Receptor-Defined Subtypes of Breast Cancer in Indigenous Populations in Africa: A Systematic Review and Meta-Analysis

Abstract

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. 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 Please see later in the article for the Editors' Summary Breast cancer is the commonest female tumor in Africa and death rates from the disease in some African countries are among the highest in the world. Breast cancer begins when cells in the breast acquire genetic changes that allow them to grow uncontrollably and to move around the body. When a breast lump is found (by mammography or manual examination), a few cells are collected from the lump (a biopsy) to look for abnormal cells and to test for the presence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) on the cells. The hormones estrogen and progesterone promote the growth of normal breast cells and of ER+ and PR+ breast cancer cells. HER2 also controls the growth of breast cells. The receptor status of breast cancer is a major determinant of treatment options and prognosis (likely outcome). ER+ tumors, for example, are more receptive to hormonal therapy and have a better prognosis than ER− tumors, whereas HER2+ tumors, which make large amounts of HER2, are more aggressive than HER2− tumors. Breast cancer is treated by surgically removing the lump or the whole breast (mastectomy) if the tumor has already spread, before killing any remaining cancer cells with chemotherapy or radiotherapy. In addition, ER+, PR+, and HER2+ tumors are treated with drugs that block these receptors (including tamoxifen and trastuzumab), thereby slowing breast cancer growth. ER+ tumors predominate in white women but the proportion of ER+ tumors among US-born black women is slightly lower. The frequency of different receptor-defined subtypes of breast cancer in indigenous populations in Africa is currently unclear but policy makers need this information to help them decide whether routine receptor status testing should be introduced across Africa. Because receptor status is a major determination of treatment options and outcomes, it would be more important to introduce receptor testing if all subtypes are present in breast cancers in indigenous African women and if no one subtype dominates than if most breast cancers in these women are ER+. In this systematic review (a study that uses pre-defined criteria to identify all the research on a given topic) and meta-analysis (a statistical approach that combines the results of several studies), the researchers examine the distribution of receptor-defined breast cancer subtypes in indigenous populations in Africa. The researchers identified 54 relevant studies from North Africa involving 12,284 women with breast cancer (mainly living in Egypt or Tunisia) and 26 studies from sub-Saharan Africa involving 4,737 women with breast cancer (mainly living in Nigeria or South Africa) and used the data from these studies to calculate the proportions of ER+, PR+, and HER2+ tumors (the number of receptor-positive tumors divided by the number of tumors with known receptor status) across Africa. The proportion of ER+ tumors varied markedly between studies, ranging between 0.40 and 0.80 in North Africa and between 0.20 and 0.70 in sub-Saharan Africa. Among prospectively collected samples (samples collected specifically for receptor-status testing; studies that determined the receptor status of breast cancers using stored samples reported a lower proportion of ER+ disease than studies that used prospectively collected...