Tumour cell invasion into blood vessels is significantly related to breast cancer subtypes and decreased survival

2016 ◽  
Vol 70 (4) ◽  
pp. 313-319 ◽  
Author(s):  
Tor A Klingen ◽  
Ying Chen ◽  
Ingunn M Stefansson ◽  
Gøril Knutsvik ◽  
Karin Collett ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Screening Program ◽  
Interval Cancer ◽  
Population Based ◽  
Blood Vessel Invasion ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Increased Risk ◽  
Basic Features

AimsVascular invasion in breast cancer is associated with increased risk of recurrence, metastases and death from disease. However, there are few studies discriminating between blood vessel invasion (BVI) and lymphatic vessel involvement (LVI).MethodsA population-based series of 282 breast cancers was examined (200 screen-detected and 82 interval patients) with respect to BVI and LVI in addition to basic features and molecular subtypes, using CD31 and D2-40 antibodies. This series is part of the prospective Norwegian Breast Cancer Screening Program.ResultsThe frequency of LVI and BVI was 25% and 15%, respectively. BVI was associated with HER2-positive and basal-like tumours, and several features of aggressive breast cancer, whereas LVI showed weaker associations. BVI was the strongest factor to predict interval cancer presentation. BVI showed significant associations with recurrence-free survival and disease-specific survival in univariate and multivariate analyses, whereas LVI was not significant.ConclusionsOur findings indicate that BVI by tumour cells is strongly associated with aggressive tumour features including a basal-like phenotype, and BVI was an independent prognostic factor in contrast to what was found for LVI.

scholarly journals Identification of Long Noncoding RNAs as Predictors of Survival in Triple-Negative Breast Cancer Based on Network Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Xiao-Xiao Li ◽  
Li-Juan Wang ◽  
Jie Hou ◽  
Hong-Yang Liu ◽  
Rui Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Network Analysis ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Breast Cancers ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes

Breast cancer is the most common cancer observed in adult females, worldwide. Due to the heterogeneity and varied molecular subtypes of breast cancer, the molecular mechanisms underlying carcinogenesis in different subtypes of breast cancer are distinct. Recently, long noncoding RNAs (lncRNAs) have been shown to be oncogenic or play important roles in cancer suppression and are used as biomarkers for diagnosis and therapy. In this study, we identified 134 lncRNAs and 6,414 coding genes were differentially expressed in triple-negative (TN), human epidermal growth factor receptor 2- (HER2-) positive, luminal A-positive, and luminal B-positive breast cancer. Of these, 37 lncRNAs were found to be dysregulated in all four subtypes of breast cancers. Subtypes of breast cancer special modules and lncRNA-mRNA interaction networks were constructed through weighted gene coexpression network analysis (WGCNA). Survival analysis of another public datasets was used to verify the identified lncRNAs exhibiting potential indicative roles in TN prognosis. Results from heat map analysis of the identified lncRNAs revealed that five blocks were significantly displayed. High expressions of lncRNAs, including LINC00911, CSMD2-AS1, LINC01192, SNHG19, DSCAM-AS1, PCAT4, ACVR28-AS1, and CNTFR-AS1, and low expressions of THAP9-AS1, MALAT1, TUG1, CAHM, FAM2011, NNT-AS1, COX10-AS1, and RPARP-AS1 were associated with low survival possibility in TN breast cancers. This study provides novel lncRNAs as potential biomarkers for the therapeutic and prognostic classification of different breast cancer subtypes.

