scholarly journals Texture Analysis Using Semiquantitative Kinetic Parameter Maps from DCE-MRI: Preoperative Prediction of HER2 Status in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Lirong Song ◽  
Chunli Li ◽  
Jiandong Yin
Keyword(s):  
Breast Cancer ◽  
Kinetic Parameter ◽  
Prediction Models ◽  
Texture Features ◽  
Imaging Biomarkers ◽  
Her2 Status ◽  
Training Set ◽  
Her2 Positive ◽  
Test Set ◽  
Dce Mri

ObjectiveTo evaluate whether texture features derived from semiquantitative kinetic parameter maps based on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can determine human epidermal growth factor receptor 2 (HER2) status of patients with breast cancer.Materials and MethodsThis study included 102 patients with histologically confirmed breast cancer, all of whom underwent preoperative breast DCE-MRI and were enrolled retrospectively. This cohort included 48 HER2-positive cases and 54 HER2-negative cases. Seven semiquantitative kinetic parameter maps were calculated on the lesion area. A total of 55 texture features were extracted from each kinetic parameter map. Patients were randomly divided into training (n = 72) and test (n = 30) sets. The least absolute shrinkage and selection operator (LASSO) was used to select features in the training set, and then, multivariate logistic regression analysis was conducted to establish the prediction models. The classification performance was evaluated by receiver operating characteristic (ROC) analysis.ResultsAmong the seven prediction models, the model with features extracted from the early signal enhancement ratio (ESER) map yielded an area under the ROC curve (AUC) of 0.83 in the training set (sensitivity of 70.59%, specificity of 92.11%, and accuracy of 81.94%), and the highest AUC of 0.83 in the test set (sensitivity of 57.14%, specificity of 100.00%, and accuracy of 80.00%). The model with features extracted from the slope of signal intensity (SIslope) map yielded the highest AUC of 0.92 in the training set (sensitivity of 82.35%, specificity of 97.37%, and accuracy of 90.28%), and an AUC of 0.79 in the test set (sensitivity of 92.86%, specificity of 68.75%, and accuracy of 80.00%).ConclusionsTexture features derived from kinetic parameter maps, calculated based on breast DCE-MRI, have the potential to be used as imaging biomarkers to distinguish HER2-positive and HER2-negative breast cancer.

Correlation between contrast-enhanced cone-beam breast computed tomography features and prognostic staging in breast cancer

2021 ◽  
Author(s):  
Wei-mei Ma ◽  
Jiao Li ◽  
Shuang-gang Chen ◽  
Pei-qiang Cai ◽  
Shen Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Goodness Of Fit ◽  
Characteristic Curve ◽  
Cone Beam ◽  
Imaging Biomarkers ◽  
Training Set ◽  
Test Set ◽  
Ps Ii ◽  
Contrast Enhanced ◽  
Significant Difference

Objective: To evaluate whether contrast-enhanced cone-beam breast CT (CE-CBBCT) features can risk-stratify prognostic stage in breast cancer. Methods: Overall, 168 biopsy-proven breast cancer patients were analysed: 115 patients in the training set underwent scanning using v. 1.5 CE-CBBCT between August 2019 and December 2019, whereas 53 patients in the test set underwent scanning using v. 1.0 CE-CBBCT between May 2012 and August 2014. All patients were restaged according to the American Joint Committee on Cancer eighth edition prognostic staging system. Following the combination of CE-CBBCT imaging parameters and clinicopathological factors, predictors that were correlated with stratification of prognostic stage via logistic regression were analysed. Predictive performance was assessed according to the area under the receiver operating characteristic curve (AUC). Goodness-of-fit of the models was assessed using the Hosmer-Lemeshow test. Results: As regards differentiation between prognostic stage (PS) I and II/III, increased tumour-to-breast volume ratio (TBR), rim enhancement pattern, and the presence of penetrating vessels were significant predictors for PS II/III disease (p < 0.05). The AUCs in the training and test sets were 0.967 [95% confidence interval (CI) 0.938–0.996; p < 0.001] and 0.896 (95% CI, 0.809–0.983; p = 0.001), respectively. Two features were selected in the training set of PS II vs III, including tumour volume [odds ratio (OR)=1.817, p = 0.019] and calcification (OR = 4.600, p = 0.040), achieving an AUC of 0.790 (95% CI, 0.636–0.944, p = 0.001). However, there was no significant difference in the test set of PS II vs III (P＞0.05). Conclusion: CE-CBBCT imaging biomarkers may provide a large amount of anatomical and radiobiological information for the pre-operative distinction of prognostic stage. Advances in knowledge: CE-CBBCT features have distinctive promise for stratification of prognostic stage in breast cancer.

