Breast Disease - Volume 40, issue 4

Authors: Hamdy, Omar | Farouk, Omar | El-Badrawy, Adel | Denewer, Adel | Setit, Ahmed

Article Type: Review Article

Abstract: Sentinel lymph node biopsy (SLNB) has efficiently replaced axillary lymph node dissection (ALND) in axillary staging in node-negative breast cancer patients. Dual sentinel lymph node (SLN) localization using radioisotopes and blue dye is the standard technique for SLN mapping. Yet, nuclear medicine facilities are not widely available worldwide. In Japan, Computed tomography lymphography (CTLG) is presented as an SLN mapping technique which was first suggested in 2003 by Suga et al. Multiple subsequent studies confirmed the efficacy of CTLG in SLN mapping in breast cancer. Further applications of the technique followed; such as prediction of SLN metastasis using CTLG, the use …of CTLG guided SLN biopsy after neoadjuvant therapy, video-assisted CTLG guided SLN biopsy, the use of real-time virtual sonography with 3-D CTLG, and preoperative localization of the CTLG mapped SLN using either real-time virtual sonography (RVS) guided Indocyanine green (ICG) injection or its marking using liquid charcoal and silver wire and the use of SPIO enhanced magnetic resonance imaging (MRI) for prediction of metastasis in SLNs detected by CTLG. This efficacy and variable applications open the door for conducting wide-scale randomized controlled trials to suggest using CTLG as an efficient alternative for the use of radioisotopes in SLN mapping in breast cancer patients, especially in low and middle-income countries. Show more

Keywords: Sentinel lymph node, CT lymphography, breast cancer, axillary lymph node dissection, localization, metastasis

DOI: 10.3233/BD-201046

Citation: Breast Disease, vol. 40, no. 4, pp. 219-225, 2021

Authors: Ghaffari, Hadi | Tavakoli, Ahmad | Nafissi, Nahid | Farahmand, Mohammad | Ghorbani, Saied | Moochani, Somayeh Sadat | Hashemi-Bahremani, Mohammad | Alebouyeh, Mahmoud Reza | Monavari, Seyed Hamidreza

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVES: The role of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infections in breast cancer pathology is not well understood. Our study aimed to investigate the association of HCMV and EBV infections with breast cancer and distinguish the types of positive EBV and LMP-1 samples in Iranian patients. METHODS: Seventy-two formalin-fixed paraffin-embedded (FFPE) breast cancer tissues were analyzed between December 2014 and April 2016. Samples were analyzed for HCMV and EBV using nested-PCR and conventional PCR assays, respectively. Statistical analysis was performed using SPSS software version 18. RESULTS: Overall, HCMV and EBV genomes were detected …in 6.9% and 16.7% of FFPE breast cancer tissues, respectively. Clinical factors were not statistically associated with the presence of HCMV and EBV. CONCLUSION: In this study, we reported EBV and LMP-1 typing in breast carcinoma cases for the first time in Iran. Our findings indicate that HCMV and EBV infections are not associated with the development of breast cancer. Show more

Keywords: HCMV, EBV, breast cancer, carcinoma

DOI: 10.3233/BD-201019

Citation: Breast Disease, vol. 40, no. 4, pp. 227-233, 2021

Authors: Farahani, Najmeh | Mohagheghi, Fathollah | Mosayebi, Ghasem | Ghazavi, Ali | Ganji, Ali

Article Type: Research Article

Abstract: BACKGROUND: The exact immunopathological mechanisms in the progression of breast cancer are not clearly understood, but various factors including CD8 T lymphocytes have lethal properties on tumor cells. On the other hand, interleukin-37 (IL-37), as a new member of the IL-1 family, is an anti-inflammatory cytokine. The exact role of IL-37 in breast cancer has not yet been determined. OBJECTIVE: This study aimed to evaluate the CD8 T lymphocytes count and IL-37 gene expression in newly diagnosed breast cancer patients with and without metastasis. METHODS: In this study, blood samples from 36 metastatic and 36 non-metastatic breast …cancer patients and 36 healthy individuals as control were collected. After RNA extraction and cDNA synthesis, the relative gene expression was performed using real-time PCR. Also, counting the CD8 T lymphocytes was done by flow cytometry technique. RESULTS: The results of this study showed that the gene expression of IL-37 in blood samples of metastatic and non-metastatic breast cancer patients was significantly lower than in healthy individuals (P < 0.05). The relative gene expression of the IL-37 in ER+ /PR+ /HER2+ patients with non-metastatic breast cancer had a significant increase compared to HER2+ patients (P < 0.05). Also, CD8 T lymphocytes count in the samples of patients including non-metastatic and metastatic breast cancer was significantly decreased compared to the healthy individuals (P < 0.05). CONCLUSIONS: Our findings provide evidence that IL-37 gene expression and CD8 T lymphocytes count, significantly decreased in non-metastatic and metastatic breast cancer. Considering the possible effects of IL-37 on TCD8 cells in tumor immune responses, more research will be done to benefit from the therapeutic effects of this cytokine in the future. Show more

