scholarly journals Comprehensive analysis of structural variants in breast cancer genomes using single molecule sequencing

2019 ◽  
Author(s):  
Sergey Aganezov ◽  
Sara Goodwin ◽  
Rachel Sherman ◽  
Fritz J. Sedlazeck ◽  
Gayatri Arun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Molecule ◽  
Large Scale ◽  
Treatment Options ◽  
Copy Number Variants ◽  
Cancer Cell Line ◽  
Breast Cancer Patients ◽  
Structural Variants ◽  
Cancer Genomes ◽  
Long Read

Improved identification of structural variants (SVs) in cancer can lead to more targeted and effective treatment options as well as advance our basic understanding of disease progression. We performed whole genome sequencing of the SKBR3 breast cancer cell-line and patient-derived tumor and normal organoids from two breast cancer patients using 10X/Illumina, PacBio, and Oxford Nanopore sequencing. We then inferred SVs and large-scale allele-specific copy number variants (CNVs) using an ensemble of methods. Our findings demonstrate that long-read sequencing allows for substantially more accurate and sensitive SV detection, with between 90% and 95% of variants supported by each long-read technology also supported by the other. We also report high accuracy for long-reads even at relatively low coverage (25x-30x). Furthermore, we inferred karyotypes from these data using our enhanced RCK algorithm to present a more accurate representation of the mutated cancer genomes, and find hundreds of variants affecting known cancer-related genes detectable only through long-read sequencing. These findings highlight the need for long-read sequencing of cancer genomes for the precise analysis of their genetic instability.

scholarly journals Comprehensive analysis of structural variants in breast cancer genomes using single-molecule sequencing

2020 ◽  
Vol 30 (9) ◽  
pp. 1258-1273 ◽  
Author(s):  
Sergey Aganezov ◽  
Sara Goodwin ◽  
Rachel M. Sherman ◽  
Fritz J. Sedlazeck ◽  
Gayatri Arun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Molecule ◽  
Comprehensive Analysis ◽  
Structural Variants ◽  
Single Molecule Sequencing ◽  
Cancer Genomes

scholarly journals Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line

2017 ◽  
Author(s):  
Maria Nattestad ◽  
Sara Goodwin ◽  
Karen Ng ◽  
Timour Baslan ◽  
Fritz J. Sedlazeck ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Progression ◽  
Single Molecule ◽  
Transcriptome Sequencing ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Structural Variations ◽  
Depth Analysis ◽  
Long Read

AbstractThe SK-BR-3 cell line is one of the most important models for HER2+ breast cancers, which affect one in five breast cancer patients. SK-BR-3 is known to be highly rearranged although much of the variation is in complex and repetitive regions that may be underreported. Addressing this, we sequenced SK-BR-3 using long-read single molecule sequencing from Pacific Biosciences, and develop one of the most detailed maps of structural variations (SVs) in a cancer genome available with nearly 20,000 variants present, most of which were missed by prior efforts. Surrounding the important HER2 locus, we discover a complex sequence of nested duplications and translocations, suggesting a punctuated progression. Full-length transcriptome sequencing further revealed several novel gene fusions within the nested genomic variants. Combining long-read genome and transcriptome sequencing enables an in-depth analysis of how SVs disrupt the transcriptome and sheds new light on the complexity of cancer progression.

Laboratory indicators predict axillary nodal pathologic complete response after neoadjuvant therapy in breast cancer

2021 ◽  
Author(s):  
Peng Chen ◽  
Tong Zhao ◽  
Zhao Bi ◽  
Zhao-Peng Zhang ◽  
Li Xie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Neoadjuvant Therapy ◽  
Predictive Factors ◽  
Molecular Subtype ◽  
Treatment Options ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Logistic Analysis

 The purpose was to integrate clinicopathological and laboratory indicators to predict axillary nodal pathologic complete response (apCR) after neoadjuvant therapy (NAT). The pretreatment clinicopathological and laboratory indicators of 416 clinical nodal-positive breast cancer patients who underwent surgery after NAT were analyzed from April 2015 to 2020. Predictive factors of apCR were examined by logistic analysis. A nomogram was built according to logistic analysis. Among the 416 patients, 37.3% achieved apCR. Multivariate analysis showed that age, pathological grading, molecular subtype and neutrophil-to-lymphocyte ratio were independent predictors of apCR. A nomogram was established based on these four factors. The area under the curve (AUC) was 0.758 in the training set. The validation set showed good discrimination, with AUC of 0.732. In subtype analysis, apCR was 23.8, 47.1 and 50.8% in hormone receptor-positive/HER2-, HER2+ and triple-negative subgroups, respectively. According to the results of the multivariate analysis, pathological grade and fibrinogen level were independent predictors of apCR after NAT in HER2+ patients. Except for traditional clinicopathological factors, laboratory indicators could also be identified as predictive factors of apCR after NAT. The nomogram integrating pretreatment indicators demonstrated its distinguishing capability, with a high AUC, and could help to guide individualized treatment options.

