Neoadjuvant pegylated liposomal doxorubicin- and epirubicin-based combination therapy regimens for early breast cancer: a multicenter retrospective case-control study.

PURPOSE: This study aimed to compare the effectiveness and safety of pegylated liposomal doxorubicin (PLD)-based and epirubicin-based combination therapy regimen as neoadjuvant therapy for early breast cancer. METHODS: Patients with stage I-III breast cancer who underwent neoadjuvant therapy followed by surgery between January 2018 and December 2019 were retrospectively reviewed. The primary outcome was pathological complete response (pCR) rate. The secondary outcome was radiologic complete response (rCR) rate. Outcomes were compared between treatment groups PLD-cyclophosphamide followed by docetaxel (LC-T group) or epirubicin-cyclophosphamide followed by docetaxel (EC-T group), using both propensity-score matched (matched) and unmatched data. RESULTS: Data were analyzed from patients who received neoadjuvant LC-T (n = 178) or EC-T (n = 181) treatment. The overall pCR rate and rCR rate were higher in the LC-T group compared with the EC-T group (unmatched pCR: 25.3% vs. 15.5%, p = 0.026; rCR: 14.7% vs. 6.7%, p = 0.016; matched pCR: 26.9% vs. 16.1%, p = 0.034; rCR: 15.5% vs. 7.4%, p = 0.044). Analysis by molecular subtype showed that compared with EC-T treatment, LC-T treatment achieved significantly greater pCR rate in triple-negative subtype and greater rCR rate in Her2 (+) subtype. CONCLUSIONS: Neoadjuvant PLD-based therapy may be a potential option for patients with early-stage breast cancer. The current results warrant further investigation.

Impact of BRCA mutation on the survival and risk of contralateral breast cancer in Asian breast cancer patients.

PURPOSE: Breast cancer is increasing around the globe, including Asia. We aimed to examine the survival and risk of contralateral breast cancer (CBC) in Asian breast cancer patients with BRCA mutations. METHODS: A total of 128 breast cancer patients with germline BRCA mutations and 4,754 control breast cancer patients were enrolled. Data on clinical-pathologic characteristics, survival, and CBC were collected from the medical record. The rates of survival and CBC were estimated by Kaplan-Meier method. RESULTS: The mean age of onset in BRCA mutation carriers was significantly younger than control patients (BRCA vs. Non-BRCA: 43.9 vs. 53.2 years old). BRCA mutation carriers had a higher proportion of triple-negative breast cancer (TNBC) (52%) than control patients (12%, p < 0.001). The risk of CBC was significantly higher in BRCA mutation patients than in control cases (hazard ratio (HR) = 3.95, 95% CI 2.71-5.75); when stratified by genotype, the HRs (95%CI) were 4.84 (3.00-7.82) for BRCA1 and 3.13 (1.78-5.49) for BRCA2 carriers, respectively. Moreover, BRCA1 mutation patients with triple-negative breast cancer (TNBC) as their first breast cancer had the highest risk of CBC (HR = 5.55, 95% CI 3.29-9.34). However, we did not observe any differences in relapse-free survival and overall survival between mutation carriers and control patients. CONCLUSION: Our study suggest that BRCA patients had a significantly higher risk of developing CBC, particularly for BRCA1 mutation carriers with TNBC as the first breast cancer.

Neoadjuvant afatinib with paclitaxel for triple-negative breast cancer and the molecular characteristics in responders and non-responders.

