The latest medical research on Breast Cancer
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about breast cancer gathered by our medical AI research bot.
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The quality of life in neoadjuvant versus adjuvant therapy of esophageal cancer treatment trial (QUINTETT): Randomized parallel clinical superiority trial.Thoracic Cancer
We compared the health-related quality of life (HRQOL) in patients undergoing trimodality therapy for resectable stage I-III esophageal cancer.
A total of 96 patients were randomized to standard neoadjuvant cisplatin and 5-fluorouracil chemotherapy plus radiotherapy (neoadjuvant) followed by surgical resection or adjuvant cisplatin, 5-fluorouracil, and epirubicin chemotherapy with concurrent extended volume radiotherapy (adjuvant) following surgical resection.
There was no significant difference in the functional assessment of cancer therapy-esophageal (FACT-E) total scores between arms at 1 year (p = 0.759) with 36% versus 41% (neoadjuvant vs. adjuvant), respectively, showing an increase of ≥15 points compared to pre-treatment (p = 0.638). The HRQOL was significantly inferior at 2 months in the neoadjuvant arm for FACT-E, European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-OG25), and EuroQol 5-D-3 L in the dysphagia, reflux, pain, taste, and coughing domains (p < 0.05). Half of patients were able to complete the prescribed neoadjuvant arm chemotherapy without modification compared to only 14% in the adjuvant arm (p < 0.001). Chemotherapy related adverse events of grade ≥2 occurred significantly more frequently in the neoadjuvant arm (100% vs. 69%, p < 0.001). Surgery related adverse events of grade ≥2 were similar in both arms (72% vs. 86%, p = 0.107). There were no 30-day mortalities and 2% vs. 10% 90-day mortalities (p = 0.204). There were no significant differences in either overall survival (OS) (5-year: 35% vs. 32%, p = 0.409) or disease-free survival (DFS) (5-year: 31% vs. 30%, p = 0.710).
Trimodality therapy is challenging for patients with resectable esophageal cancer regardless of whether it is given before or after surgery. Newer and less toxic protocols are needed.
TIGIT/CD47 dual high expression predicts prognosis and is associated with immunotherapy response in lung squamous cell carcinoma.Thoracic Cancer
Recent studies indicated that T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) and cluster of differentiation 47 (CD47) have emerged as new potential immunotherapy targets. However, the roles of TIGIT and CD47 in lung squamous cell carcinoma (LUSC) have not been fully illustrated.
The specimens and clinicopathological information from 190 LUSC patients who underwent surgeries in our center were retrospectively collected. Immunohistochemical staining for TIGIT and CD47 was conducted. Transcriptional and clinical data of 479 LUSC were downloaded from The Cancer Genome Atlas (TCGA).
In the TCGA LUSC cohort, 142 (29.6%) cases were TIGIT/CD47 dual high expression at RNA level. The expression levels of TIGIT and CD47 were significantly correlated (p < 0.001). The proportions of patients with high TIGIT expression (p = 0.001) and high TIGIT/CD47 dual high expression (p = 0.049) were both higher in female cases. Advanced TNM stage (p = 0.006) and TIGIT/CD47 dual high expression (p = 0.047) were independent prognostic factors for LUSC. In the 190 LUSC cohort of our center, 75 (39.5%) cases were TIGIT/CD47 dual high expression at protein level. Cross-table analysis showed a correlation between TIGIT and CD47 expression. Older age (p = 0.001), advanced TNM stage (p < 0.001) and TIGIT/CD47 dual high expression (p = 0.046) were independent prognostic factors in our cohort.
We found that TIGIT and CD47 dual high expression was associated with poor prognosis in LUSC. We speculated that patients with dual high expression of CD47/TIGIT might be suitable for new target immunotherapy in the future.
