scholarly journals Pattern of Time-to-Surgery in Patients With Breast Cancer at Different Stages of the COVID-19 Pandemic

2022 ◽  
Vol 11 ◽  
Author(s):  
Ruixian Chen ◽  
Jiqiao Yang ◽  
Xin Zhao ◽  
Zhoukai Fu ◽  
Zhu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Time Delay ◽  
Cancer Patients ◽  
Clinicopathological Features ◽  
Excision Biopsy ◽  
Time Interval ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Time To Surgery ◽  
Three Stages

BackgroundThe management of cancer surgeries is under unprecedented challenges during the COVID-19 pandemic, and the breast cancer patients may face a time-delay in the treatment. This retrospective study aimed to present the pattern of time-to-surgery (TTS) and analyze the features of breast cancer patients under the different stages of the COVID-19 pandemic.MethodsPatients who received surgeries for breast cancers at West China Hospital between February 15, 2020 and April 30, 2020 (the outbreak and post-peak stages), and between March 10, 2021 and May 25, 2021 (the normalization stage) were included. TTS was calculated as the time interval between the pathological diagnosis and surgical treatment of breast cancer patients. And the pandemic was divided into three stages based on the time when the patients were pathologically diagnosed and the severity of pandemic at that time point. TTS, demographic and clinicopathological features were collected from medical records.ResultsA total of 367 patients were included. As for demographic features, it demonstrated statistically significant differences in insurance type (p<0.001) and regular screening (p<0.001), as well as age (p=0.013) and menstrual status (p=0.004). As for clinicopathological features, axillary involvement (p=0.019) was a factor that differed among three stages. The overall TTS was 23.56 ± 21.39 days. TTS for patients who were diagnosed during the outbreak of COVID-19 were longer than those diagnosed during pandemic post-peak and normalization stage (p<0.001). Pandemic stage (p<0.001) and excision biopsy before surgery (OR, 6.459; 95% CI, 2.225-18.755; p=0.001) were markedly correlated with the TTS of patients.ConclusionsTTS of breast cancer patients significantly varied in different stages of the COVID-19 pandemic. And breast cancer patients’ daily lives and disease treatments were affected by the pandemic in many aspects, such as health insurance access, physical screening and change of therapeutic schedules. As the time-delay may cause negative influences on patients’ disease, we should minimize the occurrence of such time-delay. It is vital to come up with comprehensive measures to deal with unexpected situations in case the pandemic occurs.

Is There a Bias Against Obese Patients in the Treatment of Breast Cancer?

2020 ◽  
pp. 000313482098487
Author(s):  
Melinda Wang ◽  
Julian Huang ◽  
Anees B. Chagpar
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Prophylactic Mastectomy ◽  
Implicit Bias ◽  
Treatment Decision ◽  
Obese Patients ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Immediate Reconstruction

Background Patient and tumor characteristics often coincide with obesity, potentially affecting treatment decision-making in obese breast cancer patients. Independent of all of these factors, however, it is unclear whether obesity itself impacts the decision to offer patients undergoing mastectomy breast reconstruction, postmastectomy radiation therapy (PMRT), or neoadjuvant chemotherapy. We sought to determine whether implicit bias against obese breast cancer patients undergoing mastectomy plays a role in their treatment. Methods Medical records of breast cancer patients undergoing mastectomy from January 2010 to April 2018 from a single institution were retrospectively reviewed, separated into obese (BMI ≥30) and nonobese (BMI <30) categories, and compared using nonparametric statistical analyses. Results Of 972 patients, 291 (31.2%) were obese. Obese patients were more likely to have node-positive, triple-negative breast cancers ( P = .026) and were also more likely to have other comorbidities such as a history of smoking ( P = .026), hypertension ( P < .001), and diabetes ( P < .001). Receipt of immediate reconstruction and contralateral prophylactic mastectomy did not vary between obese and nonobese patients. While obese patients were more likely to undergo neoadjuvant chemotherapy (26.5% vs. 18.1%, P = .004) and PMRT (33.0% vs. 23.4%, P = .003), this did not remain significant when controlling for comorbidities and clinicopathologic confounders. Conclusion Obese patients present with more aggressive tumors and often have concomitant comorbidities. Independent of these factors, however, differences in the treatment of patients undergoing mastectomy do not seem to be affected by an implicit bias against obese patients.

