Breast Disease - Volume 41, issue 1

Authors: Leksono, Radityo Budi | Thabry, Rudy | Prihantono, Prihantono | Nahusuly, Fritz | Kasim, Firdaus | Hamdani, William | Pieter, John | Indra, Indra | Syamsu, Salman Ardi | Faruk, Muhammad

Article Type: Research Article

Abstract: INTRODUCTION: Identifying Ki67, a monoclonal antibody that recognizes proliferating cells, is important for defining the level of proliferative activity among patients with breast cancer. The purpose of our study was to evaluate the correlation between Ki67’s expression and histopathological grade, tumor size, disease-free survival (DFS), and overall survival (OS) among breast cancer patients. METHODS: Our retrospective cohort study involved examining 114 patients with breast cancer at our institution from January 2018 to December 2019. Participants were retrospectively followed to determine the progression of their disease, and their 2-year progress was examined with survival analysis, especially regarding whether they …had postoperative relapse (i.e., DFS) or had died since being diagnosed (i.e., OS). The data were processed with a chi-square test and Kaplan–Meier test, with significance set at p < 0.05. RESULT: The overexpression of Ki67 correlated significantly with histopathological grade (p = 0.001), tumor size (p = 0.001), DFS (p = 0.001), and OS (p = 0.003). CONCLUSION: Ki67’s overexpression is significantly correlated with the tumor size, DFS, and OS of patients with breast cancer. Show more

Keywords: Ki67, histopathological grade, tumor size, disease-free survival, overall survival

DOI: 10.3233/BD-229005

Citation: Breast Disease, vol. 41, no. 1, pp. 455-460, 2022

Authors: Kridis, Wala Ben | Feki, Ameni | Khmiri, Souhir | Toumi, Nabil | Chaabene, Kais | Daoud, Jamel | Ayedi, Ines | Khanfir, Afef

Article Type: Research Article

Abstract: BACKGROUND: Previous studies have shown that poor prognostic indicators of inflammatory breast cancer (IBC) include younger age at diagnosis, poorer tumor grade, negative estrogen receptor, lesser degree of pathological response in the breast and lymph nodes. METHODS: This is a retrospective study conducted over a period of 12 years between January 2008 and December 2019 at the medical oncology department at Habib Bourguiba University Hospital in Sfax. We included in this study women with confirmed IBC. We excluded patients with no histological evidence, those whose medical records were unusable. Data collection was done from patient files. The aim …of this study was to analyze the factors of poor prognosis of this entity. RESULTS: During a period of 12 years (2008–2019), 2879 cases of breast cancer were treated at Habib Bourguiba hospital in Sfax. 81 IBC were included. The incidence of IBC was 3%. The average age was 52.4 years (26–87 years). Invasive ductal carcinoma was the most frequent histological type (85.7%). Hormone receptor were positive in 64%. Human Epidermal Growth Factor Receptor-2 (HER2) was overexpressed in 35.9% of cases. The proliferation index Ki-67 was analyzed in 34 cases. It was >20% in 24 cases. Luminal A, luminal B, HER2+++ , triple negative were found in 13%, 50.7%, 16% and 20% respectively. Metastases at diagnosis were found in 38%. Poor prognostic factors significantly influencing overall survival in univariate analysis were metastatic stage, high SBR grade, lymph node involvement, in particular greater than 3 nodes, negative hormone receptors, triple-negative molecular profile and occurrence of relapse. CONCLUSION: Number of positive lymph nodes greater than 3 and the occurrence of relapse were independent prognostic factors in case of localized IBC. Metastatic stage was associated with a very poor prognosis. Show more

Keywords: Inflammatory breast cancer, overall survival, prognosis

DOI: 10.3233/BD-220034

Citation: Breast Disease, vol. 41, no. 1, pp. 461-469, 2022

Authors: Kshersagar, Jeevitaa | Damle, Mrunal N. | Bedge, Poonam | Jagdale, Rakhi | Tardalkar, Kishor | Jadhav, Dhanaji | Jagadale, Swapnali | Toro, Yashwant | Sharma, Rakesh | Joshi, Meghnad G.