BACKGROUND: The prognosis of triple-negative breast cancer (TNBC) is worse and a major proportion of TNBC expresses epidermal growth factor receptor (EGFR). Afatinib can inhibit EGFR signal pathway; however, its treatment effect for TNBC is unknown. Thus, we aimed to assess the efficacy and biomarkers of afatinib in combination with paclitaxel in a neoadjuvant setting. METHODS: Patients with stage II to III TNBC were enrolled. They received 40 mg of afatinib daily for 14 days, followed by daily afatinib and weekly paclitaxel (80 mg/m2) every 21 days for four to six cycles. To explore the mechanisms of responsiveness and non-responsiveness, 409 cancer-associated genes were sequenced. RESULTS: Twenty-one patients were enrolled and one patient achieved a complete clinical response; however, a 2 mm residual tumor was noted in the surgical specimen. Overall, 33.0% patients were responders. Fifteen patients received molecular testing. No activated mutation of EGFR or Her2 were found. Activated PI3K or JAK2 pathway were trended to associate with non-responder (p = 0.057). Mutation of homologous recombination (HR) genes were correlated with non-responsiveness (p = 0.005). Seven patients did not have altered PI3K, JAK2 or HR pathway; six (85.7%) of them were responder. Patients with the amplified DAXX gene was associated with a favorable trend of response (p = 0.109). CONCLUSION: Adding afatinib to neoadjuvant paclitaxel generated a modest effect in TNBC. Exploratory molecular analysis suggested that activated PI3K, JAK2 pathways and mutation of HR genes were associated with therapeutic non-responsiveness, and amplification of DAXX genes was associated with responsiveness to afatinib in combination with paclitaxel.

Prediction of breast cancer molecular subtypes on DCE-MRI using convolutional neural network with transfer learning between two centers.

OBJECTIVES: To apply deep learning algorithms using a conventional convolutional neural network (CNN) and a recurrent CNN to differentiate three breast cancer molecular subtypes on MRI. METHODS: A total of 244 patients were analyzed, 99 in training dataset scanned at 1.5 T and 83 in testing-1 and 62 in testing-2 scanned at 3 T. Patients were classified into 3 subtypes based on hormonal receptor (HR) and HER2 receptor: (HR+/HER2-), HER2+, and triple negative (TN). Only images acquired in the DCE sequence were used in the analysis. The smallest bounding box covering tumor ROI was used as the input for deep learning to develop the model in the training dataset, by using a conventional CNN and the convolutional long short-term memory (CLSTM). Then, transfer learning was applied to re-tune the model using testing-1(2) and evaluated in testing-2(1). RESULTS: In the training dataset, the mean accuracy evaluated using tenfold cross-validation was higher by using CLSTM (0.91) than by using CNN (0.79). When the developed model was applied to the independent testing datasets, the accuracy was 0.4-0.5. With transfer learning by re-tuning parameters in testing-1, the mean accuracy reached 0.91 by CNN and 0.83 by CLSTM, and improved accuracy in testing-2 from 0.47 to 0.78 by CNN and from 0.39 to 0.74 by CLSTM. Overall, transfer learning could improve the classification accuracy by greater than 30%. CONCLUSIONS: The recurrent network using CLSTM could track changes in signal intensity during DCE acquisition, and achieved a higher accuracy compared with conventional CNN during training. For datasets acquired using different settings, transfer learning can be applied to re-tune the model and improve accuracy. KEY POINTS: • Deep learning can be applied to differentiate breast cancer molecular subtypes. • The recurrent neural network using CLSTM could track the change of signal intensity in DCE images, and achieved a higher accuracy compared with conventional CNN during training. • For datasets acquired using different scanners with different imaging protocols, transfer learning provided an efficient method to re-tune the classification model and improve accuracy.

Positive psychological changes after breast cancer diagnosis and treatment: The role of trait resilience and coping styles.

Purpose: This study aimed to examine the relationships among trait resilience, coping styles, and perceived positive psychological changes in women's lives after breast cancer diagnosis and treatment.Design: The study adopted a cross-sectional design.Sample/Method: A total of 201 participants diagnosed with stage I-IV breast cancer were recruited. The average time since diagnosis was 39.14 months. Four rating scales were used to assess the participants' trait resilience, coping styles, perceived growth, and health-related quality of life. These are the Connor-Davidson Resilience Scale (CD-RISC), the Mini-Mental Adaptation to Cancer Scale (Mini-MAC), the Chinese Posttraumatic Growth Inventory (PTGI), and the Functional Assessment of Cancer Therapy Scale-Breast (FACT-B).Findings: Hierarchical analysis showed that trait resilience significantly predicted high levels of perceived growth and health-related quality of life. This effect was moderated by Positive-Acceptance coping. The study also found that Negative-Affect coping had a direct effect on lowering health-related quality of life but had no influence on perceived growth.Conclusions: These findings highlight the facilitating effect of trait resilience and Positive-Acceptance coping on the psychological well-being and perceived growth among breast cancer outpatients.Implications: Trait resilience may be a protective, even facilitating factor of cancer adaptation. The knowledge that trait resilience offers a way to enhance wellness after cancer diagnosis and treatments may be useful in a clinical setting.

