scholarly journals Prognostic significance of receptor expression discordance between primary and recurrent breast cancers: a meta-analysis

2021 ◽  
Author(s):  
Sho Shiino ◽  
Graham Ball ◽  
Binafsha M. Syed ◽  
Sasagu Kurozumi ◽  
Andrew R. Green ◽  
...  
Keyword(s):  
Distant Metastasis ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Outcome Data ◽  
Receptor Expression ◽  
Her2 Status ◽  
Breast Cancers ◽  
Recurrent Tumors ◽  
Recurrent Breast

Abstract Purpose This meta-analysis aimed to investigate whether receptor (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor 2 [HER2]) discordances between primary and recurrent breast cancers affect patients’ survival. Methods Search terms contained ER, PR, and HER2 status details in both primary and recurrent tumors (local recurrence or distant metastasis) in addition to survival outcome data (overall survival [OS] or post-recurrence survival [PRS]). Results Loss of ER or PR in recurrent tumors was significantly associated with shorter OS as compared with receptor-positive concordance (hazard ratio [HR], 1.67; 95% confidence interval [% CI] 1.37–2.04; p < 0.00001 and HR, 1.45; 95% CI 1.21–1.75; p < 0.0001, respectively). Similar trends were observed in groups with only distant metastasis. Gain of ER was a significant predictor of longer PRS as compared with receptor-negative concordance (HR, 0.76; 95% CI 0.59–0.97; p = 0.03). Gain of PR was not a significant predictor of longer survival compared with receptor-negative concordance, but it could be related to better OS at distant metastasis. Both HER2 of loss and gain could be related to poor outcomes. Conclusion This meta-analysis showed that receptor conversion in recurrent tumors may affect patient survival as compared with receptor concordance.

scholarly journals Relative Prognostic Value of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Operable Oesophagogastric Cancer

ISRN Surgery ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
David S. Y. Chan ◽  
Fiona Campbell ◽  
Paul Edwards ◽  
Bharat Jasani ◽  
Geraint T. Williams ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
High Specificity ◽  
Endoscopic Biopsy ◽  
Receptor Expression ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Her2 Receptor ◽  
Her2 Positive ◽  
Predictive Values

Aims. The aim of this study was to determine the prognostic significance of HER2 receptor expression in operable oesophagogastric adenocarcinoma. Methods. Eighty-five consecutive patients diagnosed with oesophagogastric adenocarcinoma [18 oesophageal (OC), 32 junctional (JC) and 35 gastric (GC)] undergoing potentially curative resection were studied retrospectively. Immunohistochemistry was used to determine HER2 status at endoscopic biopsy and resection specimen. The primary outcome measure was survival. Results. Twenty (24%) patients had HER2 positive tumours which was commoner in JC (14/32, 44% versus 2/18, 11% in OC and 4/35, 11% in GC, P=0.003). The sensitivity, specificity, positive and negative predictive values of HER2 status at endoscopic biopsy were 56%, 93%, 63%, 91% respectively (weighted Kappa=0.504, P<0.0001). Five-year survival in OC HER2 positive negative was 100% and 36% (P=0.167) compared with 14% and 44% (P=0.0726) in JC and 50% and 46% (P=0.942) in GC respectively. Conclusions. Endoscopic biopsy had a high specificity and negative predictive value in determining HER2 status. Patients with JC had a significantly higher rate of HER2 overexpression and this was associated with a nonsignificant poorer survival trend. A larger study is needed to confirm these findings because of the implications for neoadjuvant and adjuvant chemotherapy regimens.

scholarly journals The effect of smoking on biological change of recurrent breast cancer

2020 ◽  
Author(s):  
Koji Takada ◽  
Shinichiro Kashiwagi ◽  
Yuka Asano ◽  
Wataru Goto ◽  
Rika Kouhashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Expression Patterns ◽  
Tumor Biology ◽  
Growth Factor Receptor ◽  
Cancer Recurrence ◽  
Smoking History ◽  
Her2 Expression ◽  
Recurrent Tumors ◽  
Recurrent Breast

