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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      The Prognostic Impact of Hormonal Receptor and HER-2 Expression Discordance in Metastatic Breast Cancer Patients

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          Abstract

          Background

          Hormone receptor (HR) and human epidermal growth factor receptor (HER2) discordance between primary and metastatic breast cancer lesions is common. However, its impact on long-term survival remains unclear. We aimed to determine the prognostic value of this discordance in patients with metastaticf breast cancer (MBC).

          Methods

          A total of 270 patients with MBC who were underwent re-biopsy of progressive metastases at Zhejiang Cancer Hospital from January 1, 2012 to December 31, 2015 with patients consent and then review their primary tumors pathological findings. The HR and HER2 status in both primary and progressive metastatic lesions was determined by immunohistochemistry and/or fluorescence in situ hybridization. The discordance rates were correlated with the clinicopathologic characteristics, metastatic lesions, salvage treatment, and survival analysis in this population.

          Results

          A total of 142 (52.6%) MBC patients were diagnosed with discordant HR and HER2 status. Alterations in estrogen receptor (ER), progesterone receptor (PR), and HER2 status were observed in 20.70%, 37.78%, and 11.48% cases, respectively. Chemotherapy (P=0.0192) and endocrine therapy (P=0.048) significantly affected the conversion of HR status. Endocrine therapy was positively correlated with PR discordance (P=0.002), while ER discordance was associated with adjuvant chemotherapy (P=0.031). Survival analysis showed that ER status alterations between primary and metastatic lesions were associated with overall survival (P=0.002). The clinical prognosis was significantly worse with HR losses than with persistent HR positivity (P=0.023). In Cox multivariate analysis, the loss of HR expression and conversion to triple negative were independent prognostic indicators.

          Conclusion

          Discordance in HR status between primary and metastatic lesions may impact the prognosis of MBC, and HR conversion has independent prognostic value.

          Most cited references27

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          Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2009

          Michael Gnant, A Goldhirsch, J. N. Ingle … (2009)
          The 11th St Gallen (Switzerland) expert consensus meeting on the primary treatment of early breast cancer in March 2009 maintained an emphasis on targeting adjuvant systemic therapies according to subgroups defined by predictive markers. Any positive level of estrogen receptor (ER) expression is considered sufficient to justify the use of endocrine adjuvant therapy in almost all patients. Overexpression or amplification of HER2 by standard criteria is an indication for anti-HER2 therapy for all but the very lowest risk invasive tumours. The corollary is that ER and HER2 must be reliably and accurately measured. Indications for cytotoxic adjuvant therapy were refined, acknowledging the role of risk factors with the caveat that risk per se is not a target. Proliferation markers, including those identified in multigene array analyses, were recognised as important in this regard. The threshold for indication of each systemic treatment modality thus depends on different criteria which have been separately listed to clarify the therapeutic decision-making algorithm.
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            Use of Biomarkers to Guide Decisions on Systemic Therapy for Women With Metastatic Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.

            Catherine Van Poznak, Mark Somerfield, Robert C. Bast … (2015)
            To provide recommendations on the appropriate use of breast tumor biomarker assay results to guide decisions on systemic therapy for metastatic breast cancer.
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              A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases.

              Aron Goldhirsch, Giancarlo Pruneri, Giuseppe Curigliano … (2013)
              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. 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. 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%, 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). 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. Copyright © 2013 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Onco Targets Ther
                Journal ID (iso-abbrev): Onco Targets Ther
                Journal ID (publisher-id): OTT
                Journal ID (pmc): ott
                Title: OncoTargets and therapy
                Publisher: Dove
                ISSN (Electronic): 1178-6930
                Publication date (Electronic): 28 January 2020
                Publication date Collection: 2020
                Volume: 13
                Pages: 853-863
                Affiliations
                [1 ]The Second Clinical Medical College of Zhejiang Chinese Medical University , Hangzhou, Zhejiang 310022, People’s Republic of China;
                [2 ]Department of Medical Oncology, Fujian Cancer Hospital , Fuzhou, Fujian 350014, People’s Republic of China
                [3 ]Department of Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences , Hangzhou, Zhejiang, People’s Republic of China
                Author notes
                Correspondence: Xiaojia Wang Department of Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences , Hangzhou, Zhejiang310022, People’s Republic of ChinaTel +86 13906500190 Email wxiaojia0803@163.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-5390-1991
                http://orcid.org/0000-0001-5693-1152
                http://orcid.org/0000-0002-6838-4050
                Article
                Publisher ID: 231493
                DOI: 10.2147/OTT.S231493
                PMC ID: 6996483
                PubMed ID: 32099389
                SO-VID: c02e7d6c-5f94-4135-bc84-5408ef297309
                Copyright © © 2020 Yang et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 18 September 2019
                Date accepted : 21 December 2019
                Page count
                Figures: 1, Tables: 6, References: 28, Pages: 11
                Funding
                This study was funded by the National Natural Science Foundation of China (Grant Number: 81672597), the National Clinical Key Specialty Construction Program, Fujian Natural Science Foundation (grant number 2018J0105, 13181509), and Training Project of Young Talents in Fujian Health System (grant number 2015-ZQN-JC-6).
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: breast cancer,hormone receptor,receptor discordance,recurrent
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: breast cancer, hormone receptor, receptor discordance, recurrent

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