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Fulltext The biopsy of nonpalpable breast lesions detected on mammography

Zulfiqar MA, Nair S, Lily M, Norizan MA

Med J Malaysia, 1999 Dec;54(4):471-7.
PMID: 11072464

This is a review of the positive biopsy rate of nonpalpable breast lesions detected on mammography. The histology of 130 hookwire excision biopsy from 1990 to 1995 and the cytology of 39 stereotactic fine needle aspiration cytology in 1995 were reviewed. The yearly positive biopsy rate of each procedure was determined. In 1990, the positive biopsy rate for hookwire excision biopsy was 15%, in 1991 20%, in 1992 11%, in 1993 17%, in 1994 33% and in 1995 39%. In 1995, the positive biopsy rate for stereotactic fine needle aspiration cytology was 21%. The positive biopsy rate for hookwire excision biopsy had improved from 15% in 1990 to 39% in 1995.

Matched MeSH terms: Breast/pathology*
Fulltext Prebiopsy localization of nonpalpable breast lesions

Zulfiqar A, Param V, Meah FA, Nair S, Siti-Aishah MA, Norizan A

Med J Malaysia, 1993 Sep;48(3):317-24.
PMID: 8183145

Radiologically guided localization procedures are indicated pre-operatively when breast lesions are nonpalpable. The results of 42 percutaneous hookwire localizations over a period of 3 years are described. Of the total, 7 (17%) were found to be malignant. Biopsy was indicated by mammographically detected mass in 48%, by microcalcifications in 40% and by microcalcifications with an associated mass in 12%.

Matched MeSH terms: Breast/pathology*
Quantitative comparison of apoptosis to cell proliferation and p53 protein in breast carcinomas

Zheng WQ, Zhan RZ

Anal. Quant. Cytol. Histol., 1998 Feb;20(1):1-6.
PMID: 9513685

To clarify the correlation between apoptosis and tumor cell proliferative activity in human breast cancer and to investigate their relevance to p53 protein.

Matched MeSH terms: Carcinoma, Ductal, Breast/pathology
Fulltext Guideline implementation for breast healthcare in low- and middle-income countries: early detection resource allocation

Yip CH, Smith RA, Anderson BO, Miller AB, Thomas DB, Ang ES, et al.

Cancer, 2008 Oct 15;113(8 Suppl):2244-56.
PMID: 18837017 DOI: 10.1002/cncr.23842

A key determinant of breast cancer outcome in any population is the degree to which cancers are detected at early stages of disease. Populations in which cancers are detected at earlier stages have lower breast cancer mortality rates. The Breast Health Global Initiative (BHGI) held its third Global Summit in Budapest, Hungary in October 2007, bringing together internationally recognized experts to address the implementation of breast healthcare guidelines for early detection, diagnosis, and treatment in low- and middle-income countries (LMCs). A multidisciplinary panel of experts specifically addressed the implementation of BHGI guidelines for the early detection of disease as they related to resource allocation for public education and awareness, cancer detection methods, and evaluation goals. Public education and awareness are the key first steps, because early detection programs cannot be successful if the public is unaware of the value of early detection. The effectiveness and efficiency of screening modalities, including screening mammography, clinical breast examination (CBE), and breast self-examination, were reviewed in the context of resource availability and population-based need by the panel. Social and cultural barriers should be considered when early detection programs are being established, and the evaluation of early detection programs should include the use of well developed, methodologically sound process metrics to determine the effectiveness of program implementation. The approach and scope of any screening program will determine the success of any early detection program as measured by cancer stage at diagnosis and will drive the breadth of resource allocation needed for program implementation.

Matched MeSH terms: Breast/pathology
Fulltext The Breast Clinic in University Hospital--a four-month survey

Yip CH, Alhady SF, Jayaram G

Med J Malaysia, 1995 Sep;50(3):268-71.
PMID: 8926907

The breast clinic in the university Hospital Kuala Lumpur was started in August 1993 to cater for the increasing number of women seeking treatment for breast complaints. A four-month survey carried out from January to April 1994 found that Chinese women are more "breast conscious" than Malay and Indian women. The majority of patients were in the reproductive age group. Benign breast diseases form the majority of cases of breast diseases seen. The pick-up rate for new cases of breast cancer was 3.1%. Fine needle aspiration biopsy had a 100% sensitivity during the four-month study, and was a quick method of obtaining a diagnosis.

Study site: Breast clinic, University Malaya Medical Centre (UMMC)

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
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
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
Fulltext Concurrent massive breast enlargement, myasthenia gravis and dermopathy as manifestations of penicillamine toxicity in a Wilson's disease patient

Tan SS, Latif SA, Poh WY

Med J Malaysia, 2012 Jun;67(3):323-5.
PMID: 23082426 MyJurnal

Penicillamine toxicity in Wilson's disease has been well reported but rarely seen now as newer agents are being used. We present a case who developed multiple rare complications of Penicillamine concurrently. Our patient is one of three siblings on Penicillamine, she was the only one who developed massive breast enlargement four months after commencing Penicillamine therapy, as well as dermatological adverse reactions and myasthenia gravis three more months later. All the adverse effects improved soon after substitution of the offending agent with Trientine.

