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Fulltext Presentation of Breast Cancer and Impact of Patient Navigation on Timeliness of Diagnosis and Treatment and on Adherence to Treatment Recommendations in a Multicenter Network in Malaysia

Jaganathan M, Ang BH, Ali A, Sharif SZ, Mohamad M, Mohd Khairy A, et al.

JCO Glob Oncol, 2024 Mar;10:e2300297.
PMID: 38484197 DOI: 10.1200/GO.23.00297

PURPOSE: Breast cancer deaths disproportionately affect women living in low- and middle-income countries (LMICs). Patient navigation has emerged as a cost-effective and impactful approach to enable women with symptoms or suspicious mammogram findings to access timely diagnosis and patients with breast cancer to access timely and appropriate multimodality treatment. However, few studies have systematically evaluated the impact of patient navigation on timeliness of diagnosis and treatment in LMICs.
METHODS: We established a nurse- and community-navigator-led navigation program in breast clinics of four public hospitals located in Peninsular and East Malaysia and evaluated the impact of navigation on timeliness of diagnosis and treatment.
RESULTS: Patients with breast cancer treated at public hospitals reported facing barriers to accessing care, including having a poor recognition of breast cancer symptoms and low awareness of screening methods, and facing financial and logistics challenges. Compared with patients diagnosed in the previous year, patients receiving navigation experienced timely ultrasound (84.0% v 65.0%; P < .001), biopsy (84.0% v 78.0%; P = .012), communication of news (63.0% v 40.0%; P < .001), surgery (46% v 36%; P = .008), and neoadjuvant therapy (59% v 42%, P = .030). Treatment adherence improved significantly (98.0% v 87.0%, P < .001), and this was consistent across the network of four breast clinics.
CONCLUSION: Patient navigation improves access to timely diagnosis and treatment for women presenting at secondary and tertiary hospitals in Malaysia.

Matched MeSH terms: Breast/pathology
Fulltext Evaluating the effectiveness of stain normalization techniques in automated grading of invasive ductal carcinoma histopathological images

Voon W, Hum YC, Tee YK, Yap WS, Nisar H, Mokayed H, et al.

Sci Rep, 2023 Nov 22;13(1):20518.
PMID: 37993544 DOI: 10.1038/s41598-023-46619-6

Debates persist regarding the impact of Stain Normalization (SN) on recent breast cancer histopathological studies. While some studies propose no influence on classification outcomes, others argue for improvement. This study aims to assess the efficacy of SN in breast cancer histopathological classification, specifically focusing on Invasive Ductal Carcinoma (IDC) grading using Convolutional Neural Networks (CNNs). The null hypothesis asserts that SN has no effect on the accuracy of CNN-based IDC grading, while the alternative hypothesis suggests the contrary. We evaluated six SN techniques, with five templates selected as target images for the conventional SN techniques. We also utilized seven ImageNet pre-trained CNNs for IDC grading. The performance of models trained with and without SN was compared to discern the influence of SN on classification outcomes. The analysis unveiled a p-value of 0.11, indicating no statistically significant difference in Balanced Accuracy Scores between models trained with StainGAN-normalized images, achieving a score of 0.9196 (the best-performing SN technique), and models trained with non-normalized images, which scored 0.9308. As a result, we did not reject the null hypothesis, indicating that we found no evidence to support a significant discrepancy in effectiveness between stain-normalized and non-normalized datasets for IDC grading tasks. This study demonstrates that SN has a limited impact on IDC grading, challenging the assumption of performance enhancement through SN.

Matched MeSH terms: Breast/pathology
Fulltext Spectrum of imaging findings of papillary breast disease: A radiopathological review in a tertiary center

Fadzli F, Rahmat K, Ramli MT, Rozalli FI, Hooi TK, Fadzli AN, et al.