Predicting chemo-brain in breast cancer survivors using multiple MRI features and machine-learning.

PURPOSE: Breast cancer (BC) is the most common cancer in women worldwide. There exist various advanced chemotherapy drugs for BC; however, chemotherapy drugs may result in brain damage during treatment. When a patient's brain is changed in response to chemo drugs, it is termed chemo-brain. In this study, we aimed to construct machine-learning models to detect the subtle alternations of the brain in postchemotherapy BC patients. METHODS: Nineteen BC patients undergoing chemotherapy and 20 healthy controls (HCs) were recruited for this study. Both groups underwent resting-state functional MRI and generalized q-sampling imaging (GQI). RESULTS: Logistic regression (LR) with GQI indices in standardized voxel-wise analysis, LR with mean regional homogeneity in regional summation analysis, decision tree classifier (CART) with generalized fractional anisotropy in voxel-wise analysis, and XGBoost (XGB) with normalized quantitative anisotropy had formidable performances in classifying subjects into a chemo-brain group or an HC group. Classifying the brain MRIs of HC and postchemotherapy patients by conducting leave-one-out cross-validation resulted in the highest accuracy of 84%, which was attained by LR, CART, and XGB with multiple feature sets. CONCLUSIONS: In our study, we constructed the machine-learning models that were able to identify chemo-brains from normal brains. We are hopeful that these results will be helpful in clinically tracking chemo-brains in the future.

Investigation of chemotherapy-induced brain structural alterations in breast cancer patients with generalized q-sampling MRI and graph theoretical analysis.

BACKGROUND: Breast neoplasms are the most common cancer among women in Taiwan. Cognitive deficits are common complications of breast cancer survivors treated with chemotherapy. The most frequently observed disorders involve executive function and memory impairment. With improvements in tumor intervention and the consequent increase in the number of cancer survivors, the quality of life of patients has become an important issue. We are interested in the early effects of chemotherapy on the brain structures of patients. In addition, generalized q-sampling imaging (GQI), a wide range of q-space datasets for a more accurate and sophisticated diffusion MR approach, was first used in this topic. METHODS: As diffusion tensor imaging (DTI) is associated with restrictions in the resolution of crossing fibers, we attempted to use GQI, which can overcome these difficulties and is advantageous over DTI for tractography of the crossing fibers. This cross-sectional study included two groups: breast cancer survivors who had completed their chemotherapy (n = 19) and healthy controls (n = 20). All participants underwent diffusion MRI exams and neuropsychological assessments. We included four parts in our image analysis, i.e., voxel-based statistical analysis, multiple regression analysis, graph theoretical analysis and network-based statistical analysis. RESULTS: The results from the voxel-based statistical analysis showed significantly lower GFA and NQA values in the breast cancer group than those in the control group. We found significant positive correlations between the FACT-Cog and GQI indices. In the graph theoretical analysis, the breast cancer group demonstrated significantly longer characteristic path length. Adjuvant chemotherapy affected the integrity of white matter and resulted in poor cognitive performance, as indicated by the correlations between the neuropsychological assessment scales and the GQI indices. In addition, it was found that the characteristic path lengths in the breast cancer group increased, indicating that the brain network integration became worse. CONCLUSIONS: Our study demonstrated alterations in structural brain networks and associated neuropsychological deficits among breast cancer survivors.

A Phase I/II study of the combination of lapatinib and oral vinorelbine in HER2-positive metastatic breast cancer.

