Receptor-defined subtypes of breast cancer in indigenous populations in Africa: a systematic review and meta-analysis

Abstract

Background: Breast cancer is the most common female cancer in Africa. Receptor-defined subtypes are a major determinant of treatment options and disease outcomes but there is considerable uncertainty regarding the frequency of poor prognosis estrogen receptor (ER) negative subtypes in Africa. We systematically reviewed publications reporting on the frequency of breast cancer receptor-defined subtypes in indigenous populations in Africa.

Methods and findings: Medline, Embase, and Global Health were searched for studies published between 1st January 1980 and 15th April 2014. Reported proportions of ER positive (ER+), progesterone receptor positive (PR+), and human epidermal growth factor receptor-2 positive (HER2+) disease were extracted and 95% CI calculated. Random effects meta-analyses were used to pool estimates. Fifty-four studies from North Africa (n=12,284 women with breast cancer) and 26 from sub-Saharan Africa (n=4,737) were eligible. There was marked between-study heterogeneity in the ER+ estimates in both regions (I2>90%), with the majority reporting proportions between 0.40 and 0.80 in North Africa and between 0.20 and 0.70 in sub-Saharan Africa. Similarly, large between-study heterogeneity was observed for PR+ and HER2+ estimates (I2>80%, in all instances). Meta-regression analyses showed that the proportion of ER+ disease was 10% (4%-17%) lower for studies based on archived tumor blocks rather than prospectively collected specimens, and 9% (2%-17%) lower for those with ≥ 40% versus those with <40% grade 3 tumors. For prospectively collected samples, the pooled proportions for ER+ and triple negative tumors were 0.59 (0.56-0.62) and 0.21 (0.17-0.25), respectively, regardless of region. Limitations of the study include the lack of standardized procedures across the various studies; the low methodological quality of many studies in terms of the representativeness of their case series and the quality of the procedures for collection, fixation, and receptor testing; and the possibility that women with breast cancer may have contributed to more than one study.

Conclusions: The published data from the more appropriate prospectively measured specimens are consistent with the majority of breast cancers in Africa being ER+. As no single subtype dominates in the continent availability of receptor testing should be a priority, especially for young women with early stage disease where appropriate receptor-specific treatment modalities offer the greatest potential for reducing years of life lost. Please see later in the article for the Editors' Summary.

Figure 1. Breast cancer ranking among women for (a) incidence and (b) mortality, Africa, 2012 .

Figure 2. Flow diagram detailing study identification, screening, and eligibility.

Many abstracts could fit into more than one exclusion category; these were allocated to the first eligible category in the order listed here.

Figure 3. Proportion of ER+, PR+, and HER2+ disease (ranked by increasing magnitude), North and sub-Saharan Africa.

IBC, inflammatory breast cancer; LABC, non-IBC locally advanced breast cancer; N-IBC, non-inflammatory breast cancer. *These studies provided only a combined HR estimate for tumors that were either ER+ or PR+ or ER+ and/or PR+ ([29]; [43]; [52]; [63]; [64]; [71]). These HR estimates were included in both the ER+ and PR+ plots.

Figure 4. Proportion of ER+ disease by study design, North and sub-Saharan Africa.

IBC, inflammatory breast cancer; LABC, non-IBC locally advanced breast cancer; N-IBC, non-inflammatory breast cancer. *These studies provided only a combined HR estimate for tumors that were either ER+ or PR+ or ER+ and/or PR+ ([29]; [43]; [52]; [63]; [64]; [71]).

Figure 5. Proportion of ER+ disease by year of diagnosis, North and sub-Saharan Africa.

IBC: inflammatory breast cancer; LABC: non-IBC locally advanced breast cancer; N-IBC: non-inflammatory breast cancer. *These studies provided only a combined HR estimate for tumors that were either ER+ or PR+ or ER+ and/or PR+ ([29]; [43]; [52]; [63]; [64]; [71]).

Figure 6. Proportion of ER+ disease by tumor grade, North and sub-Saharan Africa.

IBC, inflammatory breast cancer; LABC, non-IBC locally advanced breast cancer; N-IBC: non-inflammatory breast cancer. *These studies provided only a combined HR estimate for tumors that were either ER+ or PR+ or ER+ and/or PR+ ([43]; [52]; [63]; [64]; [71]).

Figure 7. Proportion of ER+ disease by timing of receptor testing, North and sub-Saharan Africa.

IBC, inflammatory breast cancer; LABC, non-IBC locally advanced breast cancer; N-IBC, non-inflammatory breast cancer. *These studies provided only a combined HR estimate for tumors that were either ER+ or PR+ or ER+ and/or PR+ ([29]; [43]; [52]; [63]; [64]; [71]).

Figure 8. Proportion of ER+ disease by sub-regions within North and sub-Saharan Africa.

IBC, inflammatory breast cancer; LABC, non-IBC locally advanced breast cancer; N-IBC, non-inflammatory breast cancer. North-Western Africa: Morocco, Algeria, and Tunisia; North-Eastern Africa: Egypt, Sudan, and Libya; Eastern Africa: Kenya, Uganda, Tanzania, and Madagascar; Western Africa: Ghana, Mali, Nigeria, and Senegal; Sothern Africa: South Africa. *These studies provided only a combined HR estimate for tumors that were either ER+ or PR+ or ER+ and/or PR+ ([29]; [43]; [52]; [63]; [64]; [71]). **Lower limit of 95% confidence interval for I² statistic truncated at 0.

Figure 9. Frequency of tumor subtypes by year of diagnosis, grade, and timing of receptor testing.

Figure 10. International and ethnic comparisons in the proportion of ER+ disease.

IBC, inflammatory breast cancer; N-IBC, non-inflammatory breast cancer; Nk, information not given in the original paper; SEER, Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, US (data downloaded from using the same methods as in [9]); SSA, sub-Saharan Africa.