Journal Article
. 2020 Sep;184(3).
doi: 10.1007/s10549-020-05902-0.

Racial and ethnic disparities in 21-gene recurrence scores, chemotherapy, and survival among women with hormone receptor-positive, node-negative breast cancer

Yunan Han 1 Zhi-Feng Miao 2 Min Lian 3 Lindsay L Peterson 4 Graham A Colditz 1 Ying Liu 5 
  • PMID: 32929567
  •     43 References


Purpose: Cutoffs of the 21-gene recurrence score (RS), a commonly used genomic assay for hormone receptor-positive breast cancer, have been updated. Little is known about racial/ethnic differences in RS results, RS-guided chemotherapy use, and outcomes on updated cutoff (RS ≥ 31 defined as high-risk) in the real-world setting.

Methods: A total of 81,937 women [75.0% whites, 7.7% blacks, 8.3% Asian American/Pacific Islanders (AAPIs), and 9.0% Hispanics] diagnosed with hormone receptor-positive breast cancer between 2004 and 2015, who received the 21-gene assay, were identified from the Surveillance, Epidemiology, and End Results. Logistic regressions estimated the race-associated odds ratios (ORs) of RS and chemotherapy use. Cox regressions estimated the race-associated hazard ratios (HRs) of breast cancer-specific and all-cause mortality.

Results: Compared with white women, black women were more likely to have RS-defined high-risk tumors (adjusted OR [aOR] 1.29; 95% CI 1.16-1.42). In high RS, blacks had lower odds of chemotherapy use (aOR 0.76; 95% CI 0.62-0.94) than whites, particularly among women ≥ 65 years (aOR 0.51; 95% CI 0.35-0.76), while AAPI and Hispanic women had no variation in chemotherapy use compared with whites in high RS. Black women had a higher risk of breast cancer-specific mortality (HR 1.37; 95% CI 1.12-1.67) and all-cause mortality compared with white women after adjusting for demographic and pathological factors, county-level socioeconomic deprivation, treatments and RS; AAPIs had lower mortality and Hispanics had similar mortality.

Conclusions: Black women were more likely to have a high-risk RS tumor and less likely to receive chemotherapy in the group of high RS, especially those ≥ 65 years. Further studies are needed to identify barriers to chemotherapy in black patients with high RS scores.

Keywords: 21-gene; Breast cancer; Chemotherapy; Oncotype DX; Race; Recurrence score; Survival.