Article Type: Research Article

Abstract: OBJECTIVE: In this study, the profiling of the expression of major histocompatibility complex (MHC) class I-related chain A and B (MICA/B) in human breast cancer tumor tissue, saliva, and urine samples of breast cancer patients and control is carried out. MICA/B is ligand of NKG2D receptor expressed on malignant cells. The release of MICA/B from tumor tissue comprises an immune escape mechanism that impairs antitumor immunity. Based on this literature we explored the potential of soluble MICA (sMICA) as a marker in breast cancer (BC). METHODS: The expression was profiled by using immunohistochemistry (MICA/B), western blot (MICA/B) and …ELISA (MICA). RESULTS: The optical density of western blot of MICA/B in different stages of BC illustrated significant difference as per one way analysis of variance and significant difference with stage III and IV by Dunnett’s multiple comparisons test respectively. Analysis of sMICA in serum, saliva and urine of BC patients revealed significantly higher levels (median 41.0 ± 4.1 pg/ml in pre-treatment sera, 181.9 ± 1.6 pg/ml in saliva and 90.7 ± 1.7 pg/ml in urine) than in control (median <1.2 pg/ml). The elevated levels of sMICA were related to the cancer stage. CONCLUSIONS: The elevated levels of sMICA were observed in patients with well differentiated cancer while the poor expression of sMICA was observed in patients with poorly differentiated tumors. Tumor immunity is impaired by the release of MICA in the biofluids and may be useful for detection and diagnosis of the stage of BC. Show more

Keywords: Breast cancer, MICA/B, sMICA/B

DOI: 10.3233/BD-220023

Citation: Breast Disease, vol. 41, no. 1, pp. 471-480, 2022

Authors: Manginstar, Christian | Oley, Mendy Hatibie | Oley, Maximillian Christian | Merung, Marselus | Langi, Fima Lanra Fredrik G. | Kepel, Billy Johnson | Rusli, Lie Venny | Islam, Andi Asadul | Faruk, Muhammad

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide and a leading cause of death in Indonesia. The primary treatment of locally advanced BC is neoadjuvant chemotherapy (NAC). The rapid proliferation of tumor cells in a neoplastic microenvironment is largely due to hypoxia, which also encourages the development of chemoresistant BC. The master regulator of the hypoxia response is hypoxia-inducible factor-1α (HIF-1α). The response evaluation criteria in solid tumors (RECIST) is an objective response metric that demonstrates the efficacy of a NAC based mostly on the size of the tumor. Ca15-3 is the protein product of the MUC1 …gene and is the most widely used serum marker in BC. The purpose of this study is to investigate the relationship between HIF-1α and RECIST and between Ca15-3 and RECIST and to assess the relationship among all of them in BC. METHODS: This observational study used the prospective cohort method included 11 patients with histopathologically confirmed BC, specifically invasive ductal carcinoma. We evaluated the changes in HIF-1α and Ca15-3 serum levels using ELISA and measured tumor lesions with RECIST. The procedure was carried out twice. Serum levels were measured at baseline, and after receiving two cycles of NAC (5 weeks). RESULTS: Among the 11 patients included in this study, HIF-1α, Ca15-3, and RECIST decreased significantly after NAC. The changes in RECIST correlated with Ca15-3: each unit decrease in RECIST score was associated with a 0.3-unit decrease in Ca15-3 levels (p = 0.019). CONCLUSIONS: There was a decrease in HIF-1α, followed by a decrease in Ca15-3 and RECIST in response to chemotherapy. There was a statistically significant correlation between Ca15-3 and response to chemotherapy. This study evidences the relationship between factors that shape the local tumor microenvironment. Show more

Keywords: Breast cancer, neoadjuvant chemotherapy, ductal carcinoma, Ca15-3, RECIST, HIF1α

DOI: 10.3233/BD-229004

Citation: Breast Disease, vol. 41, no. 1, pp. 481-487, 2022

Authors: Fahdrin, Andi | Sampepajung, Elridho | Pieter, John | Kasim, Firdaus | Smaradhania, Nilam | Prihantono, Prihantono | Mariana, Nita | Sampepajung, Daniel | Faruk, Muhammad

Article Type: Research Article

Abstract: INTRODUCTION: The relationship between increased platelet count and cancer classification stage has long been established. The prevalence of thrombocytosis varies from 10% to 57% in cancer patients. The pathogenesis of thrombocytosis in malignancy is uncertain. However, there is evidence that tumor cells secrete humoral factors that can cause thrombocytosis. Preoperative thrombocytosis is a poor prognostic variable in malignancies. This study investigated the correlation between platelet count and breast cancer stage. METHODS: This cross-sectional study was conducted from February 2020 to January 2021. Patient data were collected from medical records. The study population comprised breast cancer patients at Dr. …Wahidin Sudirohusodo Makassar. The staging examinations were based on the tumor, node, metastasis (TNM) classification according to the American Joint Committee on Cancer (AJCC) 8th Edition. RESULTS: The study group comprised 171 breast cancer patients of varying ages. Metastasis was present in five (2.92%) patients and absent in 166 (97.8%) patients. Analyses found no statistically significant differences between the three staging groups based on the platelet count (p = 0.952). CONCLUSION: There was no statistically significant relationship between increased platelet count and staging according to the TNM classification in breast cancer patients. Show more