PALB2 germline mutations in a multi-gene panel testing cohort of 1905 breast-ovarian cancer patients in Argentina.Breast Cancer
PALB2 variants have been scarcely described in Argentinian and Latin-American reports. In this study, we describe molecular and clinical characteristics of PALB2 mutations found in multi-gene panels (MP) from breast-ovarian cancer (BOC) families in different institutions from Argentina.
We retrospectively identified PALB2 pathogenic (PV) and likely pathogenic (LPV) variants from a cohort of 1905 MP results, provided by one local lab (Heritas) and SITHER (Hereditary Tumor Information System) public database. All patients met hereditary BOC clinical criteria for testing, according to current guidelines.
The frequency of PALB2 mutations is 2.78% (53/1905). Forty-eight (90.5%) are PV and five (9.5%) are LPV. Most of the 18 different mutations (89%) are nonsense and frameshift types and 2 variants are novel. One high-rate recurrent PV (Y551*) is present in 43% (23/53) of the unrelated index cases. From the 53 affected carriers, 94% have BC diagnosis with 14% of bilateral cases. BC phenotype is mainly invasive ductal (78%) with 62% of hormone-receptor positive and 22% of triple negative tumors. Self-reported ethnic background of the cohort is West European (66%) and native Latin-American (20%) which is representative of Buenos Aires and other big urban areas of the country.
This is the first report describing molecular and clinical characteristics of PALB2 carriers in Argentina. Frequency of PALB2 PV in Argentinian HBOC families is higher than in other reported populations. Y551* is a recurrent mutation that seems to be responsible for almost 50% of PALB2 cases.
The association between breast density and breast cancer pathological response to neoadjuvant chemotherapy.Breast Cancer
Mammographic Density (MD) refers to the amount of fibroglandular breast tissue present in the breast and is an established risk factor for developing breast cancer. The ability to evaluate treatment response dynamically renders neoadjuvant chemotherapy (NACT) the preferred treatment option in many clinical scenarios. Previous studies have suggested that MD can predict patients likely to achieve a pathological complete response (pCR) to NACT. We aimed to determine whether there is a causal relationship between BI-RADS breast composition categories for breast density at diagnosis and the pCR rate and residual cancer burden score (RCB) by performing a retrospective review on consecutive breast cancer patients who received NACT in a tertiary referral centre from 2015 to 2021.
The Mann-Whitney U Test was used to test for differences between two independent groups (i.e. those who achieved pCR and those who did not). A binary logistic regression model was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) for an association between the independent variables of molecular subtype, MD, histological grade and FNA positivity and the dependant variable of pCR. Statistical analysis was conducted with SPSS (IBM SPSS for Mac, Version 26.0; IBM Corp).
292 patients were included in the current study. There were 124, 155 and 13 patients in the BI-RADS MD category b, c and d, respectively. There were no patients in the BI-RADS MD category a. The patients with less dense breast composition (MD category b) were significantly older than patients with denser breast composition (MD category c, d) (p = 0.001) and patients who had a denser breast composition (MD category d) were more likely to have ER+ tumours. There was no significant difference in PgR status, HER2 status, pathological complete response (pCR), FNA positivity, or RCB class dependent upon the three MD categories. A binary logistic regression revealed that patients with HER2-enriched breast cancer and triple-negative breast cancer are more likely to achieve pCR with an OR of 3.630 (95% CI 1.360-9.691, p = 0.010) and 2.445 (95% CI 1.131-5.288, p = 0.023), respectively.
Whilst dense MD was associated with ER positivity and these women were less likely to achieve a pCR, MD did not appear to independently predict pCR post-NACT.
Breast reconstruction and quality of life five years after cancer diagnosis: VICAN French National cohort.Breast Cancer
Women with breast cancer (BC) who have a mastectomy may subsequently undergo breast reconstruction (BR). This study aimed to identify (1) factors associated with having BR, (2) factors associated with immediate BR (IBR) and delayed BR (DBR), and (3) associations between no BR, IBR and DBR and physical and mental quality of life (QoL) 5 years after diagnosis.