Comorbidity and survival disparities among black and white patients with breast cancer.
C Martin Tammemagi, David Nerenz, +2 authors, David Nathanson.
JAMA, 2005 Oct 13; 294(14). PMID: 16219879
Highly Cited.
21-Gene assay as predictor of chemotherapy benefit in HER2-negative breast cancer.
Charles E Geyer, Gong Tang, +8 authors, Norman Wolmark.
NPJ Breast Cancer, 2018 Nov 21; 4. PMID: 30456299    Free PMC article.
Disparity in Breast Cancer Late Stage at Diagnosis in Missouri: Does Rural Versus Urban Residence Matter?
Faustine Williams, Emmanuel Thompson.
J Racial Ethn Health Disparities, 2016 Jun 09; 3(2). PMID: 27271063    Free PMC article.
Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.
Soonmyung Paik, Gong Tang, +11 authors, Norman Wolmark.
J Clin Oncol, 2006 May 25; 24(23). PMID: 16720680
Highly Cited.
Oncotype Dx assay and breast cancer in the United States: usage and concordance with chemotherapy.
Lindsey Enewold, Ann M Geiger, JoAnne Zujewski, Linda C Harlan.
Breast Cancer Res Treat, 2015 Apr 11; 151(1). PMID: 25859924
Neighborhood socioeconomic deprivation, tumor subtypes, and causes of death after non-metastatic invasive breast cancer diagnosis: a multilevel competing-risk analysis.
Min Lian, Maria Pérez, +4 authors, Donna B Jeffe.
Breast Cancer Res Treat, 2014 Sep 23; 147(3). PMID: 25234843    Free PMC article.
Prospective Validation of a 21-Gene Expression Assay in Breast Cancer.
Joseph A Sparano, Robert J Gray, +28 authors, George W Sledge.
N Engl J Med, 2015 Sep 29; 373(21). PMID: 26412349    Free PMC article.
Highly Cited.
Racial and Ethnic Differences in Breast Cancer Survival: Mediating Effect of Tumor Characteristics and Sociodemographic and Treatment Factors.
Erica T Warner, Rulla M Tamimi, +9 authors, Ann H Partridge.
J Clin Oncol, 2015 May 13; 33(20). PMID: 25964252    Free PMC article.
Highly Cited.
Underutilization of gene expression profiling for early-stage breast cancer in California.
Rosemary D Cress, Yingjia S Chen, +2 authors, Kenneth W Kizer.
Cancer Causes Control, 2016 Apr 22; 27(6). PMID: 27097910    Free PMC article.
The influence of marital status on the stage at diagnosis, treatment, and survival of older women with breast cancer.
Cynthia Osborne, Glenn V Ostir, +2 authors, James S Goodwin.
Breast Cancer Res Treat, 2005 Sep 27; 93(1). PMID: 16184457
Development and clinical utility of a 21-gene recurrence score prognostic assay in patients with early breast cancer treated with tamoxifen.
Soonmyung Paik.
Oncologist, 2007 Jul 03; 12(6). PMID: 17602054
Impacts of Neighborhood Characteristics on Treatment and Outcomes in Women with Ductal Carcinoma In Situ of the Breast.
Shiyang Zhang, Ying Liu, +3 authors, Graham A Colditz.
Cancer Epidemiol Biomarkers Prev, 2018 Aug 16; 27(11). PMID: 30108100    Free PMC article.
Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
Freddie Bray, Jacques Ferlay, +3 authors, Ahmedin Jemal.
CA Cancer J Clin, 2018 Sep 13; 68(6). PMID: 30207593
Highly Cited.
US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status.
Nadia Howlader, Sean F Altekruse, +4 authors, Kathleen A Cronin.
J Natl Cancer Inst, 2014 Apr 30; 106(5). PMID: 24777111    Free PMC article.
Highly Cited.
Molecular Characterization and Mortality From Breast Cancer in Men.
Suleiman Alfred Massarweh, George W Sledge, +3 authors, Steven Shak.
J Clin Oncol, 2018 Mar 28; 36(14). PMID: 29584547    Free PMC article.
A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.
Soonmyung Paik, Steven Shak, +12 authors, Norman Wolmark.
N Engl J Med, 2004 Dec 14; 351(27). PMID: 15591335
Highly Cited.
21-Gene Recurrence Score Assay As a Predictor of Adjuvant Chemotherapy Administration for Early-Stage Breast Cancer: An Analysis of Use, Therapeutic Implications, and Disparity Profile.
Jagar Jasem, Arya Amini, +4 authors, Peter Kabos.
J Clin Oncol, 2016 Mar 24; 34(17). PMID: 27001563    Free PMC article.
Breast-cancer-specific mortality in patients treated based on the 21-gene assay: a SEER population-based study.
Valentina I Petkov, Dave P Miller, +21 authors, Steven Shak.
NPJ Breast Cancer, 2017 Jul 20; 2. PMID: 28721379    Free PMC article.
Highly Cited.
Race and hormone receptor-positive breast cancer outcomes in a randomized chemotherapy trial.
Joseph A Sparano, Molin Wang, +9 authors, Nancy E Davidson.
J Natl Cancer Inst, 2012 Jan 18; 104(5). PMID: 22250182    Free PMC article.
Clinical utility of gene-expression signatures in early stage breast cancer.
Maryann Kwa, Andreas Makris, Francisco J Esteva.
Nat Rev Clin Oncol, 2017 Jun 01; 14(10). PMID: 28561071
Highly Cited. Review.
Intrinsic breast tumor subtypes, race, and long-term survival in the Carolina Breast Cancer Study.
Katie M O'Brien, Stephen R Cole, +6 authors, Robert C Millikan.
Clin Cancer Res, 2010 Dec 21; 16(24). PMID: 21169259    Free PMC article.
Highly Cited.
Disparities in breast cancer stage at diagnosis in urban and rural adult women: a systematic review and meta-analysis.
Sallyanne Nguyen-Pham, Janni Leung, Deirdre McLaughlin.
Ann Epidemiol, 2014 Jan 28; 24(3). PMID: 24462273