Keywords: Metastatic breast cancer, IL-37, CD8 T lymphocytes

DOI: 10.3233/BD-201055

Citation: Breast Disease, vol. 40, no. 4, pp. 235-240, 2021

Authors: Ewida, Heba A. | Shabayek, Marwa | Seleem, Mae

Article Type: Research Article

Abstract: OBJECTIVE: Molecular markers for the detection of breast cancer and its different types, grades, and stages lack enough sensitivity and specificity. This study evaluates the expression of miRNAs 9 and 342 in sera of different types, grades, and stages of BC. Moreover, the assessment of their sensitivity, specificity, diagnostic, and prognostic role in detecting different types of BC. METHODS: Blood was collected from 200 females outpatients, divided into five groups each 40 subjects: control, benign breast tumor, estrogen receptor (ER+ )/progesterone receptor (PR+ ) BC, human epidermal growth factor receptor (HER+ ) BC, and triple-negative BC. BC subjects …were further subdivided according to grade and stage. Expressions of miRNAs 9 and 342 were measured for all subjects by real-time polymerase chain reaction (RT-PCR). RESULTS: Results showed that serum expression of both miRNAs 9 and 342 can be used for the diagnosis of different types of BC. Their expression can be used to significantly differentiate between different grades and stages of BC. MiRNAs 9 and 342 showed high sensitivity of 92.5% and specificity of (81.2 and 88.7%), respectively, for triple-negative BC. CONCLUSION: The expressions of miRNAs 9 and 342 provide potential roles as serological biomarkers for the diagnosis and prognosis of different types, grades, and stages of BC. Show more

Keywords: Breast, cancer, miRNA 9, miRNA 342, diagnosis, prognosis

DOI: 10.3233/BD-201076

Citation: Breast Disease, vol. 40, no. 4, pp. 241-250, 2021

Authors: Yustisia, Ika | Amriani, Rini | Cangara, Husni | Syahrijuita, Syahrijuita | Alfian Zainuddin, A. | Natsir, Rosdiana

Article Type: Research Article

Abstract: BACKGROUND: The role of gluconeogenesis in cancer cells as the reverse pathway for glycolysis is not well known. Several studies of gluconeogenesis in cancer cells still show conflicting results. Expression of key enzymes such as FBP1 and LDHB in cancer tissues may explain the role of gluconeogenesis in tumor development. OBJECTIVE: This study aimed to analyze the expression of FBP1 and LDHB in fibroadenomas and invasive cancers of the breast. METHODS: The immunohistochemical staining technique was used to show the expression of FBP1 and LDHB in formalin-fixed, paraffin-embedded blocks of 32 fibroadenomas and 31 invasive breast …cancer samples. RESULTS: FBP1 was expressed by the majority of fibroadenoma (68.7%) and invasive breast cancer (71%) samples. LDHB expression in fibroadenomas was significantly higher than in invasive breast cancers (P = 0.029). The expression of these two enzymes was found in invasive, lobular, and tubular breast carcinoma, and at well, moderately, and poorly differentiated breast malignancy. CONCLUSIONS: High expression of FBP1 and LDHB was found in fibroadenomas and invasive breast cancers. A higher level of LDHB expression was observed in fibroadenomas. These results may indicate the enzymes’ role in the pathogenesis of both breast diseases. Show more

Keywords: FBP1, LDHB, gluconeogenesis, fibroadenomas, breast cancers

DOI: 10.3233/BD-201035

Citation: Breast Disease, vol. 40, no. 4, pp. 251-256, 2021

Authors: Pavese, Francesco | Parisi, Alessandro | Rotondaro, Silvia | Cocciolone, Valentina | Pierorazio, Giovanni | Sidoni, Tina | Verna, Lucilla | Porzio, Giampiero | Ficorella, Corrado | Cannita, Katia