Medicine (Baltimore), 2021 Apr 23;100(16):e25297.
PMID: 33879660 DOI: 10.1097/MD.0000000000025297

To evaluate the clinical and imaging findings of papillary breast neoplasm and review the pathologic correlation at a tertiary center.Retrospective study of patients diagnosed with benign and malignant papillary lesions between 2008 to 2018. 147 patients were identified with histology diagnosis of papillary lesions. The clinical, imaging, and pathological characteristics were reviewed.Patient cohort included 147 women diagnosed with papillary lesions (mean age at diagnosis 53.8 years) and were divided into 3 histology groups (benign, atypical, and malignant). Common clinical presentations were breast lump (n = 60) and nipple discharge (n = 29), 48 patients were asymptomatic.Only 37 were detected as a mass lesion on mammogram. The presence of mass lesion on mammogram was the most common feature in all 3 papillary lesion groups, and with the presence of asymmetric density, were the 2 mammographic features significantly associated (P

Matched MeSH terms: Breast/pathology
Fulltext Indication of high lipid content in epithelial-mesenchymal transitions of breast tissues

Sabtu SN, Sani SFA, Looi LM, Chiew SF, Pathmanathan D, Bradley DA, et al.

Sci Rep, 2021 Feb 05;11(1):3250.
PMID: 33547362 DOI: 10.1038/s41598-021-81426-x

The epithelial-mesenchymal transition (EMT) is a crucial process in cancer progression and metastasis. Study of metabolic changes during the EMT process is important in seeking to understand the biochemical changes associated with cancer progression, not least in scoping for therapeutic strategies aimed at targeting EMT. Due to the potential for high sensitivity and specificity, Raman spectroscopy was used here to study the metabolic changes associated with EMT in human breast cancer tissue. For Raman spectroscopy measurements, tissue from 23 patients were collected, comprising non-lesional, EMT and non-EMT formalin-fixed and paraffin embedded breast cancer samples. Analysis was made in the fingerprint Raman spectra region (600-1800 cm-1) best associated with cancer progression biochemical changes in lipid, protein and nucleic acids. The ANOVA test followed by the Tukey's multiple comparisons test were conducted to see if there existed differences between non-lesional, EMT and non-EMT breast tissue for Raman spectroscopy measurements. Results revealed that significant differences were evident in terms of intensity between the non-lesional and EMT samples, as well as the EMT and non-EMT samples. Multivariate analysis involving independent component analysis, Principal component analysis and non-negative least square were used to analyse the Raman spectra data. The results show significant differences between EMT and non-EMT cancers in lipid, protein, and nucleic acids. This study demonstrated the capability of Raman spectroscopy supported by multivariate analysis in analysing metabolic changes in EMT breast cancer tissue.

Matched MeSH terms: Breast/pathology
Fulltext Diagnostic accuracy of tomosynthesis-guided vacuum assisted breast biopsy of ultrasound occult lesions

Bohan S, Ramli Hamid MT, Chan WY, Vijayananthan A, Ramli N, Kaur S, et al.

Sci Rep, 2021 01 08;11(1):129.
PMID: 33420200 DOI: 10.1038/s41598-020-80124-4

This study aims to evaluate the diagnostic accuracy of digital breast tomosynthesis-guided vacuum assisted breast biopsy (DBT-VABB) of screening detected suspicious mammographic abnormalities comprising of calcifications, asymmetric densities, architectural distortions and spiculated masses. In this institutionally approved study, a total of 170 (n = 170) DBT-VABB were performed, 153 (90%) were for calcifications, 8 (4.7%) for spiculated mass, 5 (2.9%) for asymmetric density and 4 (2.4%) for architectural distortion. All these lesions were not detected on the corresponding ultrasound. Histopathology results revealed 140 (82.4%) benign, 9 (5.3%) borderline and 21 (12.4%) malignant lesions. The total upgrade rate at surgery was 40% for atypical ductal hyperplasia and 5.9% for ductal carcinoma in-situ. 3.6% discordant benign lesions showed no upgrade. DBT-VABB showed 100% specificity, 91.3% sensitivity and 100% positive predictive value (PPV) for detecting malignant lesions. The negative predictive value (NPV) was 80%. 2 (1.2%) patients had mild complications and 1 (0.6%) had severe pain. Our study showed that DBT-VABB was a safe and reliable method, with high sensitivity, specificity, PPV and NPV in the diagnosis of non-palpable benign and malignant breast lesions. Our data also confirmed the accuracy of DBT-VABB in detecting malignant lesions and we suggest further surgical excision in borderline lesions for a more accurate diagnostic evaluation.