Matched MeSH terms: Breast/pathology*
Cytogenetic analysis of invasive breast cancer: a study of 27 Asian patients

Tan PH, Lui WO, Ong P, Lau LC, Tao M, Chong Y

Cancer Genet. Cytogenet., 2000 Aug;121(1):61-6.
PMID: 10958943

Tumor cytogenetic analysis from 27 patients with breast cancer diagnosed at the Singapore General Hospital revealed complex karyotypic aberrations in 12 cases. The study group comprised 25 women and 2 men, ranging in age from 33 to 78 years (median 52 years). Ethnic distribution consisted of 22 Chinese, 3 Malaysian, and 2 Indian patients. Pathologic assessment disclosed 24 invasive ductal, 2 invasive mucinous, and 1 mixed invasive mucinous and ductal carcinomas. Histologic grading showed 3 grade 1, 10 grade 2, and 12 grade 3 tumors; 2 cancers were not graded, because they had been subjected to prior chemotherapy. Tumor sizes ranged from 1.5 to 10 cm (median 3 cm). Eleven cases were axillary node negative, whereas the remaining 16 node-positive cancers affected as many as 3 nodes in 8 cases and 4 or more nodes in another 8. Twenty cases demonstrated estrogen-receptor positivity, and 8 cases progesterone-receptor positivity. The spectrum of cytogenetic abnormalities involved chromosomes 1, 3, 6, 7, 8, 11, 16, and 17 and ranged from gains and deletions of both long and short arms, trisomy, monosomy, and other rearrangements. There was a trend toward the presence of karyotypic abnormalities in tumors of higher grade.

Matched MeSH terms: Carcinoma, Ductal, 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*
Factors associated with HER2 overexpression in breast cancer: Experience in an Asian developing country

Tan GH, Choo WY, Taib NA, Yip CH

Asian Pac J Cancer Prev, 2009;10(5):837-40.
PMID: 20104975

INTRODUCTION: The HER2 gene is amplified in up to 30% of human breast cancers, leading to overexpression of the HER2 protein on the cell surface. Overexpression of HER2 is associated with a more aggressive cancer and hence a poorer overall survival.
OBJECTIVE: To evaluate the association between clinico-pathological features and HER2 overexpression in breast cancer.
METHODS: This is a retrospective study conducted in the Department of Surgery, University Malaya Medical Centre. The association between HER2 overexpression, determined by immunohistochemistry, and other clinicopathological factors was evaluated in 996 patients with newly diagnosed breast cancer treated from 2005 to 2007 using univariate and multivariate logistic regression.
RESULTS: HER2 overexpression occurred in 30.3% of patients. On bivariate analysis, HER2 overexpression was inversely related to ER expression (p<0.01) and PR expression (p<0.01). This overexpression was associated with a higher tumour grade, lymphovascular positivity and infiltrating ductal carcinoma subtype. On multivariate analysis, HER2 overexpression was significantly associated with higher tumour grade (p= 0.018, CI 1.25-11.04), PR negativity (p= 0.002, CI 0.30-0.77) and lymphovascular positivity (p= 0.042, CI 1.01-2.12).
CONCLUSIONS: HER2 overexpression was observed in 30.3% of Malaysian female breast cancer patients. This group of patients represents a more aggressive subtype of breast cancer with higher tumour grade, PR negativity and lymphovascular positivity. No significant relationship was established between HER2 overexpression and age, race, lymph node, ER, pathology subtype and stage of disease from this study.

Matched MeSH terms: Carcinoma, Ductal, Breast/pathology
Fulltext Clinical characteristics of triple-negative breast cancer: experience in an Asian developing country

Tan GH, Taib NA, Choo WY, Teo SH, Yip CH

Asian Pac J Cancer Prev, 2009 Jul-Sep;10(3):395-8.
PMID: 19640180

INTRODUCTION: Triple negative (TN) breast cancers are defined by a lack of expression of oestrogen, progesterone, and HER2 receptors. They tend to have a higher grade, with a poorer outcome compared to non-TN breast cancers.
OBJECTIVE: The aim of this study is to determine the incidence of TN breast cancer in an Asian country consisting of Malays, Chinese and Indians, and to determine the factors associated with this type of breast cancer.
RESULTS: The incidence of TN breast cancer in the University Malaya Medical Center is 17.6%. There is no significant difference amongst the Malays, Chinese and Indians. In bivariate analysis, TN breast cancer was significantly associated with younger age and Grade 3. However, in multivariate analysis using logistic regression, TN breast cancer was only associated with Grade 3.
CONCLUSION: The incidence of TN breast cancer in our study is similar to other studies, and associated with a higher grade.
Study site: University Malaya Medical Centre (UMMC)

Matched MeSH terms: Carcinoma, Ductal, Breast/pathology*
Breast cancer detection from MR images through an auto-probing discrete Fourier transform system

Sim KS, Chia FK, Nia ME, Tso CP, Chong AK, Abbas SF, et al.