Article Type: Brief Report

Abstract: BACKGROUND: Despite the increase in chances of cure for early breast cancer (EBC) patients, approximately 20–45% of them will experience a disease recurrence, particularly bone metastases in 60–80% of cases, which occur more frequently in luminal subtypes. Endocrine therapy (ET) has always been the milestone of adjuvant treatment for hormone receptor-positive EBC patients, leading to indubitable reduction of disease recurrence risk. However, adjuvant aromatase inhibitors (AIs) therapy may promote a progressive decrease in bone mineral density (BMD), which can lead to osteoporosis. The increased bone resorption associated with osteoporosis may provide fertile soil for cancer growth and accelerate the development …of bone metastases. PATIENTS AND METHODS: In this single-institution cohort study, we performed a retrospective analysis of “luminal-like” EBC patients who experienced bone recurrence after a subsequent disease free interval. The aim of the study was to evaluate the median time to skeletal recurrence (TSkR). RESULTS: 143 patients experienced bone recurrence. Median TSkR was 54 months (95%CI: 45–65). Among patients who received adjuvant AIs median TSkR was 35 months (95%CI: 25–54), while among patients who did not was 61 months (95%CI: 50–80) (HR = 1.45 [95%CI: 0.97–2.17], p = 0.0644). After adjusting for TNM stage (AJCC 8th edition), adjuvant AIs treatment was significantly related to a shorter TSkR (HR = 1.60 [95%CI: 1.06–2.42], p = 0.0244). Adjuvant Tamoxifen, adjuvant AIs/Tamoxifen and no-treatment did not revealed to be associated to TSkR. CONCLUSIONS: In this cohort of EBC patients with bone recurrence, AIs treatment seems to be related to a shorter TSkR. AIs-induced bone resorption might represent the underlying mechanism. Show more

Keywords: Bone relapse, osteoporosis, breast cancer, endocrine therapy, aromatase inhibitors, bone resorption, skeletal metastases

DOI: 10.3233/BD-201036

Citation: Breast Disease, vol. 40, no. 4, pp. 257-262, 2021

Authors: Valinezhad Sani, Fatemeh | Alamolhodaei, Nafiseh Sadat | Rashidpoor, Hatam | Gharaee, Melika Ehtesham | Behravan, Javad | Mosaffa, Fatemeh

Article Type: Research Article

Abstract: BACKGROUND: Chronic inflammation is considered to be a risk factor for carcinogenesis, tumor development and metastasis by providing tumor-related factors. OBJECTIVES: We aimed to evaluate the effect of cytokine interleukin-1β (IL-1β) as a key mediator of inflammation on multidrug resistance associated protein 2 (MRP2) expression and tamoxifen toxicity in estrogen receptor positive (ER+) MCF-7 breast cancer cells. METHODS: The effects of IL-1β on tamoxifen toxicity following 20-day treatment of MCF-7 cells with IL-1β and/or 17β-estradiol (E2) were measured by MTT assay. Furthermore, the effects of IL-1β and/or E2 on the mRNA expression and protein levels of …MRP2 and NF-κB (p65) in breast cancer cells were evaluated by QRT-PCR and Western blot analysis, respectively. RESULTS: Treatment of breast cancer cells with IL-1β+ E2 decreased the sensitivity to 4-OH tamoxifen compared to both E2-treated and untreated cells. The mRNA expression levels of MRP2 and NF-κB (p65) were significantly increased following treatment with IL-1β+ E2, compared to control. In addition, breast cancer cells treatment with IL-1β+ E2 increased protein expression of MRP2 and it had no significant effect on NF-κB/p65 protein expression in these cells. CONCLUSION: Increased expression of mRNA and protein level of MRP2 following 20-day treatment of MCF-7 cells with IL-1β + E2 might be a possible elucidation for the increased tamoxifen resistance which was observed in these cells. More researches are essential to clarify the molecular mechanisms of inflammation on drug-resistance in the tumor environment in order to reducing or eliminating chemotherapy resistance and developing more effective treatment strategies. Show more

Keywords: IL-1β, MRP2, NF-κB/p65, Tamoxifen, breast cancer

DOI: 10.3233/BD-201056

Citation: Breast Disease, vol. 40, no. 4, pp. 263-268, 2021

Authors: de Vasconcelos Gaspar, Andreia | Melo, Luís | Geraldes, Fernanda | Belo, Joana | Águas, Fernanda