Keywords: American Joint Committee on Cancer, breast cancer, platelet counts, staging

DOI: 10.3233/BD-229007

Citation: Breast Disease, vol. 41, no. 1, pp. 489-493, 2022

Authors: Elbalka, Saleh S. | Metwally, Islam H. | Hassan, Amany | Eladl, Ahmed E. | Shoman, Ahmed M. | Jawad, Mohamed | Shahda, Eman | Abdelkhalek, Mohamed

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer is a common women's disease. Usually, oestrogen is blamed in the aetiology and correlated with the prognosis; however, androgens are recently raising concern about its role in the breast cancer treatment and prognosis. METHODS: In this study we retrieved archival paraffin blocks of breast cancer patients and stained it for androgen. Thereafter, we compared clinico-epidemiologic parameters, histopathology, neoadjuvant response and recurrence rate and pattern among patients with and without androgen receptor (AR) expression. RESULTS: In total, 119 patients fulfilled enrolment criteria; AR expression were present in 77.3% of the patients. AR expression was …associated with less grade III (6.8% versus 36.4%), and less triple negative (6.2% versus 25%), but similar overall recurrence rate (25% versus 22.2%). However, distant recurrence was significantly higher in androgen positive patients (91.3% versus 33.3% of all recurrences). CONCLUSION: Androgen expression appears to be common among breast cancer, but with no clear implication in tumour aggressiveness or effect on the rate of recurrence. However, being commonly associated with distant spread may have an impact on survival of the patients. Show more

Keywords: Hormonal receptors, androgen expression, molecular types, breast cancer recurrence

DOI: 10.3233/BD-220037

Citation: Breast Disease, vol. 41, no. 1, pp. 495-502, 2022

Authors: Muecke, Ralph | Dubois, Clara | Micke, Oliver | Keinki, Christian | Huebner, Jutta

Article Type: Research Article

Abstract: BACKGROUND: In breast cancer patients, there is an elevated risk of developing osteoporosis during treatment which should be addressed by optimizing 25(OH) levels. OBJECTIVE: The aim was to assess the prescription, information and physician-patient communication on vitamin D and bone density in Germany. METHODS: We developed a standardized questionnaire concerning bone density measurement, vitamin D (blood level testing, prescription), information and communication regarding vitamin D. The questionnaire was distributed at the annual meeting of all group leaders of the Women’s Cancer Support Association to all participants. RESULTS: Overall, 224 participants completed the questionnaire; 77.7% …reported having had at least one bone density measurement test. The number was 84.4% in patients treated with aromatase inhibitor and 43.7% reported that their bone density was too low. In total, 51.3% patients reported at least one vitamin D blood test and 45.1% reported that vitamin D had been primarily addressed by a physician. As many as 74.1% of those reporting a test result had a deficiency; 91.6% of those with a low level got a prescription and 28.4% took vitamin D autonomously. CONCLUSIONS: The awareness on risk of osteoporosis, prevention, early diagnosis and treatment are insufficiently addressed in a patient group with high risk of osteoporosis. More attention should be paid to the phenomenon of vitamin D deficiency or insufficiency in routine care. Show more

Keywords: Vitamin D, breast cancer, endocrine therapy, patient information needs, patient-physician communication, osteoporosis

DOI: 10.3233/BD-210070

Citation: Breast Disease, vol. 41, no. 1, pp. 503-511, 2022

Authors: Mosavi, Zeinb | Bashi Zadeh Fakhar, Haniyeh | Rezaei-Tavirani, Mostafa | Akbari, Mohamd Esmaeel | Rostami, Forouzan

Article Type: Research Article

Abstract: BACKGROUND AND AIM: DCIS is the most common type of non-invasive breast cancer, accounting for about 15 to 30%. Proteome profile is used to detect biomarkers in the tissues of breast cancer patients by mass spectrometry. This study aimed to obtain the expression profile of DCIS proteome, and the expression profile of invasive biomarkers, and finally to introduce a dedicated biomarker panel to facilitate the prognosis and early detection for in situ breast cancer patients. METHODS AND MATERIALS: In this study, 10 patients with breast cancer (DCIS) were studied. Benign (marginal) and cancerous tissue samples were obtained …from patients for proteomics experiments. Initially, all tissue proteins were extracted using standard methods, and the proteins were separated using two-dimensional electrophoresis. Then, the expression amount of the extracted proteins was determined by ITRAQ. The data were analysed by R software, and gene ontology was utilised for describing the protein in detail. RESULTS: 30 spots on gel electrophoresis were found in the tumor tissue group (sample), and 15 spots in the margin group (control) with P < 0.05. Healthy and cancerous tissue gels showed that 5 spots had different expression. VWF, MMP9, ITGAM, MPO and PLG protein spots were identified using the site www.ebi.ac.uk/IPI . Finally, protein biomarkers for breast tumor tissue with margin were introduced with the names of P04406, P49915, P05323, P06733, and P02768. DISCUSSION: There are 5 critical proteins in inducing cancer pathways especially complement and coagulation cascades. The hall markers of a healthy cell to be cancerous are proliferation, invasion, angiogenesis, and changes in the immune system. Hence, regulation of protein plays a key role in developing recurrence to breast cancer in margins. Show more