Systematic Review.
Statistical Assessment of Neighborhood Socioeconomic Deprivation Environment in Spatial Epidemiologic Studies.
Min Lian, James Struthers, Ying Liu.
Open J Stat, 2016 Jul 15; 6(3). PMID: 27413589    Free PMC article.
Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study.
Mitch Dowsett, Jack Cuzick, +11 authors, Steven Shak.
J Clin Oncol, 2010 Mar 10; 28(11). PMID: 20212256
Highly Cited.
Association Between Out-Of-Pocket Costs, Race/Ethnicity, and Adjuvant Endocrine Therapy Adherence Among Medicare Patients With Breast Cancer.
Albert J Farias, Xianglin L Du.
J Clin Oncol, 2016 Dec 31; 35(1). PMID: 28034069    Free PMC article.
Racial disparities in omission of oncotype DX but no racial disparities in chemotherapy receipt following completed oncotype DX test results.
David J Press, Abiola Ibraheem, +3 authors, Dezheng Huo.
Breast Cancer Res Treat, 2017 Nov 29; 168(1). PMID: 29181717
Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer.
Joseph A Sparano, Robert J Gray, +27 authors, George W Sledge.
N Engl J Med, 2018 Jun 05; 379(2). PMID: 29860917    Free PMC article.
Highly Cited.
Underlying causes of the black-white racial disparity in breast cancer mortality: a population-based analysis.
Idan Menashe, William F Anderson, Ismail Jatoi, Philip S Rosenberg.
J Natl Cancer Inst, 2009 Jul 09; 101(14). PMID: 19584327    Free PMC article.
Treatment quality and outcomes of African American versus white breast cancer patients: retrospective analysis of Southwest Oncology studies S8814/S8897.
Dawn L Hershman, Joseph M Unger, +5 authors, Kathy S Albain.
J Clin Oncol, 2009 Mar 25; 27(13). PMID: 19307504    Free PMC article.
Age-related crossover in breast cancer incidence rates between black and white ethnic groups.
William F Anderson, Philip S Rosenberg, +2 authors, Ruth M Pfeiffer.
J Natl Cancer Inst, 2008 Dec 11; 100(24). PMID: 19066264    Free PMC article.
21-Gene Recurrence Score and Locoregional Recurrence in Node-Positive/ER-Positive Breast Cancer Treated With Chemo-Endocrine Therapy.
Eleftherios P Mamounas, Qing Liu, +14 authors, Norman Wolmark.
J Natl Cancer Inst, 2017 Jan 27; 109(4). PMID: 28122895    Free PMC article.
Racial Differences in 21-Gene Recurrence Scores Among Patients With Hormone Receptor-Positive, Node-Negative Breast Cancer.
Andreana N Holowatyj, Michele L Cote, +5 authors, Kristen S Purrington.
J Clin Oncol, 2018 Jan 18; 36(7). PMID: 29341832    Free PMC article.
Referral, receipt, and completion of chemotherapy in patients with early-stage breast cancer older than 65 years and at high risk of breast cancer recurrence.
Diana S M Buist, Jessica Chubak, +9 authors, Rebecca A Silliman.
J Clin Oncol, 2009 Aug 19; 27(27). PMID: 19687341    Free PMC article.
Socioeconomic disparities in health: pathways and policies.
Nancy E Adler, Katherine Newman.
Health Aff (Millwood), 2002 Mar 20; 21(2). PMID: 11900187
Highly Cited. Review.
21-Gene recurrence scores: racial differences in testing, scores, treatment, and outcome.
Mary Jo Lund, Marina Mosunjac, +7 authors, Ruth M O'Regan.
Cancer, 2011 Jul 02; 118(3). PMID: 21720988
The effect of marital status on breast cancer-related outcomes in women under 65: A SEER database analysis.
Leslie Hinyard, Lorinette Saphire Wirth, Jennifer M Clancy, Theresa Schwartz.
Breast, 2016 Dec 25; 32. PMID: 28012410
Clinical relevance of the 21-gene Recurrence Score® assay in treatment decisions for patients with node-positive breast cancer in the genomic era.
Eleftherios P Mamounas, Christy A Russell, +2 authors, Kathy S Albain.
NPJ Breast Cancer, 2018 Aug 30; 4. PMID: 30155517    Free PMC article.
Breast cancer stage variation and survival in association with insurance status and sociodemographic factors in US women 18 to 64 years old.
Christine D Hsu, Xiaoyan Wang, +2 authors, Kimberly J Johnson.
Cancer, 2017 Apr 26; 123(16). PMID: 28440864
Racial Differences in PAM50 Subtypes in the Carolina Breast Cancer Study.
Melissa A Troester, Xuezheng Sun, +16 authors, Charles M Perou.
J Natl Cancer Inst, 2017 Sep 02; 110(2). PMID: 28859290    Free PMC article.
Racial variation in adjuvant chemotherapy initiation among breast cancer patients receiving oncotype DX testing.
Megan C Roberts, Morris Weinberger, +5 authors, Stephanie B Wheeler.
Breast Cancer Res Treat, 2015 Jul 29; 153(1). PMID: 26216535    Free PMC article.
Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial.
Kathy S Albain, William E Barlow, +20 authors, Breast Cancer Intergroup of North America.
Lancet Oncol, 2009 Dec 17; 11(1). PMID: 20005174    Free PMC article.
Highly Cited.
Racial Differences in Adjuvant Endocrine Therapy Use and Discontinuation in Association with Mortality among Medicare Breast Cancer Patients by Receptor Status.
Albert J Farias, Xianglin L Du.
Cancer Epidemiol Biomarkers Prev, 2017 May 19; 26(8). PMID: 28515111    Free PMC article.
Missed opportunities: racial disparities in adjuvant breast cancer treatment.
Nina A Bickell, Jason J Wang, +5 authors, Amber A Guth.
J Clin Oncol, 2006 Mar 22; 24(9). PMID: 16549830
Highly Cited.