Matched MeSH terms: Breast/pathology
Fulltext Diagnostic accuracy of digital breast tomosynthesis in combination with 2D mammography for the characterisation of mammographic abnormalities

Sanmugasiva VV, Ramli Hamid MT, Fadzli F, Rozalli FI, Yeong CH, Ab Mumin N, et al.

Sci Rep, 2020 11 26;10(1):20628.
PMID: 33244075 DOI: 10.1038/s41598-020-77456-6

This study aims to assess the diagnostic accuracy of digital breast tomosynthesis in combination with full field digital mammography (DBT + FFDM) in the charaterisation of Breast Imaging-reporting and Data System (BI-RADS) category 3, 4 and 5 lesions. Retrospective cross-sectional study of 390 patients with BI-RADS 3, 4 and 5 mammography with available histopathology examination results were recruited from in a single center of a multi-ethnic Asian population. 2 readers independently reported the FFDM and DBT images and classified lesions detected (mass, calcifications, asymmetric density and architectural distortion) based on American College of Radiology-BI-RADS lexicon. Of the 390 patients recruited, 182 malignancies were reported. Positive predictive value (PPV) of cancer was 46.7%. The PPV in BI-RADS 4a, 4b, 4c and 5 were 6.0%, 38.3%, 68.9%, and 93.1%, respectively. Among all the cancers, 76% presented as masses, 4% as calcifications and 20% as asymmetry. An additional of 4% of cancers were detected on ultrasound. The sensitivity, specificity, PPV and NPV of mass lesions detected on DBT + FFDM were 93.8%, 85.1%, 88.8% and 91.5%, respectively. The PPV for calcification is 61.6% and asymmetry is 60.7%. 81.6% of cancer detected were invasive and 13.3% were in-situ type. Our study showed that DBT is proven to be an effective tool in the diagnosis and characterization of breast lesions and supports the current body of literature that states that integrating DBT to FFDM allows good characterization of breast lesions and accurate diagnosis of cancer.

Matched MeSH terms: Breast/pathology*
Fulltext Structural Studies of Epithelial Mesenchymal Transition Breast Tissues

Mohd Sobri SN, Abdul Sani SF, Sabtu SN, Looi LM, Chiew SF, Pathmanathan D, et al.

Sci Rep, 2020 02 06;10(1):1997.
PMID: 32029810 DOI: 10.1038/s41598-020-58932-5

At the supramolecular level, the proliferation of invasive ductal carcinoma through breast tissue is beyond the range of standard histopathology identification. Using synchrotron small angle x-ray scattering (SAXS) techniques, determining nanometer scale structural changes in breast tissue has been demonstrated to allow discrimination between different tissue types. From a total of 22 patients undergoing symptomatic investigations, different category breast tissue samples were obtained in use of surgically removed tissue, including non-lesional, benign and malignant tumour. Structural components of the tissues were examined at momentum transfer values between q = 0.2 nm-1 and 1.5 nm-1. From the SAXS patterns, axial d-spacing and diffuse scattering intensity were observed to provide the greatest discrimination between the various tissue types, specifically in regard to the epithelial mesenchymal transition (EMT) structural component in malignant tissue. In non-lesional tissue the axial period of collagen is within the range 63.6-63.7 nm (formalin fixed paraffin embedded (FFPE) dewaxed) and 63.4 (formalin fixed), being 0.9 nm smaller than in EMT cancer-invaded regions. The overall intensity of scattering from cancerous regions is a degree of magnitude greater in cancer-invaded regions. Present work has found that the d-spacing of the EMT positive breast cancer tissue (FFPE (dewaxed)) is within the range 64.5-64.7 nm corresponding to the 9th and 10th order peaks. Of particular note in regard to formalin fixation of samples is that no alteration is observed to occur in the relative differences in collagen d-spacing between non-lesional and malignant tissues. This is a matter of great importance given that preserved-sample and also retrospective study of samples is greatly facilitated by formalin fixation. Present results indicate that as aids in tissue diagnosis SAXS is capable of distinguishing areas of invasion by disease as well as delivering further information at the supramolecular level.

