Combining conventional ultrasound and ultrasound elastography to predict HER2 status in patients with breast cancer.
Frontiers in physiology
Identifying the HER2 status of breast cancer patients is important for treatment options. Previous studies have shown that ultrasound features are closely related to the subtype of breast cancer. In this study, we used features of conventional ultrasound and ultrasound elastography to predict HER2 status. The performance of model (AUROC) with features of conventional ultrasound and ultrasound elastography is higher than that of the model with features of conventional ultrasound (0.82 vs. 0.53). The SHAP method was used to explore the interpretability of the models. Compared with HER2- tumors, HER2+ tumors usually have greater elastic modulus parameters and microcalcifications. Therefore, we concluded that the features of conventional ultrasound combined with ultrasound elastography could improve the accuracy for predicting HER2 status.
10.3389/fphys.2023.1188502
Evaluating the HER-2 status of breast cancer using mammography radiomics features.
Zhou Jing,Tan Hongna,Bai Yan,Li Jie,Lu Qing,Chen Rushi,Zhang Menghuan,Feng Qin,Wang Meiyun
European journal of radiology
PURPOSE:The aim of our study was to evaluate the HER-2 status in breast cancer patients using mammography (MG) radiomics features. METHODS:A total of 306 Chinese female patients with invasive ductal carcinoma of no special type (IDC-NST) enrolled from January 2013 to July 2018 were divided into a training set (n = 244) and a testing set (n = 62). One hundred and eighty-six radiomics features were extracted from digital MG images based on the training set. The least absolute shrinkage and selection operator (LASSO) method was used to select the optimal predictive features for HER-2 status from the training set. Both support vector machine (SVM) and logistic regression models were employed based on the selected features. The area under the receiver operating characteristic (ROC) curves (AUCs) of the training set and testing set were used to evaluate the predictive performance of the models. RESULTS:Compared with the SVM model, the performance of the logistic regression model using a combination of cranial caudal (CC) and mediolateral oblique (MLO) MG views was optimal. In the training set, the sensitivity, specificity, accuracy and area under the curve (AUC) values of the logistic regression model for evaluating HER-2 status based on quantitative radiomics features were 87.29%, 58.73%, 80.00% and 0.846 (95% confidence interval (CI), 0.800-0.887), respectively, and in the testing set, the values were 73.91%, 68.75%, 77.00% and 0.787 (95% CI, 0.673-0.885), respectively. CONCLUSIONS:Radiomics features could be an efficient tool for the preoperative evaluation of HER-2 status in patients with breast cancer.
10.1016/j.ejrad.2019.108718
Explainable breast cancer molecular expression prediction using multi-task deep-learning based on 3D whole breast ultrasound.
Insights into imaging
OBJECTIVES:To noninvasively estimate three breast cancer biomarkers, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) and enhance performance and interpretability via multi-task deep learning. METHODS:The study included 388 breast cancer patients who received the 3D whole breast ultrasound system (3DWBUS) examinations at Xijing Hospital between October 2020 and September 2021. Two predictive models, a single-task and a multi-task, were developed; the former predicts biomarker expression, while the latter combines tumor segmentation with biomarker prediction to enhance interpretability. Performance evaluation included individual and overall prediction metrics, and Delong's test was used for performance comparison. The models' attention regions were visualized using Grad-CAM + + technology. RESULTS:All patients were randomly split into a training set (n = 240, 62%), a validation set (n = 60, 15%), and a test set (n = 88, 23%). In the individual evaluation of ER, PR, and HER2 expression prediction, the single-task and multi-task models achieved respective AUCs of 0.809 and 0.735 for ER, 0.688 and 0.767 for PR, and 0.626 and 0.697 for HER2, as observed in the test set. In the overall evaluation, the multi-task model demonstrated superior performance in the test set, achieving a higher macro AUC of 0.733, in contrast to 0.708 for the single-task model. The Grad-CAM + + method revealed that the multi-task model exhibited a stronger focus on diseased tissue areas, improving the interpretability of how the model worked. CONCLUSION:Both models demonstrated impressive performance, with the multi-task model excelling in accuracy and offering improved interpretability on noninvasive 3DWBUS images using Grad-CAM + + technology. CRITICAL RELEVANCE STATEMENT:The multi-task deep learning model exhibits effective prediction for breast cancer biomarkers, offering direct biomarker identification and improved clinical interpretability, potentially boosting the efficiency of targeted drug screening. KEY POINTS:Tumoral biomarkers are paramount for determining breast cancer treatment. The multi-task model can improve prediction performance, and improve interpretability in clinical practice. The 3D whole breast ultrasound system-based deep learning models excelled in predicting breast cancer biomarkers.
10.1186/s13244-024-01810-9
Imaging features of automated breast volume scanner: Correlation with molecular subtypes of breast cancer.
Zheng Feng-Yang,Lu Qing,Huang Bei-Jian,Xia Han-Sheng,Yan Li-Xia,Wang Xi,Yuan Wei,Wang Wen-Ping
European journal of radiology
OBJECTIVES:To investigate the correlation between the imaging features obtained by an automated breast volume scanner (ABVS) and molecular subtypes of breast cancer. METHODS:We examined 303 malignant breast tumours by ABVS for specific imaging features and by immunohistochemical analysis to determine the molecular subtype. ABVS imaging features, including retraction phenomenon, shape, margins, echogenicity, post-acoustic features, echogenic halo, and calcifications were analysed by univariate and multivariate logistic regression analyses to determine the significant predictive factors of the molecular subtypes. RESULTS:By univariate logistic regression analysis, the predictive factors of the Luminal-A subtype (n=128) were retraction phenomenon (odds ratio [OR]=10.188), post-acoustic shadowing (OR=5.112), and echogenic halo (OR=3.263, P<0.001). The predictive factors of the Human-epidermal-growth-factor-receptor-2-amplified subtype (n=39) were calcifications (OR=6.210), absence of retraction phenomenon (OR=4.375), non-mass lesions (OR=4.286, P<0.001), absence of echogenic halo (OR=3.851, P=0.035), and post-acoustic enhancement (OR=3.641, P=0.008). The predictors for the Triple-Negative subtype (n=47) were absence of retraction phenomenon (OR=5.884), post-acoustic enhancement (OR=5.255, P<0.001), absence of echogenic halo (OR=4.138, P=0.002), and absence of calcifications (OR=3.363, P=0.001). Predictors for the Luminal-B subtype (n=89) had a relatively lower association (OR≤2.328). By multivariate logistic regression analysis, retraction phenomenon was the strongest independent predictor for the Luminal-A subtype (OR=9.063, P<0.001) when present and for the Triple-Negative subtype (OR=4.875, P<0.001) when absent. CONCLUSIONS:ABVS imaging features, especially retraction phenomenon, have a strong correlation with the molecular subtypes, expanding the scope of ultrasound in identifying breast cancer subtypes with confidence.
10.1016/j.ejrad.2016.11.032
Intra- and peritumoral radiomics features based on multicenter automatic breast volume scanner for noninvasive and preoperative prediction of HER2 status in breast cancer: a model ensemble research.