scholarly journals Loss of HER2 Positivity after Trastuzumab in HER2-Positive Gastric Cancer: Is Change in HER2 Status Significantly Frequent?

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Yu Ishimine ◽  
Akira Goto ◽  
Yoshito Watanabe ◽  
Hidetaka Yajima ◽  
Suguru Nakagaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Residual Tumor ◽  
Her2 Status ◽  
Resected Specimen ◽  
Her2 Positive ◽  
Curative Intent ◽  
Course Of Disease ◽  
Trastuzumab Therapy ◽  
Her2 Positivity

Trastuzumab has recently been introduced as a treatment for HER2-positive metastatic and/or unresectable gastric cancer (MUGC); however, compared with breast cancer, some issues concerning HER2 and trastuzumab therapy for gastric cancer remain unclear. A 74-year-old woman received trastuzumab-containing chemotherapy for HER2-positive MUGC. She had a marked response to 8 months of chemotherapy, and gastrectomy and hepatic metastasectomy with curative intent were performed. The resected specimen showed complete loss of HER2 positivity in the residual tumor. For MUGC, a change in HER2 status during the course of the disease with or without chemotherapy has rarely been reported. However, in breast cancer, a significant frequency of change in HER2 status during the course of disease has been reported, and reevaluation of HER2 positivity in metastatic/recurrent sites is recommended. The choice of trastuzumab for MUGC is currently based on the HER2 status of the primary tumor at the time of initial diagnosis, without reassessment of HER2 status during the course of disease and/or in metastatic/recurrent sites, on the assumption that HER2 status is stable. However, our case casts doubt on the stability of HER2 in gastric cancer.

scholarly journals Centromere 17 copy number gain reflects chromosomal instability in breast cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kyoungyul Lee ◽  
Hyun Jeong Kim ◽  
Min Hye Jang ◽  
Sejoon Lee ◽  
Soomin Ahn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Copy Number ◽  
Chromosomal Instability ◽  
Copy Number Gain ◽  
Next Generation Sequencing Data ◽  
Her2 Status ◽  
Sequencing Data ◽  
Her2 Positive ◽  
Ki 67 ◽  
Positive Linear Correlation

AbstractChromosomal instability (CIN) is known to be associated with prognosis and treatment response in breast cancer. This study was conducted to determine whether copy number gain of centromere 17 (CEP17) reflects CIN, and to evaluate the prognostic and predictive value of CIN in breast cancer. CIN status was determined by summing copy number gains of four centromeric probes (CEP1, CEP8, CEP11, and CEP16) based on fluorescence in situ hybridization and CIN scores were calculated using next generation sequencing data. High CIN was associated with adverse clinicopatholgical parameters of breast cancer. Among them, positive HER2 status, high Ki-67 index and CEP17 copy number gain were found to be independent predictors of high CIN. High CIN was associated with poor clinical outcome of the patients in the whole group, as well as in luminal/HER2-negative and HER2-positive subtypes. CEP17 copy number was significantly higher in the high-CIN-score group than in the low-CIN-score group. A positive linear correlation between the mean CEP17 copy number and the CIN score was found. In conclusion, CEP17 copy number was confirmed as a useful predictor for CIN in breast cancer, and high CIN was revealed as an indicator of poor prognosis in breast cancer.

