Background
The outbreaks of infectious diseases, such as coronavirus disease 2019 (COVID-19), have seriously affected the normal work and life of the public, as well as the normal diagnosis and ...treatment of other diseases due to their strong infectivity, high population susceptibility, and diverse clinical manifestations. Breast and thyroid specialists in non-hotspot epidemic areas of COVID-19 must consider factors, including epidemic prevention and control, breast and thyroid cancers and diseases diagnosis and treatment, and access to medical resources to make a reasonable treatment choice and optimize the treatment process.
Methods
A cohort study was designed under our center’s epidemic prevention and control strategy. The study was conducted between February 3 and April 19, 2020, to explore the safety of clinical diagnosis and treatment of breast and thyroid cancer patients during the epidemic. All the outpatients, inpatients, day-time chemotherapy patients, targeted therapy patients, and relevant medical staff in the observation period in the Department of Breast and Thyroid Surgery in Southwest Hospital in Chongqing municipality, China, were included to investigate the detection and infection rate of COVID-19 and suspected patients.
Results
During the observation period, 27,117 patients were admitted to the outpatient unit. We performed 394 inpatient surgeries and 411 day-time surgeries. In our center, 1,046 and 663 patients received day-time chemotherapy and targeted therapy, respectively. All the patients were diagnosed and treated promptly and safely. Three suspected COVID-19 patients were identified in the outpatient unit. Healthcare staff achieved a “zero” infection of COVID-19.
Conclusion
The spread and cross-infection of COVID-19 can be avoided in non-hotspot epidemic areas based on scientific prevention and control, and cancer patients can be diagnosed and treated on time. The prevention and control measure implemented in the COVID-19 epidemic for diagnosing and treating cancer patients was effective and can be referenced for other infectious disease outbreaks.
Chemotherapy is still the main adjuvant strategy in the treatment of cancer, however, chemoresistance is also frequently encountered. Autophagy inhibition has been widely accepted as a promising ...therapeutic strategy in cancer, while the lack of effective and specific autophagy inhibitors hinders its application. Here we found that dichloroacetate (DCA), a small molecule compound, could significantly inhibit the autophagy induced by Doxorubicin in breast cancer cells. And DCA markedly enhances Doxorubicin-induced breast cancer cell death and anti-proliferation in vitro. But the sensitization to Dox of DCA was significantly reduced through induction of autophagy by rapamycin. Moreover, the combined therapy of Dox and DCA could significantly inhibit tumor growth in vivo and prolong mouse survival time. Taken together, we demonstrate that DCA could inhibit doxorubicin-inducing autophagy and provide a novel strategy for improving the anti-cancer efficacy of chemotherapy.
•Doxorubicin (Dox) induces autophagy in breast cancer cell.•DCA sensibilizes MDA-MB-231 cells to Dox through inhibiting autophagy.•Induction autophagy by rapamycin impaired the sensitizing effects of DCA to Dox.•Synergistic inhibition of tumor growth in mice treated with Dox and DCA.
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and the targeted therapies are lacking for this type of cancer. We previously demonstrated that Huaier ...effectively improve 5-year OS and DFS in stage III TNBC patients, and the polysaccharides of Huaier (PS-T) have been identified as the major components of Huaier. However, the mechanisms of anti-tumor action of PS-T is unclear. This study aimed to investigate the effect of PS-T on TNBC cell invasion and migration. This study showed that PS-T inhibited cell invasion and migration both in vitro and in vivo by inducing autophagy to suppress epithelial-mesenchymal transition (EMT). Autophagy inhibitor LY294002 or knockdown of ATG5 suppressed the inhibitory effects of PS-T. In addition, as a key transcription factor controlling EMT initiation, Snail was found to be degraded by PS-T induced autophagy. In addition, overexpression of Snail reversed the inhibitory effects of PS-T. Furthermore, it was confirmed that the expression of Snail was inversely correlated with LC3 and associated with poor prognosis using immunohistochemistry and TCGA database analysis, respectively. This study demonstrated that PS-T could inhibit EMT in breast cancer cells by inducing autophagy to degrade Snail protein, thus improving the prognosis of TNBC, offering potential treatment alternatives for TNBC patients.