Predominance of RAD21 and ERBB2 amplification and progesterone receptor positivity in tumors of the right breast support breast cancer lateralization.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12557-e12557
Author(s):  
Zachary Spigelman ◽  
Jo-Ellen Murphy
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Cancer Patients ◽  
Breast Tumors ◽  
Left Breast ◽  
Breast Cancers ◽  
Her2 Expression ◽  
Breast Cancer Patients ◽  
The Right ◽  
Chi Square Analysis

e12557 Background: Biologic lateralization broadly impacts breast cancer. Malignancies originating in the left breast compared to the right breast tend to be more frequent, larger and of poorer prognosis. Left breast tumors respond differently to HER2-neu signaling and have lateralized Ki67 expression. In a prior study a right-left asymmetry in the neutrophil/lymphocyte ratio (NLR) of breast cancers was identified (ASCO 2018, e13094). As a follow-up, retrospective analysis of results from comprehensive genomic profiling (CGP) of right and left side breast cancer specimens was performed to determine a potential genomic etiology for the observed NLR lateralization. Methods: Tumors from 43 consecutive breast cancer patients underwent analysis for all classes of genomic alterations by hybrid capture-based CGP (Foundation Medicine). The CGP results from the 25 left- and 18 right-sided breast cancer samples were analyzed along with the histologic grade and status of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression. Results: In this cohort of advanced breast cancer patients (stage 3-4), no statistically significant differences in lateralization were identified based on patient age, tumor stage, or frequency of ER or Her2 expression (Table). A predominance of PR positivity (p=0.14 chi square analysis) and amplifications in the ERBB2 (p=0.37) and RAD21 (p=0.08) genes were detected in right side tumors. Conclusions: Together with the prior study, trends in asymmetry based on genomic, pathologic, and immunohistologic differences have been detected in breast cancers, including an increased incidence of ERBB2 and RAD21 amplification in right-side breast tumors in this cohort. The predominance of lower PR positivity in the left breast tumors may be due to preferential hypermethylation, consistent with reports that it mediates biologic lateralization changes, downregulates PR expression, and alters amplification rates. Epigenetic methylation, may contribute to asymmetric breast cancer biology and have implications for therapeutic strategy. Further study is warranted.[Table: see text]

scholarly journals Regression of Triple-Negative Breast Cancer in a Patient-Derived Xenograft Mouse Model by Monoclonal Antibodies against IL-12 p40 Monomer

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 259
Author(s):  
Madhuchhanda Kundu ◽  
Sumita Raha ◽  
Avik Roy ◽  
Kalipada Pahan
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Transforming Growth Factor ◽  
Healthy Controls ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Patient Derived Xenograft

Although some therapies are available for regular breast cancers, there are very few options for triple-negative breast cancer (TNBC). Here, we demonstrated that serum level of IL-12p40 monomer (p40) was much higher in breast cancer patients than healthy controls. On the other hand, levels of IL-12, IL-23 and p40 homodimer (p402) were lower in serum of breast cancer patients as compared to healthy controls. Similarly, human TNBC cells produced greater level of p40 than p402. The level of p40 was also larger than p402 in serum of a patient-derived xenograft (PDX) mouse model. Accordingly, neutralization of p40 by p40 mAb induced death of human TNBC cells and tumor shrinkage in PDX mice. While investigating the mechanism, we found that neutralization of p40 led to upregulation of human CD4+IFNγ+ and CD8+IFNγ+ T cell populations, thereby increasing the level of human IFNγ and decreasing the level of human IL-10 in PDX mice. Finally, we demonstrated the infiltration of human cytotoxic T cells, switching of tumor-associated macrophage M2 (TAM2) to TAM1 and suppression of transforming growth factor β (TGFβ) in tumor tissues of p40 mAb-treated PDX mice. Our studies identify a possible new immunotherapy for TNBC in which p40 mAb inhibits tumor growth in PDX mice.

