Breast carcinoma: molecular markers and subtypes to predict patients at risk of developing metastatic disease

Objective

To identify molecular markers and molecular subtypes in breast carcinoma that predict patients at higher risk of developing bone, brain, and visceral metastasis.

Methods

Immunohistochemical analysis using a panel of antibodies against ER, PR, Her2, EGFR, CK5/6, CK14, Ki67, E-cadherin, Bcl2 and p53 was performed on tissue microarray sections of breast carcinoma with bone, brain and visceral metastasis (33, 13 and 30 cases) and 483 cases of breast carcinoma without metastasis. Using standard methods of scoring, the expression levels of receptors and subtype distribution (luminal A, luminal B, Her2, basal, triple negative) were compared within these groups.

Results

When compared with breast tumours without metastases, bone metastases were significantly associated with ER (P = 0.01) and E-cadherin (P = 0.014) positive breast tumours, brain metastases were significantly associated with ER (P = 0.01) and PR (P = 0.001) positive breast tumours, and visceral metastases were significantly associated with ER (P < 0.0001), PR (P = 0.013), Ki67 (P = 0.009), EGFR (P = 0.01) and p53 (P = 0.002) positive breast tumours. The triple-negative subtype was significantly associated with breast tumours with bone (P = 0.001) and brain (P < 0.001) metastases, while the basal subtype was significantly associated with breast tumours with visceral metastases (P = 0.005), when compared with breast tumours without metastatic disease. There was a significant association with tumour size >2 cm in breast tumours with bone (P = 0.021) and visceral metastases (P < 0.001), compared with breast tumours without metastatic disease.

Conclusion

We have shown that, using immunohistochemistry, a standard panel of molecular markers of breast carcinoma can be of significant value in predicting sites of metastases.