Skip to main content

Advertisement

SpringerLink
Log in

Race and breast cancer survival by intrinsic subtype based on PAM50 gene expression

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

Abstract

To evaluate whether differences in PAM50 breast cancer (BC) intrinsic (Luminal A, Luminal B, Basal-like, and HER2-enriched) subtypes help explain the Black–White BC survival disparity. Utilizing a stratified case-cohort design, this study included 1,635 women from the Pathways and Life After Cancer Epidemiology cohorts, selecting women with tumors based upon IHC classification, recurrences, and deaths.One millimeter punches were obtained from tumor tissue, and expression of the PAM50 genes for molecular subtype was determined by RT-qPCR of extracted RNA. Cox proportional hazards models were used to analyze associations between race and BC outcomes, adjusted for PAM50 BC subtype. All tests of statistical significance were two-sided. Black women had a higher prevalence of the Basal-like BC subtype. Adjusted for potential confounding variables and disease characteristics at diagnosis, Black women had higher risks of recurrence (HR 1.65, 95 % CI 1.06–2.57) and breast cancer-specific mortality (HR 1.71, 95 % CI 1.02–2.86) than White women, but adjusting further for subtype did not attenuate survival disparities. By contrast, Hispanic women had a lower risk of recurrence (HR 0.54, 95 % CI 0.30–0.96) than Whites. Among those with the Basal-like subtype, Black women had a similar recurrence risk as women in other race groups but a higher recurrence risk for all other subtypes. Hispanic women had a lower recurrence risk within each subtype, though associations were not significant, given limited power. Although Black women had a higher risk of the Basal-like subtype, which has poor prognosis, this did not explain the Black–White BC survival disparity.

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

References

  1. Tannenbaum SL, Koru-Sengul T, Miao F, Byrne MM (2013) Disparities in survival after female breast cancer diagnosis: a population-based study. Cancer Causes Control 24(9):1705–1715

    Article  PubMed  Google Scholar 

  2. Sail K, Franzini L, Lairson D, Du X (2012) Differences in treatment and survival among African-American and Caucasian women with early stage operable breast cancer. Ethn Health 17(3):309–323

    Article  PubMed  Google Scholar 

  3. American Cancer Society (2009) Cancer facts and figures—2009. American Cancer Society, Atlanta

    Google Scholar 

  4. Chlebowski RT, Chen Z, Anderson GL, Rohan T, Aragaki A, Lane D, Dolan NC, Paskett ED, McTiernan A, Hubbell FA et al (2005) Ethnicity and breast cancer: factors influencing differences in incidence and outcome. J Natl Cancer Inst 97(6):439–448

    Article  PubMed  Google Scholar 

  5. Deshpande AD, Jeffe DB, Gnerlich J, Iqbal AZ, Thummalakunta A, Margenthaler JA (2009) Racial disparities in breast cancer survival: an analysis by age and stage. J Surg Res 153(1):105–113

    Article  PubMed Central  PubMed  Google Scholar 

  6. McBride R, Hershman D, Tsai WY, Jacobson JS, Grann V, Neugut AI (2007) Within-stage racial differences in tumor size and number of positive lymph nodes in women with breast cancer. Cancer 110(6):1201–1208

    Article  PubMed  Google Scholar 

  7. Tammemagi CM, Nerenz D, Neslund-Dudas C, Feldkamp C, Nathanson D (2005) Comorbidity and survival disparities among black and white patients with breast cancer. JAMA 294(14):1765–1772

    Article  PubMed  CAS  Google Scholar 

  8. Parise CA, Caggiano V (2013) Disparities in race/ethnicity and socioeconomic status: risk of mortality of breast cancer patients in the California Cancer Registry, 2000–2010. BMC Cancer 13(1):449

    Article  PubMed Central  PubMed  Google Scholar 

  9. Pinheiro PS, Williams M, Miller EA, Easterday S, Moonie S, Trapido EJ (2011) Cancer survival among Latinos and the Hispanic Paradox. Cancer Causes Control 22(4):553–561

    Article  PubMed  Google Scholar 

  10. Silber JH, Rosenbaum PR, Clark AS, Giantonio BJ, Ross RN, Teng Y, Wang M, Niknam BA, Ludwig JA, Wang W et al (2013) Characteristics associated with differences in survival among black and white women with breast cancer. JAMA 310:389–397