BACKGROUND: The combination of lapatinib and oral vinorelbine for HER2 positive metastatic breast cancer (MBC) is convenient but with uncertain toxicity profiles. A Phase I/II study was designed to understand the tolerability and efficacy of this combination treatment. METHOD: Female MBC patients with HER2 positive were eligible. Lapatinib was given once daily and oral vinorelbine was given on Days 1 and 8 of a 21-day cycle. A 3 + 3 standard dose-escalation rule was applied in the Phase I study. The primary endpoint of the Phase II study was PFS. In the Phase II part, because no DLT was observed in the first 20 patients, vinorelbine dose-escalation was permitted if no significant toxicities after the first cycle was observed. RESULT: From June 2009 to February 2013, 46 patients were enrolled in Phase I (n = 15) and II (n = 31) studies. Median age was 52.8 (range 34.3-84.0); 28 (60.9%) patients were ER positive. In the Phase I study, two patients had DLTs (neutropenia (n = 2), diarrhea (n = 1)). The MTD was determined at lapatinib 1000 mg plus oral vinorelbine 50 mg/m2. In the Phase II study, 11 patients safely had vinorelbine escalated to 60 mg/m2 on cycle 2. The median PFS was 5.6 months (95% CI 5.2-5.9); 6 (19.4%) patients had PR; the clinical benefit rate was 38.7%. Six patients had disease control over 2 years. CONCLUSION: Lapatinib 1000 mg and oral vinorelbine 50 mg/m2 were tolerable with manageable toxicities. Escalation to vinorelbine 60 mg/m2 is feasible if no significant toxicities after the first cycle. Clinical efficacy was demonstrated with long-term responders observed.

Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial.

BACKGROUND: Trastuzumab resistance is a key therapeutic challenge in metastatic breast cancer. We postulated that broader inhibition of ErbB receptors with afatinib would improve clinical outcomes compared with HER2 inhibition alone in patients who had progressed on previous trastuzumab treatment. LUX-Breast 1 compared afatinib plus vinorelbine with trastuzumab plus vinorelbine for such patients with HER2-positive metastatic breast cancer. METHODS: We did this open-label trial at 350 hospitals in 41 countries worldwide. We enrolled female patients with HER2-overexpressing metastatic breast cancer who had progressed on or following adjuvant trastuzumab or first-line treatment of metastatic disease with trastuzumab. Participants were randomly assigned (2:1) to receive oral afatinib (40 mg/day) plus intravenous vinorelbine (25 mg/m(2) per week) or intravenous trastuzumab (2 mg/kg per week after 4 mg/kg loading dose) plus vinorelbine. Randomisation was done centrally and stratified by previous trastuzumab treatment (adjuvant vs first-line treatment), hormone receptor status (oestrogen receptor and progesterone receptor positive vs others), and region. The primary endpoint was progression-free survival, assessed in the intention-to-treat population. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT01125566. FINDINGS: Between Aug 26, 2010, and April 26, 2013, we enrolled 508 patients: 339 assigned to the afatinib group and 169 assigned to the trastuzumab group. Recruitment was stopped on April 26, 2013, after a benefit-risk assessment by the independent data monitoring committee was unfavourable for the afatinib group. Patients on afatinib plus vinorelbine had to switch to trastuzumab plus vinorelbine, afatinib monotherapy, vinorelbine monotherapy, or receive treatment outside of the trial. Median follow-up was 9·3 months (IQR 3·7-16·0). Median progression-free survival was 5·5 months (95% CI 5·4-5·6) in the afatinib group and 5·6 months (5·3-7·3) in the trastuzumab group (hazard ratio 1·10 95% CI 0·86-1·41; p=0·43). The most common drug-related adverse events of grade 3 or higher were neutropenia (190 [56%] of 337 patients in the afatinib group vs 102 [60%] of 169 patients in the trastuzumab group), leucopenia (64 [19%] vs 34 [20%]), and diarrhoea (60 [18%] vs none). INTERPRETATION: Trastuzumab-based therapy remains the treatment of choice for patients with HER2-positive metastatic breast cancer who had progressed on trastuzumab. FUNDING: Boehringer Ingelheim.

Relationship between antidepressant prescription and breast cancer: a population based study in Taiwan.

OBJECTIVE: To investigate the association between antidepressant prescription and breast cancer. METHODS: The National Health Research Institute in Taiwan provided a database of 1 000 000 random subjects for this study. We identified 14 737 new antidepressant female users who were more than 15 years old during 1999-2005 with at least 10 prescriptions and one year exposure to an antidepressant. These were matched 1:1 by age and residence to non-antidepressant users from the same database to compare the risk of breast cancer. RESULTS: In a model adjusted by age, residence, insurance amount, and depressive disorder, antidepressant prescription was not associated with breast cancer risk. This held true for both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants. CONCLUSIONS: There was no evidence for an association between antidepressant prescription and the risk of breast cancer. Copyright © 2015 John Wiley & Sons, Ltd.

