Discordances in ER, PR and HER2 receptors between primary and recurrent/metastatic lesions and their impact on survival in breast cancer patients

Yang, Yufeng; Liao, Ying‐Yang; Yang, Mei; Peng, Ning-Fu; Xie, Shu-Rui; Xie, Yan-Fang

doi:10.1007/s12032-014-0214-2

Cited by 61 publications

(47 citation statements)

References 25 publications

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“…In a subgroup analysis of HER2-positive breast cancers with ALN metastasis, we found that distant metastasis was more frequently seen in the FNA-HER2 negative group than in the FNA-HER2 positive group, which was statistically significant. A recent study has shown that breast cancer patients with HER2 discordance between primary and metastatic tumors had worse overall survival and post-recurrence survival compared to the concordant group [36]. Considering this with our own results, it may be inferred that patients with HER2-positive breast cancer may have poor prognoses in the case of HER2-discordant ALN metastasis, relative to those with HER2-concordant ALN metastasis.…”

Section: Discussionsupporting

confidence: 74%

HER2 Expression in Fine Needle Aspirates of Lymph Nodes Detected by Preoperative Axillary Ultrasound in Breast Cancer Patients

Choi

Kim

et al. 2014

PLoS ONE

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The purpose of this study was to assess the usefulness of HER2 levels in ultrasonographically guided fine-needle aspiration biopsy (US-FNA) aspirates of axillary lymph nodes (ALNs) in the determination of lymph node metastasis or the characterization of primary breast cancer, and to correlate the HER2 levels in US-FNA aspirates (FNA-HER2s) of metastatic ALNs with the HER2 statuses of corresponding primary breast cancers. An institutional review board approved the study. Between January and October 2010, 164 patients with 167 ALNs examined by US-FNA were included. FNA-HER2s of ALNs were measured by chemiluminescence immunoassay, and they were correlated with cytologic/final diagnoses. Receiver operating characteristics (ROC) curve analysis was performed to evaluate the diagnostic ability to differentiate benign and metastatic ALNs. Additionally, FNA-HER2s of metastatic ALNs were correlated with HER2 status and other clinicopathologic variables of the primary breast cancers. Among the 167 ALNs, 138 were metastatic and 29 were benign. The mean FNA-HER2 (6.3 ng/ml) of metastatic ALNs was higher than that of benign ALNs. All 29 benign ALNs showed no measurable value of FNA-HER2 (0.0 ng/ml). The area under the ROC curves of FNA-HER2 of ALNs was 0.679 for the diagnosis of ALN metastasis. The FNA-HER2 statuses of 108 metastatic ALNs (79.4%) were concordant with the HER2 statuses of the corresponding primary breast cancers. In a subgroup analysis of HER2-positive cancers with ALN metastasis, distant metastasis was significantly associated with FNA-HER2-negativity of metastatic ALNs (P = 0.04). Although FNA-HER2 of ALNs did not improve the diagnostic performance of FNA cytology in preoperative diagnosis of ALN metastasis of overall patients, FNA-HER2-positive metastatic ALNs were significantly associated with HER2-positivity of primary breast cancers. Additionally, FNA-HER2 analysis of ALN may help to develop more personalized treatment protocol for breast cancer patients by determining the concordance or discordance of HER2 status between primary cancers and metastatic ALNs.

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Section: Discussionsupporting

confidence: 74%

HER2 Expression in Fine Needle Aspirates of Lymph Nodes Detected by Preoperative Axillary Ultrasound in Breast Cancer Patients

Choi

Kim

et al. 2014

PLoS ONE

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“…However, no change in OS was noted between concordant and discordant groups in that study [14]. Different results were seen in a study in China, which showed worse OS for patients who had receptors discordance in the biopsy [15]. However, in a review of 13 recent major studies regarding biopsy in MBC, the impact of this procedure on survival was not clear [16].…”

