Journal
ONCOTARGET
Volume 8, Issue 33, Pages 55550-55561Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.15548
Keywords
breast cancer; distant metastases; receptor conversion; effusions
Categories
Funding
- Dutch Cancer Society [UU 2011-5195]
- Philips Consumer Lifestyle
- Dutch Cancer Society KWF/Alpe d'HuZes Bas Mulder Award
- Netherlands Organization for Scientific Research NWO VIDI
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Discordance in estrogen receptor alpha (ERa), 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. ERa, 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 ERa+ or PR+ to ERa-/PR- and 3-4% from ERa-/PR-to ERa+ or PR+. For HER2, conversion was observed in 6% of cases. Importantly, receptor conversion for ERa (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 ERa, 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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