Article Type: Research Article

Abstract: OBJECTIVE: Description of breast pathology in adolescents. METHODS: A retrospective descriptive study of adolescents who were referred to the Gynecology consultation of a tertiary pediatric hospital for suspected breast pathology, in the period from the 1st June 2011 to the 30th December 2018. RESULTS: One hundred and two female adolescents (11 to 18 years old) with suspected breast pathology were referred (6% of the motives for consultation), with confirmation in 58 (56.9%), who were included in the study. The reasons for referral were breast masses (66%), anomalies in breast size or symmetry (29%) and infection (5%). …Of breast masses, the most frequent diagnosis was fibroadenoma (76%), followed by fibro-cystic pathology (18%). In most cases, a conservative approach was chosen, with clinical and imaging surveillance. Surgery was required in 29% of these cases. Anomalies in breast size and symmetry were observed in 17 adolescents. Two adolescents were submitted to symmetrization, after 18 years of age. Infectious and inflammatory pathology occurred in three cases: two mastitis and one retroareolar cyst. The approach consisted mainly of antibiotherapy. There were no cases of malignant breast disease. CONCLUSION: Lumps or breast masses are the most frequent breast pathology in adolescence, and in the majority of cases surveillance was recommended, as they are a mere sign of hormonal oscillations at this age. Objective examination and/or breast ultrasound are usually enough to make the diagnosis. The approach must be mainly conservative, since malignancy is extremely rare in this age group. Show more

Keywords: Adolescent, breast diseases

DOI: 10.3233/BD-201043

Citation: Breast Disease, vol. 40, no. 4, pp. 269-274, 2021

Authors: El-Badrawy, Adel

Article Type: Research Article

Abstract: BACKGROUND: Multiple primary malignancies are two or more malignancies in an individual without any relationship between the tumors. The development of improved diagnostic techniques, increased survival of cancer patients and the growing life expectancy have all contributed to the increased frequency of this phenomenon. OBJECTIVE: The aim of this study is to review the multidetector computed tomography (MDCT) findings of synchronous breast carcinoma and other solid malignancies. METHODS: This retrospective study included 65 patients confirmed with diagnosis of synchronous breast carcinoma and other solid malignancies. CT scanning was performed using 128 MDCT in all patients. All …one hundred-thirty malignancies underwent pathological evaluation. RESULTS: Out of 4120 patients with breast carcinoma; 65 patients were diagnosed with other synchronous primary solid malignancy. All one hundred-thirty malignancies were confirmed pathologically. Breast carcinoma detected in all 65 patients; of them metastatic breast carcinoma detected in 8 patients. Hepatocellular carcinoma was detected in 18 patients, Non-Hodgkin lymphoma (NHL) in 12 patients, endometrial carcinoma in 8 patients, uterine sarcoma in 3 patients, malignant mixed Müllerian tumor in one patient, ovarian carcinoma in 5 patients, renal cell carcinoma in 4 patients, thyroid carcinoma in 4 patients, gastric carcinoma in 2 patients, colonic carcinoma in 2 patients, ano-rectal carcinoma in one patient, hilar cholangiocarcinoma in 2 patients, malignant melanoma in 2 patients and bronchogenic carcinoma in one patient. CONCLUSIONS: Patients with breast carcinoma have a risk of other synchronous primary malignancy. So, careful preoperative examination is recommended to improve the patients’ prognosis. MDCT scanning is accurately imaging modality for evaluation of synchronous breast carcinoma and other solid malignancies. The aim of treatment in cancer patients should always be curative even in the presence of multiple malignancies. Show more

Keywords: Breast carcinoma, synchronous malignancy, computed tomography

DOI: 10.3233/BD-201065

Citation: Breast Disease, vol. 40, no. 4, pp. 275-281, 2021

Authors: Tagliati, Corrado | Lanni, Giuseppe | Cerimele, Federico | Di Martino, Antonietta | Calamita, Valentina | Lucidi Pressanti, Gabriella | Mingliang, Ying | Giuseppetti, Gian Marco | Argalia, Giulio | Giovagnoni, Andrea

Article Type: Case Report

Abstract: We present a case of ductal carcinoma in situ within a fibroadenoma. Breast cancer arising within fibroadenoma incidence ranges from 0.125% to 0.02%, and ductal carcinoma in situ is not the most frequent malignancy that can be found within a fibroadenoma. Dynamic contrast-enhanced magnetic resonance imaging showed an oval mass with circumscribed margins and dark internal septations, suspicious for fibroadenoma. According to European Society of Breast Radiology diffusion-weighted imaging consensus, mean apparent diffusion coefficient value obtained by drawing a small region of interest on the lesion apparent diffusion coefficient map showed a low diffusion level. Therefore, ductal carcinoma in situ …within a fibroadenoma was diagnosed at final pathology after surgical excision. Show more

Keywords: Breast cancer, fibroadenoma, ductal carcinoma in situ, ADC

DOI: 10.3233/BD-201080

Citation: Breast Disease, vol. 40, no. 4, pp. 283-286, 2021