Abstract

IntroductionDouble-peaked time distributions of the mortality hazard function have been reported for breast cancer patients from Western populations treated with mastectomy alone. These are thought to reflect accelerated tumour growth at micrometastatic sites mediated by angiogenesis after primary tumour removal as well as tumor dormancy. Similar data are not available for Asian populations. We sought to investigate whether differences exist in the pattern of mortality hazard function between Western breast cancer patients and their Asian counterparts in Singapore, which may suggest underlying differences in tumor biology between the two populations.MethodsWe performed a retrospective cohort study of female unilateral breast cancer patients diagnosed in Singapore between October 1994 and June 1999. Data regarding patient demographics, tumour characteristics and death were available. Overall survival curves were calculated using the Kaplan-Meier method. The hazard rate was calculated as the conditional probability of dying in a time interval, given that the patient was alive at the beginning of the interval. The life table method was used to calculate the yearly hazard rates.ResultsIn the 2,105 women identified, 956 patients (45.4%) had mastectomy alone. Demographic characteristics were as follows: 86.5% were Chinese, 45.2% were postmenopausal, 38.9% were hormone receptor positive, 54.6% were node negative and 44.1% had high histological grade. We observed a double-peaked mortality hazard pattern, with a first peak in mortality achieving its maximum between years 2 and 4 after mastectomy, and a second large peak in mortality during year 9. Analyses by subgroups revealed a similar pattern regardless of T stage, or node or menopausal status. This pattern was also noted in high-grade tumors but not in those that were well to moderately differentiated. The double-peaked pattern observed in Singaporean women was quantitatively and qualitatively similar to those reported in Western series.ConclusionOur study confirms the existence of a double-peaked process in Asian patients, and it gives further support to the tumour dormancy hypothesis after mastectomy.

Highlights

  • Double-peaked time distributions of the mortality hazard function have been reported for breast cancer patients from Western populations treated with mastectomy alone

  • These are thought to reflect accelerated tumour growth at micrometastatic sites mediated by angiogenesis after primary tumour removal as well as tumor dormancy

  • Our study confirms the existence of a doublepeaked process in Asian patients, and it gives further support to the tumour dormancy hypothesis after mastectomy

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Summary

Introduction

Double-peaked time distributions of the mortality hazard function have been reported for breast cancer patients from Western populations treated with mastectomy alone. The time to event curve describes the cumulative event-free time distribution at a given point after accrual in clinical trials It is widely reported throughout the oncology literature, it does not give direct information regarding changes in event probability over time. It is somewhat counterintuitive that independent researchers have discovered double-peaked relapse and mortality hazard plots in breast cancer patients treated with mastectomy alone [2,3,4,5,6,7,8,9,10] Such double-peaked patterns defy explanation by classical Gompertian tumour kinetics within micrometastatic foci.

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