Originally published as JCO Early Release 10.1200/JCO.2008.19.6873 on August 24 2009

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Population Differences in Breast Cancer: Survey in Indigenous African Women Reveals Over-Representation of Triple-Negative Breast Cancer

Dezheng Huo, Francis Ikpatt, Andrey Khramtsov, Jean-Marie Dangou, Rita Nanda, James Dignam, Bifeng Zhang, Tatyana Grushko, Chunling Zhang, Olayiwola Oluwasola, David Malaka, Sani Malami, Abayomi Odetunde, Adewumi O. Adeoye, Festus Iyare, Adeyinka Falusi, Charles M. Perou, Olufunmilayo I. Olopade

From the Department of Health Studies, and Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL; Institut Pasteur, Dakar, Sénégal; University of Ibadan, Ibadan; Usman Danfodio University Teaching Hospital, Sokoto; Ebonyi State University Teaching Hospital, Abakaliki, Nigeria; and University of North Carolina, Chapel Hill, NC.

Corresponding author: Olufunmilayo I. Olopade, MD, Center for Clinical Cancer Genetics and Global Health, Department of Medicine, Section of Hematology/Oncology, University of Chicago, 5841 S Maryland Ave, MC 2115, Chicago, IL 60637; e-mail: folopade{at}medicine.bsd.uchicago.edu.

Purpose Compared with white women, black women experience a disproportionate burden of aggressive breast cancer for reasons that remain unknown and understudied. In the first study of its kind, we determined the distribution of molecular subtypes of invasive breast tumors in indigenous black women in West Africa.

Patients and Methods The study comprised 507 patients diagnosed with breast cancer between 1996 and 2007 at six geographic regions in Nigeria and Senegal. Formalin-fixed and paraffin-embedded sections were constructed into tissue microarrays and immunostained with 15 antibodies. Five molecular subtypes were determined, and hierarchical cluster analysis was conducted to explore subgroups for unclassified cases.

Results The mean (± standard deviation) age of 378 patients in the first cohort was 44.8 ± 11.8 years, with the majority of women presenting with large (4.4 ± 2.0 cm) high-grade tumors (83%) in advanced stages (72% node positive). The proportions of estrogen receptor (ER) –positive, progesterone receptor–positive, and human epidermal growth factor receptor 2 (HER2) –positive tumors were 24%, 20%, and 17%, respectively. Triple negativity for these markers was predominant, including basal-like (27%) and unclassified subtype (28%). Other subtypes were luminal A (27%), luminal B (2%), and HER2 positive/ER negative (15%). The findings were replicated in the second cohort of 129 patients. The unclassified cases could be grouped into a bad prognosis branch, with expression of vascular endothelial growth factor, B-cell lymphoma extra-large protein, and Cyclin E, and a good prognosis branch, with expression of B-cell lymphoma protein 2 and Cyclin D1.

Conclusion These findings underscore the urgent need for research into the etiology and treatment of the aggressive molecular subtypes that disproportionately affect young women in the African diaspora.

D. Huo and F. Ikpatt contributed equally to the study.

Supported by the National Cancer Institute (Grants No. CA-RO1 89085-01A, P50-CA58223-09A1, P50 CA125183, P50 ES012382, and P30 CA14599-32), the Entertainment Industry National Women's Cancer Research Alliance, and the Breast Cancer Research Foundation.

Presented in part at the 2007 Annual Meeting of the American Association for Cancer Research, April 14-18, 2007, Los Angeles, CA; and at the 40th Annual Meeting of the American Society of Clinical Oncology, June 5-8, 2004, New Orleans, LA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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