Scientific reports
The aim to investigate the predictive efficacy of automatic breast volume scanner (ABVS), clinical and serological features alone or in combination at model level for predicting HER2 status. The model weighted combination method was developed to identify HER2 status compared with single data source model method and feature combination method. 271 patients with invasive breast cancer were included in the retrospective study, of which 174 patients in our center were randomized into the training and validation sets, and 97 patients in the external center were as the test set. Radiomics features extracted from the ABVS-based tumor, peritumoral 3 mm region, and peritumoral 5 mm region and clinical features were used to construct the four types of the optimal single data source models, Tumor, R3mm, R5mm, and Clinical model, respectively. Then, the model weighted combination and feature combination methods were performed to optimize the combination models. The proposed weighted combination models in predicting HER2 status achieved better performance both in validation set and test set. For the validation set, the single data source model, the feature combination model, and the weighted combination model achieved the highest area under the curve (AUC) of 0.803 (95% confidence interval [CI] 0.660-947), 0.739 (CI 0.556,0.921), and 0.826 (95% CI 0.689,0.962), respectively; with the sensitivity and specificity were 100%, 62.5%; 81.8%, 66.7%; 90.9%,75.0%; respectively. For the test set, the single data source model, the feature combination model, and the weighted combination model attained the best AUC of 0.695 (95% CI 0.583, 0.807), 0.668 (95% CI 0.555,0.782), and 0.700 (95% CI 0.590,0.811), respectively; with the sensitivity and specificity were 86.1%, 41.9%; 61.1%, 71.0%; 86.1%, 41.9%; respectively. The model weighted combination was a better method to construct a combination model. The optimized weighted combination models composed of ABVS-based intratumoral and peritumoral radiomics features and clinical features may be potential biomarkers for the noninvasive and preoperative prediction of HER2 status in breast cancer.
10.1038/s41598-024-55838-4
Nomogram Utilizing ABVS Radiomics and Clinical Factors for Predicting ≤ 3 Positive Axillary Lymph Nodes in HR+ /HER2- Breast Cancer with 1-2 Positive Sentinel Nodes.
Academic radiology
BACKGROUND:In HR+ /HER2- breast cancer patients with ≤ 3 positive axillary lymph nodes (ALNs), genomic tests can streamline chemotherapy decisions. Current studies, centered on tumor metrics, miss broader patient insights. Automated Breast Volume Scanning (ABVS) provides advanced 3D imaging, and its potential synergy with radiomics for ALN evaluation is untapped. OBJECTIVE:This study sought to combine ABVS radiomics and clinical characteristics in a nomogram to predict ≤ 3 positive ALNs in HR+ /HER2- breast cancer patients with 1-2 positive sentinel lymph nodes (SLNs), guiding clinicians in genetic test candidate selection. METHODS:We enrolled 511 early-stage breast cancer patients: 362 from A Hospital for training and 149 from B Hospital for validation. Using LASSO logistic regression, primary features were identified. A clinical-radiomics nomogram was developed to predict the likelihood of ≤ 3 positive ALNs in HR+ /HER2- patients with 1-2 positive SLNs. We assessed the discriminative capability of the nomogram using the ROC curve. The model's calibration was confirmed through a calibration curve, while its fit was evaluated using the Hosmer-Lemeshow (HL) test. To determine the clinical net benefits, we employed the Decision Curve Analysis (DCA). RESULTS:In the training group, 81.2% patients had ≤ 3 metastatic ALNs, and 83.2% in the validation group. We developed a clinical-radiomics nomogram by analyzing clinical characteristics and rad-scores. Factors like positive SLNs (OR=0.077), absence of negative SLNs (OR=11.138), lymphovascular invasion (OR=0.248), and rad-score (OR=0.003) significantly correlated with ≤ 3 positive ALNs. The clinical-radiomics nomogram, with an AUC of 0.910 in training and 0.882 in validation, outperformed the rad-score-free clinical nomogram (AUCs of 0.796 and 0.782). Calibration curves and the HL test (P values 0.688 and 0.691) confirmed its robustness. DCA showed the clinical-radiomics nomogram provided superior net benefits in predicting ALN burden across specific threshold probabilities. CONCLUSION:We developed a clinical-radiomics nomogram that integrated radiomics from ABVS images and clinical data to predict the presence of ≤ 3 positive ALNs in HR+ /HER2- patients with 1-2 positive SLNs, aiding oncologists in identifying candidates for genomic tests, bypassing ALND. In the era of precision medicine, combining genomic tests with SLN biopsy refines both surgical and systemic patient treatments.
10.1016/j.acra.2024.01.026
Predicting the molecular subtypes of breast cancer using nomograms based on three-dimensional ultrasonography characteristics.
Frontiers in oncology
Background:Molecular subtyping of breast cancer is commonly doneforindividualzed cancer management because it may determines prognosis and treatment. Therefore, preoperativelyidentifying different molecular subtypes of breast cancery can be significant in clinical practice.Thisretrospective study aimed to investigate characteristic three-dimensional ultrasonographic imaging parameters of breast cancer that are associated with the molecular subtypes and establish nomograms to predict the molecular subtypes of breast cancers. Methods:A total of 309 patients diagnosed with breast cancer between January 2017and December 2019 were enrolled. Sonographic features were compared between the different molecular subtypes. A multinomial logistic regression model was developed, and nomograms were constructed based on this model. Results:The performance of the nomograms was evaluated in terms of discrimination and calibration.Variables such as maximum diameter, irregular shape, non-parallel growth, heterogeneous internal echo, enhanced posterior echo, lymph node metastasis, retraction phenomenon, calcification, and elasticity score were entered into the multinomial model.Three nomograms were constructed to visualize the final model. The probabilities of the different molecular subtypes could be calculated based on these nomograms. Based on the receiver operating characteristic curves of the model, the macro-and micro-areaunder the curve (AUC) were0.744, and 0.787. The AUC was 0.759, 0.683, 0.747 and 0.785 for luminal A(LA), luminal B(LB), human epidermal growth factor receptor 2-positive(HER2), and triple-negative(TN), respectively.The nomograms for the LA, HER2, and TN subtypes provided good calibration. Conclusions:Sonographic features such as calcification and posterior acoustic features were significantly associated with the molecular subtype of breast cancer. The presence of the retraction phenomenon was the most important predictor for the LA subtype. Nomograms to predict the molecular subtype were established, and the calibration curves and receiver operating characteristic curves proved that the models had good performance.
10.3389/fonc.2022.838787
HER2-Low Breast Cancer: a New Subtype?
