Abstract P4-09-13: Predicting Potential Patterns of Metastatic Spread and Outcomes in Breast Cancer
Authors: Purushotham A , Agbaje O , Shamil E , Cariati M , Pinder S , Holmberg L. 
Published: April 2011

Background: Metastasis progression in breast cancer can be viewed as a stepwise sequence of events that occurs with distinct temporal patterns and in unique organ sites. Our previous results indicate that metastatic spread occurs along distinct pathways governed by biological characteristics of the primary tumour.

Aim: To examine clinical and histopathological factors that predict for patterns of metastatic spread and survival in breast cancer. Materials and Methods: A study population consisting of 5569 patients diagnosed with breast cancer between 1975 and 2006 was studied. Median follow-up was 7.7 years, interquartile range (IQR) 3.4-14.3 years. The median metastasis-free interval was 6.7 years, IQR 2.6-14.6 years. Survival analysis was performed using Kaplan-Meier method and group comparisons made with a log-rank test. Both univariate and stepwise Cox proportional hazard models were used to investigate the relationship between prognostic factors and breast cancer survival. Results: Of 5569 patients, 1718 (31%) developed distant metastasis; 499 (29%) to bone, 990 (58%) to other organs and 229 (13%) to bone followed by a second metastatic event in another organ site within 6 months after the first event (bone + 2nd site).

Patterns of metastatic spread: In univariate analysis, ER-ve tumours were 45% more likely to spread to other organs or to bone + 2nd site. Grade 3 cancers, compared with grade 1 tumours, had a 2-fold increase in the likelihood of metastasising to bone only, 4-fold to bone + 2nd site and 7.5-fold to other organs. In multivariate analysis, node positivity, higher grade and larger tumour size predicted for metastasis to bone or any other organ site whilst node positivity and ER negativity predicted for metastasis to bone + 2nd site. Patients &gt;70 years were 60% less likely to have bone metastasis compared with patients &lt;50 years. ER+ve tumours did not show an increased predilection to bone metastasis on multivariate analysis. Survival from 1st onset of metastasis (breast cancer-related deaths): The median survival in months [95% CI] for patients who developed bone metastasis was 24 [21,26], bone + 2nd site 12 [9, 13] and other organ sites 14 [13, 16] months, respectively. There was a highly significant exponential decrease in survival with increasing age (P&lt;0.02). This effect was even more pronounced in those patients &gt;70 years age who developed bone + 2nd site metastasis (5 times greater hazard of dying compared with &lt;50 years), and was further amplified in grade 3 tumours in this group of patients. Furthermore, node positivity and grade 3 tumours had the maximum negative effect on survival in this group compared with patients who had metastasised to bone only or to other organ sites. Conclusion: The clinical and histopathological factors that predict for patterns of metastatic spread and survival in breast cancer in this large cohort support some previous observations, refute others and demonstrate new findings. These observations merit further investigation and, potentially, future trials of adjuvant therapy that are designed according to predictive patterns of metastatic spread.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-13.