Retrospective analysis of metastatic behaviour of breast cancer subtypes

Abstract

Among breast cancer patients who develop distant metastases, there is marked variability in the clinical course, including metastasis pattern. Here, we present a retrospective study of breast cancer patients who all developed distant metastases focusing on the association between breast cancer subtype and clinical course, including organ-specific metastasis. Tissue microarrays (TMAs) were assembled and stained for ER, PR, HER2, EGFR, CK5/6, CK14, E-Cadherin, TP53 and Ki67 for 263 breast cancer patients with metastatic disease. Tumours were classified into ER+/HER2-/Ki67high, ER+/HER2-/Ki67low, ER+/HER2+, ER-/HER2+ and ER-/HER2- groups. Relevant data related to metastasis pattern, metastasis timeline, systemic treatment and survival were retrieved. Associations between site-specific relapse and patient/tumour characteristics were assessed with multivariate models using logistic regression. Median time for development of distant metastasis was 30 months (range 0-15.3 years); 75.8 % of the distance metastases developed in the first 5 years after treatment of the primary tumour. Patients with ER-/HER2- tumours had a median overall survival of 27 months; those with HER2+ tumours of 52 months; those with ER+/HER2-/Ki67high of 76 months and those with ER+/HER2-/Ki67low of 79 months. Bone was the most common site for distant metastasis (70.6 %) followed by liver (54.5 %) and lung (31.4 %), respectively. Visceral metastasis was found in 76.8 % of the patients. Patients with ER-/HER2- tumours developed visceral metastases in 81 % and bone metastases in 55.2 %; those with HER2+ tumours developed visceral metastases in 77.4 % and bone metastases in 69.8 %; those with ER+/HER2-/Ki67high developed visceral metastases in 75.7 % and bone metastases in 87.8 % and those with ER+/HER2-/Ki67low developed visceral metastases in 76.9 % and bone metastases in 73.1 %. In metastatic breast cancer patients, tumour subtypes are associated with survival and pattern of distant metastases. These associations are of help in choices for surveillance and therapy in individual patients.

Fig. 1

Metastasis-specific (a) and overall (b) survival curves of breast cancer patients with and without visceral metastasis. Kaplan–Meier plots of patients show that tumours with visceral metastasis had worse survival outcomes than the tumours without visceral organ metastasis. Patients who had visceral metastasis had shorter survival time from detection of metastasis to last event and from the initial diagnosis of the disease to last event (p = 0.009 and 0.073, respectively)

Fig. 2

Metastasis-specific (a) and overall (b) survival curves of breast cancer patients according to tumour subtypes. ER oestrogen receptor, PR progesterone receptor, HER2 human epidermal growth factor receptor type 2. Kaplan–Meier plots of patients show that ER−/HER2− had worse survival outcomes compared to other tumour subtypes. Patients with hormone receptor-negative (ER−/HER2−) tumours had shorter survival time from detection of metastatic disease to last event and from the initial diagnosis of the disease to last event (p < 0.001)