Matched MeSH terms: Breast/pathology; Carcinoma, Ductal, Breast/pathology*
Follow-up of B3 breast lesions without residual microcalcifications post vacuum-assisted biopsy, can contrast-enhanced digital mammography help?

Bicchierai G, Nori J, De Benedetto D, Boeri C, Vanzi E, Bianchi S, et al.

Breast J, 2020 02;26(2):299-302.
PMID: 31486197 DOI: 10.1111/tbj.13598
Matched MeSH terms: Carcinoma, Ductal, Breast/pathology
Fulltext The association between methods of biopsy and survival following breast cancer: A hospital registry based cohort study

Kong YC, Bhoo-Pathy N, O'Rorke M, Subramaniam S, Bhoo-Pathy NT, See MH, et al.

Medicine (Baltimore), 2020 Feb;99(6):e19093.
PMID: 32028433 DOI: 10.1097/MD.0000000000019093

Percutaneous biopsy in breast cancer has been associated with an increased risk of malignant cell seeding. However, the importance of these observations remains obscure due to lack of corroborating evidence from clinical studies. We determined whether method of biopsy is associated with breast cancer survival. This hospital registry-based cohort study included 3416 non-metastatic breast cancer patients diagnosed from 1993 to 2011 in a tertiary setting. Factors associated with biopsy methods were assessed. Multivariable Cox regression analysis was used to determine the independent prognostic impact of method of biopsy. Overall, 990 patients were diagnosed by core needle biopsy (CNB), 1364 by fine needle aspiration cytology (FNAC), and 1062 by excision biopsy. Excision biopsy was significantly associated with more favorable tumor characteristics. Radiotherapy modified the prognostic impact of biopsy method (Pinteraction breast cancer, further studies are warranted.

Matched MeSH terms: Breast/pathology
Chronic granulomatous mastitis with axillary lymphadenopathy in a nulliparous woman

Rajendran D, Chew BS, Wong MW, Cheong YT

Med J Malaysia, 2019 12;74(6):564-565.
PMID: 31929493

Chronic Granulomatous Mastitis (CGM) is a rare disorder and this generally occurs in young women with a recent history of lactation. Development of this disease in nulliparous women are rare with an incidence of 10%. Axillary lymphadenopathy is seen in 15% of cases diagnosed with CGM. We present a case of CGM in a 23- year-old nulliparous woman presenting with a breast mass and multiple axillary lymphadenopathy. To the best of our knowledge there are no documented cases of both these rare clinical features occurring simultaneously. The use of oral steroids prevented surgery and effectively induced remission.

Matched MeSH terms: Breast/pathology*
A novel method of determining breast cancer risk using parenchymal textural analysis of mammography images on an Asian cohort

Tan M, Mariapun S, Yip CH, Ng KH, Teo SH

Phys Med Biol, 2019 01 31;64(3):035016.
PMID: 30577031 DOI: 10.1088/1361-6560/aafabd

Historically, breast cancer risk prediction models are based on mammographic density measures, which are dichotomous in nature and generally categorize each voxel or area of the breast parenchyma as 'dense' or 'not dense'. Using these conventional methods, the structural patterns or textural components of the breast tissue elements are not considered or ignored entirely. This study presents a novel method to predict breast cancer risk that combines new texture and mammographic density based image features. We performed a comprehensive study of the correlation of 944 new and conventional texture and mammographic density features with breast cancer risk on a cohort of Asian women. We studied 250 breast cancer cases and 250 controls matched at full-field digital mammography (FFDM) status for age, BMI and ethnicity. Stepwise regression analysis identified relevant features to be included in a linear discriminant analysis (LDA) classifier model, trained and tested using a leave-one-out based cross-validation method. The area under the receiver operating characteristic (AUC) and adjusted odds ratios (ORs) were used as the two performance assessment indices in our study. For the LDA trained classifier, the adjusted OR was 6.15 (95% confidence interval: 3.55-10.64) and for Volpara volumetric breast density, 1.10 (0.67-1.81). The AUC for the LDA trained classifier was 0.68 (0.64-0.73), compared to 0.52 (0.47-0.57) for Volpara volumetric breast density (p breast cancer risk assessment based models. Parenchymal texture analysis has an important role for stratifying breast cancer risk in women, which can be implemented to routine breast cancer screening strategies.