    Article  PubMed  CAS  Google Scholar 

  11. Chatterjee NA, He Y, Keating NL (2013) Racial differences in breast cancer stage at diagnosis in the mammography era. Am J Public Health 103(1):170–176

    Article  PubMed  Google Scholar 

  12. Simon MS, Lamerato L, Krajenta R, Booza JC, Ruterbusch JJ, Kunz S, Schwartz K (2012) Racial differences in the use of adjuvant chemotherapy for breast cancer in a large urban integrated health system. Int J Breast Cancer 2012:453985

    Article  PubMed Central  PubMed  Google Scholar 

  13. Dehal A, Abbas A, Johna S (2013) Racial disparities in clinical presentation, surgical treatment and in-hospital outcomes of women with breast cancer: analysis of nationwide inpatient sample database. Breast Cancer Res Treat 139(2):561–569

    Article  PubMed  Google Scholar 

  14. Smith EC, Ziogas A, Anton-Culver H (2013) Delay in surgical treatment and survival after breast cancer diagnosis in young women by race/ethnicity. JAMA Surg 148(6):516–523

    Article  PubMed  Google Scholar 

  15. Nurgalieva ZZ, Franzini L, Morgan RO, Vernon SW, Liu CC, Du XL (2013) Impact of timing of adjuvant chemotherapy initiation and completion after surgery on racial disparities in survival among women with breast cancer. Med Oncol 30(1):419

    Article  PubMed  CAS  Google Scholar 

  16. Balasubramanian BA, Demissie K, Crabtree BF, Strickland PA, Pawlish K, Rhoads GG (2012) Black Medicaid beneficiaries experience breast cancer treatment delays more frequently than whites. Ethn Dis 22(3):288–294

    PubMed  Google Scholar 

  17. Du XL, Fang S, Meyer TE (2008) Impact of treatment and socioeconomic status on racial disparities in survival among older women with breast cancer. Am J Clin Oncol 31(2):125–132

    Article  PubMed  Google Scholar 

  18. Akinyemiju TF, Soliman AS, Johnson NJ, Altekruse SF, Welch K, Banerjee M, Schwartz K, Merajver S (2013) Individual and neighborhood socioeconomic status and healthcare resources in relation to black-white breast cancer survival disparities. J Cancer Epidemiol 2013:490472

    Article  PubMed Central  PubMed  Google Scholar 

  19. Dignam JJ (2001) Efficacy of systemic adjuvant therapy for breast cancer in African-American and Caucasian women. J Natl Cancer Inst Monogr 30:36–43

    Article  PubMed  Google Scholar 

  20. Albain KS, Unger JM, Crowley JJ, Coltman CA Jr (2009) Hershman DL: racial disparities in cancer survival among randomized clinical trials patients of the Southwest Oncology Group. J Natl Cancer Inst 101(14):984–992

    Article  PubMed Central  PubMed  Google Scholar 

  21. Perou C (2013) PL01-03: the therapeutic implications of genome sequencing and expression analyses for breast cancer. In: American Association of Cancer Research (AACR), Washington

  22. Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S et al (2006) Race, breast cancer subtypes, and survival in the Carolina breast cancer study. JAMA 295(21):2492–2502

    Article  PubMed  CAS  Google Scholar 

  23. O’Brien KM, Cole SR, Tse CK, Perou CM, Carey LA, Foulkes WD, Dressler LG, Geradts J, Millikan RC (2010) Intrinsic breast tumor subtypes, race, and long-term survival in the Carolina breast cancer study. Clin Cancer Res 16(24):6100–6110

    Article  PubMed Central  PubMed  Google Scholar 

  24. Ma H, Lu Y, Malone KE, Marchbanks PA, Deapen DM, Spirtas R, Burkman RT, Strom BL, McDonald JA, Folger SG et al (2013) Mortality risk of black women and white women with invasive breast cancer by hormone receptors, HER2, and p53 status. BMC Cancer 13:225

    Article  PubMed Central  PubMed  Google Scholar 

  25. Haque R, Ahmed S, Schottinger J, Kwan M, Shi J, Chung J, Inzhakova G, Avila C, Kleinman K, Fletcher S (2012) PS1-05: disparities in breast cancer survival by molecular subtype and race/ethnicity; HMORN 2012 conference. Clin Med Res 10(3):145