Current treatment options in oncology
OPINION STATEMENT:Breast cancer (BC) guidelines subdivide the disease into three main groups, namely hormone receptor (HR)-positive HER2-negative, HER2-positive, and triple-negative BC (TNBC). The natural history of the HER2-positive subtype has changed since the introduction of HER-targeted therapies, which demonstrated benefit only in case of HER2 overexpression (IHC, score 3+) or gene amplification. Such observation may depend on direct drug inhibition of HER2 downstream signaling, which is needed for survival and proliferation in HER2-addicted BC. Clinically focused categories cannot comprehensively describe biology, as almost half of the currently defined HER2-negative BCs show some degree of IHC expression and have been recently renamed as HER2-low. Why? As technological breakthroughs enable the synthesis of antibody-drug conjugates (ADCs), target antigens may be viewed not only as a biological switch to be turned on-off by targeted drugs but also as an anchor for ADC docking and tethering. As trastuzumab deruxtecan (T-DXd) has already proven in the clinical trial DESTINY-Breast04, even fewer HER2 available receptors on cancer cells may be sufficient for a clinical benefit. So, for HR-negative HER2-low subtype (~40% of TNBCs), though only 58 patients had been enrolled in DESTINY-Breast04, the observed benefit, together with the dismal prognosis of TNBC, warrants the use of T-DXd. Notably, another topoisomerase-based ADC, sacituzumab govitecan, has already been granted approval for pretreated TNBC (ASCENT). As no head-to-head comparison has been performed, the choice relies on regulatory approvals at the time of patient assessment, critical appraisal of available evidence, and careful evaluation of possible cross-resistance with sequential use of ADCs. As for HR-positive HER2-low disease (~60% of HR-positive tumors), DESTINY-Breast04 provides solid evidence for T-DXd prioritization in either second or third treatment lines. Although the remarkable activity observed in this setting favorably compares with outcomes observed in treatment-naive patients, the ongoing DESTINY-Breast06 will clarify the role of T-DXd in this population.
10.1007/s11864-023-01068-1
Correlation of shear-wave elastography parameters with the molecular subtype and axillary lymph node status in breast cancer.
Clinical imaging
PURPOSE:To examine correlations between shear-wave elastography (SWE) parameters with molecular subtype and axillary lymph node (LN) status of breast cancer. METHODS:We retrospectively analyzed 545 consecutive women (mean age, 52.7 ± 10.7 years; range, 26-83) with breast cancer who underwent preoperative breast ultrasound with SWE between December 2019 and January 2021. SWE parameters (E, E, and E) and the histopathologic information from surgical specimens including histologic type, histologic grade, size of invasive cancer, hormone receptor and HER2 status, Ki-67 proliferation index, and axillary LN status were analyzed. The relationships between SWE parameters and histopathologic findings were analyzed using an independent sample t-test, one-way ANOVA test with Tukey's post hoc test, and logistic regression analyses. RESULTS:Higher stiffness values of SWE were associated with larger lesion size (>20 mm) on ultrasound, high histologic grade, larger invasive cancer size (>20 mm), high Ki-67, and axillary LN metastasis. E and E were the lowest in the luminal A-like subtype, and all three parameters were the highest in the triple-negative subtype. Lower value of E was independently associated with the luminal A-like subtype (P = 0.04). Higher value of E was independently associated with axillary LN metastasis for tumors ≤ 20 mm (P = 0.03). CONCLUSION:Increases in the tumor stiffness values on SWE were significantly associated with aggressive histopathologic features of breast cancer. Lower stiffness values were associated with the luminal A-like subtype, and tumors with higher stiffness values were associated with axillary LN metastasis in small breast cancers.
10.1016/j.clinimag.2023.06.006
The use of longitudinal CT-based radiomics and clinicopathological features predicts the pathological complete response of metastasized axillary lymph nodes in breast cancer.
BMC cancer
BACKGROUND:Accurate assessment of axillary status after neoadjuvant therapy for breast cancer patients with axillary lymph node metastasis is important for the selection of appropriate subsequent axillary treatment decisions. Our objectives were to accurately predict whether the breast cancer patients with axillary lymph node metastases could achieve axillary pathological complete response (pCR). METHODS:We collected imaging data to extract longitudinal CT image features before and after neoadjuvant chemotherapy (NAC), analyzed the correlation between radiomics and clinicopathological features, and developed models to predict whether patients with axillary lymph node metastasis can achieve axillary pCR after NAC. The clinical utility of the models was determined via decision curve analysis (DCA). Subgroup analyses were also performed. Then, a nomogram was developed based on the model with the best predictive efficiency and clinical utility and was validated using the calibration plots. RESULTS:A total of 549 breast cancer patients with metastasized axillary lymph nodes were enrolled in this study. 42 independent radiomics features were selected from LASSO regression to construct a logistic regression model with clinicopathological features (LR radiomics-clinical combined model). The AUC of the LR radiomics-clinical combined model prediction performance was 0.861 in the training set and 0.891 in the testing set. For the HR + /HER2 - , HER2 + , and Triple negative subtype, the LR radiomics-clinical combined model yields the best prediction AUCs of 0.756, 0.812, and 0.928 in training sets, and AUCs of 0.757, 0.777 and 0.838 in testing sets, respectively. CONCLUSIONS:The combination of radiomics features and clinicopathological characteristics can effectively predict axillary pCR status in NAC breast cancer patients.
10.1186/s12885-024-12257-y
Feasibility of using negative ultrasonography results of axillary lymph nodes to predict sentinel lymph node metastasis in breast cancer patients.
Cancer medicine
Knowledge of the pathology of axillary lymph nodes (ALN) in breast cancer patients is critical for determining their treatment. Ultrasound is the best noninvasive evaluation for the ALN status. However, the correlation between negative ultrasound results and the sentinel lymph nodes (SLN) pathology remains unknown. To test the hypothesis that negative ultrasound results of ALN predict the negative pathology results of SLN in breast cancer patients, we assessed the association between ALN ultrasonography-negative results and the SLN pathology in 3115 patients with breast cancer recruited between October 2010 and April 2016 from a single cancer center, prospective database. Of these patients who met the inclusion criteria, 2317 (74.4%) had no SLN pathological metastasis. In the univariate analysis, other 798 patient with positive SLN tended to be under age 40 and premenopausal, having large tumor sizes (>2 cm), higher histological grade of primary tumor, positive hormone receptors, and negative HER-2 status (P < .05 for all). In the multivariate analysis, menstrual status, tumor size, ER status and histological types of primary tumor remained to be independent predictors for SLN pathological metastasis. The area under curve (AUC) was 0.658 (95% CI = 0.637-0.679), P > .05. In conclusion, only a 74.4% consistency between ALN ultrasonography-negative results and negative pathological SLN results, although menstrual status, tumor size, histologic subtypes of primary tumor and ER status were found to be statistically independent predictors of positive SLN among patients negative for ALN ultrasonography. Therefore, the present study suggests that negative ultrasound results of ALN do not adequately predict the negative pathology results of SLN in breast cancer patients.
10.1002/cam4.1606
Association and predictive value of contrast‑enhanced ultrasound features with axillary lymph node metastasis in primary breast cancer.
Oncology letters
Primary breast cancer is the most common malignant tumor in women worldwide, and axillary lymph node metastasis (ALNM) is an important marker of disease progression in patients with breast cancer. The objective of the present study was to analyze the association between contrast-enhanced ultrasound (CEUS) features and ALNM in primary breast cancer and its predictive value. A total of 120 patients with breast cancer were assigned to the non-metastatic group (n=70) and metastatic group (n=50). The factors influencing ALNM were explored by multivariate logistic regression analysis. The consistency of CEUS, ordinary ultrasonography and pathological examination in the diagnosis of the ALNM of breast cancer was evaluated by consistency testing. The sensitivity, specificity and consistency rate of CEUS features and ordinary ultrasonography were analyzed by receiver operating characteristic curve and four-fold table analyses. High enhancement amplitude, centripetal enhancement sequence, increased maximum cortical thickness, high peak intensity and a larger area under the curve of lymph nodes were more commonly found in the metastatic group than in the non-metastatic group. The lymph node aspect ratio and time to peak were lower in the metastatic group than the non-metastatic group. The time to peak was a protective factor for ALNM in patients with breast cancer. The sensitivity, specificity and coincidence rate with pathological examination of CEUS in the diagnosis of ALNM were 92.00, 90.00 and 90.83%, while these of ordinary ultrasonography were 76.00, 80.00 and 78.33%, respectively. The consistency test indicated that CEUS and pathological examination were consistent in the diagnosis of ALNM in patients with breast cancer, with a κ value of 0.816, indicating a good consistency. The κ value of ordinary ultrasonography and pathological examination was 0.763, also indicating a good consistency. However, these results indicate that CEUS is more valuable than ordinary ultrasonography in the diagnosis of ALNM in cases of breast cancer. In conclusion, the present study indicates that CEUS features were influencing factors associated with ALNM in patients with breast cancer and may serve as an important reference for the preoperative prediction of ALNM in breast cancer.
