Inherited Breast Cancer in Nigerian Women

Abstract

PurposeAmong Nigerian women, breast cancer is diagnosed at later stages, is more frequently triple-negative disease, and is far more frequently fatal than in Europe or the United States. We evaluated the contribution of an inherited predisposition to breast cancer in this population.Patients and MethodsCases were 1,136 women with invasive breast cancer (mean age at diagnosis, 47.5 ± 11.5 years) ascertained in Ibadan, Nigeria. Patients were selected regardless of age at diagnosis, family history, or prior genetic testing. Controls were 997 women without cancer (mean age at interview, 47.0 ± 12.4 years) from the same communities. BROCA panel sequencing was used to identify loss-of-function mutations in known and candidate breast cancer genes.ResultsOf 577 patients with information on tumor stage, 86.1% (497) were diagnosed at stage III (241) or IV (256). Of 290 patients with information on tumor hormone receptor status and human epidermal growth factor receptor 2, 45.9% (133) had triple-negative breast cancer. Among all cases, 14.7% (167 of 1,136) carried a loss-of-function mutation in a breast cancer gene: 7.0% in BRCA1, 4.1% in BRCA2, 1.0% in PALB2, 0.4% in TP53, and 2.1% in any of 10 other genes. Odds ratios were 23.4 (95% CI, 7.4 to 73.9) for BRCA1 and 10.3 (95% CI, 3.7 to 28.5) for BRCA2. Risks were also significantly associated with PALB2 (11 cases, zero controls; P = .002) and TP53 (five cases, zero controls; P = .036). Compared with other patients, BRCA1 mutation carriers were younger (P < .001) and more likely to have triple-negative breast cancer (P = .028).ConclusionAmong Nigerian women, one in eight cases of invasive breast cancer is a result of inherited mutations in BRCA1, BRCA2, PALB2, or TP53, and breast cancer risks associated with these genes are extremely high. Given limited resources, prevention and early detection services should be especially focused on these highest-risk women.

USPSTF Recommendations for BRCA1 and BRCA2 Testing in the Context of a Transformative National Cancer Control Plan

“…and BRCA2 mutations in a cohort of Nigerian patients with breast cancer, and mutation rates as high as 25% are reported in patients with breast and ovarian cancer in India. 7,8 These rates are comparable to the BRCA1 and BRCA2 mutation rates initially characterized in patients of Ashkenazi ancestry with breast cancer. Large biobanking studies of unselected general populations are also finding higher frequencies of BRCA1 and BRCA2 mutations than expected.…”

BRCA1andBRCA2pathogenic sequence variants in women of African origin or ancestry

“…Note that only 11 published studies were found that included male BRCA1/2 PSV carriers, but no additional BRCA1/2 PSVs were identified from these reports. Forty‐eight studies were included in the present report: 16 studies of Sub‐Saharan Africans (Awadelkarim et al, ; Biunno et al, ; Diez et al, ; Elimam et al, ; Fackenthal et al, ; Fackenthal et al, ; Francies et al, ; Gao et al, ; Luyeye Mvila et al, ; Stoppa‐Lyonnet et al, ; van der Merwe et al, ; Zhang et al, ; Zhang et al, ; Zhang, Fackenthal, Huo, Zheng, & Olopade, ; Zheng et al, ; Zoure et al, ), 27 of African Americas (Arena et al, ; Arena et al, ; Arena et al, ; Castilla et al, ; Churpek et al, ; Dangel et al, ; Futreal et al, ; Ganguly, Dhulipala, Godmilow, & Ganguly, ; Q. Gao, Neuhausen, Cummings, Luce, & Olopade, ; Q. Gao, Sveen, Cummings, & Olopde, ; Q. Gao et al, ; Gayol et al, ; Haffty et al, ; Hall et al, ; John et al, ; Kanaan et al, ; Kedar‐Barnes et al, ; Lynce et al, ; Martin et al, ; Miki et al, ; Nanda et al, ; Olopade et al, ; Pal et al, ; Pal et al, ; Pal, Permuth‐Wey, Holtje, & Sutphen, ; Panguluri et al, ; Shen et al, ; Sutphen & Ferlita, ; Whitfield‐Broome, Dunston, & Brody, ), and three of Afro‐Caribbean populations (Akbari et al, ; Donenberg et al, ; Donenberg et al, ) and one study reporting SRAA of unspecified geography (Hall et al, ). From these papers, we identified 414 BRCA1 and 187 BRCA2 PSVs, and 108 unique BRCA1 and 103 unique BRCA2 PSVs.…”

“…Note that only 11 published studies were found that included male BRCA1/ 2 PSV carriers, but no additional BRCA1/2 PSVs were identified from these reports. Forty-eight studies were included in the present report: 16 studies of Sub-Saharan Africans (Awadelkarim et al, 2007;Biunno et al, 2014;Diez et al, 2011;Elimam et al, 2017;Fackenthal et al, 2005;Fackenthal et al, 2012;Francies et al, 2015;Gao et al, 2000;Luyeye Mvila et al, 2014;Stoppa-Lyonnet et al, 1997;van der Merwe et al, 2012;Zhang et al, 2009;Zhang et al, 2012;Zhang, Fackenthal, Huo, Zheng, & Olopade, 2010;Zheng et al, 2018;Zoure et al, 2018), 27 of African Americas (Arena et al, 1996);Arena et al, 1997;Arena et al, 1998;Castilla et al, 1994;Churpek et al, 2015;Dangel et al, 1999;Futreal et al, 1994;Ganguly, Dhulipala, Godmilow, & Ganguly, 1998;Q. Gao, Neuhausen, Cummings, Luce, & Olopade, 1997;Q.…”

First person profile: Olufunmilayo “Funmi” Olopade, MD, FACP

“…Using state‐of‐the‐art genomic technologies for their analysis, the study’s multinational team published its findings from more than 20 years of research in the August 21, 2018, issue of Journal of Clinical Oncology . Of the 1136 women with invasive breast cancer who were enrolled in the study, the disease among Nigerian women who had mutations in their breast cancer genes was far more advanced than in women in the United States with the same genetic mutations, the authors note.…”