The potential benefit of trastuzumab-based therapy upon lapatinib progression in heavily preatreated patients with advanced HER2 positive breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11576-e11576
Author(s):  
Anastasios L. Boutis ◽  
Sofia Chatzileontiadou ◽  
Nikolaos Diamantopoulos ◽  
Athanasios Pouptsis ◽  
Chariklia Fotiou
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Ductal Carcinoma ◽  
Advanced Breast ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Metastatic Setting ◽  
Increased Risk

e11576 Background: Overexpression of human epidermal growth factor receptor 2 (HER2) occurring in about 20% of breast cancers is associated with increased risk of disease recurrence and worse prognosis. Despite the advent of therapies that target HER2, particularly, trastuzumab and lapatinib, that have altered the natural course of HER2-positive advanced breast cancer, tumor progression remains inevitable. New agents are in clinical development, but up to date there are limited data to direct the treatment of patients after lapatinib progression. Methods: We retrospectively searched for HER2-positive advanced breast cancer patients treated at our clinic, who received both trastuzumab-based therapy and lapatinib upon trastuzumab-progression in the metastatic setting. Thirty patients, all female, suffering from HER2-positive advanced breast cancer were identified. HER-2 positivity was assessed by immunohistochemistry (IHC 3+) or chromogenic in situ hybridization (CISH+). Results: Of the 30 patients, 83.3% had invasive ductal carcinoma; 60% had positive hormone receptor status, and 80% grade 3 tumours. Half of the patients received adjuvant trastuzumab. Median age was 57 years, range 37-79 years. 36.6% were switched to lapatinib after a median of three (range 2-6 lines) trastuzumab-based treatment lines. In 8 pts (37.5%) trastuzumab was re-started after lapatinib progression. In 7 of these patients, trastuzumab was combined with chemotherapy. Median progression free survival and overall survival in these patients was 4.75 and 8.87 months respectively. 3 patients received bevacizumab-based therapy upon lapatinib failure. Conclusions: Trastuzumab rechallenge after lapatinib progression may be active in a subgroup of heavily pre-treated patients. Clinical benefit of this strategy has to be balanced especially in limited resource settings with unavailability of novel agents or early phase clinical trials. As of now, there is no uniform accepted standard to define the optimal treatment approach of patients upon lapatinib progression showing the real need for new therapies in this population.

The association between breast density and HER2-positive breast cancer: A population-based case-control study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12556-e12556
Author(s):  
Vivian Tan ◽  
Jennifer Payne ◽  
Nicole Paquet ◽  
Sian Iles ◽  
Daniel Rayson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Density ◽  
Breast Screening ◽  
Hormone Replacement ◽  
Menopausal Status ◽  
Population Based ◽  
Case Control ◽  
Mammographic Breast Density ◽  
Her2 Positive ◽  
Increased Risk

e12556 Background: Little is known about the association between mammographic breast density and the subtypes of breast cancer including HER2-positive breast cancers (HER2-BrCa). The objective of this study was to assess the strength of association between breast density and HER2-BrCa in a population-based screening program. Methods: This is a population-based case-control breast cancer study of women aged 40 to 75 who underwent digital breast screening from 2009 to 2015 in Nova Scotia, Canada. Cases included women diagnosed with HER2-BrCa at screen or before their next screen (interval); controls included women without screen-detected cancer matched to cases by age and year of screen. Measures of mammographic breast density (percent density, BI-RADS-4th and -5th edition) were obtained from automated software (densitasai) and linked with clinical risk factor data (age, parity, total breast volume, post-menopausal status, hormone replacement therapy, family history and history of core biopsy). The association between breast density and cancer risk was assessed by calculating the odds ratios [OR] with 95% confidence intervals using multivariable logistic regression. Results: A total of 209 cases (median age, 58.8 years) and 6812 controls (median age, 59.4 years) were included. The risk of HER2-BrCa increased with increasing levels of percent breast density. High breast density according to BIRADS-4th and -5th editions was significantly associated with HER2-BrCa: BIRADS -4th 3/4 vs 1: OR 2.50 (1.68 - 3.68); BIRADS-5th C/D vs A: OR 2.58 (1.71 - 4.01). The association between higher breast density and increased risk of HER2-BrCa remained after adjustment for clinical factors. Conclusions: The risk of HER2-BrCa was associated with progressively higher mammographic breast density, although to a lesser extent than breast cancer in general. Accurate risk models including breast density may support the development of more breast-screening protocols that can lead to more strategic use of healthcare resources.

