We thank Matikas, Foukakis, and Bergh for their insightful comments on our paper. We chose to exclude cytology papers and focused on distant metastases because we aimed to analyze maximally homogeneous studies and implemented strict inclusion and exclusion criteria to exclude factors potentially introducing heterogeneity. We absolutely agree that the fine needle aspiration biopsy (FNAB) facilitates tissue sampling of metastases, which is very much within the current diagnostic arsenal, and would like to underline that we do not state anywhere in our paper that ‘FNAB of metastatic sites is not an appropriate diagnostic modality.’ However, to our knowledge, the accuracy of receptor status in distant metastatic breast disease diagnosed by FNAB has not been thoroughly evaluated despite its widespread use. Most studies address locoregional or lymph node metastases, which were beyond the focus of our review (1). The study of Lindstrom et al. mixes locoregional and distant metastases (2), potentially adding heterogeneity in the receptor conversion data. Furthermore, by assessing immunohistochemistry and immunocytochemistry together, extra variables are added to the equation, despite the 90% concordance reported between both techniques. We definitely welcome further studies on FNAB of distant breast cancer metastases to obtain more evidence. In the meantime, we have published a cell block study on receptor conversion in pleural and peritoneal effusions (3). Indeed, Karlsson et al. (4) showed concordance between core needle biopsies (CNBs) and FNABs. Nevertheless, numbers are low (human epidermal growth factor receptor 2 [HER2] only assessed in 12 FNABs). Also, the varying FNAB numbers for estrogen receptor, progesterone receptor, and HER2 suggest that analysis for all three markers on FNAB was often not feasible, as has been reported in other studies (5). Moreover, the authors state, “In the assessment of biomarker status, priority was given for IHC (I. specimen or II. CNB) and finally ICC (III. FNAB),” which suggests a preference for CNB. As mentioned in our paper, due to sampling error, tumor necrosis, or tumor fibrosis, it is a common limitation of FNAB that only a small amount of cells is available for immunostaining, which may lead to a false-negative interpretation in tumors that express some markers focally and heterogeneously (6). We agree that FNAB could be an alternative method to sample bone metastases and circumvent decalcification-induced influence, but we disagree that this is used widely, being technically only feasible when the bone cortex has been disrupted. Indeed, in the majority of studies about bone metastases, tissue is obtained via CNB (7), necessitating the use of decalcifying agents, not FNAB. Finally, the authors express their concerns about our statement that further prospective studies are needed. As we stated in our Discussion, we agree that randomized controlled trials in this setting no longer seem to be ethical. However, we believe that solid data regarding the effect of treatment decisions on outcome are lacking because in the reported prospective studies thus far, not all patients displaying receptor conversion were treated accordingly. Moreover, as mentioned, data on patient outcomes are conflicting (6). Note Affiliations of authors: Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands (WAMES, CBM, PJvD); Department of Medical Oncology, University Medical Center Utrecht Cancer Center, Utrecht, the Netherlands (KPMS, EvdW). References 1 Rautiainen S , Masarwah A , Sudah M et al. , Axillary lymph node biopsy in newly diagnosed invasive breast cancer: Comparative accuracy of fine-needle aspiration biopsy versus core-needle biopsy . Radiology. 2013 ; 269 1 : 54 – 60 . Google Scholar CrossRef Search ADS PubMed 2 Lindstrom LS , Karlsson E , Wilking UM et al. , Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression . J Clin Oncol. 2012 ; 30 21 : 2601 – 2608 . Google Scholar CrossRef Search ADS PubMed 3 Schrijver WAME , Schuurman K , van Rossum A et al. , Loss of steroid hormone receptors is common in malignant pleural and peritoneal effusions of breast cancer patients treated with endocrine therapy . Oncotarget . 2017 ; 8 33 : 55550 – 55561 . Google Scholar CrossRef Search ADS PubMed 4 Karlsson E , Appelgren J , Solterbeck A , Bergenheim M , Alvariza V , Bergh J. Breast cancer during follow-up and progression - a population based cohort on new cancers and changed biology . Eur J Cancer. 2014 ; 50 17 : 2916 – 2924 . Google Scholar CrossRef Search ADS PubMed 5 Amir E , Miller N , Geddie W et al. , Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer . J Clin Oncol. 2012 ; 30 6 : 587 – 592 . Google Scholar CrossRef Search ADS PubMed 6 Nassar A. Core needle biopsy versus fine needle aspiration biopsy in breast—a historical perspective and opportunities in the modern era . Diagn Cytopathol. 2011 ; 39 5 : 380 – 388 . Google Scholar CrossRef Search ADS PubMed 7 Aurilio G , Monfardini L , Rizzo S et al. , Discordant hormone receptor and human epidermal growth factor receptor 2 status in bone metastases compared to primary breast cancer . Acta Oncol. 2013 ; 52 8 : 1649 – 1656 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press. All rights reserved. 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JNCI: Journal of the National Cancer Institute – Oxford University Press
Published: Mar 29, 2018
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