Comparison of HER2 Status by Fluorescence in Situ Hybridization and Immunohistochemistry to Predict Benefit From Dose Escalation of Adjuvant Doxorubicin-Based Therapy in Node-Positive Breast Cancer Patients

2005 ◽  
Vol 23 (19) ◽  
pp. 4287-4297 ◽  
Author(s):  
Lynn G. Dressler ◽  
Donald A. Berry ◽  
Gloria Broadwater ◽  
David Cowan ◽  
Kelly Cox ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Cancer Patients ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Node Positive ◽  
Positive Breast Cancer

Purpose HER2 is a clinically important tumor marker in breast cancer; however, there is controversy regarding which method reliably measures HER2 status. We compared three HER2 laboratory methods: immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR), to predict disease-free survival (DFS) and overall survival (OS) after adjuvant doxorubicin-based therapy in node-positive breast cancer patients. Methods This is a Cancer and Leukemia Group B (CALGB) study, using 524 tumor blocks collected from breast cancer patients registered to clinical trial CALGB 8541. IHC employed CB11 and AO-11-854 monoclonal antibodies; FISH used PathVysion HER2 DNA Probe kit; PCR utilized differential PCR (D-PCR) methodology. Results Cases HER2 positive by IHC, FISH and D-PCR were 24%, 17%, and 18%, respectively. FISH and IHC were clearly related (κ = 64.8%). All three methods demonstrated a similar relationship for DFS and OS. By any method, for patients with HER2-negative tumors, there was little or no effect of dose of adjuvant doxorubicin-based therapy. For patients with HER2-positive tumors, all three methods predicted a benefit from dose-intense (high-dose) compared with low- or moderate-dose adjuvant doxorubicin-based therapy. Conclusion FISH is a reliable method to predict clinical outcome following adjuvant doxorubicin-based therapy for stage II breast cancer patients. There is a moderate level of concordance among the three methods (IHC, FISH, PCR). None of the methods is clearly superior. Although IHC-positive/FISH-positive tumors yielded the greatest interaction with dose of therapy in predicting outcome, no combination of assays tested was statistically superior.

Mutations of HER2 gene in HER2-positive metastatic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13118-13118 ◽  
Author(s):  
T. Prempree ◽  
C. Wongpaksa
Keyword(s):  
Breast Cancer ◽  
Gene Mutations ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Trastuzumab Resistance ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Primary Tumors ◽  
Trastuzumab Therapy ◽  
One Year

13118 Background: HER2 status of Breast Cancer has been assessed by IHC and FISH and used for therapeutic decision with a high degree of success. However, there were numbers of HER2-positive MBC who finally failed the Trastuzumab treatment after initial good response. Mechanisms of intrinsic and acquired Trastuzumab resistance are not yet known. Our Objective is to identify factor or factors responsible for Trastuzumab resistance. Methods: DNA extraction and Sequencing of HER2 gene were performed on primary tumors of HER2-positive 14 MBC patients undergoing Trastuzumab therapy. Re-biopsy were done on new metstatic sites of those cases discovered to have Trastuzumab resistance. Results: Of 14 MBC cases whose tumors showing positive IHC and FISH, there were no mutation found in their HER2 gene, exons 18,19, 20 and 21. However, 3 of 14 cases of MBC undergoing continuous Trastuzumab therapy with excellent response for more than one year, developed the resistance. All three cases had new metstatic sites biopsied, and showed D880N and E837Y mutations in the exon 21 of their HER2 genes. All three cases showed no response to trastuzumab therapy. Conclusions: 1) HER2-positive MBC tumors did not have any HER2 gene mutations in them. 2) Mutations arised in their HER2 gene, exon 21 may be responsible for the intrinsic and acquired Trastuzumab resistance. Additional work in this area is needed to further substantiate our findings. No significant financial relationships to disclose.