Profiling receptor tyrosine kinase fusions in Chinese breast cancers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15092-e15092
Author(s):  
Zhonghua Tao ◽  
Xichun Hu ◽  
Wen-Ming Cao ◽  
Jianxia Liu ◽  
Ting Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinase ◽  
Cancer Patients ◽  
Tyrosine Kinases ◽  
Breast Cancer Subtype ◽  
Stage Iv ◽  
Tyrosine Kinase Domain ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive

e15092 Background: Receptor tyrosine kinases (RTKs) are a class of tyrosine kinases that regulate cell-to-cell communication and control a variety of complex biological functions. Dysregulation of RTK signaling partly due to chromosomal rearrangements leads to novel tyrosine kinase fusion oncoproteins which are possibly driver alterations to cancers. Targeting some RTK fusions with specific tyrosine kinases inhibitors (TKIs) is an effective therapeutic strategy across a spectrum of RTK fusion-related cancers. However, there is still a paucity of extensive RTK fusion investigations in breast cancer. We aimed to characterize RTK fusions in Chinese breast cancer patients. Methods: An in-house sequencing database of 1440 Chinese breast cancer patients using a 520-gene NGS sequencing panel was thoroughly reviewed. RTK fusion was defined as an in-frame fusion with the tyrosine kinase domain of the RTK completely retained with the only exception of ERBB2 fusion which was not counted due to its unclear significance. Concomitant mutations and TMB were also analyzed and calculated. Patients’ clinical characteristics were retrieved from case records. Results: 27 RTK fusion-positive breast cancers (12 tissues + 15 plasmas) were identified, patients had a median age of 52 years. Triple-negative breast cancer subtype comprised 37% with luminal and HER2 positive subtypes being 40.8% and 22.2%, respectively. 77.8% of patients were at stage IV and 22.2% at stage I-III. Ten were treatment naïve. RTK fusions occurred in 2% of breast cancers in our database, compared with the prevalence of 0.6% and 1.3% in MSKCC and TCGA, respectively. In the subset of stage IV patients, our database showed a significantly higher RTK fusion frequency than that in MSKCC (3.2% vs. 0.6%, p = 0.013). FGFR2 fusions were seen most commonly (n = 7), followed by RET (n = 4), ROS1 (n = 3), NTRK3 (n = 3), BRAF (n = 2), and NTRK1 (n = 2). Other RTK fusions including ALK, EGFR, FGFR1, FGFR3, MET, and NTRK2 were identified in one patient each. Of note, the normalized abundance of RTK fusion (fusion AF/max AF) correlated negatively with TMB (r = -0.48, p = 0.017). Patients with TMB < 4 (Muts/Mb) displayed a higher fusion abundance than those with TMB ≥ 4 (Muts/Mb) (p = 0.018), suggesting a higher likelihood of subclonal nature for RTK fusions in TMB-high patients. Moreover, CREBBP mutation only co-occurred with FGFR2 fusion (p = 0.012), while NTRK3 fusion and TP53 mutation were mutually exclusive (p = 0.019). Conclusions: This is the first study comprehensively delineating the prevalence and spectrum of RTK fusions in Chinese breast cancers. Further study is ongoing to identify the enriched subpopulation which may benefit from RTK fusion inhibitors.

scholarly journals Tribbles Homolog 3 Involved in Radiation Response of Triple Negative Breast Cancer Cells by Regulating Notch1 Activation

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 127 ◽  
Author(s):  
Yueh-Chun Lee ◽  
Wen-Ling Wang ◽  
Wei-Chao Chang ◽  
Yu-Hao Huang ◽  
Guan-Ci Hong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Cancer Patients ◽  
Triple Negative ◽  
Mass Spectrometry Analysis ◽  
Radiation Response ◽  
Stem Cell Population ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Poor Prognostic Factor

