•A computer-aided diagnosis (CAD) system was proposed to diagnose breast cancer in ultrasound images.•In this study, we propose a CAD system for tumor diagnosis using an image fusion method combined ...with different image content representations and ensemble different CNN architectures on US images.•The results of our CAD system in the SNUH dataset show that the accuracy, sensitivity, specificity, precision, F1 score, and the AUC of the proposed method were 91.10%, 85.14%, 95.77%, 94.03%, 89.36%, and 0.9697, respectively. The results of our CAD system in the open dataset (BUSI) show that the accuracy, sensitivity, specificity, precision, F1 score, and the AUC of the proposed method were 94.62%, 92.31%, 95.60%, 90%, 91.14%, and 0.9711, respectively.
Breast ultrasound and computer aided diagnosis (CAD) has been used to classify tumors into benignancy or malignancy. However, conventional CAD software has some problems (such as handcrafted features are hard to design; conventional CAD systems are difficult to confirm overfitting problems, etc.). In our study, we propose a CAD system for tumor diagnosis using an image fusion method combined with different image content representations and ensemble different CNN architectures on US images. The CNN-based method proposed in this study includes VGGNet, ResNet, and DenseNet. In our private dataset, there was a total of 1687 tumors that including 953 benign and 734 malignant tumors. The accuracy, sensitivity, specificity, precision, F1 score and the AUC of the proposed method were 91.10%, 85.14%, 95.77%, 94.03%, 89.36%, and 0.9697 respectively. In the open dataset (BUSI), there was a total of 697 tumors that including 437 benign lesions, 210 malignant tumors, and 133 normal images. The accuracy, sensitivity, specificity, precision, F1 score, and the AUC of the proposed method were 94.62%, 92.31%, 95.60%, 90%, 91.14%, and 0.9711. In conclusion, the results indicated different image content representations that affect the prediction performance of the CAD system, more image information improves the prediction performance, and the tumor shape feature can improve the diagnostic effect.
Patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)-targeted therapy have a worse prognosis than those who ...have no residual cancer. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy.
We conducted a phase 3, open-label trial involving patients with HER2-positive early breast cancer who were found to have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab. Patients were randomly assigned to receive adjuvant T-DM1 or trastuzumab for 14 cycles. The primary end point was invasive disease-free survival (defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause).
At the interim analysis, among 1486 randomly assigned patients (743 in the T-DM1 group and 743 in the trastuzumab group), invasive disease or death had occurred in 91 patients in the T-DM1 group (12.2%) and 165 patients in the trastuzumab group (22.2%). The estimated percentage of patients who were free of invasive disease at 3 years was 88.3% in the T-DM1 group and 77.0% in the trastuzumab group. Invasive disease-free survival was significantly higher in the T-DM1 group than in the trastuzumab group (hazard ratio for invasive disease or death, 0.50; 95% confidence interval, 0.39 to 0.64; P<0.001). Distant recurrence as the first invasive-disease event occurred in 10.5% of patients in the T-DM1 group and 15.9% of those in the trastuzumab group. The safety data were consistent with the known safety profile of T-DM1, with more adverse events associated with T-DM1 than with trastuzumab alone.
Among patients with HER2-positive early breast cancer who had residual invasive disease after completion of neoadjuvant therapy, the risk of recurrence of invasive breast cancer or death was 50% lower with adjuvant T-DM1 than with trastuzumab alone. (Funded by F. Hoffmann-La Roche/Genentech; KATHERINE ClinicalTrials.gov number, NCT01772472 .).
MONARCH 2 is a global, randomized, double‐blind, phase 3 study of abemaciclib/placebo + fulvestrant in patients with hormone receptor positive, human epidermal growth factor receptor 2‐negative ...advanced breast cancer. The East Asian population comprised 212 (31.7%) of the 669 intent‐to‐treat population in the MONARCH 2 trial. Consistent with the primary analysis, this subpopulation analysis of East Asian patients indicated progression‐free survival benefit in the abemaciclib arm. The median overall survival was not reached in the abemaciclib arm and was 48.9 months in the placebo arm (hazard ratio 0.80; 95% confidence interval 0.52–1.24; p = 0.377). In addition, other efficacy endpoints, including time to chemotherapy, chemotherapy free survival, and time to second disease progression, indicated benefit in the abemaciclib arm. This analysis found no new safety concerns with longer follow‐up. These findings support the positive benefit–risk balance of the MONARCH 2 regimen in East Asian patients with hormone receptor positive, human epidermal growth factor receptor 2‐negative advanced breast cancer.
