Estrogen receptor conversion in bone, liver and lung metastases from breast cancer

Abstract

Breast cancer treatment is dictated by biomarker status which has been documented to convert between primary tumor and metastases, potentially altering patient management. We investigated breast biomarker conversion in metastases to bone, liver, and lung and its correlation with clinicopathologic factors, prognosis and genetic alterations. Within our cohort of bone (n = 35), liver (n = 20), and lung (n = 13) metastases, there was no significant differences in age at initial diagnosis, sex, laterality, tumor type, and tumor grade of primary tumors. Primary tumors that metastasized to bone and liver had higher ER positivity and intensity as well as more PR positivity than those that metastasized to the lung. Fifteen percent (15 %) of our population (10 out of 68 cases) demonstrated ER conversion, most frequently in liver (35 % in liver vs. 5.7 % in bone, 7.7 % in lung; p < 0.01). Of these, 7 cases converted from positive to negative while 3 (all liver metastases) converted from negative to positive. Cases with any ER conversion were found to have a significantly shorter median survival compared to non-converted cases (12 vs. 38 months; p < 0.0001). We also found TP53 mutations in 2 of 3 cases with conversion from negative to positive and PIK3CA mutations in 4 of 6 cases with conversion from positive to negative. Our study demonstrated that the liver is a metastatic site with a higher chance for ER conversion than bone and lung, and ER conversion from negative to positive is likely to be seen in liver metastasis. Moreover, ER conversions, no matter in which direction, are associated with worse prognosis.