To understand the current knowledge base of the global burden of premenopausal and postmenopausal breast cancer, we searched PubMed, with no date restrictions, with the terms: (“pre-menopausal breast cancer” OR “post-menopausal breast cancer” OR “early onset breast cancer”) AND (“global” OR “international”) AND (“incidence” OR “mortality” OR “trends”). We restricted our search to articles published in English. The results of this search provided evidence for aetiological and survival differences between premenopausal and postmenopausal breast cancer, and an indication of global variation in incidence and mortality.
Added value of this study
To our knowledge, this is the first study to investigate the global burden and trends of premenopausal and postmenopausal breast cancer. We highlight variations in the premenopausal and postmenopausal breast cancer incidence and mortality burden by development level and geographical region, and the increasing burden of premenopausal and postmenopausal breast cancer worldwide. Notable findings include increases in incidence exclusively in premenopausal ages in high-income countries, and that the largest increases in postmenopausal breast cancer were primarily in countries undergoing socioeconomic transitions. Finally, case-fatality of premenopausal and postmenopausal breast cancer was greatest in low-income and middle-income countries (LMICs), highlighting inequities in the mortality burden worldwide.
Implications of all the available evidence
Our findings will be useful for health-care planning, because early diagnosis and access to breast cancer treatment remain crucial in LMICs. Moreover, they will inform prevention initiatives, because we suggest that efforts seeking to decrease obesity and alcohol consumption, and increase physical activity and breastfeeding, are warranted in all world regions to curb the future breast cancer burden.
We aimed to quantify the burden of breast cancer incidence and mortality in 2018 and to assess the long-term trends in breast cancer incidence for the period 1998–2012 in 41 countries, by menopausal status. Our objective is to inform future research and assist policy makers with cancer control initiatives.
Methods
Study population
We did a population-based study to assess the global burden of breast cancer incidence and mortality in 2018 and to investigate incidence trends over a 15-year period. Our study population comprised women diagnosed with invasive breast cancer, defined with the International Classification of Diseases version 10 code C50. We classified menopausal status using age at diagnosis or death as a proxy, because cancer registries do not routinely obtain menopausal information. We defined premenopausal cases and deaths as those arising in women younger than 50 years; postmenopausal cases and deaths were classified as those that occurred from age 50 years onwards. We chose the cutoff point of 50 years because, internationally, the average age of natural menopause is 45–55 years5 so we selected the mean of 50 years.
Data sources
To assess variations in the global burden of premenopausal and postmenopausal breast cancer, we used the GLOBOCAN Cancer Today database from the International Agency for Research on Cancer (IARC). GLOBOCAN provides estimates of breast cancer incidence and mortality for 185 countries by sex and age group, with the most recent estimates applying to 2018. Estimates are also provided by continent, UN subregional group,6 and the UNDP's four-level human development index (HDI), which is a summary measure that includes life expectancy, expected and mean years of schooling, and gross national income.7
To assess long-term trends in premenopausal and postmenopausal breast cancer, we used cancer incidence data from IARC's Cancer in Five Continents plus (CI5plus) database, which includes consecutive annual incidence data from 108 national or subnational cancer registries, representing 43 countries, for the longest period available (up to 2012).8 To include countries that spanned globally representative geographies and resource levels, we used the 15-year period of 1998–2012 to estimate trends in incidence, because data were predominantly only from high-income countries before 1998. Ultimately, incidence trends were estimated for 41 countries, of which 18 were represented nationally and 23 were represented subnationally. Because disparities exist in cancer incidence in the USA by ethnic origin,9 results for the USA are provided in the categories white, black, Native (American Indian and Alaskan Native), and Asian (Asian and Pacific Islander).
Statistical analysis
We calculated truncated age-standardised incidence rates (ASIRs) and age-standardised mortality rates (ASMRs) per 100 000 using the world standard population developed by Segi10 and modified by Doll and Cook.11 We estimated case-fatality percentages by dividing the ASMR by the ASIR and multiplying by 100. To assess temporal trends, we calculated the average annual percent change (AAPC) and 95% CI by fitting a generalised linear regression model for the natural logarithm of the ASIR and year as a linear trend, with a Gaussian distribution and identity link function. All statistical analyses were done using Stata version 13.0.
Role of the funding source
No funding was received for this study. The corresponding author had full access to all data in the study and had final responsibility for the decision to submit for publication.
Results
Overall, an estimated 2·1 million breast cancer cases were diagnosed in women worldwide in 2018, equating to an ASIR of 19·7 cases of premenopausal breast cancer per 100 000 and 152·6 cases of postmenopausal breast cancer per 100 000 (table). A great burden of premenopausal breast cancer was noted in low-income and middle-income countries (LMICs). For example, 55·2% of total breast cancer cases in low HDI countries were premenopausal; this percentage decreased with each increase in development level, with only 20·7% of breast cancer cases occurring before age 50 years in very high HDI countries. Despite this decrease, very high HDI countries had the highest ASIRs for both premenopausal (30·6 per 100 000) and postmenopausal (253·6 per 100 000) breast cancer, approximately double the corresponding ASIRs in medium and low HDI countries. For postmenopausal breast cancer, a linear relation was noted between the ASIR and HDI level, when incidence rose with each increase in HDI level. However, the relation between premenopausal ASIR and HDI was not as explicit, with the lowest ASIR seen in medium HDI countries (14·0 per 100 000), and similar ASIRs noted in low and high HDI countries (18·1 and 19·6 per 100 000, respectively).
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