MONARCH 2 is a randomized, double‐blind, phase 3 study of abemaciclib/placebo + fulvestrant in patients with hormone receptor positive, human epidermal growth factor receptor 2‐negative advanced breast cancer. We analyzed on OS, PFS, safety, time to chemotherapy, chemotherapy free survival, and time to second disease progression. This subpopulation analysis of East Asian patients indicated the positive benefit‐risk balance of the abemaciclib arm therapy.
Abstract
Background
The incidence of breast cancer among younger East Asian women has been increasing rapidly over recent decades. This international collaborative study systemically compared the ...differences in age-specific incidences and pathological characteristics of breast cancer in East Asian women and women of predominantly European ancestry.
Methods
We excerpted analytic data from six national cancer registries (979 675 cases) and eight hospitals (18 008 cases) in East Asian countries and/or regions and, for comparisons, from the US Surveillance, Epidemiology, and End Results program database. Linear regression analyses of age-specific incidences of female breast cancer and logistic regression analyses of age-specific pathological characteristics of breast cancer were performed. All statistical tests were two-sided.
Results
Unlike female colorectal cancer, the age-specific incidences of breast cancer among East Asian women aged 59 years and younger increased disproportionally over recent decades relative to rates in US contemporaries. For years 2010–2014, the estimated age-specific probability of estrogen receptor positivity increased with age in American patients, whereas that of triple-negative breast cancer (TNBC) declined with age. No similar trends were evident in East Asian patients; their probability of estrogen receptor positivity at age 40–49 years was statistically significantly higher (odd ratio OR = 1.50, 95% confidence interval CI = 1.36 to 1.67, P < .001) and of TNBC was statistically significantly lower (OR = 0.79, 95% CI = 0.71 to 0.88, P < .001), whereas the probability of ER positivity at age 50–59 years was statistically significantly lower (OR = 0.88, 95% CI = 0.828 to 0.95, P < .001). Subgroup analyses of US Surveillance, Epidemiology, and End Results data showed similarly distinct patterns between East Asian American and white American patients.
Conclusions
Contrasting age-specific incidences and pathological characteristics of breast cancer between East Asian and American women, as well as between East Asian Americans and white Americans, suggests racial differences in the biology.
Summary Background Findings from the randomised phase 3 NeoALTTO trial in women with HER2-positive early breast cancer showed that the combination of lapatinib and trastuzumab significantly improved ...rates of pathological complete response compared with either drug alone. Here, we report data for the prespecified secondary endpoints of event-free and overall survival, and assess the association between these outcomes and pathological complete response. Methods We enrolled women with HER2-positive early breast cancer and randomly assigned them to receive oral lapatinib (1500 mg), intravenous trastuzumab (4 mg/kg loading dose followed by 2 mg/kg), or lapatinib (1000 mg) plus trastuzumab (same dose as for single agent) in combination for 6 weeks, followed by an additional 12 weeks of the assigned anti-HER2 therapy in combination with weekly paclitaxel (80 mg/m2 ). Definitive surgery was done 4 weeks after the last dose of paclitaxel. After surgery, women received three cycles of FEC (fluorouracil 500 mg/m2 plus epirubicin 100 mg/m2 plus cyclophosphamide 500 mg/m2 ) given intravenously every 3 weeks, followed by 34 weeks of the same assigned neoadjuvant anti-HER2 therapy. The primary endpoint was pathological complete response. Secondary endpoints included event-free and overall survival (intention-to-treat analysis), and the association between pathological complete response and event-free or overall survival (analysed by landmark analysis at 30 weeks after randomisation). Follow-up is ongoing, and the trial is registered with ClinicalTrials.gov , number NCT00553358. Findings 455 patients were enrolled: 154 (34%) were assigned to the lapatinib group, 149 (33%) to the trastuzumab group, and 