10.3892/ol.2024.14231
Characteristics of regional lymph node metastasis in breast cancer and construction of a nomogram model based on ultrasonographic analysis: a retrospective study.
World journal of surgical oncology
OBJECTIVE:The ultrasonographic characteristics of lymph node metastasis in breast cancer patients were retrospectively analyzed, and a predictive nomogram model was constructed to provide an imaging basis for better clinical evaluation. METHODS:B-mode ultrasound was used to retrospectively analyze the imaging characteristics of regional lymph nodes and tumors. Pathological examination confirmed the presence of lymph node metastasis in breast cancer patients. Univariable and multivariable logistic regression analyses were performed to analyze the risk factors for lymph node metastasis. LASSO regression analysis was performed to screen noninvasive indicators, and a nomogram prediction model was constructed for breast cancer patients with lymph node metastasis. RESULTS:A total of 187 breast cancer patients were enrolled, including 74 patients with lymph node metastasis in the positive group and 113 patients without lymph node metastasis in the negative group. Multivariate analysis revealed that pathological type (OR = 4.58, 95% CI: 1.44-14.6, p = 0.01), tumor diameter (OR = 1.37, 95% CI: 1.07-1.74, p = 0.012), spiculated margins (OR = 7.92, 95% CI: 3.03-20.67, p < 0.001), mixed echo of the breast tumor (OR = 37.09, 95% CI: 3.49-394.1, p = 0.003), and unclear lymphatic hilum structure (OR = 16.07, 95% CI: 2.41-107.02, p = 0.004) were independent risk factors for lymph node metastasis. A nomogram model was constructed for predicting breast cancer with lymph node metastasis, incorporating three significantly correlated indicators identified through LASSO regression analysis, namely, tumor spiculated margins, cortical thickness of lymph nodes, and unclear lymphatic hilum structure. The receiver operating characteristic (ROC) curve revealed that the area under the curve (AUC) was 0.717 (95% CI, 0.614-0.820) for the training set and 0.817 (95% CI, 0.738-0.890) for the validation set. The Hosmer-Lemeshow test results for the training set and the validation set were p = 0.9148 and p = 0.1648, respectively. The prediction nomogram has good diagnostic performance. CONCLUSIONS:B-mode ultrasound is helpful in the preoperative assessment of breast cancer patients with lymph node metastasis. The predictive nomogram model, which is based on logistic regression and LASSO regression analysis, is clinically safe, reliable, and highly practical.
10.1186/s12957-024-03498-z
Predictive value of combining clinicopathological, multimodal ultrasonic characteristics in axillary lymph nodal metastasis burden of patients with cT1-2N0 breast cancer.
Clinical hemorheology and microcirculation
OBJECTIVE:To improving diagnosis of axillary lymph node metastasis (ALNM), we assessed the value of combining clinicopathological, conventional ultrasound, SWE features in the cT1-2N0 breast cancer patients. METHODS:Retrospective analysis of 285 patients with cT1-2N0 breast cancer who underwent preoperative ultrasound examination of the lesion and axillary, with shear wave elastography (SWE) of the lesions. According to the postoperative pathological results, they were divided into ≤2 metastatic ALNs group (low nodal burden, LNB) and > 2 metastatic ALNs group (high nodal burden, HNB). Binary logistic regression analysis was used to screen independent risk factors and establish prediction models. The best cut-off value of continuous variables is determined by the receiver operating characteristic curve, and the performance of the prediction model is evaluated. RESULTS:Presence of lymphovascular invasion (OR = 7.966, P = 0.010), tumor size (OR = 2.485, P = 0.019), Emean of intratumor (OR = 0.939, P = 0.002) and cortical thickness of lymph node (OR = 9.277, P < 0.001) were independent risk predictors for HNB of cT1-2N0 Group. The predictive model of combined method had better performance in predicting HNB of cT1-2N0 compared with models based on SWE and conventional ultrasound alone (area under the curve: 0.824 vs 0.658, P < 0.001; 0.824 vs 0.789, P = 0.035). CONCLUSIONS:The predictive models of combined method obtained from significant clinicopathological and ultrasonographic features can potentially improve the diagnosis and individual treatment of ALNM in patients with cT1-2N0 breast cancer.
10.3233/CH-221398
Predictive value for axillary lymph node metastases in early breast cancer: Based on contrast-enhanced ultrasound characteristics of the primary lesion and sentinel lymph node.
Clinical hemorheology and microcirculation
OBJECTIVE:To evaluate the value of contrast-enhanced ultrasound (CEUS) characteristics based on primary lesion combined with lymphatic contrast-enhanced ultrasound (LCEUS) patterns of SLN in predicting axillary lymph node metastasis (ALNM) with T1-2N0 breast cancer. METHODS:A retrospective study was conducted in 118 patients with clinically confirmed T1-2N0 breast cancer. Conventional ultrasound (CUS) and CEUS characteristics of the primary lesion and enhancement patterns of SLN were recorded. The risk factors associated with ALNM were selected by univariate and binary logistic regression analysis, and the receiver operating characteristic (ROC) curve was drawn for the evaluation of predictive ALNM metastasis performance. RESULTS:Univariate analysis showed that age, HER-2 status, tumor size, nutrient vessels, extended range of enhancement lesion, and the enhancement patterns of SLN were significant predictive features of ALNM. Further binary logistic regression analysis indicated that the extended range of enhancement lesion (p < 0.001) and the enhancement patterns of SLN (p < 0.001) were independent risk factors for ALNM. ROC analysis showed that the AUC of the combination of these two indicators for predicting ALNM was 0.931 (95% CI: 0.887-0.976, sensitivity: 75.0%, specificity: 99.8%). CONCLUSION:The CEUS characteristics of primary lesion combined with enhancement patterns of SLN are highly valuable in predicting ALNM and can guide clinical axillary surgery decision-making in early breast cancer.
10.3233/CH-231973
Predictive risk factors for sentinel lymph node metastasis using preoperative contrast-enhanced ultrasound in early-stage breast cancer patients.