Breast cancer subtype and screening sensitivity in the Quebec Mammography Screening Program

2018 ◽  
Vol 26 (3) ◽  
pp. 154-161
Author(s):  
Linda Perron ◽  
Sue-Ling Chang ◽  
Jean-Marc Daigle ◽  
Nathalie Vandal ◽  
Isabelle Theberge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammography Screening ◽  
Triple Negative ◽  
Screening Program ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Luminal B ◽  
Mammography Screening Program ◽  
Screening Sensitivity

Objective In mammography screening, interval cancers present a problem. The metric ‘screening sensitivity’ monitors both how well a programme detects cancers and avoids interval cancers. To our knowledge, the effect of breast cancer surrogate molecular subtypes on screening sensitivity has never been evaluated. We aimed to measure the 2-year screening sensitivity according to breast cancer subtypes. Methods We studied 734 women with an invasive breast cancer diagnosed between 2003 and 2007 after participating in one regional division of Quebec’s Mammography Screening Program. They represented 83% of all participating women with an invasive BC diagnosis in that region for that period. Tumours were categorized into ‘luminal A-like’, ‘luminal B-like’, ‘triple-negative’ and ‘HER2-positive’ subtypes. We used logistic regression and marginal standardization to estimate screening sensitivity, sensitivity ratios (SR) and sensitivity differences. We also assessed the mediating effect of grade. Results Adjusted 2-year screening sensitivity was 75.4% in luminal A-like, 66.1% in luminal B-like, 52.9% in triple-negative and 45.3% in HER2-positive, translating into sensitivity ratios of 0.88 (95% confidence interval [CI] = 0.78–0.98) for luminal B-like, 0.70 (CI = 0.56–0.88) for triple-negative and 0.60 (CI = 0.39–0.93) for HER2-positive, when compared with luminal A-like. Grade entirely mediated the subtype-sensitivity association for triple negative and mediated it partly for HER2-positive. Screening round (prevalent vs. incident) did not modify results. Conclusion There was substantial variation in screening sensitivity according to breast cancer subtypes. Aggressive phenotypes showed the lowest sensitivity, an effect that was mediated by grade. Tailoring screening according to women’s subtype risk factors might eventually lead to more efficient programs.

scholarly journals Dose-Reduced Trastuzumab Emtansine: Active and Safe in Acute Hepatic Dysfunction

2015 ◽  
Vol 8 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Adam Sharp ◽  
Stephen R.D. Johnston
Keyword(s):  
Breast Cancer ◽  
Metastatic Disease ◽  
Hepatic Dysfunction ◽  
Metastatic Breast ◽  
Receptor Expression ◽  
Trastuzumab Emtansine ◽  
Breast Cancers ◽  
Her2 Receptor ◽  
Her2 Positive ◽  
Cancer Subtypes

Breast cancer is the most common cancer in women worldwide. The majority of deaths attributed to breast cancer are a result of metastatic disease, and 30% of early breast cancers (EBC) will develop distant disease. The 5-year survival of patients with metastatic disease is estimated at 23%. Breast cancer subtypes continue to be stratified histologically on oestrogen, progesterone and human epidermal growth factor-2 (HER2) receptor expression. HER2-positive breast cancers represent 25% of all breast cancer diagnoses. The therapies available for metastatic breast cancer (MBC) are expanding, in particular within the field of HER2-positive disease, with the approval of trastuzumab, pertuzumab, lapatinib and trastuzumab emtansine (TDM-1). Recently, TDM-1 has been shown to improve progression-free survival in HER2 MBC when compared to capecitabine and lapatinib in clinical studies. Its main toxicities are deranged liver function tests and thrombocytopenia. There have also been cases of acute liver failure. Therefore, its use in acute hepatic dysfunction, to our knowledge, has been neither studied nor reported. We report a patient with progressive HER2-positive MBC who had previously responded to multiple HER2-targeted therapies that presented with acute hepatic dysfunction. She was treated with dose-reduced TDM-1 safely, with clear evidence of rapid biochemical, clinical and radiological response. This allowed dose escalation of TDM-1, and the patient maintains an ongoing response.

scholarly journals Association of interleukin 10 rs1800896 polymorphism with susceptibility to breast cancer: a meta-analysis