HER2 status testing by immunohistochemical and fFluorescence in situ hybridization in China

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22233-e22233
Author(s):  
W. Tao ◽  
J. Zefei ◽  
Z. Xuan ◽  
L. Xiaobing ◽  
Z. Shaohua ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Her2 Status ◽  
Central Laboratory ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Clinical Prognosis ◽  
Her2 Testing ◽  
Regional Laboratory

e22233 Background: HER2 gene overexpression is associated with aggressive breast cancer and poor clinical prognosis. Humanized anti-HER2 monoclonal antibody trastuzumab, which is targeted HER2 protein has showed to improve overall survival in patients with HER2-positive breast cancer in both the metastatic and adjuvant settings. There are some differences in HER2 positive rate among difference reports in China. This study tested HER2 status by immunohistochemistry(IHC) and fluorescence in situ hybridization (FISH) and compared HER2 testing at central and regional laboratories in China. Methods: Assessment of HER2 status was performed by FISH using the HercepTeast kit at central laboratory and by IHC using commercial available anti-HER2 probe in formalin-fixed and paraffin-embedded tissue section of 280 breast cancer samples. IHC HER2 testing was performed on 149 samples in the central laboratory. IHC HER2 testing was performed on 80 samples at both central laboratory and regional laboratory. Results: 280 samples were tested 373 times testing by IHC and FISH. The results were showed in table 1 . 80 samples was tested by IHC at central and regional laboratory and testing results of 36.4% samples were accordant (K=0.038). 94.1% IHC3+ at central laboratory were HER2 FISH positive and 83.3% IHC 3+ at regional laboratory were HER2 FISH positive. 86.7% IHC 2+ at central laboratory were HER2 FISH positive and 62.7% IHC 2+ at regional laboratory were HER2 FISH positive. 17 samples were observed HER2 FISH positive in the 27 IHC 0/1+ tested at regional laboratoty. So good correlation was obsearved between FISH HER2 status and IHC results from central laboratory but not from regional laboratory. Conclusions: This study emphasized the important of accurate HER2 testing. HER2 FISH test should be performed for the IHC 2+ samples. Even HER2 FISH test maybe performed for IHC 0/1 sample according to clinical characteristics in China in order to make the patients have targeted therapy chance. [Table: see text] No significant financial relationships to disclose.

Should liver metastases of breast cancer be biopsied to improve treatment choice?

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. CRA1008-CRA1008 ◽  
Author(s):  
M. A. Locatelli ◽  
G. Curigliano ◽  
L. Fumagalli ◽  
V. Bagnardi ◽  
G. Aurilio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Treatment Choice ◽  
Her2 Status ◽  
Her2 Positive ◽  
Tissue Samples ◽  
Er Positive ◽  
Group A ◽  
Group B

CRA1008 Background: Decision making on systemic treatment of women with metastatic breast cancer is based on features like estrogen receptor (ER), progesterone receptor (PgR), and HER2 status assessed on the primary tumor. We evaluated the concordance of receptor status between primary tumor and liver metastases (mts) and its impact on treatment choice. Methods: We retrospectively analyzed a database including ultrasound guided liver biopsies performed from 1995 to 2008. All tissue samples, both from primary tumor and liver mts, were analyzed for ER, PgR and HER2 status. Clinical and biological data were obtained from medical charts. Differences between proportions were evaluated using the Pearson chi-square test. Results: We identified 255 consecutive patients (pts) with matched primary and liver tissue samples. Median time from primary diagnosis to liver biopsy was 3.4 years (range 0-18.3 years). Changes in ER status were observed in 41/255 pts (16.0%). 16/58 pts (27.6%) changed from ER-negative to ER-positive and 25/197 pts (12.7%) changed from ER-positive to ER-negative (p=0.0066). Changes in PgR status were observed in 76/255 pts (29.8%). 18/91 pts (19.8%) changed from PgR-negative to -positive and 58/164 pts (64.6%) from PgR-positive to PgR-negative (p <0.0001). 12/52 pts (23.1%) changed from ER- and PgR-negative to ER- or PgR-positive (group A) and 27/203 pts (13.3%) changed from ER- or PgR-positive to ER- and PgR-negative (group B) (p=0.087). In the group A the treatment of 4/12 pts (33.3%) was changed after biopsy: 2/4 started endocrine treatment (HT) and 2/4 stopped it. In group B the treatment of 18/27 pts (66.6%) was changed after biopsy: 17/18 stopped HT. Changes in HER2 status were observed in 22/167 pts (13.1%): 6/116 pts (5.1%) changed from HER2-negative to HER2-positive and 16/51 pts (31.4%) changed from HER2-positive to negative (p≤0.0001). In this group pts started and/or stopped a trastuzumab containing treatment after biopsy. Conclusions: There was a discordance in receptor status between primary tumor and liver mts, which led to change in therapy for 48/255 of pts (18.8%). Biopsy of metastases for reassessment of biological features should be considered in all pts when safe and easy to perform, since it is likely to impact treatment choice. No significant financial relationships to disclose.