Qiao Jianghua,Li Juntao,Wang Lina,Guo Xiaoxia,Bian Xiaolin,Lu Zhenduo
Gland surgery
Background:Sentinel lymph node biopsy (SLNB) is the standard procedure for axillary staging in clinically node-negative (cN0) breast cancer patients. The positive rate of SLNs in cN0 stage patients ranges from 20.5% to 25.5%, so identifying appropriate candidates for SLNB is quite challenging. The aims of this study were to assess whether contrast-enhanced ultrasound (CEUS) could be utilized to noninvasively predict SLN metastasis, and to explore the predictive value of the involved factors. Methods:Between May 2016 and May 2018, 217 consenting breast cancer patients undergoing SLNB were enrolled. Before the surgery, CEUS was utilized to identify the SLNs, and predict whether metastasis had occurred according to their enhancement pattern. Blue dye was also used to identify the SLNs during SLNB. The rates of identification and accuracy of both methods were recorded. The predictive outcomes of SLNs identified by CEUS were recorded and compared with the pathological diagnosis. Results:Of the 217 cases, SLNs in 212 cases were successfully identified, comprising 208 cases identified by CEUS and 206 cases by blue dye, with no significant difference between the two methods (P=0.6470). A total of 78 cases were predicted SLN-positive preoperatively by CEUS, comprising 61 cases of SLN metastasis confirmed by pathology and 17 cases of no SLN metastasis, and 130 cases were predicted SLN-negative by CEUS, comprising 6 cases of SLN metastasis and 124 cases of no SLN metastasis. The sensitivity of CEUS preoperative prediction was 91.0%, the specificity was 87.9%, the positive and negative predictive values were 78.2% and 95.4%, respectively, and the accuracy was 88.9%. The maximum diameter size of positive SLNs predicted by CEUS was greater than that of negative SLNs (mean value 1.67±0.06 . 1.40±0.05 cm, P=0.0007). Similarly, the primary tumor size predicted SLN-positive by CEUS was greater than that in patients with negative SLNs (mean value 2.64±0.12 . 1.79±0.09 cm, P<0.0001). Conclusions:CEUS accurately identified SLNs and can be used to noninvasively predict SLN metastasis in early-stage breast cancer patients. However, the primary tumor size and the SLN size should not be overlooked by clinicians when judging the status of SLNs. This novel method may be a recommended strategy for identifying appropriate SLNB candidates.
10.21037/gs-20-867
Adding contrast-enhanced ultrasound markers to conventional axillary ultrasound improves specificity for predicting axillary lymph node metastasis in patients with breast cancer.
Du Li-Wen,Liu Hong-Li,Gong Hai-Yan,Ling Li-Jun,Wang Shui,Li Cui-Ying,Zong Min
The British journal of radiology
OBJECTIVE:To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) combined with conventional ultrasound of axillary lymph nodes (ALNs) in predicting metastatic ALNs in patients with breast cancer. METHODS:This retrospective study included 259 patients with breast cancer who underwent conventional ultrasound and CEUS. The parameters and patterns evaluated on conventional ultrasound included short axis diameter (S), long axis/short axis (L/S) ratio, cortical thickness, resistive index (RI), lymph node (LN) morphology of greyscale ultrasound, hilum and vascular pattern. Meanwhile, enhancement pattern, wash-in time, time to peak (TP), maximum signal intensity, and duration of contrast enhancement were evaluated on CEUS. Univariate and multiple logistic regression analyses were performed to identify independent factors of ALN status. Three models (conventional ultrasound, CEUS, and combined parameters) were established. Receiver operating characteristic (ROC) curves were applied to evaluate the accuracy of the three predictive models. RESULTS:On conventional axillary ultrasound, LN morphology and vascular pattern were independent factors in predicting metastatic ALNs. On CEUS, maximum signal intensity, duration of contrast enhancement, and TP were independent factors in predicting metastatic ALNs. When combining conventional ultrasound and CEUS features, five independent factors obtained from the conventional ultrasound and CEUS were associated with ALN status. ROC curve analysis showed that the use of CEUS markers combined with conventional ultrasound features (AUC = 0.965) was superior to the use of CEUS markers (AUC = 0.936) and conventional ultrasound features alone (AUC = 0.851). CONCLUSION:Combining conventional ultrasound and CEUS features can enable discrimination of ALN status better than the use of CEUS and conventional ultrasound features alone. ADVANCES IN KNOWLEDGE:The axillary lymph node status in breast cancer patients impacts the treatment decision. Our ultrasonic data demonstrated that CEUS features of ALNs in breast cancer patients could be image markers for predicting ALN status. Combining conventional ultrasound and CEUS features of ALNs can improve specificity discrimination of ALN status better than the use of CEUS and the conventional ultrasound features alone, which will help the treatment planning optimization.
10.1259/bjr.20200874
Correlation between the contrast-enhanced ultrasound image features and axillary lymph node metastasis of primary breast cancer and its diagnostic value.
Xu H,Xu G L,Li X D,Su Q H,Dong C Z
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
PURPOSE:To analyze the correlation between contrast-enhanced ultrasound image features and axillary lymph node metastasis of primary breast cancer and its diagnostic value. METHODS:In this study, 64 patients with axillary lymph node metastasis of primary breast cancer diagnosed and treated in our hospital from February 2011 to March 2013 were collected as an observation group, and 54 patients without axillary lymph node metastasis were collected as a control group. All patients underwent a contrast-enhanced ultrasound examination, and the correlation between the contrast-enhanced ultrasound image features and axillary lymph node metastasis and its diagnostic value were analyzed. They were divided into two groups according to their survival conditions: the group with good efficacy and group with poor efficacy, and the prognostic factors of breast cancer in the two groups were analyzed. RESULTS:There were statistical differences in the peripheral acoustic halo, blood flow classification, ratio of length to diameter (L/D), maximum cortical thickness, and enhancement mode of lymph nodes between the two groups (p < 0.05). The area under ROC curve for diagnosis of axillary lymph node metastasis by contrast-enhanced ultrasound was 0.854, sensitivity was 83.33%, and specificity was 87.5%; L/D and enhancement mode were independent prognostic factors for breast cancer. CONCLUSIONS:Contrast-enhanced ultrasound image features have diagnostic and prognostic value for axillary lymph node metastasis of breast cancer.
10.1007/s12094-020-02407-6
Long term outcome data from the EORTC 75111-10114 ETF/BCG randomized phase II study: Pertuzumab and trastuzumab with or without metronomic chemotherapy for older patients with HER2-positive metastatic breast cancer, followed by T-DM1 after progression.
Breast (Edinburgh, Scotland)
INTRODUCTION:Older patients are at higher risk of chemotherapy-induced toxicity, raising interest in less toxic anti-HER2 regimens for older persons with HER2-positive (HER2+) metastatic breast cancer (MBC). PATIENTS AND METHODS:This phase II study randomized (1:1) patients with HER2+ MBC, aged 70+ or frail 60+, to first line chemotherapy with metronomic oral cyclophosphamide (M) + Trastuzumab (T) and Pertuzumab (P) or TP alone. T-DM1 was offered in case of progression. RESULTS:In total, 39 and 41 patients were randomized to TP and TPM arm respectively. Median follow-up is 54.0 months. 24-month PFS was 18.7% (95% CI 8.2-32.4) and 28.7% (95% CI 15.8-43.0), respectively. A total of 49 (61.3%) patients died of whom 37 (75.5%) from disease progression; number of deaths per arm was 27 (69.2%) for TP and 22 (53.7%) for TPM. There was no significant difference in OS between the two arms (median OS TP vs TPM: 32.1 vs 37.5 months, p 0.25). Among the 40 patients who have started T-DM1 after disease progression on TP/TPM, PFS rate at 6 months after start of T-DM1 was 43.6% (95% CI: 27.7-58.5) and grade 3 or higher AE occurred in 18 pts (45%). CONCLUSIONS:Metronomic chemotherapy-based dual blockade (TPM), followed by T-DM1 after progression, provides an active and relatively well tolerated treatment option in an older/frail HER2+ MBC population, with a median survival of over 3 years. Nevertheless, the majority of this older/frail population died from breast cancer, highlighting the need for well tolerated and efficacious treatments in these patients.