Comput Biol Med, 2014 Jun;49:46-59.
PMID: 24736203 DOI: 10.1016/j.compbiomed.2014.03.003

A computer-aided detection auto-probing (CADAP) system is presented for detecting breast lesions using dynamic contrast enhanced magnetic resonance imaging, through a spatial-based discrete Fourier transform. The stand-alone CADAP system reduces noise, refines region of interest (ROI) automatically, and detects the breast lesion with minimal false positive detection. The lesions are then classified and colourised according to their characteristics, whether benign, suspicious or malignant. To enhance the visualisation, the entire analysed ROI is constructed into a 3-D image, so that the user can diagnose based on multiple views on the ROI. The proposed method has been applied to 101 sets of digital images, and the results compared with the biopsy results done by radiologists. The proposed scheme is able to identify breast cancer regions accurately and efficiently.

Matched MeSH terms: Breast/pathology
Fine needle aspiration cytology of the breast: an analysis of 1,094 aspirates

Sharifah NA, Hayati AR, Meah F, al-Rashid Z

Malays J Pathol, 1993 Jun;15(1):53-8.
PMID: 8277791

Our experience with 1,094 consecutive fine needle aspirations (FNAs) of the breast in 918 cases is presented. Correlation between the FNA cytology and subsequent histology of the lesions was available in 211 cases. FNA had a sensitivity rate of 87.3%, a specificity rate of 99.3% and a positive predictive value of 98.2%. A false negative diagnosis rate of 5.1% occurred. The overall diagnostic accuracy rate was 95.7%.

Matched MeSH terms: Breast/pathology*
Carcinoma of the pancreas: resection outcome at the University Hospital Kuala Lumpur

Shahrudin MD

Int Surg, 1997 Jul-Sep;82(3):269-74.
PMID: 9372373

Recent studies have demonstrated a reduction in the morbidity and mortality of pancreatic resection and improvement in the actuarial 5-year survival for patients with resected ductal adenocarcinoma. We reviewed the clinico-pathological characteristics of patients who underwent resection with curative intent for ductal adenocarcinoma of the pancreas between 1980 and 1993.

Matched MeSH terms: Carcinoma, Ductal, 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 Computer aided detection of breast density and mass, and visualization of other breast anatomical regions on mammograms using graph cuts

Saidin N, Mat Sakim HA, Ngah UK, Shuaib IL

Comput Math Methods Med, 2013;2013:205384.
PMID: 24106523 DOI: 10.1155/2013/205384

Breast cancer mostly arises from the glandular (dense) region of the breast. Consequently, breast density has been found to be a strong indicator for breast cancer risk. Therefore, there is a need to develop a system which can segment or classify dense breast areas. In a dense breast, the sensitivity of mammography for the early detection of breast cancer is reduced. It is difficult to detect a mass in a breast that is dense. Therefore, a computerized method to separate the existence of a mass from the glandular tissues becomes an important task. Moreover, if the segmentation results provide more precise demarcation enabling the visualization of the breast anatomical regions, it could also assist in the detection of architectural distortion or asymmetry. This study attempts to segment the dense areas of the breast and the existence of a mass and to visualize other breast regions (skin-air interface, uncompressed fat, compressed fat, and glandular) in a system. The graph cuts (GC) segmentation technique is proposed. Multiselection of seed labels has been chosen to provide the hard constraint for segmentation of the different parts. The results are promising. A strong correlation (r = 0.93) was observed between the segmented dense breast areas detected and radiological ground truth.

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
Anterior uveal and episcleral metastases from carcinoma of the breast

Reddy SC, Madhavan M, Mutum SS

Ophthalmologica, 2000 Sep-Oct;214(5):368-72.
PMID: 10965254 DOI: 10.1159/000027523

Breast carcinoma is the most common primary tumor producing intraocular metastasis. Metastases to the iris and ciliary body are relatively rare. The authors report a case of a 61-year-old lady, operated for carcinoma of the left breast 3 years back, who presented with symptoms and signs of acute narrow-angle glaucoma in the right eye. A diffuse whitish plaque-like mass in the upper nasal quadrant of the iris with an episcleral nodule on the limbus in the corresponding area and all the signs of acute narrow-angle glaucoma were present in the right eye. Intraocular pressure was controlled medically. Fine-needle aspiration cytology from the episcleral nodule showed malignant cells. Histopathology of the excised nodule showed metastatic poorly differentiated carcinoma, and the cellular pattern was similar to the carcinoma of the breast. There was no other metastasis anywhere in the body. Fine-needle aspiration cytology from an external lesion of the eye is a less invasive and easier procedure than paracentesis to diagnose the metastatic nature of the lesions. The rare features in our case are the clinical presentation as acute glaucoma and the ocular structures being the first and only site of metastasis.

Matched MeSH terms: Carcinoma, Ductal, Breast/pathology

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