Matched MeSH terms: Breast/pathology*
Fulltext Association of BRCA1- and BRCA2-deficiency with mutation burden, expression of PD-L1/PD-1, immune infiltrates, and T cell-inflamed signature in breast cancer

Wen WX, Leong CO

PLoS One, 2019;14(4):e0215381.
PMID: 31022191 DOI: 10.1371/journal.pone.0215381

Immune checkpoint inhibitors have demonstrated effective anti-tumour response in cancer types with high mutation burden (e.g. melanoma) and in subset of cancers with features of genomic instability (e.g. mismatch-repair deficiency). One possible explanation for this effect is the increased expression of immune checkpoint molecules and pre-existing adaptive immune response in these cancers. Given that BRCA1 and BRCA2 are integral in maintaining genomic integrity, we hypothesise that the inactivation of these genes may give rise to breast cancers with such immunogenic phenotype. Therefore, using two large series of publicly available breast cancer datasets, namely that from The Cancer Genome Atlas and Wellcome Trust Institute, we sought to investigate the association between BRCA1- and BRCA2-deficiency with features of genomic instability, expression of PD-L1 and PD-1, landscape of inferred tumour-infiltrating immune cells, and T-cell inflamed signature in breast cancers. Here, we report that BRCA1 and BRCA2-deficient breast cancers were associated with features of genomic instability including increased mutation burden. Interestingly, BRCA1-, but not BRCA2-, deficient breast cancers were associated with increased expression of PD-L1 and PD-1, higher abundance of tumour-infiltrating immune cells, and enrichment of T cell-inflamed signature. The differences in immunophenotype between BRCA1- and BRCA2-deficient breast cancers can be attributed, in part, to PTEN gene mutation. Therefore, features of genomic instability such as that mediated by BRCA1- and BRCA2- deficiency in breast cancer were necessary, but not always sufficient, for yielding T cell-inflamed tumour microenvironment, and by extension, predicting clinical benefit from immunotherapy.

Matched MeSH terms: Breast/pathology
A Brief Review on Breast Carcinoma and Deliberation on Current Non Invasive Imaging Techniques for Detection

Vairavan R, Abdullah O, Retnasamy PB, Sauli Z, Shahimin MM, Retnasamy V

Curr Med Imaging Rev, 2019;15(2):85-121.
PMID: 31975658 DOI: 10.2174/1573405613666170912115617

BACKGROUND: Breast carcinoma is a life threatening disease that accounts for 25.1% of all carcinoma among women worldwide. Early detection of the disease enhances the chance for survival.
DISCUSSION: This paper presents comprehensive report on breast carcinoma disease and its modalities available for detection and diagnosis, as it delves into the screening and detection modalities with special focus placed on the non-invasive techniques and its recent advancement work done, as well as a proposal on a novel method for the application of early breast carcinoma detection.
CONCLUSION: This paper aims to serve as a foundation guidance for the reader to attain bird's eye understanding on breast carcinoma disease and its current non-invasive modalities.

Matched MeSH terms: Breast/pathology
Single-nucleotide polymorphisms and mRNA expression of CYP1B1 influence treatment response in triple negative breast cancer patients undergoing chemotherapy

Abdul Aziz AA, Md Salleh MS, Mohamad I, Krishna Bhavaraju VM, Mazuwin Yahya M, Zakaria AD, et al.

