Discordant biomarker expression is seen between primary and recurring/metastatic tumors in a number of different cancer types. “The phenotype of breast cancer cells changes throughout the natural history of the disease, and it has prognostic consequences,” said Dr Isabel Blancas López-Barajas of Granada, Spain. Dr Blancas López-Barajas presented the results of a single-center, retrospective study of 45 breast cancer patients, in which the differential expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and the cellular marker for proliferation Ki-67 were evaluated in primary and relapsed tumors.
Two populations of patients were included in this study: patients who had a local and complete resected relapse and patients with a metastatic biopsied disease. To identify changes in the 4 biomarkers over time, assessments were made from the pathologist report of the primary tumor and from the biopsy of the relapse. For patients with local disease, end points were relapse-free survival (RFS) and overall survival (OS). For patients with metastatic disease, end points were progression-free survival (PFS) and OS.
Conversion rates were statistically significant for all biomarkers between the primary breast tumor and relapse. Conversion rates of 34.8% for Ki-67 (P = 0.046), 20% for ER (P = 0.001), 20% for PR (P <0.001), and 15.6% for HER2 (P <0.001) were observed. In the local disease group, conversion was not significantly associated with RFS for any of the assessed biomarkers. For tumors with high Ki-67 (≥14%), the mean RFS was 27.1 months (95% confidence interval [CI], 19.6-36.2); for tumors with low Ki-67 (<14%), the mean RFS was 69.5 months (95% CI, 0.0-145.0) (P = 0.262). Similarly, in the metastatic disease group, conversion was not significantly associated with PFS for any of the assessed biomarkers. For tumors with high Ki-67, the mean PFS was 18.2 months (95% CI, 10.3-26.0); for tumors with low Ki-67, the mean PFS was 53.0 months (95% CI, 13.4-92.7) (P = 0.272).
With regard to OS, local tumors that converted from ER-positive to ER-negative were associated with a statistically significant reduction in mean OS: ER-positive (178.6 months; 95% CI, 154.7-202.4) versus ER-negative (72 months; 95% CI, 17.7-126.3) (P = 0.001). Conversion of the other biomarkers did not have a significant association with mean OS. In the metastatic disease group, only conversion to ER-negative or PR-negative was associated with significant reductions in mean OS: ER-positive (137.7 months; 95% CI, 105.9-169.5) versus ER-negative (43.1 months; 95% CI, 8.3-77.9) (P = 0.043); PR-positive (144.6 months; 95% CI, 108.1-181.0) versus PR-negative (70 months; 95% CI, 27.3-112.8) (P = 0.027).
These data confirm that significant biomarker conversion occurs between primary breast cancer tumors and relapse. Furthermore, conversion to ER-negative status for locally relapsed tumors or metastases, or conversion to PR-negative status in metastases, were associated with a worse prognosis in terms of OS. “The changes seen in this study reinforce [the] need to perform confirmatory biopsy of relapses in order to establish a correct therapeutic treatment and to get an accurate prognosis,” said Dr Blancas López-Barajas.