Abstract Background: The selection of treatment for a patient with breast cancer largely relies on the cancer subtype. However, this process is complicated by changes in tumor biology at relapse. Smoking has been identified as a risk factor for breast cancer. The direct effect of a tobacco component delivered via blood circulation on the mammary gland tissue and subsequent DNA damage have been proposed to explain the association between cigarette smoking and breast cancer carcinogenesis. This postulation is supported by both tissue culture and animal studies demonstrating that the associated DNA damage further alters breast cancer cells, as indicated by an increased proliferative capacity and malignant transformation. In this study, we aimed to explore the relationship between changes in Estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) each receptor at recurrence, and smoking and the prognosis after recurrence.Methods: This retrospective study included 989 patients with primary breast cancer who developed relapse after surgery and 50 patients who underwent regenerative biopsy or surgery from December 2007 to March 2018. ER, PgR, and HER2 expression in the primary and recurrent lesions was evaluated using immunohistochemistry, and the correlations of these expression patterns with smoking history (pack-years) were examined.Results: When ER was evaluated in recurrent tumors, negative and positive conversions were recognized in 3 (6.0%) and 1 patient (2.0%), respectively. When PgR was evaluated, negative conversion was recognized in 15 patients (30.0%). When HER2 was evaluated, positive conversion was recognized in 6 patients (12.0%). Consequently, we observed a change in the intrinsic subtype in in 5 patients with recurrent tumors (10.0%). Although most clinical factors were not correlated with smoking, a positive conversion of HER2 in recurrence was significantly more frequent among smokers than among non-smokers (p=0.024).Conclusions: Biological changes during breast cancer recurrence should be given careful clinical consideration because they affect treatment after recurrence. Our results suggest that smoking may induce increased HER2 expression in recurrent breast tumors.

Prognostic Significance of Aneurysm Sac Shrinkage After Endovascular Aneurysm Repair

2020 ◽  
Vol 27 (5) ◽  
pp. 857-868 ◽  
Author(s):  
George A. Antoniou ◽  
Aws Alfahad ◽  
Stavros A. Antoniou ◽  
Francesco Torella
Keyword(s):  
Meta Analysis ◽  
Prognostic Significance ◽  
Endovascular Aneurysm Repair ◽  
Outcome Data ◽  
Late Complications ◽  
Case Control Studies ◽  
Random Effects Models ◽  
Secondary Interventions ◽  
Advanced Search ◽  
Aneurysm Repair

Purpose: To investigate whether patients who develop aneurysm sac shrinkage following endovascular aneurysm repair (EVAR) have better outcomes than patients with a stable or increased aneurysm sac. Materials and Methods: The Healthcare Databases Advanced Search interface developed by the National Institute for Health and Care Excellence was used to interrogate MEDLINE and EMBASE. Thesaurus headings were adapted accordingly. Case-control studies were identified comparing outcomes in patients demonstrating aneurysm sac shrinkage after EVAR with those of patients with a stable or expanded aneurysm sac. Pooled estimates of dichotomous outcome data were calculated using the odds ratio (OR) and 95% confidence interval (CI). Meta-analysis of time-to-event data was conducted using the inverse-variance method; the results are reported as a summary hazard ratio (HR) and 95% CI. Summary outcome estimates were calculated using random-effects models. Results: Eight studies were included in quantitative synthesis reporting a total of 17,096 patients (8518 patients with sac shrinkage and 8578 patients without sac shrinkage). The pooled incidence of sac shrinkage at 12 months was 48% (95% CI 40% to 56%). Patients with aneurysm sac shrinkage had a significantly lower hazard of death (HR 0.73, 95% CI 0.60 to 0.87), secondary interventions (HR 0.42, 95% CI 0.29 to 0.62), and late complications (HR 0.37, 95% CI 0.24 to 0.56) than patients with a stable or increased aneurysm sac. Furthermore, their odds of rupture were significantly lower than those in patients without shrinkage (OR 0.09, 95% CI 0.02 to 0.36). Conclusion: Sac regression is correlated to improved survival and a reduced rate of secondary interventions and EVAR-related complications. The prognostic significance of sac regression should be considered in surveillance strategies. Intensified surveillance should be applied in patients who fail to achieve sac regression following EVAR.

Breast cancer in systemic lupus erythematosus (SLE): receptor status and treatment

Lupus ◽  
2017 ◽  
Vol 27 (1) ◽  
pp. 120-123 ◽  
Author(s):  
K Chan ◽  
A E Clarke ◽  
R Ramsey-Goldman ◽  
W Foulkes ◽  
B Tessier Cloutier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systemic Lupus Erythematosus ◽  
General Population ◽  
Lupus Erythematosus ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Her2 Status ◽  
Breast Cancers ◽  
Systemic Lupus ◽  
Receptor Status

Objective There is a decreased risk of breast cancer in systemic lupus erythematosus (SLE) versus the general population; little is known regarding the receptor status of breast cancers in SLE, or treatment. Methods Breast cancer cases occurring after SLE diagnosis were ascertained through linkage with tumor registries. We determined breast cancer positivity for estrogen receptors (ER), progesterone receptors (PR), and/or Human Epidermal Growth Factor Receptor 2 (HER2), as well as cancer treatment. Results We obtained information on ER, PR, and/or HER2 status for 63 SLE patients with breast cancer. Fifty-three had information on ER and/or PR status; 36 of these (69%) were ER positive. Thirty-six of the 63 had information on HER2 status; of these, 26 had complete information on all three receptors. Twenty-one of these 26 (81%) were HER2 negative; seven of 26(27%) were triple negative. All but one patient underwent surgery; 11.5% received both non-tamoxifen chemotherapy and radiotherapy, 16.4% radiotherapy without non-tamoxifen chemotherapy, and 14.7% received non-tamoxifen chemotherapy without radiotherapy. Conclusion ER positivity was similar to historical general population figures, with a trend toward a higher proportion of triple-negative breast cancers in SLE (possibly reflecting the relatively young age of our SLE patients).

