Prospective evaluation of the conversion rate in the receptor status between primary breast cancer and metastasis: results from the GEICAM 2009-03 ConvertHER study

Abstract

The objective of this study was to determine the conversion rate of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER) and progesterone receptor (PR) between primary tumors and metastatic lesions in advanced breast cancer. Patients with suspected diagnosis of locally recurrent or metastatic breast cancer, either at first relapse or after successive disease progressions, who had an appropriately preserved sample from a primary tumor and were scheduled for a biopsy of the recurrent lesion, were included. Blinded determinations of receptor status on paired samples were performed by immunohistochemistry and fluorescence in situ hybridization at a central laboratory and compared with those performed locally. Overall, 196 patients were included and 184 patients were considered evaluable. Reasons for non-evaluability included the inability to perform biopsy (n = 4) or biopsy results showing normal tissue (n = 3), benign disease (n = 3) or a second neoplasia (n = 2). Conversion rates determined at local level were higher than those determined centrally (HER2: 16 vs. 3 %, ER: 21 vs. 13 %, PR: 35 vs. 28 %, respectively). There was substantial agreement regarding the expression of HER2 in primary tumors and metastases, and ER at metastases, between local and central laboratories. PR at any site and ER at primary site showed moderate agreement. Oncologists altered their treatment plans in 31 % of patients whose tumor subtype had changed. These results reinforce the recommendation for performing confirmatory biopsies of metastases, not only to avoid misdiagnosis of breast cancer relapse, but also to optimize treatment (clinicaltrials.gov identifier: NCT01377363).

Discordance in Hormone Receptor Status Among Primary, Metastatic, and Second Primary Breast Cancers: Biological Difference or Misclassification?

“…We found that 34% of ER conversion and 17% of PR conversion could be due to technical misclassification. This finding is in line with a recent prospective study showing that the conversion rate for ER was 21% in local laboratories and 13% in a central laboratory (38% relative reduction) and that the conversion rate for PR was 35% and 28% in local and central laboratories, respectively (i.e., 20% relative reduction) [25]. After correcting for misclassification, less than 3% of primary tumor and metastatic pairs showed a negative-to-positive receptor change.…”

Challenges in the management of advanced, ER-positive, HER2-negative breast cancer

“…Prospective studies that include central review of all pathology have estimated the prevalence of the discordance of ER and HER2 receptor status between the primary and metastatic site to be 10-13% and 3%, respectively, notably lower than when assessed locally. 40,41 Of note, in these studies 8-10% of tested samples showed loss of ER expression, compared to 2-3% with a gain in ER; HER2 gain occurred slightly more frequently than HER2 loss (2-3% compared to 0-1%, respectively), 40,41 although other analyses found HER2 loss and gain to occur at a similar frequency. 42,43 The clinical implications of this change in receptor status are less well understood.…”

Dose Escalation of Tamoxifen in Patients with Low Endoxifen Level: Evidence for Therapeutic Drug Monitoring—The TADE Study

“…This study was commenced in March 2010 and since then other studies have shown that tamoxifen dose escalation can lead to an increase in endoxifen level (27)(28)(29)(30). However, our study is notable as dose escalation occurred regardless of CYP2D6 genotype, and medications that were known to inhibit CYP2D6 metabolism were not an exclusion criteria allowing independent assessment of these factors.…”