A pilot study of bevacizumab combined with etoposide and cisplatin in breast cancer patients with leptomeningeal carcinomatosis.

BACKGROUND: Elevated vascular endothelial growth factor (VEGF) was associated with poor prognosis in leptomeningeal carcinomatosis and anti-angiogenic therapy was found to prolong the survival of mice in preclinical studies. This prospective pilot study investigated the efficacy of anti-VEGF therapy plus chemotherapy in patients with leptomeningeal carcinomatosis originating from breast cancer. METHODS: Eligible patients were scheduled to receive bevacizumab combined with etoposide and cisplatin (BEEP) every 3 weeks for a maximum of 6 cycles or until unacceptable toxicity. The primary objective was the central nervous system (CNS)-specific response rate, which was defined as disappearance of cancer cells in the cerebrospinal fluid (CSF) and an improved or stabilized neurologic status. The impact of VEGF inhibition on etoposide penetration into the CSF was analyzed. RESULTS: Eight patients were enrolled. The CNS-specific response rate was 60% in 5 evaluable patients. According to intent-to-treat analysis, the median overall survival of the eight patients was 4.7 months (95% confidence interval, CI, 0.3-9.0) and the neurologic progression-free survival was 4.7 months (95% CI 0-10.5). The most common grade 3/4 adverse events were neutropenia (23.1%), leukopenia (23.1%), and hyponatremia (23.1%). The etoposide concentrations in the CSF were much lower than those in plasma, and bevacizumab did not increase etoposide delivery to the CSF. CONCLUSIONS: BEEP exhibited promising efficacy in breast cancer patients with leptomeningeal carcinomatosis. Additional studies are warranted to verify its efficacy and clarify the role of anti-angiogenic therapy in this disease. TRIAL REGISTRATION: ClinicalTrials.gov identifying number NCT01281696 .

Unroofing hepatectomy: a facilitating approach for resection of deep-seated hepatocellular carcinoma adjacent to major intrahepatic vessels in cirrhotic patients.

BACKGROUND AND OBJECTIVES: Unroofing hepatectomy, an alternative approach to remove a deep-seated hepatocellular carcinoma (HCC) adjacent to major intrahepatic vessels by peel-off technique after sacrificing the overlying noncancerous liver, may result in tumor exposure without resection margin. The aim of the study was to examine the value of this approach in cirrhotic patients. METHODS: Between 1998 and 2012, 51 cirrhotic patients underwent unroofing hepatectomy for deep-seated newly-diagnosed HCC adjacent to major intrahepatic vessels (group A). Another 274 cirrhotic patients with similar tumor size and without gross major vessel involvement in the same period were selected as the control cohort (group B). The patients' clinicopathological characteristics, the early and long-term outcomes of the two groups were compared. RESULTS: The HCCs in group A had a significantly higher rate of tumor encapsulation, smaller number of associated satellite nodules, and smaller amount of resected liver weight. Postoperative complication and 90-day mortality rates were similar, but group A patients had a significant better 5-year disease-free (56% vs. 32%, P = 0.011) and overall survival rates (82% vs. 53%, P = 0.008). CONCLUSIONS: In selected cirrhotic patients, unroofing hepatectomy facilitates resection of deep-seated HCC adjacent to major intrahepatic vessels with acceptable early and long-term results.

Mental adjustment at different phases in breast cancer trajectory: re-examination of factor structure of the Mini-MAC and its correlation with distress.