Use of mutational profiling of metastatic ER+/HER2- breast cancers and the coexistence of KRAS, MET, BRAF, and FGFR3 with PIK3CA mutations.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11003-11003
Author(s):  
Debora Fumagalli ◽  
Roberto Salgado ◽  
Carmen Criscitiello ◽  
Lina Pugliano ◽  
Ioanna Laios ◽  
...  
Keyword(s):  
Hormonal Treatment ◽  
Primary Diagnosis ◽  
Outcome Data ◽  
Her2 Status ◽  
Breast Cancers ◽  
Genetic Changes ◽  
Pik3ca Mutations ◽  
Paired Samples ◽  
Adjuvant Hormonal Treatment ◽  
High Concordance

11003 Background: ER+/HER2- breast cancers (BCs) constitute the most frequent BC subtype. Their response to endocrine therapy and degree of estrogen dependence are heterogeneous. There is little data available about the genetic changes associated with disease progression in this subtype. This information could facilitate drug development. Methods: A series of 132 ER+/HER2- BC patients diagnosed between 1982 and 2008, with known local-regional (n=10) or distant (n=98) relapse or both (n=24), and available FFPE blocks from their primary (P; n=132) and paired relapse (R; n=49) were identified at a single institution. ER and HER2 status were centrally confirmed. 120 mutations from 11 actionable genes and PTEN protein expression were determined using Fluidigm-based real-time PCR and IHC, respectively. Results: At primary diagnosis, median age was 57 years (27-90); median tumor size 2.5 cm (0.5-11); 75% had positive nodes, 26.5% were pre-menopausal; 80% received adjuvant hormonal treatment. Mutation frequency in P and R samples is presented in the Table. PIK3CA mutations were identified in 44% (58/132) P samples. HRAS, AKT1 and PIK3CA mutations were mutually exclusive. 62.5% (5/8) of KRAS-mutated, 75% (6/8) of MET-mutated, 100% (2/2) of BRAF-mutated and 33.3% (1/3) of FGFR3-mutated P had coexistent PIK3CA mutations. For the 49 evaluated pairs, high concordance for the mutations status was found between P and R. Conclusions: KRAS, BRAF, MET and FGFR3 mutations, found at relatively high frequency in this population of relapsed ER+/HER2- BCs, could represent clinically relevant targets and contribute to mechanisms of recurrence, particularly in PIK3CA-mutated BCs. Mutation profiling of additional paired samples is ongoing and clinical outcome data will be presented. [Table: see text]

Differences in vascular endothelial growth factor receptor expression and correlation with the degree of enhancement in medulloblastoma

2014 ◽  
Vol 14 (2) ◽  
pp. 121-128 ◽  
Author(s):  
Shawn L. Hervey-Jumper ◽  
Hugh J. L. Garton ◽  
Darryl Lau ◽  
David Altshuler ◽  
Douglas J. Quint ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Perioperative Complications ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Extent Of Resection ◽  
Receptor Expression ◽  
Vascular Endothelial ◽  
Significant Difference ◽  
Endothelial Growth Factor

Object Vascular endothelial growth factor (VEGF) is the major proangiogenic factor in many solid tumors. Vascular endothelial growth factor receptor (VEGFR) is expressed in abundance in pediatric patients with medulloblastoma and is associated with tumor metastasis, poor prognosis, and proliferation. Gadolinium enhancement on MRI has been suggested to have prognostic significance for some tumors. The association of VEGF/VEGFR and Gd enhancement in medulloblastoma has never been closely examined. The authors therefore sought to evaluate whether Gd-enhancing medulloblastomas have higher levels of VEGFR and CD31. Outcomes and survival in patients with enhancing and nonenhancing tumors were also compared. Methods A retrospective analysis of patients with enhancing, nonenhancing, and partially enhancing medulloblastomas was performed. Primary end points included risk stratification, extent of resection, and perioperative complications. A cohort of 3 enhancing and 3 nonenhancing tumors was selected for VEGFR and CD31 analysis as well as microvessel density measurements. Results Fifty-eight patients were analyzed, and 20.7% of the medulloblastomas in these patients were nonenhancing. Enhancing medulloblastomas exhibited strong VEGFR1/2 and CD31 expression relative to nonenhancing tumors. There was no significant difference in perioperative complications or patient survival between the 2 groups. Conclusions These results suggest that in patients with medulloblastoma the presence of enhancement on MRI may correlate with increased vascularity and angiogenesis, but does not correlate with worse patient prognosis in the short or long term.

