Abstract P6-05-07: Discordance in estrogen receptor, progesterone receptor and HER-2/neu status between primary and metastatic breast cancer: A systematic review

Abstract

Abstract BACKGROUND AND OBJECTIVE Systemic treatment choices for metastatic breast cancer are based, in part, on the estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor (HER2) status of the primary cancer. Receptor discordance between primary and associated metastases is well recognized and could have important therapeutic implications. A systematic review of all relevant studies was conducted to assess the extent of discordance in ER, PR and HER2 status between primary breast cancers and their paired metastases. METHODS A search was performed using EMBASE (1980-2013), Medline (1966-2013) and Cochrane Central Register of Controlled Trials (CENTRAL, 2013 issue 1), references of included studies, relevant review articles and conference abstracts. Only English-language cohort studies reporting ER, PR, and HER2 expression for matching primary breast cancer and metastatic sites were eligible. Title and abstract screening was performed by one reviewer; full text articles of potentially relevant citations were independently screened by two reviewers. Using pre-defined criteria, two reviewers performed data extraction of the included studies, as well as methodologic quality assessment (QUADAS-2) and risk of bias assessment. Disagreements by reviewers were adjudicated by consensus. Median discordance and interquartile range (IQR) of discordance of each of the biomarkers (ER, PR, HER2) between primary breast cancer and their paired metastases were calculated. Association between receptor discordance and site of metastasis site was also explored. RESULTS Of the 5034 citations identified, 58 studies (representing a total of 3,522 matched primary and metastatic pairs) met our inclusion criteria. Studies were generally small, as reflected by the median number of matched pairs of 42 (range 4-370). Median discordance rates between primary and paired metastases were 18% (IQR10–29%) for ER, 23% (IQR16–43%) for PR and 9% (IQR 4–14%) for HER2 respectively. Discordance rates were higher if the metastatic site was a lymph node [ER: 42% (42–60%); PR: 48% (46–50%); HER2: 25% (11–38%)] as compared to all other sites of disease (e.g. bone marrow, lung, liver and brain) [ER: 25% (14-42%); PR: 36%(19-45)%; HER2: 13% (5-21%)]. Overall, receptor loss was more common than receptor gain across all metastatic sites. CONCLUSION This is the first systematic review we are aware of, that evaluates the extent, direction, and relationship of ER, PR and HER2 discordance between primary breast cancer and their paired metastases. Discordance varied from 10-60% depending on the receptor type and site of metastasis. When discordance occurs, loss of a biomarker is most common and most frequent with PR. These results could have important therapeutic implications in the treatment of recurrent and metastatic breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-07.