Intrinsic Breast Tumor Subtypes, Race, and Long-Term Survival in the Carolina Breast Cancer Study

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Clinical Cancer Research (Impact Factor: 8.72). 12/2010; 16(24):6100-10. DOI: 10.1158/1078-0432.CCR-10-1533
Source: PubMed

ABSTRACT Previous research identified differences in breast cancer-specific mortality across 4 intrinsic tumor subtypes: luminal A, luminal B, basal-like, and human epidermal growth factor receptor 2 positive/estrogen receptor negative (HER2(+)/ER(-)).
We used immunohistochemical markers to subtype 1,149 invasive breast cancer patients (518 African American, 631 white) in the Carolina Breast Cancer Study, a population-based study of women diagnosed with breast cancer. Vital status was determined through 2006 using the National Death Index, with median follow-up of 9 years.
Cancer subtypes luminal A, luminal B, basal-like, and HER2(+)/ER(-) were distributed as 64%, 11%, 11%, and 5% for whites, and 48%, 8%, 22%, and 7% for African Americans, respectively. Breast cancer mortality was higher for participants with HER2(+)/ER(-) and basal-like breast cancer compared with luminal A and B. African Americans had higher breast cancer-specific mortality than whites, but the effect of race was statistically significant only among women with luminal A breast cancer. However, when compared with the luminal A subtype within racial categories, mortality for participants with basal-like breast cancer was higher among whites (HR = 2.0, 95% CI: 1.2-3.4) than African Americans (HR = 1.5, 95% CI: 1.0-2.4), with the strongest effect seen in postmenopausal white women (HR = 3.9, 95% CI: 1.5-10.0).
Our results confirm the association of basal-like breast cancer with poor prognosis and suggest that basal-like breast cancer is not an inherently more aggressive disease in African American women compared with whites. Additional analyses are needed in populations with known treatment profiles to understand the role of tumor subtypes and race in breast cancer mortality, and in particular our finding that among women with luminal A breast cancer, African Americans have higher mortality than whites.

