Research article

Recurrence dynamics does not depend on the recurrence site

Romano Demicheli¹ , Elia Biganzoli^2,3 , Patrizia Boracchi³ , Marco Greco⁴ and Michael W Retsky⁵

¹  Department of Medical Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, via Venezian 1, Milano 20133, Italy

²  Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, via Venezian 1, Milano 20133, Italy

³  Medical Statistics and Biometry, Università di Milano, via Venezian 1, Milano 20133, Italy

⁴  Breast Surgery, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, via Venezian 1, Milano 20133, Italy

⁵  Department of Vascular Biology, Children's Hospital and Harvard Medical School, Enders Building, 10th Floor, 300 Longwood Avenue, Boston, MA, USA

author email corresponding author email

Breast Cancer Research 2008, 10:R83doi:10.1186/bcr2152

Published:	9 October 2008

See related editorial by Chambers and Goss, http://breast-cancer-research.com/content/10/6/114

Abstract

Introduction

The dynamics of breast cancer recurrence and death, indicating a bimodal hazard rate pattern, has been confirmed in various databases. A few explanations have been suggested to help interpret this finding, assuming that each peak is generated by clustering of similar recurrences and different peaks result from distinct categories of recurrence.

Methods

The recurrence dynamics was analysed in a series of 1526 patients undergoing conservative surgery at the National Cancer Institute of Milan, Italy, for whom the site of first recurrence was recorded. The study was focused on the first clinically relevant event occurring during the follow up (ie, local recurrence, distant metastasis, contralateral breast cancer, second primary tumour), the dynamics of which was studied by estimating the specific hazard rate.

Results

The hazard rate for any recurrence (including both local and distant disease relapses) displayed a bimodal pattern with a first surge peaking at about 24 months and a second peak at almost 60 months. The same pattern was observed when the whole recurrence risk was split into the risk of local recurrence and the risk of distant metastasis. However, the hazard rate curves for both contralateral breast tumours and second primary tumours revealed a uniform course at an almost constant level. When patients with distant metastases were grouped by site of recurrence (soft tissue, bone, lung or liver or central nervous system), the corresponding hazard rate curves displayed the typical bimodal pattern with a first peak at about 24 months and a later peak at about 60 months.

Conclusions

The bimodal dynamics for early stage breast cancer recurrence is again confirmed, providing support to the proposed tumour-dormancy-based model. The recurrence dynamics does not depend on the site of metastasis indicating that the timing of recurrences is generated by factors influencing the metastatic development regardless of the seeded organ. This finding supports the view that the disease course after surgical removal of the primary tumour follows a common pathway with well-defined steps and that the recurrence risk pattern results from inherent features of the metastasis development process, which are apparently attributable to tumour cells.