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,Natalie Ter Hoeve,Paul J Van Diest,Ton Peeters,Wilbert Zwart,Cathy B Moelans,Annelot Van Rossum

doi:10.18632/oncotarget.15548

Willemijne A.M.E Schrijver, Karianne Schuurman + Show 6 more

Open Access

https://doi.org/10.18632/oncotarget.15548

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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.

Highlights

Each year, around 550.000 women die from the consequences of breast cancer [1], largely due to metastatic relapse
We report IHC staining of ERα, progesterone receptor (PR), androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) complemented with HER2 in situ hybridization in 69 patients with primary breast carcinomas and their matched malignant peritoneal and/or pleural effusions and solid distant metastases
Decreased hormone receptor levels in malignant pleural and peritoneal effusions In total, 69 female breast cancer patients were included in this study with a median age at diagnosis of the primary tumor of 56 years (Table 1)

Summary

Introduction

Around 550.000 women die from the consequences of breast cancer [1], largely due to metastatic relapse. In around 30% of patients with metastatic breast cancer, the pleural cavity is involved [2, 3] and less frequently the pericardial and peritoneal cavities [4, 5]. Immunohistochemistry (IHC) plays a valuable role in effusion cytology for the identification of metastatic malignancy. Inclusion of hormone receptor status assessment could direct treatment decision-making. This is underlined by the finding that tamoxifen treatment showed a therapeutic benefit in patients with ERα-positive malignant pleural effusions [9,10,11]

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Conclusion