OBJECTIVE: The aim of this study is twofold. First, it aims to determine the factor structure of the Mini-Mental Adjustment to Cancer (Mini-MAC) Scale by using confirmatory factor analysis (CFA) to compare the three-factor, four-factor, and five-factor structures among 340 Taiwanese breast cancer patients. Second, it aims to test the difference in the correlations of coping strategies and the outcome measures between two populations: one-month newly diagnosed and five-year long-term survival patients. METHODS: Two samples, composed of 142 newly diagnosed and 198 long-term survival breast cancer patients, were recruited. Cancer-specific coping and distress were assessed via the Mini-MAC Scale and the Hospital Anxiety and Depression Scale (HADS), respectively. RESULTS: The CFA confirmed Watson's original five-factor structure fit the data best. The correlation difference between the two samples lies in the fighting spirit (FS), which correlated negatively with distress among the newly diagnosed sample but had no correlation among the long-term survivors. Moreover, fatalism (FA) was found to correlate positively with distress. CONCLUSIONS: The five-factor structure represents a more psychometrically sound measure of psychological adjustment in the current data set. The findings also support the argument that the relationships between coping and distress vary, to some degree, at different phases in the cancer trajectory. FS is only a positive predictor of psychological adjustment among newly diagnosed patients. Because of the exclusion of two items, FA showed a positive correlation with distress, a result that contradicts previous findings. Further theoretical and practical implications for FS and FA are discussed.

Consistency of breast density measured from the same women in four different MR scanners.

PURPOSE: To compare the breast volume (BV), fibroglandular tissue volume (FV), and percent density (PD) measured from breast MRI of the same women using four different MR scanners. METHODS: The study was performed in 34 healthy Asian volunteers using two 1.5T (GE and Siemens) and two 3T (GE and Philips) MR scanners. The BV, FV, and PD were measured on nonfat-suppressed T1-weighted images using a comprehensive computer algorithm-based segmentation method. The scanner-to-scanner measurement difference, and the coefficient of variation (CV) among the four scanners were calculated. The measurement variation between two density morphological patterns presenting as the central type and the intermingled type was separately analyzed and compared. RESULTS: All four scanners provided satisfactory image quality allowing for successful completion of the segmentation processes. The measured parameters between each pair of MR scanners were highly correlated, with R(2) ≥ 0.95 for BV, R(2) ≥ 0.99 for FV, and R(2) ≥ 0.97 for PD in all comparisons. The mean percent differences between each pair of scanners were 5.9%-7.8% for BV, 5.3%-6.5% for FV, 4.3%-7.3% for PD; with the overall CV of 5.8% for BV, 4.8% for FV, and 4.9% for PD. The variation of FV was smaller in the central type than in the intermingled type (p = 0.04). CONCLUSIONS: The results showed that the variation of FV and PD measured from four different MR scanners is around 5%, suggesting the parameters measured using different scanners can be used for a combined analysis in a multicenter study.

Prognostic and predictive factors of eribulin in patients with heavily pre-treated metastatic breast cancer.

ABSTRACT: A predictive marker for efficacy of eribulin administered as different lines of treatment in metastatic breast cancer (MBC) has not been identified. We aimed to determine the predictive factors for efficacy of eribulin administered as different lines of treatment in MBC patients.This restrospective cohort study included 49 heavily pre-treated MBC patients who received either eribulin monotherapy or combination therapy with eribulin and anti-Her2 therapy. Associations between clinical response of eribulin-based treatment, time-to-treatment failure (TTF), and possible predictive markers were investigated.Patients' median age was 55 years; 65% were ER+; 43% were HER2+; and 16% were triple-negative. Median TTF was 5.23 months and longer in non-visceral metastases patients. Eastern Cooperative Oncology Group (ECOG) status was 0-1; eribulin as ≥2nd-line treatment; eribulin combined with dual blockades; lymphocyte-monocyte ratio (LMR) ≥3; and monocyte-lymphocyte ratio (MLR) <0.4. In patients with eribulin as >3rd-line treatment, univariate analysis showed that ECOG status was 0-1, and LMR ≥3 and MLR <0.4 were associated with a low risk of TTF. Multivariate analysis showed that ECOG status 0-1 was an independent protective factor. Leukopenia and neutropenia were the most common manageable adverse events.ECOG status is an independent predictor for TTF, while LMR and MLR may have an interactive effect with other biomarkers (e.g., ECOG status) to predict response in MBC patients receiving eribulin as ≥2nd-line treatment.

Sleep Quality and Related Factors in Patients with Breast Cancer: A Cross-Sectional Study in Taiwan.