10.1016/j.breast.2022.05.004
Breast MRI for evaluating patients with metastatic axillary lymph node and initially negative mammography and sonography.
Ko Eun Young,Han Boo-Kyung,Shin Jung Hee,Kang Seok Seon
Korean journal of radiology
OBJECTIVE:We wanted to investigate the ability of breast MR imaging to identify the primary malignancy in patients with axillary lymph node metastases and initially negative mammography and sonography, and we correlated those results with the conventional imaging. MATERIALS AND METHODS:From September 2001 to April 2006, 12 patients with axillary lymph node metastases and initially negative mammography and sonography underwent breast MR imaging to identify occult breast carcinoma. We analyzed the findings of the MR imaging, the MR-correlated mammography and the second-look sonography. We followed up both the MR-positive and MR-negative patients. RESULTS:MR imaging detected occult breast carcinoma in 10 of 12 (83%) patients. Two MR-negative patients were free of carcinoma in the ipsilateral breast during their follow-up period (39 and 44 months, respectively). In nine out of 10 patients, the MR-correlated mammography and second-look sonography localized lesions that were not detected on the initial exam. All the non-MR-correlated sonographic abnormalities were benign. CONCLUSION:Breast MR imaging can identify otherwise occult breast cancer in patients with metastatic axillary lymph nodes. Localization of the lesions through MR-correlated mammography and second-look sonography is practically feasible in most cases.
10.3348/kjr.2007.8.5.382
Discordance rate of HER2 status in primary breast carcinomas versus synchronous axillary lymph node metastases: a multicenter retrospective investigation.
Ieni Antonio,Barresi Valeria,Caltabiano Rosario,Cascone Anna Maria,Del Sordo Rachele,Cabibi Daniela,Zeppa Pio,Lanzafame Salvatore,Sidoni Angelo,Franco Vito,Tuccari Giovanni
OncoTargets and therapy
BACKGROUND:Human epidermal growth factor receptor 2 (HER2) is considered to be a therapeutic and prognostic marker in the management of breast carcinoma (BC), although discordance rates between primary and metastatic or locally recurrent lesions have been reported. METHODS:One hundred and forty-eight paraffin-embedded BC tissues from patients of mean age 59.27 (33-96) years and corresponding synchronous lymph node metastases were collected and retrospectively studied using immunohistochemistry and fluorescence in situ hybridization to evaluate HER2 status. Fleiss-Cohen weighted k statistics were used to assess the concordance rate between HER2 status of the primary BC and the synchronous metastatic lesions. RESULTS:The overall concordance rate for HER2 was 95.28%. Eighty-nine cases were concordantly HER2-negative in primary BC and nodal metastases, and 52 cases were HER2-positive in both primary and metastatic tumors. Changes in HER2 status between primary BC and corresponding synchronous metastases were observed in seven (4.72%) cases. Three of the discordant cases were HER2-negative in the primary tumor and HER2-positive in the metastases, while four cases were HER2-positive in the primary BC and HER2-negative in the metastases. No significant correlations were identified between HER2 status and expression of hormone receptors, growth fraction (Ki-67), or other histopathological parameters (pT, pN, grade). CONCLUSION:Simultaneous determination of HER2 in BC and corresponding metastatic lymph nodes is not mandatory, but may strongly influence the therapeutic management. It was demonstrated that loss of HER2 amplification results in worse post-relapse survival and overall survival in BC patients and, on the other hand, a gain in HER2 expression in metastatic lymph nodes of BC may allow the possibility of a targeted treatment. Thus, our opinion is that significant prognostic information may be obtained by simultaneous assessment of HER2 status in both primary and synchronous metastatic BC.
10.2147/OTT.S65294
Dual HER2 blockade in the first-line treatment of metastatic breast cancer - A retrospective population-based observational study in Danish patients.
Christensen Thomas,Berg Tobias,Nielsen Lise Birk,Andersson Michael,Jensen Maj-Britt,Knoop Ann
Breast (Edinburgh, Scotland)
OBJECTIVES:Randomized clinical trials do not include a population that truly reflects a real-world population, due to their inclusion and exclusion criteria. This leads to concerns about the applicability of these studies in a clinical practice. In the present study, we aim to describe the clinical and demographic characteristics, treatment patterns, and clinical outcomes in a population of patients with HER2-positive metastatic breast cancer who received pertuzumab and trastuzumab as first-line treatment in a real-world setting. METHODS:The database of the Danish Breast Cancer Group was used to assemble data on patients included in the period April 2013 to August 2017. The primary endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS:A cohort of 291 patients with a median age of 58 years was registered. Hereof 112 (38%) patients with de novo disease (primary disseminated) and 179 (62%) with recurrence. The median follow-up for OS was 24.1 months. The median OS was 41.8 months (95% CI, 37.7 to NE) and the median PFS was 15.8 months (95% CI, 14.0 to 19.9). For de novo patients alone, the median OS was not reached whereas the median PFS was 17.9 months (95% CI, 14.3 to 27.3). Hazard ratios for patients receiving vinorelbine showed comparable results as for the whole population. CONCLUSION:This heterogeneous patient population in a real-world setting had a PFS comparable with what could be expected from the related randomized trial. The de novo patients had better OS and PFS as compared to patients with recurrence.
10.1016/j.breast.2020.03.002
Impacts of clinicopathological factors on efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer.
Breast (Edinburgh, Scotland)
BACKGROUND:The previous second-line treatment for HER2-positive metastatic breast cancer were ado-trastuzumab emtansine (T-DM1); however, its activity is decreased in tumors with heterogenous, reduced, or loss of HER2 expression. Trastuzumab deruxtecan (T-DXd) has recently been developed as a novel antibody-drug conjugate to overcome resistance to T-DM1. However, clinical evidence on its ability to overcome this resistance is limited. MATERIALS AND METHODS:We retrospectively analyzed data for patients with HER2-positive metastatic breast cancer who received T-DXd at our institution from April 2020 to March 2021. We evaluated the associations between clinicopathological and molecular biomarkers and the efficacy of T-DXd. RESULTS:Twenty-two patients were enrolled in this study. The median progression-free survival (PFS) was 9.7 months (95% confidence interval [CI], 7.0-not reached [NR]), and the objective response rate (ORR) was 61.9%. The ORR and PFS were comparable between patients with HER2 immunohistochemistry scores of 3+ and 2+/1+ at initial diagnosis (ORR: 50.0% vs. 72.7%, p = 0.39; median PFS, 9.7 months [95%CI, 2.6-NR] vs. 8.3 months [95%CI, 7.1-NR]; hazard ratio, 1.86 [95%CI, 0.53-6.57], p = 0.34). Two patients with heterogenous HER2 expression had a partial response or long stable disease (≥6 months). Three of four patients with re-biopsy samples after anti-HER2 targeted therapy and with latest HER2 immunohistochemistry scores of 1+ experienced partial responses (75.0%) to T-DXd, but none had responded to prior T-DM1. CONCLUSIONS:T-DXd demonstrated favorable activity in clinical practice. Moreover, T-DXd showed meaningful benefit in patients with heterogeneity, reduction, or loss of HER2 expression.
