Loss of steroid hormone receptors is common in malignant pleural and peritoneal effusions of breast cancer patients treated with endocrine therapy

Willemijne A.M.E. Schrijver; Karianne Schuurman; Annelot van Rossum; Dutch Distant Breast Cancer Metastases Consortium; Ton Peeters; Natalie Ter Hoeve; Wilbert Zwart; Paul J. van Diest; Cathy B. Moelans

doi:10.18632/oncotarget.15548

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Clinical Research Papers:

Loss of steroid hormone receptors is common in malignant pleural and peritoneal effusions of breast cancer patients treated with endocrine therapy

Willemijne A.M.E. Schrijver, Karianne Schuurman, Annelot van Rossum, Dutch Distant Breast Cancer Metastases Consortium, Ton Peeters, Natalie Ter Hoeve, Wilbert Zwart, Paul J. van Diest and Cathy B. Moelans _

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Oncotarget. 2017; 8:55550-55561. https://doi.org/10.18632/oncotarget.15548

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Abstract

Willemijne A.M.E. Schrijver1, Karianne Schuurman2, Annelot van Rossum2, Dutch Distant Breast Cancer Metastases Consortium**, Ton Peeters1, Natalie Ter Hoeve1, Wilbert Zwart2,*, Paul J. van Diest1,* and Cathy B. Moelans1,*

1 Department of Pathology, University Medical Center Utrecht, The Netherlands

2 Division of Molecular Pathology, The Netherlands Cancer Institute, The Netherlands

* These authors have contributed equally to this work

** Members are listed in the acknowledgement

Correspondence to:

Cathy B. Moelans, email:

Keywords: breast cancer, distant metastases, receptor conversion, effusions

Received: October 26, 2016 Accepted: February 12, 2017Published: February 20, 2017

Abstract

Discordance in estrogen receptor alpha (ERα), progesterone receptor (PR), androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) status between primary breast cancers and solid distant metastases (“conversion”) has been reported previously. Even though metastatic spread to the peritoneal and pleural cavities occurs frequently and is associated with high mortality, the rate of receptor conversion and the prognostic implications thereof remain elusive.

We therefore determined receptor conversion in 91 effusion metastases (78 pleural, 13 peritoneal effusions) of 69 patients by immunohistochemistry (IHC) and in situ hybridization. Data were coupled to clinical variables and treatment history.

ERα, PR and AR receptor status converted from positive in the primary tumor to negative in the effusion metastases or vice versa in 25-30%, 30-35% and 46-51% of cases for the 1% and 10% thresholds for positivity, respectively. 19-25% of patients converted clinically relevant from “ERα+ or PR+” to ERα-/PR- and 3-4% from ERα-/PR- to “ERα+ or PR+”. For HER2, conversion was observed in 6% of cases. Importantly, receptor conversion for ERα (p = 0.058) and AR (p < 0.001) was more often seen in patients adjuvantly treated with endocrine therapy. Analogous to this observation, HER2-loss was more frequent in patients adjuvantly treated with trastuzumab (p < 0.001).

Alike solid distant metastases, receptor conversion for ERα, PR, AR and HER2 is a frequent phenomenon in peritoneal and pleural effusion metastases. Adjuvant endocrine and trastuzumab therapy imposes an evolutionary selection pressure on the tumor, leading to receptor loss in effusion metastases. Determination of receptor status in malignant effusion specimens will facilitate endocrine treatment decision-making at this lethal state of the disease, and is hence recommended whenever possible.

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Clinical Research Papers:

Loss of steroid hormone receptors is common in malignant pleural and peritoneal effusions of breast cancer patients treated with endocrine therapy

Abstract