Analyses were based on data from the national French cancer cohort VICAN, which followed a representative sample of cancer survivors, including BC survivors, for 5 years after diagnosis. BR and BR type (IBR/DBR) were identified using medico-administrative databases. The SF12 scale was used to measure mental and physical QoL. Multivariate logistic regressions were used to identify factors associated with BR, and linear models to evaluate associations between BR and BR type with QoL.
Of the 1192 BC survivors in VICAN, 32.6% (n = 388) had a mastectomy. Among them, 60.1% (n = 233) had BR. Of these, 38.6% (n = 90) and 61.4% (n = 143) had IBR and DBR, respectively. Compared with women who had BR, women who did not were more likely to be older and to have a lower level of health literacy. Compared with women who did not have BR, those with IBR had better mental QoL, while those who had either IBR or DBR had better physical QoL.
Older women and those with inadequate health literacy were less likely to have BR. This may reflect women's preferences, inequalities in care options offered after a mastectomy, and socioeconomic barriers to accessing BR. These issues need further exploration. Furthermore, BR was associated with a better long-term physical QoL. IBR was associated with better mental QoL and should be promoted when possible.
MiR-379-5p inhibits the proliferation, migration, and invasion of breast cancer by targeting KIF4A.Thoracic Cancer
Many studies have shown that microRNAs (miRNAs) play an essential role in gene regulation and tumor development. This study aimed to explore the expression of miR-379-5p and its mechanisms of affecting proliferation, migration, and invasion in breast cancer (BC).
MiRNAs and mRNAs expression data of BC and normal breast tissue samples were downloaded from the TCGA and GEO databases. qRT-PCR was used to detect the expression of miR-379-5p in human normal breast epithelial cell lines and human BC cell lines. The proliferation ability of transfected cells was detected by colony formation and EdU assays. The mobility and invasion ability of transfected cells was measured by wound healing and transwell assays. The relative protein expression of transfected cells was detected by western blot. Dual luciferase reporter assay was performed to identify the targeted binding of miR-379-5p and KIF4A.
MiR-379-5p was lowly expressed in BC tissue samples and BC cell lines. The target genes of miR-379-5p were involved in many cancer-related signaling pathways. PPI analysis and the cytoHubba algorithm of Cytoscape identified 10 genes as the hub genes. Survival analysis showed that only KIF4A expression in 10 hub genes was significantly associated with the prognosis of BC patients and was significantly upregulated in BC. Overexpression of miR-379-5p inhibited proliferation, migration, and invasion in the BC cell line MDA-MB-231, which could be reversed by KIF4A.
MiR-379-5p inhibits proliferation, migration, and invasion of BC by targeting KIF4A.
Management of Non-Mass Enhancement at Breast Magnetic Resonance in Screening Settings Referred for Magnetic Resonance-Guided Biopsy.Breast Cancer
According to the Breast Imaging and Reporting Data System (BI-RADS), one of the main limitations of MRI is diagnosing the non-mass enhancement (NME). The NME lesion is challenging since it is unique to the MRI lexicon. This study aims to report our experience with NME lesions diagnosed by MRI referred for MRI-guided biopsies and discuss the management and follow-up of these lesions.
We retrospectively evaluated all MRI-guide breast biopsies. We included all patients referred for NME breast MRI-guided biopsy in screening settings. All patients had a negative second-look mammography or ultrasonography. We correlated the distribution and internal enhancement pattern (IEP) of the NME lesions with histology. Invasive ductal carcinomas (IDC) of no special type and ductal carcinoma in situ (DCIS) were considered malignant lesions.