2020 ◽  
Vol 48 (4) ◽  
pp. 030006052090486 ◽  
Author(s):  
ZiYin Zhu ◽  
Ji-Bin Liu ◽  
Xi Liu ◽  
LinXue Qian
Keyword(s):  
Breast Cancer ◽  
Meta Analysis ◽  
Interleukin 10 ◽  
Population Based ◽  
Case Control ◽  
Recessive Model ◽  
Breast Cancers ◽  
Case Control Studies ◽  
Asian Populations ◽  
Increased Risk

Objective To evaluate the correlation between interleukin 10 (IL-10) −1082A/G polymorphism (rs1800896) and breast cancers by performing a meta-analysis. Methods The Embase and Medline databases were searched through 1 September 2018 to identify qualified articles. Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were applied to evaluate associations. Results In total, 14 case-control studies, including 5320 cases and 5727 controls, were analyzed. We detected significant associations between the IL10 −1082 G/G genotype and risk of breast cancer (AA + AG vs. GG: OR = 0.88, 95% CI = 0.80–0.97). Subgroup analyses confirmed a significant association in Caucasian populations (OR = 0.89, 95% CI = 0.80–0.99), in population-based case-control studies (OR = 0.87, 95% CI = 0.78–0.96), and in studies with ≥500 subjects (OR = 0.88, 95% CI = 0.79–0.99) under the recessive model (AA + AG vs. GG). No associations were found in Asian populations. Conclusions The IL10 −1082A/G polymorphism is associated with an increased risk of breast cancer. The association between IL10 −1082 G/G genotype and increased risk of breast cancer is more significant in Caucasians, in population-based studies, and in larger studies.

scholarly journals EP300 and SIRT1/6 Co-Regulate Lapatinib Sensitivity Via Modulating FOXO3-Acetylation and Activity in Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1067 ◽  
Author(s):  
Zimam Mahmud ◽  
Ana R. Gomes ◽  
Hee Jin Lee ◽  
Sathid Aimjongjun ◽  
Yannasittha Jiramongkol ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Target Gene ◽  
Target Genes ◽  
Ectopic Expression ◽  
Sirtuin 1 ◽  
Fine Tuning ◽  
Gene Promoters ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Cancer Subtypes

Forkhead Box O3 (FOXO3) is a tumor suppressor whose activity is fine-tuned by post-translational modifications (PTMs). In this study, using the BT474 breast cancer cells and a recently established lapatinib resistant (BT474-LapR) cell line, we observed that higher FOXO3 and acetylated (Ac)-FOXO3 levels correlate with lapatinib sensitivity. Subsequent ectopic expression of EP300 led to an increase in acetylated-FOXO3 in sensitive but not in resistant cells. Drug sensitivity assays revealed that sensitive BT474 cells show increased lapatinib cytotoxicity upon over-expression of wild-type but not acetylation-deficient EP300. Moreover, FOXO3 recruitment to target gene promoters is associated with target gene expression and drug response in sensitive cells and the inability of FOXO3 to bind its target genes correlates with lapatinib-resistance in BT474-LapR cells. In addition, using SIRT1/6 specific siRNAs and chemical inhibitor, we also found that sirtuin 1 and -6 (SIRT1 and -6) play a part in fine-tuning FOXO3 acetylation and lapatinib sensitivity. Consistent with this, immunohistochemistry results from different breast cancer subtypes showed that high SIRT6/1 levels are associated with constitutive high FOXO3 expression which is related to FOXO3 deregulation/inactivation and poor prognosis in breast cancer patient samples. Collectively, our results suggest the involvement of FOXO3 acetylation in regulating lapatinib sensitivity of HER2-positive breast cancers.