J Genet, 2018 Dec;97(5):1185-1194.
PMID: 30555068

Triple negative breast cancer (TNBC) is typically associated with poor and interindividual variability in treatment response. Cytochrome P450 family 1 subfamily B1 (CYP1B1) is a metabolizing enzyme, involved in the biotransformation of xenobiotics and anticancer drugs. We hypothesized that, single-nucleotide polymorphisms (SNPs), CYP1B1 142 C>G, 4326 C>G and 4360 A>G, and CYP1B1 mRNA expression might be potential biomarkers for prediction of treatment response in TNBC patients. CYP1B1 SNPs genotyping (76 TNBC patients) was performed using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods and mRNA expression of CYP1B1 (41 formalin-fixed paraffin embeddedblocks) was quantified using quantitative reverse transcription PCR. Homozygous variant genotype (GG) and variant allele (G) of CYP1B1 4326C>G polymorphism showed significantly higher risk for development of resistance to chemotherapy with adjusted odds ratio (OR): 6.802 and 3.010, respectively. Whereas, CYP1B1 142 CG heterozygous genotype showed significant association with goodtreatment response with adjusted OR: 0.199. CYP1B1 142C-4326G haplotype was associated with higher risk for chemoresistance with OR: 2.579. Expression analysis revealed that the relative expression of CYP1B1 was downregulated (0.592) in cancerous tissue compared with normal adjacent tissues. When analysed for association with chemotherapy response, CYP1B1 expression was found to be significantly upregulated (3.256) in cancerous tissues of patients who did not respond as opposed to those of patients who showed response to chemotherapy. Our findings suggest that SNPs together with mRNA expression of CYP1B1 may be useful biomarkers to predict chemotherapy response in TNBC patients.

Matched MeSH terms: Carcinoma, Ductal, Breast/pathology
Fulltext Breast Cancer Detection Using Infrared Thermal Imaging and a Deep Learning Model

Mambou SJ, Maresova P, Krejcar O, Selamat A, Kuca K

Sensors (Basel), 2018 Aug 25;18(9).
PMID: 30149621 DOI: 10.3390/s18092799

Women's breasts are susceptible to developing cancer; this is supported by a recent study from 2016 showing that 2.8 million women worldwide had already been diagnosed with breast cancer that year. The medical care of a patient with breast cancer is costly and, given the cost and value of the preservation of the health of the citizen, the prevention of breast cancer has become a priority in public health. Over the past 20 years several techniques have been proposed for this purpose, such as mammography, which is frequently used for breast cancer diagnosis. However, false positives of mammography can occur in which the patient is diagnosed positive by another technique. Additionally, the potential side effects of using mammography may encourage patients and physicians to look for other diagnostic techniques. Our review of the literature first explored infrared digital imaging, which assumes that a basic thermal comparison between a healthy breast and a breast with cancer always shows an increase in thermal activity in the precancerous tissues and the areas surrounding developing breast cancer. Furthermore, through our research, we realized that a Computer-Aided Diagnostic (CAD) undertaken through infrared image processing could not be achieved without a model such as the well-known hemispheric model. The novel contribution of this paper is the production of a comparative study of several breast cancer detection techniques using powerful computer vision techniques and deep learning models.

Matched MeSH terms: Breast/pathology
Fulltext Long-term exposure to insulin and volumetric mammographic density: observational and genetic associations in the Karma study

Borgquist S, Rosendahl AH, Czene K, Bhoo-Pathy N, Dorkhan M, Hall P, et al.

Breast Cancer Res, 2018 08 09;20(1):93.
PMID: 30092829 DOI: 10.1186/s13058-018-1026-7

BACKGROUND: Long-term insulin exposure has been implicated in breast cancer etiology, but epidemiological evidence remains inconclusive. The aims of this study were to investigate the association of insulin therapy with mammographic density (MD) as an intermediate phenotype for breast cancer and to assess associations with long-term elevated circulating insulin levels using a genetic score comprising 18 insulin-associated variants.
METHODS: We used data from the KARolinska MAmmography (Karma) project, a Swedish mammography screening cohort. Insulin-treated patients with type 1 (T1D, n = 122) and type 2 (T2D, n = 237) diabetes were identified through linkage with the Prescribed Drug Register and age-matched to 1771 women without diabetes. We assessed associations with treatment duration and insulin glargine use, and we further examined MD differences using non-insulin-treated T2D patients as an active comparator. MD was measured using a fully automated volumetric method, and analyses were adjusted for multiple potential confounders. Associations with the insulin genetic score were assessed in 9437 study participants without diabetes.
RESULTS: Compared with age-matched women without diabetes, insulin-treated T1D patients had greater percent dense (8.7% vs. 11.4%) and absolute dense volumes (59.7 vs. 64.7 cm3), and a smaller absolute nondense volume (615 vs. 491 cm3). Similar associations were observed for insulin-treated T2D, and estimates were not materially different in analyses comparing insulin-treated T2D patients with T2D patients receiving noninsulin glucose-lowering medication. In both T1D and T2D, the magnitude of the association with the absolute dense volume was highest for long-term insulin therapy (≥ 5 years) and the long-acting insulin analog glargine. No consistent evidence of differential associations by insulin treatment duration or type was found for percent dense and absolute nondense volumes. Genetically predicted insulin levels were positively associated with percent dense and absolute dense volumes, but not with the absolute nondense volume (percentage difference [95% CI] per 1-SD increase in insulin genetic score = 0.8 [0.0; 1.6], 0.9 [0.1; 1.8], and 0.1 [- 0.8; 0.9], respectively).
CONCLUSIONS: The consistency in direction of association for insulin treatment and the insulin genetic score with the absolute dense volume suggest a causal influence of long-term increased insulin exposure on mammographic dense breast tissue.