Keywords: Proteome, profile, DCIS, ductal carcinoma in situ

DOI: 10.3233/BD-220017

Citation: Breast Disease, vol. 41, no. 1, pp. 513-520, 2022

Authors: Dorostgoo, Zeinab | Fattahi, Asieh Sadat | Moosavi, Saide Samare | Ghafouri-Fard, Soudeh | Oskooei, Vahid Kholghi

Article Type: Research Article

Abstract: Long non-coding RNAs (lncRNAs) influence pathetiology of breast cancer. Besides, VDR and ESR1 signaling pathways are two important pathways in this malignancy. In the present mixed bioinformatics and expression assay study, we have identified lncRNAs that are co-expressed with VDR and ESR1 in breast cancer tissues and analyzed their expression in 42 paired breast cancer and non-cancerous specimens. Expression of SLC16A-AS1 was significantly lower in breast cancer tissues compared with paired non-cancerous samples (expression ratio = 0.27, P value < 0.001). Similarly, LINC00900 was down-regulated in cancer tissues compared with non-cancerous …ones (expression ratio = 0.26, P value = 0.01). There were no significant differences in the expressions of VDR and AATBC between these two sets of samples. Expression levels of VDR and AATBC were associated with histological grade (P values = 0.02 and 0.03, respectively). Moreover, expression of VDR was associated with tumor size (P  value = 0.02). Finally, expression levels of SLC16A-AS1 were associated with first pregnancy age (P value = 0.006). In brief, the results of current study further support involvement of VDR and ESR1 -associated lncRNAs in breast cancer. Show more

Keywords: Breast cancer, lncRNA, VDR, AATBC, SLC16A-AS1, LINC00900

DOI: 10.3233/BD-210083

Citation: Breast Disease, vol. 41, no. 1, pp. 521-528, 2022

Authors: Ferre, Romuald | Ghorab, Zeina | Alikhassi, Afsaneh | Curpen, Belinda

Article Type: Case Report

Abstract: Tuberculosis (TB) remains in 2022 a significant public health issue as it remains endemic in some areas of the globe, with a high prevalence in underdeveloped countries (Pujani, Khan, Hassan, Jetley, Raina, Breast Dis. , 35(3): 195–198, 2015. doi:10.3233/BD-150405 . PMID: 26406543). Pulmonary TB is the most common form, but TB can also have extrapulmonary manifestations like tubercular lymphadenopathy. Tuberculous lymphadenitis is the most extrapulmonary tuberculosis. It used to be called scrofula in the past coming from the Latin meaning breeding sow (Kokosali, Lloyd, Dent Update , 33(5): 306–308, 311, 2006. doi:10.12968/denu.2006.33.5.306 . PMID: 16841612; Oberhelman, Watchmaker, Phillips, JAMA Dermatol , 155(5): …610, 2019. doi:10.1001/jamadermatol.2018.5651 . PMID: 30942835). It is a common cause of peripheral lymphadenitis, seen mostly in the developing countries, but also reemerging among intravenous drugs users and immunocompromised population. Cervical nodes are the most commonly detected nodes in tuberculous lymphadenitis, accounting for 63% of the cases, followed by mediastinal (27%) and axillary nodes (8%) (Ahuja, Ying, Evans, King, Metreweli, Clin Radiol , 50(6): 391–395, 1995. doi:10.1016/s0009-9260(05)83136-8 . PMID: 7789023). Tuberculous lymphadenitis affects predominantly the young population and children. There is also a slight female predilection. As to our knowledge, there have not been any reported cases as post-menopausal axillary tuberculous lymphadenitis, and it is the focus of this article. Show more

Keywords: Breast cancer, tubercular lymphadenitis, mammography, ultrasound, tuberculosis, axillary lymphadenopathy

DOI: 10.3233/BD-220015

Citation: Breast Disease, vol. 41, no. 1, pp. 529-534, 2022