PubMed  CAS  Google Scholar 

  21. Lund MJ, Trivers KF, Porter PL, Coates RJ, Leyland-Jones B, Brawley OW, Flagg EW, O’Regan RM, Gabram SG, Eley JW (2009) Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA. Breast Cancer Res Treat 113:357–370. doi:10.1007/s10549-008-9926-3

    Article  PubMed  Google Scholar 

  22. Ford D, Easton DF, Peto J (1995) Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence. Am J Hum Genet 57:1457–1462

    PubMed  CAS  Google Scholar 

  23. Potter JD, Cerhan JR, Sellers TA, McGovern PG, Drinkard C, Kushi LR, Folsom AR (1995) Progesterone and estrogen receptors and mammary neoplasia in the Iowa Women’s Health Study: how many kinds of breast cancer are there? Cancer Epidemiol Biomarkers Prev 4:319–326

    PubMed  CAS  Google Scholar 

  24. Cotterchio M, Kreiger N, Theis B, Sloan M, Bahl S (2003) Hormonal factors and the risk of breast cancer according to estrogen- and progesterone-receptor subgroup. Cancer Epidemiol Biomarkers Prev 12:1053–1060

    PubMed  CAS  Google Scholar 

  25. Althuis MD, Fergenbaum JH, Garcia-Closas M, Brinton LA, Madigan MP, Sherman ME (2004) Etiology of hormone receptor-defined breast cancer: a systematic review of the literature. Cancer Epidemiol Biomarkers Prev 13:1558–1568

    PubMed  CAS  Google Scholar 

  26. Welsh ML, Buist DS, Aiello Bowles EJ, Anderson ML, Elmore JG, Li CI (2008) Population-based estimates of the relation between breast cancer risk, tumor subtype, and family history. Breast Cancer Res Treat 114(3):549–558

    Article  PubMed  Google Scholar 

  27. Bradbury AR, Olopade OI (2007) Genetic susceptibility to breast cancer. Rev Endocr Metab Disord 8:255–267

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank the participating women, mammography facilities, and radiologists for the data they have provided for this study. A list of the BCSC investigators and procedures for requesting BCSC data for research purposes are provided at: http://breastscreening.cancer.gov/.

Conflict of interest

The authors declare that they have no competing interests.

Financial support

This study was supported by a National Cancer Institute-funded Breast Cancer Surveillance Consortium co-operative agreement (U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, and U01CA70040). The collection of cancer data used in this study was supported in part by several state public health departments and cancer registries throughout the U.S. For a full description of these sources, please see: http://breastscreening.cancer.gov/work/acknowledgement.html. This publication was supported by grant number T32 CA09168 and R25-CA94880 from the National Cancer Institute, National Institutes of Health. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

Author information

Authors and Affiliations

  1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, M4-B402, P.O. Box 19024, Seattle, WA 98109-1024, USA

    Amanda I. Phipps, Kathleen E. Malone, William E. Barlow, Peggy L. Porter & Christopher I. Li

  2. School of Public Health, University of Washington, Seattle, WA, USA

    Amanda I. Phipps, Diana S. M. Buist, Kathleen E. Malone & Christopher I. Li

  3. Group Health Research Institute, Seattle, WA, USA

    Diana S. M. Buist & William E. Barlow

  4. Cancer Research and Biostatistics, Seattle, WA, USA

    William E. Barlow

  5. School of Medicine, University of Washington, Seattle, WA, USA

    Peggy L. Porter

  6. Departments of Medicine and Epidemiology and Biostatistics, University of California, San Francisco, CA, USA

    Karla Kerlikowske

Authors
  1. Amanda I. Phipps
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Diana S. M. Buist
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kathleen E. Malone
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. William E. Barlow
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peggy L. Porter
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Karla Kerlikowske
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christopher I. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amanda I. Phipps.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Phipps, A.I., Buist, D.S.M., Malone, K.E. et al. Family history of breast cancer in first-degree relatives and triple-negative breast cancer risk. Breast Cancer Res Treat 126, 671–678 (2011). https://doi.org/10.1007/s10549-010-1148-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-010-1148-9

Keywords

Search

Navigation