Abstract P4-09-07: Prediction of Outcome after Diagnosis of Metachronous Contralateral Breast Cancer
Authors: Alkner S , Bendahl P-O , Fernö M , Manjer J , Rydén L. 
Published: April 2011

Background: Contralateral breast cancer (CBC) is today treated as a new primary tumour, but the biological relationship between the first (BC1) and the second breast cancer (BC2), and the impact of a second primary tumour on prognosis is debated. Using a unique patient cohort, we have investigated whether time interval to BC2 and mode of detection are associated to prognosis.

Methods: For all patients diagnosed with metachronous CBC in the Southern Healthcare Region of Sweden from 1977-2007, information on patient, tumour, treatment characteristics, and outcome was abstracted from patients’ individual charts. The final cohort included 724 patients with metachronous CBC as primary event. Primary endpoint was distant disease-free survival (DDFS), which was measured from diagnosis of CBC. To avoid lead-time bias, we looked at risk of metastasis or breast cancer death as a primary event instead of DDFS in relation to mode of detection. Metachronous breast cancer was defined as CBC diagnosed at least three months after BC1. Age refers to age at BC1.

Results: Patients with a time interval to BC2 of less than three years had a significantly impaired DDFS (HR=1.4, p=0.01). Significance remained in multivariate analysis adjusted for age, calendar period, mode of detection of BC2, size, lymph node status, and treatment for BC 1 and BC2 (HR= 1.6, p=0.01). Subgroup analysis showed this effect to be seen primarily in patients aged &lt;50. Using an interaction analysis between age and time interval to BC2, the interaction was statistically significant in univariate (HR=0.53, p=0.03), but not in multivariate analysis. Patients diagnosed with CBC within a follow-up programme were considered asymptomatic at diagnosis (63%), while patients who first noted symptoms themselves were considered symptomatic (37%). Patients with symptoms at diagnosis were younger, had a longer time interval to BC2, had larger CBCs, and more often lymph node metastases. Using logistic regression, a significantly higher risk of later developing metastases was seen in symptomatic patients, both in univariate (HR=2.1, P&lt;0.0001) and multivariate analysis (HR=2.1, p=0.002). When exploring effect of mode of detection in relation to time interval to BC2, mode of detection remained a significant prognostic factor even when time interval to BC2 was more than ten years.

Discussion: Why CBC diagnosed within a short time interval from BC1 seems to have a worse prognosis is unclear. One explanation could bethat these tumours more often represent a metastatic spread of BC1, another that CBC diagnosed during or soon after adjuvant treatment has developed treatment resistance and a more aggressive phenotype. Mode of detection was associated with risk of metastasis even when BC2 was diagnosed more than ten years after BC 1, suggesting that a long follow-up time could be of value.

Conclusion: In a large cohort of patients with CBC, we found time interval to BC2 and mode of detection to be strong prognostic factors. CBC is today treated as a new primary tumour. The prognostic factors found in the present study could be of value in identifying patients needing intensified treatment.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-07.