Matched MeSH terms: Breast/pathology
Incidence and prognosis of non-metastatic triple negative breast cancer (TNBC) among different races in Southeast Asia

Alcantara VS, Lim GH, Lim SH, Sultana R, Lee JA

J Surg Oncol, 2017 Apr;115(5):523-537.
PMID: 28168712 DOI: 10.1002/jso.24559

BACKGROUND AND OBJECTIVES: Triple negative breast cancer (TNBC) carries a worse prognosis compared to the other subtypes. There have been conflicting studies that race may impact the prognosis of TNBC patients. We aim to determine the incidence and prognosis of TNBC among the different ethnic races in Singapore, and to determine its associated risk factors for prognosis.
METHODS: Patients diagnosed with invasive breast cancer (BC) from 2005 to 2013 at our tertiary institution were included and divided according to race and subtypes. Demographic and clinical information of non-metastatic TNBC patients were analyzed. Log-rank test, univariate and multivariate Cox proportional hazard regression models were used to find associated risk factors related with overall survival (OS) and disease-free survival (DFS).
RESULTS: Among 1227 BC patients, 129 (10.5%) had TNBC. TNBC patients had the worst OS (P: 0.0005) and DFS (P: 0.0016) among the subtypes. However, variations in race did not have any difference in OS or DFS among TNBC patients. Axillary lymph node involvement, invasive lobular histology, larger tumor size, and the presence of lymphovascular invasion (LVI) were factors associated with both poor DFS and OS among TNBC patients.
CONCLUSIONS: Racial variation did not have any impact on the prognosis of the TNBC.

Matched MeSH terms: Carcinoma, Ductal, Breast/pathology
Fulltext Outcome after neoadjuvant chemotherapy in Asian breast cancer patients

Lim LY, Miao H, Lim JS, Lee SC, Bhoo-Pathy N, Yip CH, et al.

Cancer Med, 2017 Jan;6(1):173-185.
PMID: 28000426 DOI: 10.1002/cam4.985

We aim to identify clinicopathologic predictors for response to neoadjuvant chemotherapy and to evaluate the prognostic value of pathologic complete response (pCR) on survival in Asia. This study included 915 breast cancer patients who underwent neoadjuvant chemotherapy at five public hospitals in Singapore and Malaysia. pCR following neoadjuvant chemotherapy was defined as 1) no residual invasive tumor cells in the breast (ypT0/is) and 2) no residual invasive tumor cells in the breast and axillary lymph nodes (ypT0/is ypN0). Association between pCR and clinicopathologic characteristics and treatment were evaluated using chi-square test and multivariable logistic regression. Kaplan-Meier analysis and log-rank test, stratified by other prognostic factors, were conducted to compare overall survival between patients who achieved pCR and patients who did not. Overall, 4.4% of nonmetastatic patients received neoadjuvant chemotherapy. The median age of preoperatively treated patients was 50 years. pCR rates were 18.1% (pCR ypT0/is) and 14.4% (pCR ypT0/is ypN0), respectively. pCR rate was the highest among women who had higher grade, smaller size, estrogen receptor negative, human epidermal growth factor receptor 2-positive disease or receiving taxane-based neoadjuvant chemotherapy. Patients who achieved pCR had better overall survival than those who did not. In subgroup analysis, the survival advantage was only significant among women with estrogen receptor-negative tumors. Patients with poor prognostic profile are more likely to achieve pCR and particularly when receiving taxane-containing chemotherapy. pCR is a significant prognostic factor for overall survival especially in estrogen receptor-negative breast cancers.