scholarly journals Effect and Safety of Anti-PD-1/PD-L1 Monotherapy for Metastatic Breast Cancer: A meta-analysis

2019 ◽  
Author(s):  
Yihang Qi ◽  
Xiangyi Kong ◽  
Xiangyu Wang ◽  
Jie Zhai ◽  
Yi Fang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Survival Rate ◽  
Response Rate ◽  
Meta Analysis ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Clinical Activity ◽  
Breast Cancer Patients ◽  
Severe Grade

Abstract Background. Given that no approved targeted agents for metastatic triple-negative breast cancer (mTNBC) and no opportunity of surgery for metastatic breast cancer (MBC), new treatment options are urgently to be discovered. The anti-PD-1/PD-L1 immunotherapy may be effective, and what we should be aware of is the response rate and adverse events. Methods. The PUBMED, EMBASE, Cochrane and www.clinicaltrials.gov databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1; metastatic; breast cancer. R© package Meta was used to pool incidence. Results. Six studies including 586 advanced breast cancer patients treated with anti-PD-1/PD-L1 agents were included in this meta-analysis. The anti-PD-1/PD-L1 agents include pembrolizumab, atezolizumab and avelumab. Among these patients, CR was 1.26%, PR was 7.65%, ORR was 9.85% and DCR was 18.33%. We also found that the response rate was closely associated with the expression of PD-L1 biomarker (PD-L1+ vs PD-L1-): the CR was 2.71% vs 0.00%; the PR was 9.93% vs 2.69%; the ORR was 10.62% vs 3.07%; the DCR was 17.95% vs 4.71%. 1-year overall survival rate and 6-months progression-free survival rate were 43.34% and 17.24%. Respectively, the overall incidence of AEs was 64.18% in any grade and 12.94% in severe grade. The incidence of irAEs was 14.75%. Besides, the incidence of discontinue and death due to treatment-related AEs was about 3.06% and 0.31% respectively. When the detailed AEs were analyzed, most treatment-related AEs of any grade were arthraigia, asthenia, decreased appetite; most common treatment-related AEs of severe grade were anemia, autoimmune hepatitis, diarrhea; the most common irAEs were hypothyroidism , followed by hyperthyroidism, pneumonitis and infusion-related reaction. Conclusions. Anti-PD-1/PD-L1 monotherapy showed a manageable safety profile and had a durable anti-tumor clinical activity in a subset of patients with mTNBC or MBC. PD-L1 expression may be correlated to a higher probability of clinical response.

scholarly journals Mapping and phasing of structural variation in patient genomes using nanopore sequencing

2017 ◽  
Author(s):  
Mircea Cretu Stancu ◽  
Markus J. van Roosmalen ◽  
Ivo Renkens ◽  
Marleen Nieboer ◽  
Sjors Middelkamp ◽  
...  
Keyword(s):  
Single Molecule ◽  
De Novo ◽  
Structural Variants ◽  
Human Genetic Disease ◽  
Structural Genomic ◽  
Short Read ◽  
Sequencing Technologies ◽  
Genome Wide ◽  
Long Read ◽  
Complex Structural

AbstractStructural genomic variants form a common type of genetic alteration underlying human genetic disease and phenotypic variation. Despite major improvements in genome sequencing technology and data analysis, the detection of structural variants still poses challenges, particularly when variants are of high complexity. Emerging long-read single-molecule sequencing technologies provide new opportunities for detection of structural variants. Here, we demonstrate sequencing of the genomes of two patients with congenital abnormalities using the ONT MinION at 11x and 16x mean coverage, respectively. We developed a bioinformatic pipeline - NanoSV - to efficiently map genomic structural variants (SVs) from the long-read data. We demonstrate that the nanopore data are superior to corresponding short-read data with regard to detection of de novo rearrangements originating from complex chromothripsis events in the patients. Additionally, genome-wide surveillance of SVs, revealed 3,253 (33%) novel variants that were missed in short-read data of the same sample, the majority of which are duplications < 200bp in size. Long sequencing reads enabled efficient phasing of genetic variations, allowing the construction of genome-wide maps of phased SVs and SNVs. We employed read-based phasing to show that all de novo chromothripsis breakpoints occurred on paternal chromosomes and we resolved the long-range structure of the chromothripsis. This work demonstrates the value of long-read sequencing for screening whole genomes of patients for complex structural variants.