152 (33%) to the lapatinib plus trastuzumab group. At an event follow-up of 3·77 years (IQR 3·50–4·22), 3-year event-free survival was 78% (95% CI 70–84) in the lapatinib group, 76% (68–82) in the trastuzumab group, and 84% (77–89) in the combination group. Event-free survival did not differ between the lapatinib and trastuzumab groups (HR 1·06, 95% CI 0·66–1·69, p=0·81), nor between the combination and trastuzumab groups (0·78, 0·47–1·28, p=0·33). Median survival follow-up was 3·84 years (IQR 3·60–4·24), and 3-year overall survival was 93% (95% CI 87–96) for lapatinib, 90% (84–94) for trastuzumab, and 95% (90–98) for combination therapy. Overall survival did not significantly differ between the lapatinib and trastuzumab groups (HR 0·86, 95% CI 0·45–1·63, p=0·65), nor between the combination and trastuzumab groups (0·62, 0·30–1·25, p=0·19). Landmark analyses showed that 3-year event-free survival was significantly improved for women who achieved pathological complete response compared with those who did not (HR 0·38, 95% CI 0·22–0·63, p=0·0003), as was 3-year overall survival (0·35, 0·15–0·70, p=0·005). Adverse events occurred in 149 (99%) patients receiving lapatinib, 142 (96%) patients receiving trastuzumab, and 147 (99%) patients receiving combination therapy. The most common adverse events were diarrhoea, rash or erythema, hepatic adverse events, and neutropenia (not related to FEC administration), and were consistent with known safety profiles of lapatinib and trastuzumab. Three primary and eight secondary cardiac events occurred, with no significant difference in incidence between treatment groups for primary or any cardiac events. Interpretation Although event-free survival or overall survival did not differ between treatment groups, findings from our study confirm that patients who achieve pathological complete response after neoadjuvant anti-HER2 therapy have longer event-free and overall survival than do patients without pathological complete response. Funding GlaxoSmithKline.
Background
The phase 3 KATHERINE trial demonstrated significantly improved invasive disease–free survival with adjuvant trastuzumab emtansine (T‐DM1) versus trastuzumab in patients with HER2‐positive ...early breast cancer and residual invasive disease after neoadjuvant chemotherapy plus HER2‐targeted therapy.
Methods
Patients who received taxane‐ and trastuzumab‐containing neoadjuvant therapy (with/without anthracyclines) and had residual invasive disease (breast and/or axillary nodes) at surgery were randomly assigned to 14 cycles of adjuvant T‐DM1 (3.6 mg/kg intravenously every 3 weeks) or trastuzumab (6 mg/kg intravenously every 3 weeks). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ‐C30) and breast cancer module (QLQ‐BR23) were completed at screening, at day 1 of cycles 5 and 11, within 30 days after study drug completion, and at 6‐ and 12‐month follow‐up visits.
Results
Of patients who were randomly assigned to T‐DM1 (n = 743) and trastuzumab (n = 743), 612 (82%) and 640 (86%), respectively, had valid baseline and ≥1 postbaseline assessments. No clinically meaningful changes (≥10 points) from baseline in mean QLQ‐C30 and QLQ‐BR23 scores occurred in either arm. More patients receiving T‐DM1 reported clinically meaningful deterioration at any assessment point in role functioning (49% vs 41%), appetite loss (38% vs 28%), constipation (47% vs 38%), fatigue (66% vs 60%), nausea/vomiting (39% vs 30%), and systemic therapy side effects (49% vs 36%). These differences were no longer apparent at the 6‐month follow‐up assessment, except for role functioning (23% vs 16%).
Conclusion
These data suggest that health‐related quality of life was generally maintained in both study arms over the course of treatment.
Patient‐reported outcomes are reported from the randomized, phase 3 KATHERINE trial, which demonstrated significantly improved invasive disease–free survival with adjuvant T‐DM1 compared with trastuzumab in patients who had residual invasive disease following neoadjuvant chemotherapy plus HER2‐targeted therapy. Patients who are treated with T‐DM1 have a greater incidence of any grade and grade ≥3 adverse events compared with trastuzumab‐treated patients; however, these adverse events appear to have a minimal impact on patient‐reported quality of life.