10.1016/j.breast.2022.01.002
DARPP-32 and t-DARPP in the development of resistance to anti-HER2 agents. Pre-clinical evidence from the STEP study.
Neoplasia (New York, N.Y.)
The therapeutic scenario of Human Epidermal Growth Factor Receptor 2 positive advanced breast cancer (ABC) has been recently enriched by a number of innovative agents, which are reshaping treatment sequence. While randomized trials have documented an advantage in terms of efficacy, for the newly available agents we lack effectiveness and tolerability evidence from the real-world setting. Similarly, the identification of predictive biomarkers might improve clinical decision. We herein describe the outline of a prospective/retrospective study which aims to explore the optimal sequence of treatment in HER2+, pertuzumab pre-treated ABC patients treated in II line with anti-HER2 agents in clinical practice. As part of the pre-clinical tasks envisioned by the STEP study, in vitro cell models of resistance were exploited to investigate molecular features associated with reduced efficacy of HER2 targeting agents at the transcript level. The aggressive behavior of resistant cell populations was measured by growth assessment in mouse models. This approach led to the identification of DARPP-32 and t-DARPP proteins as possible predictive biomarkers of efficacy of anti-HER2 agents. Biomarkers validation and the clinical goals will be reached through patients' inclusion into two independent cohorts, i.e., the prospective and retrospective cohorts, whose setup is currently ongoing.
10.1016/j.neo.2023.100937
Trastuzumab emtansine for HER2-positive metastatic breast cancer: Outcomes from a whole-of-population Australian cohort.
Daniels Benjamin,Kiely Belinda E,Tang Monica,Houssami Nehmat,Lord Sarah J,Pearson Sallie-Anne
Breast (Edinburgh, Scotland)
PURPOSE:We aim to describe the treatment patterns and overall survival (OS) outcomes in patients receiving trastuzumab emtansine (T-DM1) for HER2-positive metastatic breast cancer (HER2+MBC) in routine clinical care. METHODS:Retrospective, whole-of-population cohort study of people initiating T-DM1 for HER2+MBC between October 2015 and May 2019 in Australia. We used dispensing claims to estimate time-to-T-DM1 initiation, duration of treatment, and treatments administered prior to and following T-DM1 therapy. We estimated OS from T-DM1 initiation and stratified results based on whether patients received first- or second-line T-DM1 treatment. We benchmarked outcomes to those reported in the pivotal, EMILIA trial. RESULTS:345 patients initiated T-DM1: 309 as second-line therapy for HER2+MBC and 36 as first-line therapy. 51% of patients had received endocrine therapy and 98% of second-line patients received pertuzumab prior to starting T-DM1. The median age was 57 years (53 in EMILIA); median time-to-T-DM1 initiation from start of HER2-targeted therapy for HER2+MBC was 11.6 months (IQR: 7.9-16.6); median duration of T-DM1 treatment was 6.5 months (3.1-13.5; 7.6 months in EMILIA), and median OS was 19.3 months (7.9-29.5; 29.9 months in EMILIA). CONCLUSIONS:Our findings highlight differences in patient characteristics (older, more previous pertuzumab therapy) and outcomes (shorter OS) from the T-DM1 pivotal trial and provide real-world estimates that can inform patient, clinician and policy, decisions around the use of HER2-targeted therapies in routine clinical care.
10.1016/j.breast.2021.05.001
Current Standards and Future Outlooks in Metastatic Her2-Positive Breast Cancer.
Breast care (Basel, Switzerland)
Background:Approximately 20% of all breast cancer cases show overexpression or amplification of the human epidermal growth factor receptor 2 (Her2) [Cancer Epidemiol Biomarkers Prev. 2017;26(4):632-41]. With the introduction of trastuzumab, lapatinib, and pertuzumab to the realm of treatment, a new era of antibody-drug conjugates had only begun. Within the last two decades, survival for patients with this tumor subtype has fundamentally improved. Summary:Beginning with a taxane plus trastuzumab/pertuzumab followed by trastuzumab deruxtecan, the first- and second-line treatments are set in stone. With the introduction of tucatinib as a newer tyrosine kinase inhibitor in combination with capecitabine and trastuzumab, there is one efficient line of treatment available after trastuzumab deruxtecan or even earlier in selected cases with active brain metastasis. Especially for later stages of disease, several combination strategies are under investigation. There is still a lack of positive results on immune checkpoint inhibition combined with Her2-targeted therapy, but hopefully an extension to the treatment algorithm will be on its way soon. Key Messages:With the HER2CLIMB trial, patients with brain metastasis were no longer excluded from bigger trials, and international guidelines implemented its presence or absence in their decision trees [N Engl J Med. 2020;382(7):597-609]. Curing Her2-positive metastatic breast cancer, or at least living a long life with this disease, is increasingly becoming a reality.
10.1159/000528756
Evolving perspectives on the treatment of HR+/HER2+ metastatic breast cancer.
Therapeutic advances in medical oncology
Breast cancer (BC) with expression of the estrogen receptor (ER) and/or progesterone receptor (PR) protein and with overexpression/amplification of the human epidermal growth factor receptor 2 (HER2), termed hormone receptor-positive (HR+)/HER2+ BC, represents ∼10% of all BCs in the United States. HR+/HER2+ BC includes HER2+ BCs that are ER+, PR+, or both ER+ and PR+ (triple-positive BC). Although the current guideline-recommended treatment combination of anti-HER2 monoclonal antibodies plus chemotherapy is an effective first-line therapy for many patients with HER2+ advanced disease, intratumoral heterogeneity within the HR+/HER2+ subtype and differences between the HR+/HER2+ subtype and the HR-/HER2+ subtype suggest that other targeted combinations could be investigated in randomized clinical trials for patients with HR+/HER2+ BC. In addition, published data indicate that crosstalk between HRs and HER2 can lead to treatment resistance. Dual HR and HER2 pathway targeting has been shown to be a rational approach to effective and well-tolerated therapy for patients with tumors driven by HER2 and HR, as it may prevent development of resistance by blocking receptor pathway crosstalk. However, clinical trial data for such approaches are limited. Treatments to attenuate other signaling pathways involved in receptor crosstalk are also under investigation for inclusion in dual receptor targeting regimens. These include cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, based on the rationale that association of CDK4/6 with cyclin D1 may play a role in resistance to HER2-directed therapies, and others such as phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway inhibitors. Herein, we will review the scientific and clinical rationale for combined receptor blockade targeting HER2 and ER for patients with advanced-stage HR+/HER2+ disease.
10.1177/17588359231187201
Targeting HER2-low in metastatic breast cancer: an evolving treatment paradigm.
Therapeutic advances in medical oncology
The results of the Phase III DESTINY-Breast04 trial of trastuzumab deruxtecan (T-DXd) are leading to a shift in both the classification and treatment of human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. In this trial, T-DXd was associated with a substantial survival benefit among patients with hormone receptor-positive and hormone receptor-negative disease and low expression of HER2, a biomarker previously considered unactionable in this treatment setting. Herein, we discuss the evolving therapeutic pathway for HER2-low disease, ongoing clinical trials, and the potential challenges and evidence gaps arising with treatment of this patient population.