scholarly journals Annotating and Detecting Topics in Social Media Forum and Modelling the Annotation to Derive Directions-A Case Study

2021 ◽  
Author(s):  
Athira B ◽  
Josette Jones ◽  
Sumam Mary Idicula ◽  
Anand Kulanthaivel ◽  
Enming Zhang
Keyword(s):  
Breast Cancer ◽  
Social Media ◽  
Deep Learning ◽  
Cancer Patients ◽  
Learning Algorithm ◽  
Treatment Options ◽  
Healthcare Sector ◽  
Final Decision ◽  
Breast Cancer Patients ◽  
Deep Learning Algorithm

Abstract The widespread influence of social media impacts every aspect of life, including the healthcare sector. Although medics and health professionals are the final decision makers, the advice and recommendations obtained from fellow patients are significant. In this context, the present paper explores the topics of discussion posted by breast cancer patients and survivors on online forums. The study examines an online forum, Breastcancer.org, maps the discussion entries to several topics, and proposes a machine learning model based on a classification algorithm to characterize the topics. To explore the topics of breast cancer patients and survivors, approximately 1000 posts are selected and manually labeled with annotations. In contrast, millions of posts are available to build the labels. A semi-supervised learning technique is used to build the labels for the unlabeled data; hence, the large data are classified using a deep learning algorithm. The deep learning algorithm BiLSTM with BERT word embedding technique provided a better f1-score of 79.5%. This method is able to classify the following topics: medication reviews, clinician knowledge, various treatment options, seeking and providing support, diagnostic procedures, financial issues and implications for everyday life. What matters the most for the patients is coping with everyday living as well as seeking and providing emotional and informational support. The approach and findings show the potential of studying social media to provide insight into patients' experiences with cancer like critical health problems.

scholarly journals The Effect of Acupuncture in Breast Cancer–Related Lymphoedema (BCRL): A Systematic Review and Meta-Analysis

2019 ◽  
Vol 18 ◽  
pp. 153473541986691 ◽  
Author(s):  
Tsai-Ju Chien ◽  
Chia-Yu Liu ◽  
Ching-Ju Fang
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Large Scale ◽  
Meta Analysis ◽  
Lymphatic Drainage ◽  
Controlled Trials ◽  
Breast Cancer Patients ◽  
Eligibility Criteria ◽  
Randomized Controlled

Background: Breast cancer–related lymphedema (BCRL) is hard to control. Management may include lymphatic drainage, skin care, bandaging, or even surgery. Since acupuncture has been proven to affect the neurophysiology and neuroendocrine systems, it has the potential to control BCRL. Aim: To evaluate the effect of acupuncture in BCRL in randomized controlled trials. Design: A literature search was performed, following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and without language restrictions. Data Sources: Five databases were searched from inception tthrough September 2018. Only studies that fulfilled the eligibility criteria of evaluating the effect of acupuncture on lymphedema in breast cancer were included. The methodological quality of these trials was assessed using the Cochrane criteria, and meta-analysis software (RevMan 5.3) was used for analysis. Results: We examined 178 breast cancer patients from 6 trials. All included randomized controlled trials had medium to high quality, based on the modified Jadad scale. The systematic review showed that acupuncture is safe and has a trend to improve symptoms, but trials did not consistently measure outcomes. The meta-analysis showed that acupuncture produced no significant improvement in the extent of lymphedema as compared with the control intervention (−1.90; 95% confidence interval = −5.39 to 1.59, P = .29). None of the studies reported severe adverse events. Conclusions: Acupuncture is safe and has a trend to improve the lymphedema related to breast cancer, yet it did not significantly change arm circumference in BCRL. Future studies should include both subjective and objective measurements and large-scale studies are warranted.

Communication Between Physicians and Older Women With Localized Breast Cancer: Implications for Treatment and Patient Satisfaction

2002 ◽  
Vol 20 (4) ◽  
pp. 1008-1016 ◽  
Author(s):  
Wenchi Liang ◽  
Caroline B. Burnett ◽  
Julia H. Rowland ◽  
Neal J. Meropol ◽  
Lynne Eggert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Care ◽  
Treatment Options ◽  
Treatment Choice ◽  
Satisfaction With Care ◽  
Physician Communication ◽  
Breast Cancer Patients ◽  
Actual Treatment ◽  
The Impact