In recent years, traditional Chinese medicine (TCM) has been developing rapidly in cancer treatment. Huaier is a widely used fungus by TCM to treat different kinds of cancers. Its good efficacy in ...prevention of tumor recurrence and metastasis has been proven by a large number of clinical studies. In order to further investigate the efficacy and safety of Huaier granules in post-surgical therapy for stage I-III triple-negative breast cancer (TNBC) patients, we performed a case-control clinical study to observe its effects on the post-surgical safety and survival rates of these patients.
Two hundred and one TNBC patients underwent modified radical mastectomy were selected, they were admitted to our hospital between October 2010 to September 2014. The patients were randomly allocated to the experimental group (101 cases) or the control group (100 cases). Patients in the experimental group were treated with Huaier granules, by orally taking 20 g each time with 3 times a day. Medication was started during chemotherapy or at the time in 6 or 18 months after it. The control group did not receive any TCM preparations during this process. The disease-free survival (DFS) and overall survival (OS) were measured as the main outcome.
The median follow-up time was 46 months. For the 100 patients in control group, 5-year DFS and OS was 82% and 86% respectively, while 87.1% and 90.1% for the 101 patients in the experimental group. The difference was not statistically significant. However, stage III patients in the control group showed a 5-year DFS of 53.8% and OS of 65.4%, which were significantly lower than that of stage III patients in the experimental group as 81.3% and 87.5%. In the experimental group, 10 patients with 6-month medication showed disease progression, whereas only 3 patients with 18-month medication showed disease progression. This difference was statistically significant as well.
Huaier granules could play an important role in post-surgical adjuvant therapy of TNBC patients, specially by effectively increasing the DFS and OS of breast cancer patients at middle to advanced stage.
Objective:
Increasing evidence highlights the roles of N
6
-methyladenosine (m
6
A) and its regulators in oncogenesis. Herein, this study observed the associations of m
6
A regulators with breast ...cancer.
Methods:
RNA-seq profiles of breast cancer were retrieved from the Cancer Genome Atlas (TCGA) database. The expression of m
6
A regulators was analyzed in tumor and normal tissues. Their expression correlations were analyzed by Spearson test. Overall survival (OS) analysis of these regulators was then presented. Gene set enrichment analysis (GSEA) was performed in high and low YTHDF1 expression groups. The correlations of YTHDF1 expression with immune cells and tumor mutation burden (TMB) were calculated in breast cancer samples. Somatic variation was assessed in high and low YTHDF1 expression groups.
Results:
Most of m
6
A regulators were abnormally expressed in breast cancer compared to normal tissues. At the mRNA levels, there were closely relationships between them. Among them, YTHDF1 up-regulation was significantly related to undesirable prognosis (
p
= 0.025). GSEA results showed that high YTHDF1 expression was associated with cancer-related pathways. Furthermore, YTHDF1 expression was significantly correlated with T cells CD4 memory activated, NK cells activated, monocytes, and macrophages. There were higher TMB scores in YTHDF1 up-regulation group than its down-regulation group. Missense mutation and non-sense mutation were the most frequent mutation types.
Conclusion:
Our findings suggested that dysregulated m
6
A regulator YTHDF1 was predictive of survival outcomes as well as response to immunotherapy of breast cancer, and were closely related to immune microenvironment.