Reagent-saving immunohistochemistry for HER2 using non-contact alternating current electric field mixing

2018 ◽  
Vol 72 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Iku Hoshino ◽  
Kazuhiro Imai ◽  
Hiroshi Nanjo ◽  
Ryuta Nakamura ◽  
Yoshitaro Saito ◽  
...  
Keyword(s):  
Electric Field ◽  
Growth Factor Receptor ◽  
Alternating Current ◽  
Her2 Status ◽  
Breast Cancers ◽  
Clinical Tool ◽  
Her2 Positive ◽  
Specific Staining ◽  
Epidermal Growth ◽  
Current Electric Field

AimsHuman epidermal growth factor receptor 2 (HER2)-targeted agents are an effective approach to treating patients with HER2-positive breast cancer. However, the lack of survival benefit in HER2-negative patients, as well as the toxic effects and high cost of the drugs, highlight the need for accurate and prompt assessment of HER2 status. Our aim was to evaluate the clinical utility of a novel reagent-saving immunohistochemistry method (AC-IHC) that saves HER2 antibody by taking advantage of the non-contact mixing effect in microdroplets subjected to an alternating current electric field.MethodsNinety-five specimens were used from patients diagnosed with primary breast cancers identified immunohistochemically as HER2 0/1+, 2+ or 3+ using ASCO/CAP guideline-certified standard IHC. The specimens were all tested using the conventional IHC method (1:50 antibody dilution) as well as AC-IHC (1:50 dilution) and reagent-saving AC-IHC (1:100 dilution).ResultsThe reagent-saving AC-IHC produced stable results with less non-specific staining using smaller amounts of labelled antibody. Moreover, the staining and accuracy of HER2 status evaluated with the reagent-saving AC-IHC method was equal to that achieved with standard IHC.ConclusionsThese results suggest reagent-saving AC-IHC could be used as a clinical tool for accurate and stable HER2 IHC, even when reagent concentrations vary.

α-basic-crystallin expression in basal-like breast cancer and its association with brain metastasis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1025-1025
Author(s):  
H. F. Kennecke ◽  
D. Voduc ◽  
S. Leung ◽  
V. L. Cryns ◽  
C. M. Perou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Metastatic Disease ◽  
Distant Metastasis ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Chi Square ◽  
Ki 67 ◽  
Cancer Subtypes

1025 Background: Basal-like breast cancers are high grade tumors with poor prognosis, having propensity for brain and lung metastasis (Perou et al. Nature 406:747–52, 2000, Cheang et al. Clin Cancer Res 14:1368–76, 2008, Luck et al. Clin Oncol (R Coll Radiol) 20:40–5, 2008). α-basic-crystallin (αBC), a small heat shock protein with anti-apoptotic and oncogenic activity, is expressed in about half of basal-like breast cancers but only 6% of other types (Moyano et al. J Clin Invest 116:261–70, 2006). Here we investigate the association of αBC with sites of distant metastasis in a large cohort of breast cancer patients. Methods: Our cohort consists of 4046 early invasive breast cancers referred to the British Columbia Cancer Agency from 1986 to 1992. Archival paraffin tissue blocks were used to construct tissue microarrays. Breast cancer subtypes were defined using a surrogate of six immunohistochemical markers: ER, PR, HER2, Ki-67, epidermal growth factor receptor and cytokeratin 5/6. αBC immunostaining was scored by pre-established, published criteria. All documented sites of distant metastasis were abstracted by chart review according to predefined categories. The null hypothesis was tested using chi-square and Fisher's Exact tests; all tests were two-sided. Results: Among 3,248 cases with interpretable αBC data, 11% were αBC +. Among patients who developed distant metastatic disease, the 10-yr BCSS survival in αBC+ and - tumors was 12% and 29%. Sites of metastatic disease included: brain (15%), lung (35%), liver (35%) and bone (65%). Brain metastasis was significantly more common among αBC positive tumors (Fisher's Exact test p<10e-8). Basal-like tumors with brain metastasis commonly co-expressed αBC (Chi-square p=0.006). Conclusion: αBC is significantly associated with brain metastasis, particularly among basal breast cancers. These findings suggested that αBC may be involved in tumor cell metastasis and may allow early identification of a subset of patients at particularly high risk of brain metastasis. [Table: see text] No significant financial relationships to disclose.

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