10.1177/17588359231175440
Perspectives, Therapies, and Challenges for Metastatic HER2-Positive Breast Cancer.
Salkeni Mohamad Adham,Rizvi Wajeeha,Hein Kyaw,Higa Gerald M
Breast cancer (Dove Medical Press)
Even though gene amplification or protein overexpression occurs in approximately one-fifth of all breast cancers, the discovery of has, nevertheless, had profound implications for the disease. Indeed, the characterization of the receptor resulted in a number of significant advances. Structurally, unique features provided avenues for the development of numerous compounds with target-specificity; molecularly, biological constructs revealed a highly complex, internal signal transduction pathway with regulatory effects on tumor proliferation, survival, and perhaps, even resistance; and clinically, disease outcomes manifested its predictive and prognostic value. Yet despite the receptor's utility, the beneficial effects are diminished by tumor recurrence after neo- or adjuvant therapy as well as losses resulting from the inability to cure patients with metastatic disease. What these observations suggest is that while tumor response may be partially linked to uncoupling cell surface message reception and nuclear gene expression, as well as recruitment of the innate immune system, disease progression and/or resistance may involve a reprogrammable signaling mainframe that elicits alternative growth and survival signals. This review attempts to meld current perceptions related to HER2-positive metastatic breast cancer with particular attention to current biological insights and therapeutic challenges.
10.2147/BCTT.S288344
HER3, p95HER2, and HER2 protein expression levels define multiple subtypes of HER2-positive metastatic breast cancer.
Lipton Allan,Goodman Laurie,Leitzel Kim,Cook Jennifer,Sperinde Jeff,Haddad Mojgan,Köstler Wolfgang J,Huang Weidong,Weidler Jodi M,Ali Suhail,Newton Alicia,Fuchs Eva-Marie,Paquet Agnes,Singer Christian F,Horvat Reinhard,Jin Xueguang,Banerjee Joyee,Mukherjee Ali,Tan Yuping,Shi Yining,Chenna Ahmed,Larson Jeff,Lie Yolanda,Sherwood Thomas,Petropoulos Christos J,Williams Stephen,Winslow John,Parry Gordon,Bates Michael
Breast cancer research and treatment
Trastuzumab is effective in the treatment of HER2/neu over-expressing breast cancer, but not all patients benefit from it. In vitro data suggest a role for HER3 in the initiation of signaling activity involving the AKT–mTOR pathway leading to trastuzumab insensitivity. We sought to investigate the potential of HER3 alone and in the context of p95HER2 (p95), a trastuzumab resistance marker, as biomarkers of trastuzumab escape. Using the VeraTag® assay platform, we developed a dual antibody proximity-based assay for the precise quantitation of HER3 total protein (H3T) from formalin-fixed paraffin-embedded (FFPE) breast tumors. We then measured H3T in 89 patients with metastatic breast cancer treated with trastuzumab-based therapy, and correlated the results with progression-free survival and overall survival using Kaplan–Meier and decision tree analyses that also included HER2 total (H2T) and p95 expression levels. Within the sub-population of patients that over-expressed HER2, high levels of HER3 and/or p95 protein expression were significantly associated with poor clinical outcomes on trastuzumab-based therapy. Based on quantitative H3T, p95, and H2T measurements, multiple subtypes of HER2-positive breast cancer were identified that differ in their outcome following trastuzumab therapy. These data suggest that HER3 and p95 are informative biomarkers of clinical outcomes on trastuzumab therapy, and that multiple subtypes of HER2-positive breast cancer may be defined by quantitative measurements of H3T, p95, and H2T.
10.1007/s10549-013-2665-0
How we treat patients with metastatic HER2-positive breast cancer.
Nader-Marta G,Martins-Branco D,de Azambuja E
ESMO open
HER2-positive breast cancer represents 15%-20% of breast malignancies and is characterized by an aggressive behavior and high recurrence rates. Anti-HER2-directed agents represent the mainstay of treatment of patients with HER2-positive metastatic breast cancer (MBC). In this review we propose a treatment algorithm for patients with HER2-positive MBC based on the currently available literature on the topic. The combination of trastuzumab, pertuzumab and a taxane (THP) remains the preferred first-line therapy in most scenarios. Results of trials recently presented at the European Society for Medical Oncology (ESMO) Congress 2021 might have direct clinical impact in the second- and later-line settings. The randomized DESTINY-BREAST03 study compared trastuzumab deruxtecan (T-DXd) with trastuzumab emtansine (T-DM1) in patients previously treated with trastuzumab and a taxane. T-DXd significantly improved progression-free survival and showed a trend towards improved overall survival, establishing this agent as preferred second-line therapy. Treatment with T-DM1, or the combination of tucatinib, trastuzumab and capecitabine, are considered reasonable options after second-line therapy. For subsequent lines, trastuzumab duocarmazine, neratinib plus capecitabine or the continuation of trastuzumab with different chemotherapy partners are valid options. For patients experiencing disease relapse up to 6 months after completion of adjuvant therapy, as well as for those relapsing within 12 months from the completion of pertuzumab-based adjuvant treatment, we recommend T-DXd as preferred first-line option. For those relapsing between 6 and 12 months after non-pertuzumab-based adjuvant treatment, we recommend first-line THP. Finally, for patients with active brain metastasis, tucatinib-based combination represents a suitable second-line option.
10.1016/j.esmoop.2021.100343
Determinants of lymph node status in women with breast cancer: A hospital based study from eastern India.
Chakraborty Abhijit,Bose Chinmoy Kumar,Basak Jayasri,Sen Aditya Narayan,Mishra Raghwendra,Mukhopadhyay Ashis
The Indian journal of medical research
BACKGROUND & OBJECTIVES:Number of metastatic lymph nodes has a strong prognostic value in the course of breast cancer treatment, morbidity and mortality. This study was undertaken to determine the association between axillary lymph node metastasis and several variables such as age, tumour size, grade, lymphovascular invasion, oestrogen and progesterone receptor expression and HER2/neu status in patients with breast cancer. METHODS:In this study 426 (with complete information on study variables) patients with breast cancer on treatment during March 2010 to December 2013, were analyzed. TNM (tumour node matastasis) staging was evaluated. The histological grading of tumours was done according to modified Bloom-Richardson Grading System. The immunophenotype of the tumour was determined as the expression of oestrogen (ER) and progesterone (PR) receptors and Her0 2/neu status. Univariate and multivariate analyses were carried out to determine the independent predictors of metastatic lymph node. RESULTS:Among the studied patients, 44.36 per cent (189 of 426) of the patients had nodal metastases. t0 umour histology, tumour grade, size and lympho-vascular invasion were related with node positivity. On univariate analysis, age, menopause, hormone receptor status did not relate with the node metastasis. Age, tumour grade, tumour size, lympho-vascular invasion and HER2/neu expression was likely to be associated with the number of lymph node metastasis. INTERPRETATION & CONCLUSIONS:The lymph node status was associated with clinical stage, tumour grade, tumour histology and HER2/neu status. t0 hese factors may be used for better management of such patients.
10.4103/0971-5916.191761