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Available from: Katie M O'Brien, Mar 30, 2015
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    • "However, results of previous studies have indicated that variations of subtypes among populations of African, Asian and Caucasian ancestry have also a biological basis [14-16]. Americans of African ancestry have decreased incidence of breast cancer, but more frequently, they have aggressive, invasive high- grade TN tumors at younger age with increased mortality rate when compared to patients of Caucasian ancestry [13,15,17,18]. "
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    ABSTRACT: Background The frequencies of molecular breast cancer subtypes vary among different human populations. The Northeastern region of Brazil has a mixed population of African, Indigenous and European ancestry. This retrospective study investigated breast cancer subtypes and applied therapies in a public hospital of Northeastern Brazil. Methods Data of 633 patients with invasive breast cancer from 2005 to 2011 were obtained from medical records. Status of hormone receptor (HR), HER2 and Ki67 expression index of 269 out of 633 patients were used to define subtypes of Luminal A and B, HER2 and triple negative (TN) breast cancer. Expression index of Ki67 ≥ 14% was applied to distinguish Luminal A from Luminal B subtypes. Results Overall, 185 (68.77%) and 132 (49.07%) patients showed positive hormone receptor (HR+) and positive HER2 (HER2+) tumors. The mean age ranged from 53.33 to 58.25 years for patients with tumors of Luminal B and Luminal A subtypes, respectively (p = 0.0182). In general, 67.39% of patients with TN tumors aged over 50 and 19.57% aged between 31 and 40 years (p = 0.0046). The rate of small tumors (T1: ≤ 2.0 cm) varied from 22.73% to 52.46% for TN and Luminal A subtypes (p = 0.0088). The rate of high graded (G3) tumors was increased for HER2 and TN subtypes (35.29% and 34.28%) compared to Luminal A and Luminal B subtypes (3.92% and 12.62%), respectively (p < 0.0001). The five-year survival rate ranged from 92.86% to 75.00%, for Luminal A, HER2 and TN subtypes, respectively (HR: 0.260 to 1.015; 95% CI: 0.043 to 3.594; p = 0.2589). Patients with HER2 positive (HER2+) breast tumors did not receive immunotherapy and chemotherapy application varied from 54.84% to 86.49% for Luminal A and HER2 subtypes, respectively (p = 0.0131). Conclusions The results of this study revealed a high percentage of HER2+ breast tumors and an increased rate of patients with TN tumors aged over 50 years. This emphasizes the need for establishing immunotherapy as an additional therapeutic option to improve clinical outcomes for patients with HER2+ tumors and to investigate the risk factors of TN breast cancer.
    BMC Women's Health 09/2014; 14(1):110. DOI:10.1186/1472-6874-14-110 · 1.50 Impact Factor
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    • "In the second part of our study analyzing survival outcome with breast cancer intrinsic subtypes, our data from a cohort with known intrinsic subtypes provided results similar to those of previous studies in which the triple-negative subtype showed the worst outcome.17,18,19 Furthermore, to isolate the prognostic influence of the subtype from the effect of tumor burden, we conducted survival analysis using the subtypes in stage I or stages II and III. "
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    ABSTRACT: Purpose The prognosis of breast cancer has been consistently improving. We analyzed our cohort of breast cancer patients with a long-term follow up at a single center over time. Materials and Methods A total of 1889 patients with known cancer stages were recruited and analyzed between January 1991 and December 2005. Patients were classified according to the time periods (1991-1995; 1996-2000; 2001-2005). To determine intrinsic subtypes, 858 patients whose human epidermal growth receptor-2 status and Ki67 were reported between April 2004 and December 2008 were also analyzed. Results At a median follow up of 9.1 years, the 10-year overall survival (OS) rate was 80.5% for the entire cohort. On multivariate analysis for OS and recurrence-free survival (RFS), the time period was demonstrated to be a significant factor independent of conventional prognostic markers. In the survival analysis performed for each stage (I to III), OS and RFS significantly improved according to the time periods. Adoption of new agents in adjuvant chemotherapy and endocrine therapy was increased according to the elapsed time. In the patients with known subtypes, OS and RFS significantly differed among the subtypes, and the triple-negative subtype showed the worst outcome in stages II and III. Conclusion In the Korean breast cancer cohort with a long-term follow up, our data show an improved prognosis over the past decades, and harbor the contribution of advances in adjuvant treatment. Moreover, we provided new insight regarding comparison of the prognostic impact between the tumor burden and subtypes.
    Yonsei Medical Journal 09/2014; 55(5):1187-95. DOI:10.3349/ymj.2014.55.5.1187 · 1.29 Impact Factor
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    • "These targeted approaches have improved prognosis and outcome among patients with ER, PR and/or HER2 positive breast carcinomas. Patients with triple negative breast cancer (TNBC) accounting for approximately 10% to 24% of all breast cancers [8] [9] [10] [11] [12], are excluded from the benefits of such targeted therapies, however [13]. "
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    ABSTRACT: Background: Triple negative breast carcinomas (TNBC) do not benefit from hormonal or Herceptin therapies. In search of novel therapeutic targets for TNBC, interest is escalating in a subset of these tumors that are androgen receptor (AR) positive with potential benefit from anti-androgen therapy. Against this background, the frequency of AR expression alone and in combination with other markers and morphologic features was assessed to identify TNBC subtypes for targeted therapy. Methods: 400 consecutive invasive mammary carcinomas with known estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and HER2 status were selected for study. The frequency of AR positivity alone or in combination with other markers was recorded with specific attention to the morphology of AR+ TNBCs. Ki67 was evaluated in selected group of cases. ASCO/CAP guidelines were used for interpretation of the various biomarkers. Results: Of the 400 tumors, 32 (8%) carcinomas were quadruple negative (ER-, PR-, AR-, Her2-), while 50 tumors (12.5%) were triple negative (ER-, PR-, Her2-); 18 (36%) of the triple negative tumors were AR positive and 10 (55%) of these were classic apocrine carcinomas. Fourteen cases, all apocrine carcinomas, were AR and Her2 positive. All 32 QN carcinomas were poorly differentiated and they had the highest Ki67 labeling index. Conclusion: The relatively high proportion of AR+ tumors (36%) among the 50 triple negative carcinomas is an important finding in support of routine assessment of AR in at least all TNBCs and apocrine carcinomas as a potential target for therapy.
    American Journal of Cancer Research 07/2014; 4(4):353-68. · 4.17 Impact Factor
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