Section: Discussionmentioning

confidence: 94%

Biopsy of breast cancer metastases: patient characteristics and survival

et al. 2017

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BackgroundDiscordance in hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) status between primary tumors and metastatic sites for breast cancer is well established. However, it is uncertain which patient-related factors lead to biopsy when metastases are suspected and whether having a biopsy impacts survival.MethodsThe medical charts of metastatic breast cancer (MBC) patients diagnosed January 2000-August 2014 were retrospectively reviewed. A biopsy was defined as a procedure where tissue was obtained and assessed for both HR and HER2. Both bivariate and multivariate analyses were performed to assess patient characteristics related to biopsy and whether having a biopsy was associated with improved survival.ResultsOf 409 patients suspected of having MBC, 165 (40%) had a biopsy, and 34% of these had discordant HR or HER2 status when compared to the initial diagnosis. In multivariate analysis, having a biopsy was associated with: recurrence in years 2010–2014, disease-free interval of > =3 years, stage 0-IIA at presentation, suspected locoregional recurrence, being HR+/HER2-, or missing HR/HER2 at diagnosis. A similar multivariate analysis revealed that having a biopsy was associated with improved survival (HR = 0.67, p = 0.002). The association of biopsy and improved survival was noted in specific subgroups: patients with missing HR and HER2 data at initial diagnosis (p = 0.001), those without metastases in liver, lung or brain (p = 0.001), and being younger than 70 years old at recurrence (p < 0.001).ConclusionsSpecific clinical factors were associated with biopsy at the time of suspected recurrence. Having a biopsy was associated with reduced mortality.

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“…This may be due to increased expression and/or activity of co-regulators that interact with and modulate ESR1 transcriptional activity or to the selection of cells expressing ESR1 mutants that alter the pharmacology of the receptor (3-5). There is little data to suggest that loss of ESR1 is a dominant mechanism of resistance, as ESR1 loss at recurrence is observed in less than 20% of patients (6, 7). Thus, ESR1 remains a therapeutic target in breast cancers that are resistant to both first and second line endocrine interventions (8, 9).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of SERD/SERM Hybrid-CDK4/6 Inhibitor Combinations in Models of Endocrine Therapy–Resistant Breast Cancer

Wardell

Ellis

Alley

et al. 2015

Clinical Cancer Research

139

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Purpose Endocrine therapy, using tamoxifen or an aromatase inhibitor, remains first-line therapy for the management of estrogen receptor (ESR1) positive breast cancer. However, ESR1 mutations or other ligand-independent ESR1 activation mechanisms limit the duration of response. The clinical efficacy of fulvestrant, a Selective Estrogen Receptor Downregulator (SERD) that competitively inhibits agonist binding to ESR1 and triggers receptor downregulation, has confirmed that ESR1 frequently remains engaged in endocrine therapy resistant cancers. We evaluated the activity of a new class of Selective Estrogen Receptor Modulators (SERM)/SERD hybrids (SSHs) that downregulate ESR1 in relevant models of endocrine-resistant breast cancer. Building on the observation that concurrent inhibition of ESR1 and the cyclin dependent kinases 4 and 6 (CDK4/6) significantly increased progression free survival in advanced patients, we explored the activity of different SERD- or SSH-CDK4/6 inhibitor combinations in models of endocrine therapy resistant ESR1+ breast cancer. Experimental Design SERDs, SSHs, and the CDK4/6 inhibitor palbociclib were evaluated as single agents or in combination in established cellular and animal models of endocrine therapy resistant ESR1+ breast cancer. Results The combination of palbociclib with a SERDs or an SSH was shown to effectively inhibit the growth of MCF-7 cell or ESR-1 mutant patient derived tumor xenografts. In tamoxifen-resistant MCF7 xenografts the palbociclib/SERDor SSH combination resulted in an increased duration of response as compared to either drug alone. Conclusion A SERD- or SSH-palbociclib combination has therapeutic potential in breast tumors resistant to endocrine therapies or those expressing ESR1 mutations.

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Discordances in ER, PR and HER2 receptors between primary and recurrent/metastatic lesions and their impact on survival in breast cancer patients

Cited by 61 publications

References 25 publications

HER2 Expression in Fine Needle Aspirates of Lymph Nodes Detected by Preoperative Axillary Ultrasound in Breast Cancer Patients

HER2 Expression in Fine Needle Aspirates of Lymph Nodes Detected by Preoperative Axillary Ultrasound in Breast Cancer Patients

Biopsy of breast cancer metastases: patient characteristics and survival

Efficacy of SERD/SERM Hybrid-CDK4/6 Inhibitor Combinations in Models of Endocrine Therapy–Resistant Breast Cancer

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