•PFOS was associated with breast cancer risk in Taiwanese women.•Young women (age ≤ 50 years) had a high risk of breast cancer by PFOS exposure.•Women in the age less than 50 years had a higher risk ...of estrogen receptor positive tumors than those in the age over 50 years by PFHxS and PFOS exposure.
Breast cancer (BC) is a common cancer in women worldwide; however, the incidence of BC is increasing in younger women, possibly associated with the environment. Perfluoroalkyl substances (PFAS) are one of endocrine disruptors that accumulate in environment and impact human health. This study aimed to investigate whether the PFAS and BC are associated. We enrolled 120 BCE patients and 119 controls at National Taiwan University Hospital (NTUH) and also collected bio-specimen and questionnaire from 2013 to 2015. All subjects’ plasma PFAS levels were analyzed by ultra-performance liquid chromatography tandem mass spectrometry method with electrospray ionization (UHPLC-ESI-MS/MS). A logistic regression model was used to estimate the association between PFAS and BC. In the ≤50 years age group, the adjusted odds ratio (OR) was 2.34 (95% CI = 1.02, 5.38) for perfluorooctane sulfonate (PFOS) exposure per natural log unit increase. After stratifying the estrogen receptor (ER) status and age group, we obtained a positive association for PFHxS and PFOS concentrations with respect to the risk of ER positive tumors for ≤50 years age group. In conclusion, we found that PFAS were associated with the BC risk of ER positive tumors in young Taiwanese women. Further studies are needed to follow and explore whether these associations are causal.
Abstract Purpose Recognizing molecular markers is helpful for guiding treatment plans for breast cancer. This study correlated estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), ...and triple-negative breast cancer (TNBC) statuses to the degree of heterogeneity on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Materials and Methods A total of 102 biopsy-proven cancers from 102 patients between October 2010 and December 2012 were used in this study, including ER (59 positive, 43 negative), HER2 (47 positive, 55 negative), and TNBC (22 TNBC, 80 non-TNBC). At first, the tumor region was segmented by using a region growing method. Then, the region-based features were extracted by the proposed regionalization method to quantify intra-tumoral heterogeneity on breast DCE-MRI. The three-dimensional morphological features (texture features and shape feature) and the pharmacokinetic model were also extracted from the segmented tumor region. After feature extraction, a logistic regression was used to classify ER, HER2, and TNBC statuses respectively. The performances were evaluated by using receiver operating characteristic curve (ROC) curve analysis. Results The proposed region-based features achieved the accuracy of 73.53%, 82.35%, and 77.45% for ER, HER2, and TNBC classification. The corresponding area under the ROC curves (Az) achieves 0.7320, 0.8458, and 0.8328 that were better than those of texture features, shape features, and Tofts pharmacokinetic model. Conclusion The intra-tumoral heterogeneity quantified by the region-based features can be used to reflect the vasculature complexity of different molecular markers and to provide prediction information of cell surface receptors on clinical examination.
Automated whole breast ultrasound (ABUS) is an emerging screening tool for detecting breast abnormalities. In this study, a computer-aided detection (CADe) system based on multi-scale blob detection ...was developed for analyzing ABUS images. The performance of the proposed CADe system was tested using a database composed of 136 breast lesions (58 benign lesions and 78 malignant lesions) and 37 normal cases. After speckle noise reduction, Hessian analysis with multi-scale blob detection was applied for the detection of tumors. This method detected every tumor, but some nontumors were also detected. The tumor likelihoods for the remaining candidates were estimated using a logistic regression model based on blobness, internal echo, and morphology features. The tumor candidates with tumor likelihoods higher than a specific threshold (0.4) were considered tumors. By using the combination of blobness, internal echo, and morphology features with 10-fold cross-validation, the proposed CAD system showed sensitivities of 100%, 90%, and 70% with false positives per pass of 17.4, 8.8, and 2.7, respectively. Our results suggest that CADe systems based on multi-scale blob detection can be used to detect breast tumors in ABUS images.
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