The risk of breast cancer is significantly increased among obese women as the deleterious adipokines can be over secreted and beneficial adipokines can be hyposecreted. We aim to evaluate the ...association between obesity-associated adipokines and breast cancer. We searched PubMed, EMBASE, Web of Science, and Chinese Biomedical Literature (CBM) databases for studies reporting association of obesity related adipokines with breast cancer published before Sept. 15, 2015. Initially, 26783 publications were identified, and later, 119 articles were selected for further meta-analysis. Out of these 119 studies, twenty-six studies had reported adipokine levels among obese and non-obese healthy subjects and ninety-three studies had reported adipokine levels among patients with breast cancer. The subjects with BMI >25 kg/m2 had significantly lower adiponectin levels and higher leptin and tumor necrosis factor-α (TNF-α) levels than those with BMI <25 kg/m2. Decreased concentrations of adiponectin, and increased concentrations of leptin, IL-6, IL-8, TNF-α, resistin and visfatin were significantly associated with risk of breast cancer. Adipokine levels were strongly associated with breast cancer among Asian women as compared to non-Asian women. Our results might explain the relationship of obesity, adipokine levels and risk of breast cancer, especially in Asian women.
An important drawback of the traditional technique for harvesting latissimus dorsi (LD) myocutaneous flap is a long, posterior donor-site incision. Current techniques involve endoscopic or robotic ...harvesting via a combined approach of open and closed surgery, which necessitates an open axillary incision and the use of special retractors. In this paper, we introduce a fully enclosed laparoscopic technique for harvesting LD flap (LDF) using only 3 small trocar ports. This technique eliminates the need for axillary and donor-site incisions and specialized retractors and considerably reduces the incision size.
We performed laparoscopic harvesting of LDF with prosthesis implantation for immediate breast reconstruction (IBR) after nipple-sparing mastectomy in 2 patients with malignant breast neoplasm who wished to avoid a long scar on the back.
IBR using this technique was uneventful in both cases, without any donor-site complications or flap failure. Both patients were satisfied with the esthetic results of the procedure, especially the absence of a visible scar on the back.
Enclosed laparoscopic harvesting of LDF is simpler and less invasive than the traditional methods. These preliminary results warrant further evaluation in a larger population to validate the benefits of this technique.
Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency ...of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next‐generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non‐BRCA1/2 gene. Major mutant non‐BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non‐BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER‐2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non‐BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non‐BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.
What's new?
The prevalence of mutations in breast cancer predisposition genesare not well investigated in Asia. We assessed germline mutations of 40 cancer susceptibility genes in 937 consecutive selected breast cancer patients from 26 centers of China, and discovered 23.8% of participates carried the pathogenic mutation, including 6.8% with mutations in non‐BRCA1/2 genes, while TP53 and PALB2 had a relatively high mutation rates (1.9% and 1.2%).There was no factors predicted for detrimental mutations in non‐BRCA1/2 genes when treated as a whole.
Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency ...of germline mutations in 40 cancer predisposition genes, including
BRCA1
and
BRCA2
, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next‐generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in
BRCA1/2
, 61 in 15 other BC susceptibility genes and 3 in both
BRCA1/2
and non‐
BRCA1/2
gene. Major mutant non‐
BRCA1/2
genes were
TP53
(n = 18),
PALB2
(n = 11),
CHEK2
(n = 6),
ATM
(n = 6) and
BARD1
(n = 5). No factors predicted pathologic mutations in non‐
BRCA1/2
genes when treated as a whole.
TP53
mutations were associated with HER‐2 positive BC and younger age at diagnosis; and
CHEK2
and
PALB2
mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non‐
BRCA1/2
genes.
TP53
and
PALB2
had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non‐
BRCA1/2
genes, some clinical features were associated with mutations of several particular genes.
What's new?
The prevalence of mutations in breast cancer predisposition genesare not well investigated in Asia. We assessed germline mutations of 40 cancer susceptibility genes in 937 consecutive selected breast cancer patients from 26 centers of China, and discovered 23.8% of participates carried the pathogenic mutation, including 6.8% with mutations in non‐
BRCA1/2
genes, while
TP53
and
PALB2
had a relatively high mutation rates (1.9% and 1.2%).There was no factors predicted for detrimental mutations in non‐
BRCA1/2
genes when treated as a whole.