Discordance and Conversion Rates of Progesterone-, Estrogen-, and HER2/neu-Receptor Status in Primary Breast Cancer and Brain Metastasis Mainly Triggered by Hormone Therapy

Timmer, Marco; Werner, Jan-Michael; Röhn, Gabriele; Ortmann, Monika; Blau, Tobias; Cramer, Christina K.; Stavrinou, Pantelis; Krischek, Boris; Mallman, Peter; Goldbrunner, Roland

doi:10.21873/anticanres.11894

Cited by 21 publications

(20 citation statements)

References 22 publications

(32 reference statements)

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“…17 In a study, all anti-estrogen-treated tumors lost ER expression, particularly in cases involving brain metastases. 18 In this study, we demonstrated for the first time that adjuvant endocrine therapy and chemotherapy may alter PR and ER receptor profiles. Similar studies have suggested that in ER-and HER2-positive patients, endocrine therapy and trastuzumab treatment are independent factors associated with discordance.…”

Section: Discussionmentioning

confidence: 71%

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

Yang¹,

Li²,

Li³

et al. 2020

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These authors contributed equally to this work 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.

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Section: Discussionmentioning

confidence: 71%

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

Yang¹,

Li²,

Li³

et al. 2020

OTT

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“…Consequently, the role of surgery for symptomatic BM, apart from its importance in the acute situation of severe neurologic deterioration (eg by tumor-associated hemorrhages or obstruction of cerebrospinal fluid pathways), is reasonable in the context of an interdisciplinary therapeutic approach, including systemic treatment. Particularly since in the future, further molecular analysis of BM may gain importance, changes in molecular signatures in BM compared to the primary tumors 26,27 will mean sufficient material for molecular analysis is needed. The most prominent aspect influencing the decision for or against surgery therefore must be: will metastasectomy positively change the neurological condition of the patient with a high probability, to enable further specific treatment?…”

Section: Discussionmentioning

confidence: 99%

Surgical resection of symptomatic brain metastases improves the clinical status and facilitates further treatment

et al. 2020

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“…Therefore, the receptor status of the primary tumor is invalid for planning a targeted therapy against BMs, especially after hormone therapy. In these cases, new tissue collection by biopsy or resection should be required for more accurate decision-making ( 72 ).…”

Section: Molecular Biologymentioning

confidence: 99%

Mechanisms and Therapy for Cancer Metastasis to the Brain

2018

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Advances in chemotherapy and targeted therapies have improved survival in cancer patients with an increase of the incidence of newly diagnosed brain metastases (BMs). Intracranial metastases are symptomatic in 60–70% of patients. Magnetic resonance imaging (MRI) with gadolinium is more sensitive than computed tomography and advanced neuroimaging techniques have been increasingly used in the detection, treatment planning, and follow-up of BM. Apart from the morphological analysis, the most effective tool for characterizing BM is immunohistochemistry. Molecular alterations not always reflect those of the primary tumor. More sophisticated methods of tumor analysis detecting circulating biomarkers in fluids (liquid biopsy), including circulating DNA, circulating tumor cells, and extracellular vesicles, containing tumor DNA and macromolecules (microRNA), have shown promise regarding tumor treatment response and progression. The choice of therapeutic approaches is guided by prognostic scores (Recursive Partitioning Analysis and diagnostic-specific Graded Prognostic Assessment-DS-GPA). The survival benefit of surgical resection seems limited to the subgroup of patients with controlled systemic disease and good performance status. Leptomeningeal disease (LMD) can be a complication, especially in posterior fossa metastases undergoing a “piecemeal” resection. Radiosurgery of the resection cavity may offer comparable survival and local control as postoperative whole-brain radiotherapy (WBRT). WBRT alone is now the treatment of choice only for patients with single or multiple BMs not amenable to surgery or radiosurgery, or with poor prognostic factors. To reduce the neurocognitive sequelae of WBRT intensity modulated radiotherapy with hippocampal sparing, and pharmacological approaches (memantine and donepezil) have been investigated. In the last decade, a multitude of molecular abnormalities have been discovered. Approximately 33% of patients with non-small cell lung cancer (NSCLC) tumors and epidermal growth factor receptor mutations develop BMs, which are targetable with different generations of tyrosine kinase inhibitors (TKIs: gefitinib, erlotinib, afatinib, icotinib, and osimertinib). Other “druggable” alterations seen in up to 5% of NSCLC patients are the rearrangements of the “anaplastic lymphoma kinase” gene TKI (crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib). In human epidermal growth factor receptor 2-positive, breast cancer targeted therapies have been widely used (trastuzumab, trastuzumab-emtansine, lapatinib-capecitabine, and neratinib). Novel targeted and immunotherapeutic agents have also revolutionized the systemic management of melanoma (ipilimumab, nivolumab, pembrolizumab, and BRAF inhibitors dabrafenib and vemurafenib).

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Discordance and Conversion Rates of Progesterone-, Estrogen-, and HER2/neu-Receptor Status in Primary Breast Cancer and Brain Metastasis Mainly Triggered by Hormone Therapy

Cited by 21 publications

References 22 publications

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

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

Surgical resection of symptomatic brain metastases improves the clinical status and facilitates further treatment

Mechanisms and Therapy for Cancer Metastasis to the Brain

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