BACKGROUND: Sleep disturbances are common and symptomatic burden in patients with breast cancer, but they are poorly documented and managed in routine clinical practice. This descriptive and cross-sectional study evaluated factors associated with post-treatment sleep disturbances in patients with breast cancer. PATIENTS AND METHODS: Patients with breast cancer who underwent standard treatment were enrolled and surveyed for their basic demographic data and precancerous and cancer treatment-related factors; they were also administered self-report questionnaires including the Family Adaptation, Partnership, Growth, Affection, Resolve questionnaire; Impact of Event Scale; Center for Epidemiologic Studies Depression Scale; and Maudsley Personality Inventory. Their sleep disturbances were evaluated using the Pittsburgh sleep quality index (PSQI). Independent sample t test and chi-square tests were used to compare the variables between patients with or without sleep disturbance, and multivariate logistic regression analyses were conducted to detect the independent factors. RESULTS: In total, 448 patients, including 145 with PSQI ≤ 5 and 303 with PSQI > 5, completed the investigation. Multiple logistic regression analysis revealed that significantly more patients with sleep disturbances demonstrated psychological distress, severe pain, depression, and impact of stress events than patients without sleep disturbances (adjusted odds ratios [95% confidence intervals]: 2.83 [1.135-7.067], P = 0.026; 1.14 [1.023-1.280], P = 0.018; 1.08 [1.036-1.133], P < 0.001; and 1.03 [1.002-1.051], P = 0.037, respectively). CONCLUSION: Patients with breast cancer showed 67.6% prevalence of sleep disturbances after treatment. The patients with sleep disturbances were more likely to have previously experienced psychological disturbances, severe pain, depression within 5 years after diagnosis. After diagnosis for more than 5 years, higher distress caused by traumatic events still associated with sleep disturbances.

Functional and Structural Connectome Features for Machine Learning Chemo-Brain Prediction in Women Treated for Breast Cancer with Chemotherapy.

Breast cancer is the leading cancer among women worldwide, and a high number of breast cancer patients are struggling with psychological and cognitive disorders. In this study, we aim to use machine learning models to discriminate between chemo-brain participants and healthy controls (HCs) using connectomes (connectivity matrices) and topological coefficients. Nineteen female post-chemotherapy breast cancer (BC) survivors and 20 female HCs were recruited for this study. Participants in both groups received resting-state functional magnetic resonance imaging (rs-fMRI) and generalized q-sampling imaging (GQI). Logistic regression (LR), decision tree classifier (CART), and xgboost (XGB) were the models we adopted for classification. In connectome analysis, LR achieved an accuracy of 79.49% with the functional connectomes and an accuracy of 71.05% with the structural connectomes. In the topological coefficient analysis, accuracies of 87.18%, 82.05%, and 83.78% were obtained by the functional global efficiency with CART, the functional global efficiency with XGB, and the structural transitivity with CART, respectively. The areas under the curves (AUCs) were 0.93, 0.94, 0.87, 0.88, and 0.84, respectively. Our study showed the discriminating ability of functional connectomes, structural connectomes, and global efficiency. We hope our findings can contribute to an understanding of the chemo brain and the establishment of a clinical system for tracking chemo brain.

Adjuvant whole breast radiotherapy with simultaneous integrated boost to tumor bed with intensity modulated radiotherapy technique in elderly breast cancer patients.