Quantitative HER2 measurement and PI3K mutation profile in matched primary and metastatic breast cancer tissues.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 614-614
Author(s):  
Weidong Huang ◽  
Jonathan F. Lara ◽  
Richard Michaelson ◽  
Xiu Sun ◽  
Pierfranco Conte ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Catalytic Domain ◽  
Pik3ca Mutation ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Her2 Positive ◽  
Pik3ca Mutations ◽  
Meta Analyses ◽  
Negative Conversion

614 Background: HER2 status of primary breast cancer (PBC) is routinely used to determine systemic treatment for metastatic breast cancer (MBC) patients. Discordance rates of HER2 status between PBC and MBC range from 5.5% to 29% based on published meta-analyses. The clinical benefit of re-assessing HER2 in MBC tissues remains controversial. In this study, we measured quantitative HER2 expression in matched PBC and MBC tissues and correlated changes of HER2 with mutations in the catalytic domain of PI3 kinase(PIK3CA). Methods: Total HER2 protein expression (H2T) was quantified by the HERmark assay in 41 matched PBC and MBC formalin-fixed, paraffin-embedded specimens. PIK3CA mutation status in exons 9 (E545K and E542K) and 20 (H1047R) was determined using a validated pyrosequencing assay. Results: MBC samples included 5 lymph node, 13 viscera, 6 brain, and 17 soft tissue lesions (N=41). 27 (66%) cases showed higher H2T in MBC than in matched PBC; and 14 (34%) cases had higher H2T in PBC than in matched MBC, indicating an overall increase of H2T in matched MBC lesions (fold change 0.25-17.57; p=0.005, paired Wilcoxon rank sum test). HER2 positive conversion (HERmark negative/equivocal in PBC, but positive in matched MBC) was found in 6 (15%) cases, while HER2 negative conversion (HERmark positive in PBC, but negative/equivocal in matched MBC) was seen in 2 (5%) cases. HER2 status was unchanged in 33 (80%) cases. PIK3CA mutations were detected in 13 (32%) of PBC and 19 (46%) of MBC samples. Among the HER2 positive conversion cases, PIK3CA mutation was identified in 50% (3/6) PBC and 67% (4/6) MBC, compared to 0% (0/2, PBC or MBC) in the HER2 negative conversion cases. Among cases with unchanged HER2 status, PIK3CA mutation was observed in 30% (10/33) PBC and 42% (14/33) MBC. Conclusions: Quantitative HER2 assessment revealed a 20% discordance in HER2 status between matched PBC and MBC tissues, with more frequent conversion from low HER2 in PBC to high HER2 in MBC. PIK3CA mutation was observed more frequently in patients who converted from HER2 negative PBC to HER2 positive MBC. These results suggest that re-assessment of biomarkers in MBC tissues may better inform the selection of therapeutic options for patients with MBC.

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