    Article  PubMed Central  Google Scholar 

  26. Perez CA, Zumsteg ZS, Gupta G, Morrow M, Arnold B, Patil SM, Traina TA, Robson ME, Wen YH, McCormick B et al (2013) Black race as a prognostic factor in triple-negative breast cancer patients treated with breast-conserving therapy: a large, single-institution retrospective analysis. Breast Cancer Res Treat 139(2):497–506

    Article  PubMed  CAS  Google Scholar 

  27. Pacheco JM, Gao F, Bumb C, Ellis MJ, Ma CX (2013) Racial differences in outcomes of triple-negative breast cancer. Breast Cancer Res Treat 138(1):281–289

    Article  PubMed  CAS  Google Scholar 

  28. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA et al (2000) Molecular portraits of human breast tumours. Nature 406(6797):747–752

    Article  PubMed  CAS  Google Scholar 

  29. Bastien RR, Rodriguez-Lescure A, Ebbert MT, Prat A, Munarriz B, Rowe L, Miller P, Ruiz-Borrego M, Anderson D, Lyons B et al (2012) PAM50 breast cancer subtyping by RT-qPCR and concordance with standard clinical molecular markers. BMC Med Genomics 5:44

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  30. Caan B, Sternfeld B, Gunderson E, Coates A, Quesenberry C, Slattery ML (2005) Life after cancer epidemiology (LACE) study: a cohort of early stage breast cancer survivors (United States). Cancer Causes Control 16(5):545–556

    Article  PubMed  Google Scholar 

  31. Kwan ML, Ambrosone CB, Lee MM, Barlow J, Krathwohl SE, Ergas IJ, Ashley CH, Bittner JR, Darbinian J, Stronach K et al (2008) The pathways study: a prospective study of breast cancer survivorship within Kaiser Permanente Northern California. Cancer Causes Control 19(10):1065–1076

    Article  PubMed Central  PubMed  Google Scholar 

  32. Borgan O, Langholz B, Samuelsen SO, Goldstein L, Pogoda J (2000) Exposure stratified case-cohort designs. Lifetime Data Anal 6(1):39–58

    Article  PubMed  CAS  Google Scholar 

  33. Prentice RL (1986) A case-cohort design for epidemiological cohort studies and disease prevention trials. Biometrika 73:1–11

    Article  Google Scholar 

  34. Self SG, Prentice RL (1988) Asymptotic distribution theory and efficiency results for case-cohort studies. Ann Stat 16:64–81

    Article  Google Scholar 

  35. Sweeney C, Bernard P, Factor RE, Kwan M, Habel LA, Quesenberry CP Jr, Shakespear K, Weltzien E, Stijleman IJ, Davis C et al (2014) Intrinsic subtypes from PAM50 gene expression assay in a population-based breast cancer cohort: differences by age, race, and tumor characteristics. Cancer Epidemiol Biomark Prev. doi:10.1158/1055-9965.EPI-13-1023

  36. Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, Davies S, Fauron C, He X, Hu Z et al (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27(8):1160–1167

    Article  PubMed Central  PubMed  Google Scholar 

  37. Ebbert MT, Bastien RR, Boucher KM, Martin M, Carrasco E, Caballero R, Stijleman IJ, Bernard PS, Facelli JC (2011) Characterization of uncertainty in the classification of multivariate assays: application to PAM50 centroid-based genomic predictors for breast cancer treatment plans. J Clin Bioinform 1:37

    Article  Google Scholar 

  38. Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40(5):373–383

    Article  PubMed  CAS  Google Scholar 

  39. Langholz B, Jiao J (2007) Computational methods for case-cohort studies. Comput Stat Data Anal 51:3737–3748

    Article  Google Scholar 

  40. Komenaka IK, Martinez ME, Pennington RE Jr, Hsu CH, Clare SE, Thompson PA, Murphy C, Zork NM, Goulet RJ Jr (2010) Race and ethnicity and breast cancer outcomes in an underinsured population. J Natl Cancer Inst 102(15):1178–1187