BACKGROUND: Adjuvant whole breast radiotherapy is the standard of care for breast cancer patients after partial mastectomy. Intensity-modulated radiation therapy (IMRT) has been reported to reduce acute toxicities compared to conventional radiotherapy. IMRT with simultaneous integrated boost (SIB) technique can deliver higher doses to tumor bed and irradiate whole breast with a lower dose level to shorten overall treatment duration. This study presents the long-term results of adjuvant IMRT with SIB in elderly breast cancer patients who received partial mastectomy. METHODS: From January 2007 to January 2018, 93 elder breast cancer patients (≥65-year-old) who received IMRT with SIB technique after partial mastectomy were reviewed retrospectively. The axillary areas were managed with either sentinel lymph node biopsies or axillary lymph node dissection. The dose to whole breast was 50.4 Gy in 28 fractions in all patients and the dose to tumor bed was 61.6 to 66.4 Gy in 28 fractions. The primary end point is locoregional control. Secondary end points include: overall survival, breast cancer-specific survival, distant-metastases-free survival, disease-free survival, and acute and chronic toxicities. RESULTS: The median follow-up was 56.1 months. One patient had ipsilateral breast tumor recurrence, 3 patients had regional lymph node recurrence, and 9 patients had distant metastases. Death occurred in 5 patients, including 3 patients died of breast cancer progression. Five-year overall survival is 96.3% and 5-year locoregional recurrence-free survival is 96.4%. The 5-year breast cancer specific survival and 5-year distant metastases-free survival is 97.5% and 87.2%, respectively. Seven patients developed second primary cancer after RT. Eighty-one point seven percent patients had acute grade 1 dermatitis while 18.3% suffered from grade 2 dermatitis. The incidence of grade 1 pneumonitis and grade 1 stomatitis was 4.3% and 8.6%, respectively. CONCLUSIONS: Adjuvant IMRT with SIB technique is a safe and effective treatment strategy for elderly breast cancer patients after partial mastectomy.

Olaparib monotherapy for Asian patients with a germline BRCA mutation and HER2-negative metastatic breast cancer: OlympiAD randomized trial subgroup analysis.

The OlympiAD Phase III study (NCT02000622) established the clinical benefits of olaparib tablet monotherapy (300 mg twice daily) over chemotherapy treatment of physician's choice (TPC) in patients with a germline BRCA1/2 mutation (gBRCAm) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who had received ≤2 chemotherapy lines in the metastatic setting. Here, we report pre-specified analyses of data from Asian (China, Japan, Korea and Taiwan) patients in the study. All patients were randomized 2:1 to olaparib tablets (300 mg twice daily) or single-agent chemotherapy TPC (21-day cycles of either capecitabine, eribulin or vinorelbine). The primary endpoint was progression-free survival assessed by blinded independent central review. The prevalence of gBRCAm in the OlympiAD Asian subgroup screened for study recruitment was 13.5%. Patient demographics and disease characteristics of the Asian subgroup (87/302 patients) were generally well balanced between treatment arms. Asian patients in the olaparib arm achieved longer median progression-free survival, assessed by blinded independent central review, versus the chemotherapy TPC arm (5.7 vs 4.2 months; HR = 0.53 [95% CI: 0.29-0.97]), which was consistent with findings in the global OlympiAD study population. Findings on secondary efficacy and safety/tolerability outcome measures in Asian patients were also similar to those observed in the global OlympiAD study population. The OlympiAD study was not powered to detect race-related differences between treatment groups; however, the consistency of our findings with the global OlympiAD study population suggests that previously reported findings are generalizable to Asian patients.

Association of functional dorsal attention network alterations with breast cancer and chemotherapy.

Breast cancer is the most common cancer among women worldwide. Adjuvant chemotherapy has significantly reduced mortality but increased cognitive impairments, including attention function, making quality of life issues a crucial concern. This study enrolled nineteen breast cancer patients who were treated with standard chemotherapy within 6 months and 20 sex-matched healthy controls to investigate the brain effects of chemotherapy. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) with mean fractional amplitude of low-frequency fluctuation (mfALFF) analysis and were correlated with neuropsychological tests, including the Mini-Mental State Examination (MMSE), the Cognitive and Affective Mindfulness Scale-Revised (CAMS-R), and the Impact of Event Scale-Revised (IES-R), to explore the possible underlying mechanism of cognitive alternations. We found increased mfALFF over the frontoparietal lobe and decreased mfALFF over the occipital lobe in the cancer patients compared with the healthy controls; the altered brain regions may be associated with the dorsal attention network (DAN) and may be explained by a compensatory mechanism. Both MMSE and CAMS-R scores showed a positive correlation with mfALFF in the occipital lobe but a negative correlation in the frontoparietal lobe. By contrast, IES-R scores showed a positive correlation with mfALFF in the frontoparietal lobe but a negative correlation in the occipital lobe. These alterations are potentially related to the effects of both chemotherapy and psychological distress. Future research involving a larger sample size of patients with breast cancer is recommended.