PURPOSE: To identify factors associated with patient-physician communication and to examine the impact of communication on patients’ perception of having a treatment choice, actual treatment received, and satisfaction with care among older breast cancer patients. MATERIALS AND METHODS: Data were collected from 613 pairs of surgeons and their older (≥ 67 years) patients diagnosed with localized breast cancer. Measures of patients’ self-reported communication included physician- and patient-initiated communication and the number of treatment options discussed. Logistic regression analyses were conducted to examine the relationships between communication and outcomes. RESULTS: Patients who reported that their surgeons mentioned more treatment options were 2.21 times (95% confidence interval [CI], 1.62 to 3.01) more likely to report being given a treatment choice, and 1.33 times (95% CI, 1.02 to 1.73) more likely to get breast-conserving surgery with radiation than other types of treatment. Surgeons who were trained in surgical oncology, or who treated a high volume of breast cancer patients (≥ 75% of practice), were more likely to initiate communication with patients (odds ratio [OR] = 1.62; 95% CI, 1.02 to 2.56; and OR = 1.68; 95% CI, 1.01 to 2.76, respectively). A high degree of physician-initiated communication, in turn, was associated with patients’ perception of having a treatment choice (OR = 2.46; 95% CI, 1.29 to 4.70), and satisfaction with breast cancer care (OR = 2.13; 95% CI, 1.17 to 3.85) in the 3 to 6 months after surgery. CONCLUSION: Greater patient-physician communication was associated with a sense of choice, actual treatment, and satisfaction with care. Technical information and caring components of communication impacted outcomes differently. Thus, the quality of cancer care for older breast cancer patients may be improved through interventions that improve communication within the physician-patient dyad.

Different Targeting Strategies for Treating Breast Cancer Bone Metastases

2018 ◽  
Vol 24 (28) ◽  
pp. 3320-3331 ◽  
Author(s):  
Iram Irshad ◽  
Pegah Varamini
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Bone Metastasis ◽  
Treatment Options ◽  
Tumor Burden ◽  
Breast Cancer Patients ◽  
Physiological Processes ◽  
Metastatic Cells ◽  
Skeletal Complications

Background: Breast cancer is the most frequently diagnosed malignancy in women worldwide. Breast cancer tends to metastasize to bone. Around 70% of the breast cancer patients eventually develop bone metastasis. After the bone invasion, metastatic cells disrupt the balance between osteoblastic and osteoclastic activities, leading to skeletal complications, characterized by pain and pathological fractures and hence worsening the patient's quality of life. Once tumor invades the bone, it is hard to treat it with, the so-far available treatments options (e.g. bisphosphonates and denosumab). Bone metastasis should be essentially controlled, in cancer treatment and there is a strong need to explore new, more efficient therapeutic targets. This review discusses the bone physiological processes and the recent advances in exploring different pathways involved in bone metastasis. Furthermore, some novel treatment options, which are under preclinical and clinical investigations, are highlighted. Conclusion: A deeper understanding of these metastatic pathways can provide oncology researchers with novel avenues for treating bone metastasis, one of the main challenges to cure breast cancer. The restoration of healthy bone environment will not only improve the patient's quality of life but also reduces the tumor burden.

scholarly journals Systemic Treatment Options for HER2-Positive Breast Cancer Patients with Brain Metastases beyond Trastuzumab: A Literature Review

Breast Care ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. 168-171 ◽  
Author(s):  
Elena Laakmann ◽  
Volkmar Müller ◽  
Marcus Schmidt ◽  
Isabell Witzel
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Systemic Treatment ◽  
Treatment Options ◽  
Cytotoxic Agents ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Background: The incidence of brain metastases (BM) in breast cancer patients has increased. Many retrospective analyses have shown that first-line treatment with trastuzumab prolongs survival in patients with HER2-positive BM. In contrast, the evidence for other therapies targeting HER2 for patients with BM is rare. Methods: The aim of this review is to update the reader about current systemic treatment options in patients with HER2-positive metastatic breast cancer with BM who had already received trastuzumab. A literature search was performed in the PubMed database in June 2016. 30 relevant reports concerning the efficacy of trastuzumab emtansine (T-DM1), lapatinib and its combination with other cytotoxic agents, pertuzumab and novel HER2-targeting substances were identified. Results: There is limited but promising evidence for the use of T-DM1 and pertuzumab in the treatment of BM. Up to now, most reported studies used lapatinib as treatment of HER2-positive breast cancer with BM, a treatment with only a modest effect and a high toxicity profile. The combination of lapatinib with cytotoxic agents seems to result in better response rates. Conclusion: Further prospective investigations are needed to investigate the efficacy of the established and novel HER2-targeting agents on BM in HER2-positive breast cancer patients.

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