Recent studies from high-risk countries such as the US, Denmark and Ireland have shown rising incidence rates of hormone receptor (HR)-positive and falling rates of HR-negative breast cancers (BC). However, it remains unclear whether a similar pattern occurs in low-risk countries. Detailed clinical and risk factor data were collected from 2,977 female invasive BC patients (≥20 years) in Sarawak General Hospital, Malaysia, representing 93% of the population. The population-at-risk was obtained from the Department of Statistics Malaysia. Secular trends in age-standardized incidence rates were assessed using estimated average annual percent changes. Associations between established BC risk factors and tumor subtypes defined by HR or joint human epidermal growth factor receptor 2 (HR/HER2) status were examined by case-case comparisons using logistic regression. From 2006 to 2015, incidence rates increased for HR-positive cancers by 4.46%/year (95% CI = 2.19-6.78) and decreased for HR-negative cancers by 2.29%/year (95% CI = -4.31 to -0.24). When further stratified by HER2, the most contrasting difference in linear trends was observed between HR+/HER2- and HR-/HER2- subtypes. After controlling for potential confounders, cases with excess body weight (ORoverweight vs. normal = 0.82; 95% CI = 0.69-0.98; ORobese vs. normal = 0.62; 95% CI = 0.48-0.80), later age at first birth (OR≥26 years vs. <23 years = 0.82; 95% CI = 0.66-1.02), nulliparity (ORnulliparous vs. <23 years = 0.74; 95% CI = 0.59-0.94) and never-breastfeeding (ORnever vs. ever = 0.73; 95% CI = 0.55-0.97) were less frequent among HR-negative cases than among HR-positive cases. Diverging incidence trends by HR expression were similar in Sarawak and Western countries, possibly reflecting changes in the prevalence of risk factors with opposing effects by tumor subtypes in low- and high-risk populations.
Hormone receptor (HR) negative breast cancers are relatively more common in low-risk than high-risk countries and/or populations. However, the absolute variations between these different populations are not well established given the limited number of cancer registries with incidence rate data by breast cancer subtype. We, therefore, used two unique population-based resources with molecular data to compare incidence rates for the 'intrinsic' breast cancer subtypes between a low-risk Asian population in Malaysia and high-risk non-Hispanic white population in the National Cancer Institute's surveillance, epidemiology, and end results 18 registries database (SEER 18). The intrinsic breast cancer subtypes were recapitulated with the joint expression of the HRs (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor-2 (HER2). Invasive breast cancer incidence rates overall were fivefold greater in SEER 18 than in Malaysia. The majority of breast cancers were HR-positive in SEER 18 and HR-negative in Malaysia. Notwithstanding the greater relative distribution for HR-negative cancers in Malaysia, there was a greater absolute risk for all subtypes in SEER 18; incidence rates were nearly 7-fold higher for HR-positive and 2-fold higher for HR-negative cancers in SEER 18. Despite the well-established relative breast cancer differences between low-risk and high-risk countries and/or populations, there was a greater absolute risk for HR-positive and HR-negative subtypes in the US than Malaysia. Additional analytical studies are sorely needed to determine the factors responsible for the elevated risk of all subtypes of breast cancer in high-risk countries like the United States.