From January-2018 to July-2021, we included 96 women with a total of 96 lesions in the study. There were 90 benign and 6 malignant lesions with DCIS prevalence (5/6 cancers). The most frequent benign lesion type was fibrocystic changes. There were no NME lesions with diffuse or multiple area distribution features referred to MRI-guided biopsy. The positive-predictive values (PPV) were respectively 0.0%, 2.5%, 9.0%, and 11.0% for linear, focal, regional, and segmental distribution describers, and 0.0, 3.0%, 7.9%, and 50% for homogenous, heterogeneous, clumped, and clustered-ring enhancement patterns.
We observe the high potential risk for malignancy in the clustered-ring enhancement followed by the clumped pattern. Segmental distribution presented the highest predictive-positive values.
Successful treatment of induced oligometastasis and repeated oligoprogression of advanced lung adenocarcinoma with immunotherapy and radiotherapy.Thoracic Cancer
Highly active and durable systemic therapies such as targeted therapy and immunotherapy can convert widespread metastatic disease into oligometasta...
Galectin-3 enhances trastuzumab resistance by regulating cancer malignancy and stemness in HER2-positive breast cancer cells.Thoracic Cancer
The aim of this study was to explore the role of galectin-3 in human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells and the potential mechanism.
Kaplan-Meier (KM)-plot and The Cancer Genome Atlas (TCGA) databases were used to study the role of galectin-3 in the prognosis of HER2-positive breast cancer. The effects of galectin-3 on cell proliferation, migration, invasion, and colony formation ability in HER2-positive breast cancer cells were examined. The relationship between galectin-3 and important components in the HER2 pathways, including HER2, epidermal growth factor receptor (EGFR), protein kinase B (AKT), and phosphatase and tensin homolog (PTEN), was further studied. Lentivirus and CRISPR/Cas9 were used to construct stable cell lines. Cell counting kit-8 (CCK-8) and apoptosis assays were used to study the relationship between galectin-3 and trastuzumab. The effect of galectin-3 on cell stemness was studied by mammosphere formation assay. The effects of galectin-3 on stemness biomarkers and the Notch1 pathway were examined. Tumorigenic models were used to evaluate the effects of galectin-3 on tumorigenesis and the therapeutic effect of trastuzumab in vivo.
HER2-positive breast cancer patients with a high expression level of LGALS3 (the gene encoding galectin-3) messenger RNA (mRNA) showed a poor prognosis. Galectin-3 promoted cancer malignancy through phosphoinositide 3-kinase (PI3K)/AKT signaling pathway activation and upregulated stemness by activating the Notch1 signaling pathway in HER2-positive breast cancer cells. These two factors contributed to the enhancement of trastuzumab resistance in cells. Knockout of LGALS3 had a synergistic therapeutic effect with trastuzumab both in vitro and in vivo.
Galectin-3 may represent a prognostic predictor and therapeutic target for HER2-positive breast cancer.
MiR-200c-3p and miR-485-5p overexpression elevates cisplatin sensitivity and suppresses the malignant phenotypes of non-small cell lung cancer cells through targeting RRM2.Thoracic Cancer
This study intended to investigate the potential mechanism of microRNA-200c-3p (miR-200c-3p) and miR-485-5p in mediating the cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC).
Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to measure the expression of miR-200c-3p, miR-485-5p, and ribonucleotide reductase regulatory subunit M2 (RRM2) messenger RNA (mRNA). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to analyze the DDP resistance and the proliferation of NSCLC cells. Colony formation assay was used to assess cell proliferation. Transwell assays were used to evaluate cell migration and invasion. The target relationship between RRM2 and miR-200c-3p or miR-485-5p was verified using dual-luciferase reporter assay. The protein level of RRM2 was measured using Western blot assay. Animal experiments were conducted to analyze the roles of miR-200c-3p and miR-485-5p in the DDP resistance of xenograft tumors in vivo.
