Breast cancer risk factors and outcome: a global perspective

Abstract

The burden of breast cancer had been increasing in Asia. However, little is known regarding the presentation, management and outcome of breast cancer among multi-ethnic Asian women. Asian ethnicities, lifestyles, health beliefs, and even life expectancies are substantially different from those of western women, and each of these may play a distinct role in breast cancer presentation, management and prognosis. A major part of this thesis focuses on research pertaining to breast cancer in Asian women, using data from the Singapore-Malaysia Breast Cancer Registry. This registry comprises two hospital-based breast cancer databases (University Malaya Medical Center, Malaysia and National University Hospital, Singapore) which were merged to include more than 5000 breast cancer patients diagnosed between 1990 and 2007. The registry is managed by the Singapore-Malaysia Breast Cancer Working Group (SMBCWG), which is an international, multidisciplinary collaboration between epidemiologists, breast surgeons and oncologists from Singapore and Malaysia. Asian women with breast cancer were approximately a decade younger at diagnosis (median: 49 years), presented with larger tumors, and at later stages of disease, compared to their Western counterparts. About 10% of them had metastatic breast cancer at initial presentation. In this subgroup, it was found that surgical excision of the primary tumor is associated with a survival advantage, similar to findings of studies conducted in affluent Western settings. In patients with early breast cancer, a web-based prognostic tool which predicts the 10-year breast cancer outcomes and efficacy of adjuvant therapy; Adjuvant! Online, was validated. This tool which had only been validated in Caucasian settings, was found to be performing fairly well in terms of discriminative performance (area under Receiver Operating Characteristic curve: 0.73) in Asian women. However, the model was overoptimistic (by 6.7% in the overall cohort) particularly in women under 40 years and of Malay ethnicity, where survival was overestimated by approximately 20% and 15%, respectively. Adjuvant! Online may therefore need further adaptation to improve its utility in Asian settings. As ethnicity had been implicated as a prognostic factor for breast cancer survival in the West, the impact of ethnicity on survival after breast cancer in multiethnic Asian women comprising the Malays, Chinese and Indians, was evaluated. Malay patients were significantly younger at diagnosis, presented more often with unfavorable characteristics i.e. larger tumors, lymph node involvement, hormone receptor negative and poorly differentiated tumors, and were less likely to receive complete loco-regional treatment. Five-year overall survival following breast cancer was highest in the Chinese, followed by the Indians and lowest in the Malays. Compared to the Chinese, Malay ethnicity was associated with 60% higher risk of mortality independent of demographic factors, TNM stage, tumor characteristics and treatment. This survival disparity maybe explained by variations in tumor biology, psychosocial and cultural factors, treatment responsiveness and lifestyle after diagnosis of breast cancer. Based on the studies described in this thesis, it seems that Western derived knowledge on breast cancer may not be always applicable to other populations such as in Asia. Therefore, extending breast cancer research onto different Asian settings is very important.