    Article  PubMed  Google Scholar 

  41. Yood MU, Johnson CC, Blount A, Abrams J, Wolman E, McCarthy BD, Raju U, Nathanson DS, Worsham M, Wolman SR (1999) Race and differences in breast cancer survival in a managed care population. J Natl Cancer Inst 91(17):1487–1491

    Article  PubMed  CAS  Google Scholar 

  42. Sweeney C, Bernard PS, Factor RE, Kwan ML, Habel LA, Quesenberry CP, Shakespear K, Weltzien EK, Stijleman IJ, Davis CA et al (2013) Application of the PAM50 RT-qPCR-based intrinsic subtype classifier in a population-based breast cancer cohort: subtype associations with age, race, and tumor characteristics (in press)

  43. 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(9):1721–1728

    Article  PubMed  Google Scholar 

  44. Caan BJ, Sweeney C, Habel LA, Kwan M, Kroenke CH, Weltzien E et al (2013) Intrinsic subtypes from the PAM50 gene expression assay in a population-based breast cancer survivor cohort: prognostication of short and long term outcomes. Cancer Epidemiol Biomark Prev. doi:10.1158/1055-9965.EPI-13-1017

  45. Maskarinec G, Sen C, Koga K, Conroy SM (2011) Ethnic differences in breast cancer survival: status and determinants. Womens Health (Lond Engl) 7(6):677–687

    Article  Google Scholar 

  46. Bosco JL, Lash TL, Prout MN, Buist DS, Geiger AM, Haque R, Wei F, Silliman RA (2009) Breast cancer recurrence in older women five to ten years after diagnosis. Cancer Epidemiol Biomark Prev 18(11):2979–2983

    Article  Google Scholar 

  47. Elledge RM, Clark GM, Chamness GC, Osborne CK (1994) Tumor biologic factors and breast cancer prognosis among white, Hispanic, and black women in the United States. J Natl Cancer Inst 86(9):705–712

    Article  PubMed  CAS  Google Scholar 

  48. Philips BU Jr, Belasco E, Markides KS, Gong G (2013) Socioeconomic deprivation as a determinant of cancer mortality and the Hispanic paradox in Texas, USA. Int J Equity Health 12:26

    Article  PubMed  Google Scholar 

  49. Palloni A, Morenoff JD (2001) Interpreting the paradoxical in the hispanic paradox: demographic and epidemiologic approaches. Ann NY Acad Sci 954:140–174

    Article  PubMed  CAS  Google Scholar 

  50. Hershman D, McBride R, Jacobson JS, Lamerato L, Roberts K, Grann VR, Neugut AI (2005) Racial disparities in treatment and survival among women with early-stage breast cancer. J Clin Oncol 23(27):6639–6646

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Institutes of Health (R01 CA129059 and R01 CA105274). The Utah Cancer Registry is funded by Contract No. HHSN261201000026C from the National Cancer Institute Surveillance Epidemiology and End Results (SEER) program and additional support from the Utah State Department of Health and the University of Utah. PSB has an interest in Bioclassifier LLC and University Genomics.

Conflict of interest

The other authors declare they have no competing interests.

Author information

Authors and Affiliations

  1. Division of Research, Kaiser Permanente Northern California, 2000 Broadway, 5th Floor, Oakland, CA, 94612, USA

    Candyce H. Kroenke, Marilyn L. Kwan, Charles P. Quesenberry, Erin K. Weltzien, Laurel A. Habel, Adrienne Castillo, Lawrence H. Kushi & Bette J. Caan

  2. Division of Epidemiology, University of Utah, 295 Chipeta Way, Salt Lake City, UT, 84132, USA

    Carol Sweeney, Phillip S. Bernard & Rachel E. Factor

Authors
  1. Candyce H. Kroenke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carol Sweeney
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marilyn L. Kwan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Charles P. Quesenberry
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Erin K. Weltzien
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Laurel A. Habel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Adrienne Castillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Phillip S. Bernard
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Rachel E. Factor
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lawrence H. Kushi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Bette J. Caan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Candyce H. Kroenke.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kroenke, C.H., Sweeney, C., Kwan, M.L. et al. Race and breast cancer survival by intrinsic subtype based on PAM50 gene expression. Breast Cancer Res Treat 144, 689–699 (2014). https://doi.org/10.1007/s10549-014-2899-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-014-2899-5

Keywords

Search

Navigation