Breast cancer is the most common cancer for women in Taiwan and post-lumpectomy radiotherapy is one of the therapeutic strategies for this malignancy. Although the 10-year overall survival of breast cancer patients is greatly improved by radiotherapy, the locoregional recurrence is around 10% and triple negative breast cancers (TNBCs) are at a high risk for relapse. The aim of this paper is to understand the mechanisms of radioresistance in breast cancers which may facilitate the development of new treatments in sensitizing breast cancer toward radiation therapy. Tribbles homolog 3 (TRIB3) is a pseudokinase protein and known to function as a protein scaffold within cells. It has been reported that higher TRIB3 expression is a poor prognostic factor in breast cancer patients with radiotherapy. In this study, we investigate the involvement of TRIB3 in the radiation response of TNBC cells. We first found that the expression of TRIB3 and the activation of Notch1, as well as Notch1 target genes, increased in two radioresistant TNBC cells. Knockdown of TRIB3 in radioresistant MDA-MB-231 TNBC cells decreased Notch1 activation, as well as the CD24-CD44+ cancer stem cell population, and sensitized cells toward radiation treatment. The inhibitory effects of TRIB3 knockdown in self-renewal or radioresistance could be reversed by forced expression of the Notch intracellular domain. We also observed an inhibition in cell growth and accumulated cells in the G0/G1 phase in radioresistant MDA-MB-231 cells after knockdown of TRIB3. With immunoprecipitation and mass spectrometry analysis, we found that, BCL2-associated transcription factor 1 (BCLAF1), BCL2 interacting protein 1 (BNIP1), or DEAD-box helicase 5 (DDX5) were the possible TRIB3 interacting proteins and immunoprecipitation data also confirmed that these proteins interacted with TRIB3 in radioresistant MDA-MB-231 cells. In conclusion, the expression of TRIB3 in radioresistant TNBC cells participated in Notch1 activation and targeted TRIB3 expression may be a strategy to sensitize TNBC cells toward radiation therapy.

scholarly journals The Clinicopathological features and survival outcomes of patients with different metastatic sites in stage IV breast cancer

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ru Wang ◽  
Yayun Zhu ◽  
Xiaoxu Liu ◽  
Xiaoqin Liao ◽  
Jianjun He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Cancer Patients ◽  
Stage Iv ◽  
Clinicopathological Features ◽  
Breast Cancer Patients ◽  
Kaplan Meier ◽  
Stage Iv Breast Cancer ◽  
Multivariable Analyses ◽  
Metastatic Sites

Abstract Background The features and survival of stage IV breast cancer patients with different metastatic sites are poorly understood. This study aims to examine the clinicopathological features and survival of stage IV breast cancer patients according to different metastatic sites. Methods Using the Surveillance, Epidemiology, and End Results database, we restricted our study population to stage IV breast cancer patients diagnosed between 2010 to 2015. The clinicopathological features were examined by chi-square tests. Breast cancer-specific survival (BCSS) and overall survival (OS) were compared among patients with different metastatic sites by the Kaplan-Meier method with log-rank test. Univariable and multivariable analyses were also performed using the Cox proportional hazard model to identify statistically significant prognostic factors. Results A total of 18,322 patients were identified for survival analysis. Bone-only metastasis accounted for 39.80% of patients, followed by multiple metastasis (33.07%), lung metastasis (10.94%), liver metastasis (7.34%), other metastasis (7.34%), and brain metastasis (1.51%). The Kaplan-Meier plots showed that patients with bone metastasis had the best survival, while patients with brain metastasis had the worst survival in both BCSS and OS (p < 0.001, for both). Multivariable analyses showed that age, race, marital status, grade, tumor subtype, tumor size, surgery of primary cancer, and a history of radiotherapy or chemotherapy were independent prognostic factors. Conclusion Stage IV breast cancer patients have different clinicopathological characteristics and survival outcomes according to different metastatic sites. Patients with bone metastasis have the best prognosis, and brain metastasis is the most aggressive subgroup.

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