MiR-200c-3p and miR-485-5p were both downregulated in DDP-resistant NSCLC tissues and cell lines. Overexpressing miR-200c-3p or miR-485-5p suppressed the DDP resistance and malignant behaviors of NSCLC cells. MiR-200c-3p played a synergistic role with miR-485-5p in regulating the chemo-resistance and biological behaviors NSCLC cells. RRM2 was confirmed as a target of miR-200c-3p and miR-485-5p. RRM2 silencing restrained the DDP resistance and progression of NSCLC. RRM2 overexpression partly reversed miR-200c-3p or miR-485-5p-induced influences in NSCLC cells. The overexpression of miR-200c-3p or miR-485-5p aggravated DDP-mediated suppressive effect on tumor growth in vivo.
MiR-200c-3p or miR-485-5p enhanced the DDP sensitivity and suppressed the malignant behaviors of NSCLC cells partly through targeting RRM2.
Characteristics, treatment trends, and long-term outcomes of Japanese patients with pregnancy-associated breast cancer (PABC).Breast Cancer
To clarify the characteristics, treatment trends, and long-term outcomes of patients with pregnancy-associated breast cancer (PABC).
PABC includes breast cancer diagnosed during pregnancy (PBC) and breast cancer diagnosed within 1 year after childbirth or during lactation (LBC). We compared clinical characteristics of 126 patients with LBC and 49 patients with PBC who underwent surgery at our hospital from 1946 to 2018. Survival was compared between patients with LBC and those with PBC in terms of breast cancer-specific disease-free survival (BC-DFS) and overall survival (OS).
Patients with LBC were more likely to have family history, lymph node metastasis, lymphatic invasion, and to receive chemotherapy than patients with PBC. Patients with LBC showed poorer BS-DFS and OS than patients with PBC. Among patients with LBC, those treated after 2005 were older at surgery, had a smaller tumor size, received more systemic therapy, and had a more favorable prognosis than patients treated before 2004. Family history, breast cancer within 1 year after childbirth, and surgery before 2004 as well as cStage, lymph node metastasis, and lymphatic invasion were significantly associated with poor prognosis in patients with LBC. In the multivariate analysis for BC-DFS and OS among patients with PABC, LBC vs PBC did not remain as an independent prognostic factor while cStage remained.
Patients with LBC had a poorer prognosis than those with PBC, most likely due to disease progression rather than biological characteristics. Early detection and optimization of systemic treatments are critical for improving the outcomes of patients with LBC.
Identification of tumor biomarkers for pathological complete response to neoadjuvant treatment in locally advanced breast cancer.Breast Cancer
Therapeutic response predictors like age, nodal status, and tumor grade and markers, like ER/PR, HER2, and Ki67, are not reliable in predicting the response to a specific form of chemotherapy. The current study aims to identify and validate reliable markers that can predict pathological complete response (pCR) in fluorouracil, epirubicin, and cyclophosphamide (FEC)-based neoadjuvant therapy with (NACT/RT) and without concurrent radiation (NACT).
Tandem mass tag (TMT) quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify differentially expressed proteins from core needle breast biopsy between pCR (n = 4) and no-pCR (n = 4). Immunoblotting of shortlisted proteins with the tissue lysates confirmed the differential expression of the markers. Further, immunohistochemistry (IHC) was performed on formalin-fixed paraffin-embedded sections of treatment-naive core needle biopsies. In the NACT, 29 pCR and 130 no-pCR and in NACT/RT, 32 pCR and 71 no-pCR were used.
733 and 807 proteins were identified in NACT and NACT/RT groups, respectively. Ten proteins were shortlisted for validation as potential pCR-predictive markers. THBS1, TNC, and DCN were significantly overexpressed in no-pCR in both the groups. In NACT, CPA3 was significantly upregulated in the no-pCR. In NACT/RT, HnRNPAB was significantly upregulated and HMGB1 significantly downregulated in the no-pCR. HMGB1 was the only marker to show prognostic significance.
Quantitative proteomics followed by IHC identified and validated potential biomarkers for predicting patient response to therapy. These markers can be used, following larger-scale validation, in combination with routine histological analysis providing vital indications of treatment response.