A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases

Abstract

Background: The discordance in oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) status between primary and recurrent breast cancer is being intensively investigated and a large amount of data have been produced. However, results from different studies are heterogeneous and often conflicting. To highlight this issue, a meta-analysis of published data was performed. Methods: A literature search was performed using Medline, and all the studies published from 1983 to 2011 comparing changes in ER, PgR and/or HER2 status in patients with matched breast primary and recurrent tumours were included. We used random-effects models to estimate pooled discordance proportions. Results: We selected 48 articles, mostly reporting retrospective studies. Thirty-three, 24 and 31 articles were focused on ER, PgR and HER2 changes, respectively. A total of 4200, 2739 and 2987 tumours were evaluated for ER, PgR and HER2 discordance, respectively. The heterogeneity between study-specific discordance proportions was high for ER (I 2 = 91%, European Journal of Cancer (2014) 50, 277-289 A v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m ScienceDirectj o u r n a l h o m e p a g e : w w w . e j c a n c e r . c o m p < 0.0001), PgR (I 2 = 79%, p < 0.0001) and HER2 (I 2 = 77%, p < 0.0001). Pooled discordance proportions were 20% (95% confidence interval (CI): 16-35%) for ER, 33% (95% CI: 29-38%) for PgR and 8% (95% CI: 6-10%) for HER2. Pooled proportions of tumours shifting from positive to negative and from negative to positive were 24% and 14% for ER (p = 0.0183), respectively. The same figures were 46% and 15% for PgR (p < 0.0001), and 13% and 5% for HER2 (p = 0.0004). Conclusion: Our findings strengthen the concept that changes in receptor expression may occur during the natural history of breast cancer, suggesting clinical implications and a possible impact on treatment choice.

Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule 68Ga-ABY-025 in Breast Cancer Patients

“…Today, assessment of HER2 status is based on tumor biopsy. However, HER2 expression can vary between the primary tumor and metastases in up to 40% of cases (2,5,6) and metastatic HER2 expression can change over time, which could necessitate a change of therapy (7,8). Follow-up using biopsies cannot always be performed due to practical reasons or patient discomfort.…”

Synchronous Orbital and Gastric Metastasis of Invasive Lobular Breast Carcinoma, Mimic Primary Gastric Carcinoma-Case Report

“…Detailed IHC study is the most helpful method in this case. Connel et al [9] compared the IHC findings between primary gastric malignancy and metastatic gastric malignancy from breast carcinoma. Highly significant proportions of metastatic breast carcinomas were positive for ER (72%), PR (33%), GCDFP (78%), and CK5/6 (61%) compared with primary gastric carcinomas (ER, 0%; PR, 0%; GCDFP, 0%; and CK5/6, 14%).…”

Letter to the Editor regarding the paper by Aurilio et al., A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases

“…It is well known that a considerable controversy concerns the issue of hormone receptors (HRs) expression as well as HER2 status between primary breast carcinomas (BC) and metastatic sites from the same patient, as elsewhere reported in literature [1][2][3][4][5]. In particular, the discordance between primary BC and metastases from negative to positive and vice versa potentially affects the treatment regimen [5]; therefore, it has been suggested that neoplastic tissue of metastatic lesions should be systematically re-biopsied to optimally re-assess HR as well as HER2 [1,2,[4][5][6][7][8].In their meta-analysis, focusing on HER2 status, Aurilio et al documented that the pooled discordance proportion with respect to the primary breast tumour was 10% for distant metastases and 6% for loco-regional relapses. Moreover, a different pooled discordant proportion was found on the basis of the different utilised technique, since it was 10% in studies using immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH), but 5% in studies using IHC only; therefore, they conclude the observed discrepancy was not merely due to technicality.…”

“…Nevertheless, whether these changes in HER2 status may be attributed to laboratory reproducibility in techniques or to other pre-analytical fac- tors, such as not standardised inadequate fixation or, otherwise, to biological modifications and heterogeneity in tumours, still remains to be clarified. On the other hand, the hypothesis that variation in HER2 status may reflect clonal genome evolution has been stressed [7]; consequently, tumour heterogeneity may be attributable to tumour biological trend leading to clonal selection with the development of new clones, previously undetectable within the primary breast cancer. In any case, the significant discordance between HER2 status in the comparison of primary and recurrent/metastatic breast carcinomas may influence the correct treatment, determining an inappropriate use of targeted therapies [8][9][10][11].…”