The association between volumetric breast density and breast cancer subtypes among women newly diagnosed with breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13115-e13115 ◽  
Author(s):  
Wintana A. Balema ◽  
Tanya W. Moseley ◽  
Olena Weaver ◽  
Kenneth R. Hess ◽  
Abenaa M. Brewster
Keyword(s):  
Breast Cancer ◽  
Risk Factor ◽  
Breast Density ◽  
Breast Cancer Subtype ◽  
Breast Cancer Subtypes ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Volumetric Density ◽  
Increased Risk ◽  
Cancer Subtype

e13115 Background: Increased breast density is a strong risk factor for breast cancer, women with high breast density have a four to six-fold increased risk of breast cancer compared to those with low density. This study explores breast density as a risk factor for specific breast cancer subtypes in order to improve risk assessment and screening recommendations for the general population. Methods: 790 women ≥ 18 years with breast cancer were evaluated who had volumetric percent density and volumetric density grade (VDG) assessed from diagnostic mammograms obtained within 9 months of diagnosis. Breast cancer subtypes were approximated based on the estrogen receptor (ER), progesterone (PR) and Her2neu status; ER and/or PR positive/Her2 negative or positive (HR+), ER and PR negative and Her2 positive (Her2-positive) and ER, PR and Her2 negative (TN). A linear model on a log scale was conducted to evaluate the associations between percentage volumetric breast density and VDG and breast cancer subtypes and race. Results: 36% of women were < 50 years and 64% ≥50 years, 76% were white, 12% Black and 12% other race. There was no significant association between breast cancer subtype with age ( P = 0.068), BMI ( P = 0.81) or race ( P = 0.11). Women with VDG 1 or 2 were more likely to have HR+ (81.3%) than Her2-positive (5.1%) or TN subtypes (13.6%) (P = 0.024). There was no significant association between the percent volumetric breast density and breast tumor subtype or race. Conclusions: We found a significant association between lower breast density measured using VDG and the HR+ breast cancer subtype. This suggests a potential opportunity for assessing volumetric density grade for the development of individualized risk prediction models and for the identification of women who may benefit from preventive therapy to reduce HR+ breast cancer risk.

scholarly journals Left–right breast asymmetry and risk of screen-detected and interval cancers in a large population-based screening population

2020 ◽  
Vol 93 (1112) ◽  
pp. 20200154
Author(s):  
Sue M Hudson ◽  
Louise S Wilkinson ◽  
Bianca L De Stavola ◽  
Isabel dos-Santos-Silva
Keyword(s):  
Breast Cancer ◽  
Logistic Regression ◽  
Cancer Diagnosis ◽  
Linear Trend ◽  
Conditional Logistic Regression ◽  
Large Population ◽  
Interval Cancer ◽  
Population Based ◽  
Breast Cancers ◽  
Interval Cancers

Objectives: To assess the associations between automated volumetric estimates of mammographic asymmetry and breast cancers detected at the same (“contemporaneous”) screen, at subsequent screens, or in between (interval cancers). Methods: Automated measurements from mammographic images (N = 79,731) were used to estimate absolute asymmetry in breast volume (BV) and dense volume (DV) in a large ethnically diverse population of attendees of a UK breast screening programme. Logistic regression models were fitted to assess asymmetry associations with the odds of a breast cancer detected at contemporaneous screen (767 cases), adjusted for relevant confounders. Nested case–control investigations were designed to examine associations between asymmetry and the odds of: (a) interval cancer (numbers of cases/age-matched controls: 153/646) and (b) subsequent screen-detected cancer (345/1438), via conditional logistic regression. Results: DV, but not BV, asymmetry was positively associated with the odds of contemporaneous breast cancer (P-for-linear-trend (Pt) = 0.018). This association was stronger for first (prevalent) screens (Pt = 0.012). Both DV and BV asymmetry were positively associated with the odds of an interval cancer diagnosis (Pt = 0.060 and 0.030, respectively). Neither BV nor DV asymmetry were associated with the odds of having a subsequent screen-detected cancer. Conclusions: Increased DV asymmetry was associated with the risk of a breast cancer diagnosis at a contemporaneous screen or as an interval cancer. BV asymmetry was positively associated with the risk of an interval cancer diagnosis. Advances in knowledge: The findings suggest that DV and BV asymmetry may provide additional signals for detecting contemporaneous cancers and assessing the likelihood of interval cancers in population-based screening programmes.

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