Matched MeSH terms: Carcinoma, Ductal, Breast/pathology
Fulltext Novel sesquiterpene lactone analogues as potent anti-breast cancer agents

Nakagawa-Goto K, Chen JY, Cheng YT, Lee WL, Takeya M, Saito Y, et al.

Mol Oncol, 2016 06;10(6):921-37.
PMID: 27055598 DOI: 10.1016/j.molonc.2016.03.002

Triple-negative breast cancer (TNBC) is associated with high grade, metastatic phenotype, younger patient age, and poor prognosis. The discovery of an effective anti-TNBC agent has been a challenge in oncology. In this study, fifty-eight ester derivatives (DETDs) with a novel sesquiterpene dilactone skeleton were organically synthesized from a bioactive natural product deoxyelephantopin (DET). Among them, DETD-35 showed potent antiproliferative activities against a panel of breast cancer cell lines including TNBC cell line MDA-MB-231, without inhibiting normal mammary cells M10. DETD-35 exhibited a better effect than parental DET on inhibiting migration, invasion, and motility of MDA-MB-231 cells in a concentration-dependent manner. Comparative study of DETD-35, DET and chemotherapeutic drug paclitaxel (PTX) showed that PTX mainly caused a typical time-dependent G2/M cell-cycle arrest, while DETD-35 or DET treatment induced cell apoptosis. In vivo efficacy of DETD-35 was evaluated using a lung metastatic MDA-MB-231 xenograft mouse model. DETD-35 significantly suppressed metastatic pulmonary foci information along with the expression level of VEGF and COX-2 in SCID mice. DETD-35 also showed a synergistic antitumor effect with PTX in vitro and in vivo. This study suggests that the novel compound DETD-35 may have a potential to be further developed into a therapeutic or adjuvant agent for chemotherapy against metastatic TNBC.

Matched MeSH terms: Breast/pathology
Expression of DDR1 and DVL1 in invasive ductal and lobular breast carcinoma does not correlate with histological type, grade and hormone receptor status

Ameli F, Rose IM, Masir N

Asian Pac J Cancer Prev, 2015;16(6):2385-90.
PMID: 25824769

BACKGROUND: Invasive ductal (IDC) and lobular (ILC) carcinomas are the common histological types of breast carcinoma which are difficult to distinguish when poorly differentiated. Discoidin domain receptor (DDR1) and Drosophila dishevelled protein (DVL1) were recently suggested to differentiate IDC from ILC.
OBJECTIVES: To assess the expression of DDR1 and DVL1 and their association with histological type, grading and hormonal status of IDC and ILC.
MATERIALS AND METHODS: This cross sectional study was conducted on IDC and ILC breast tumours. Tumours were immunohistochemically stained for (DDR1) and (DVL1) as well as estrogen receptor (ER), progesterone receptor (PR) and C-erbB2 receptor. Demographic data including age and ethnicity were obtained from patient records.
RESULTS: A total of 51 cases (30 IDCs and 21 ILCs) were assessed. DDR1 and DVL1 expression was not significantly associated with histological type (p=0.57 and p=0.66 respectively). There was no association between DDR1 and DVL1 expression and tumour grade (p=0.32 and p=1.00 respectively), ER (p=0.62 and 0.50 respectively), PR (p=0.38 and p=0.63 respectively) and C-erbB2 expression (p=0.19 and p=0.33 respectively) in IDC. There was no association between DDR1 and DVL1 expression and tumour grade (p=0.52 and p=0.33 respectively), ER (p=0.06 and p=0.76 respectively), PR (p=0.61 and p=0.43 respectively) and C-erbB2 expression (p=0.58 and p=0.76 respectively) in ILC.
CONCLUSIONS: This study revealed that DDR1 and DVL1 are present in both IDC and ILC regardless of the tumour differentiation. More studies are needed to assess the potential of these two proteins in distinguishing IDC from ILC in breast tumours.

Matched MeSH terms: Carcinoma, Ductal, Breast/pathology

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