In a systematic review and meta-analysis, Isabel dos Santos Silva and colleagues estimate the prevalence of receptor-defined subtypes of breast cancer in North Africa and sub-Saharan Africa.
Please see later in the article for the Editors' Summary
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.
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
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.
Why Was This Study Done?
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.
What Did the Researchers Do and Find?
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 samples), the overall pooled proportions of ER+ and triple negative tumors were 0.59 and 0.21, respectively.
What Do These Findings Mean?
Although these findings highlight the scarcity of data on hormone receptor and HER2 status in breast cancers in indigenous African populations, they provide new information about the distribution of breast cancer subtypes in Africa. Specifically, these findings suggest that although slightly more than half of breast cancers in Africa are ER+, no single subtype dominates. They also suggest that the distribution of receptor-defined breast cancer subtypes in Africa is similar to that found in Western populations. The accuracy of these findings is likely to be affected by the low methodological quality of many of the studies and the lack of standardized procedures. Thus, large well-designed studies are still needed to accurately quantify the distribution of various breast cancer subtypes across Africa. In the meantime, the current findings support the introduction of routine receptor testing across Africa, especially for young women with early stage breast cancer in whom the potential to improve survival and reduce the years of life lost by knowing the receptor status of an individual's tumor is greatest.
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001720.
This study is further discussed in a PLOS Medicine
Perspective by Sulma i Mohammed
The US National Cancer Institute (NCI) provides comprehensive information about cancer (in English and Spanish), including detailed information for patients and professionals about breast cancer including an online booklet for patients
Cancer Research UK, a not-for profit organization, provides information about cancer; its detailed information about breast cancer includes sections on tests for hormone receptors and HER2 and on treatments that target hormone receptors and treatments that target HER2
Breastcancer.org is a not-for-profit organization that provides up-to-date information about breast cancer (in English and Spanish), including information on hormone receptor status and HER2 status
The UK National Health Service Choices website has information and personal stories about breast cancer; the not-for profit organization Healthtalkonline also provides personal stories about dealing with breast cancer