Breast Disease - Volume 42, issue 1

Authors: Shah, Heer | Mistry, Mittal | Patel, Nupur | Vora, Hemangini

Article Type: Research Article

Abstract: BACKGROUND: The Notch signaling pathway is an evolutionary conserved cell signaling pathway that plays an indispensable role in essential developmental processes. Aberrant activation of Notch pathway is known to initiate wide array of diseases and cancers. OBJECTIVE: To evaluate the clinical significance of Notch receptors in Triple Negative Breast Cancer. METHODS: We evaluated the association between Notch receptors and clinicopathological parameters including disease-free survival and overall survival of one hundred TNBC patients by immunohistochemistry. RESULTS: Positive expression of nuclear Notch1 receptor (18%) was found be significantly correlated with positive lymph node (p = 0.009), …high BR score (p = 0.02) and necrosis (p = 0.004) while cytoplasmic expression of Notch2 receptor (26%) was significantly correlated with metastasis (p = 0.05), worse DFS (p = 0.05) and poor OS (p = 0.02) in TNBC patients. Membrane (18%) and cytonuclear (3%) Notch3 expression were significantly associated with poorly differentiated tumors (p = 0.007), high BR score (p = 0.002) and necrosis (p = 0.03) respectively. However, cytoplasmic Notch3 and Notch4 expression were negatively correlated with poor prognostic factors. CONCLUSIONS: Our data indicated that Notch receptors play a key role in promoting TNBC and mainly, Notch2 may contribute to poor prognosis of the disease. Hence, it is implicated that Notch2 may serve as a potential biomarker and therapeutic target for TNBC. Show more

Keywords: Notch receptors, Triple Negative Breast Cancer, immunohistochemistry

DOI: 10.3233/BD-220041

Citation: Breast Disease, vol. 42, no. 1, pp. 85-100, 2023

Authors: Abdallah, Ahmed | Hamdy, Omar | Zuhdy, Mohammad | Elbalka, Saleh S. | Abdelkhalek, Mohamed | Zaid, Amir M. | Atef, Ahmed | Elmadawy, Mohamed G. | Refky , Basel | Wahab, Khaled Abdel | Bayoumi, Dalia | Ali, Khadiga M. | Metwally, Islam H. | Shetiwy, Mosab

Article Type: Research Article

Abstract: BACKGROUND: Multifocal (MFBC)/multicentric (MCBC) breast cancer is being more recognized due to the improved imaging modalities and the greater orientation with this form of breast cancer, however, optimal surgical treatment, still poses a challenge. The standard surgical treatment is mastectomy, however, breast-conserving surgeries (BCS) may be appropriate in certain situations. METHODS: A total of 464 cases of MF/MCBC out of 4798 cases of breast cancer were retrospectively analyzed from the database of the Oncology Center, Mansoura University (OCMU), between January 2008 and December 2019. RESULTS: Radiologic involvement of multiple quadrants was reported in 27.9% by ultrasonography, …19% by mammography, and 59.1% by magnetic resonance imaging. BCS was performed in 32 cases (6.9%) while 432 cases underwent a mastectomy. Postoperative pathology revealed infiltration of other quadrants grossly in 23.5%, and under the microscope in 63.6% of the examined cases. Mean disease-free and overall survival were 95.5 and 164.6 months, respectively. When compared with MFBC, MCBC showed higher pathologic tumor size (p < 0.001), higher stages (p < 0.001), higher recurrence rates (p = 0.006), and lower DFS (P = 0.009) but with similar OS (P = 0.8). CONCLUSION: Mastectomy is still the primary treatment option for MCBC with higher recurrence rates compared with MFBC. However, BCS for properly selected MFBC is considered oncologically safe, following the same rules of breast conservation for unifocal disease. Show more

Keywords: Breast, carcinoma, conservation, multicentric, outcome, survival

DOI: 10.3233/BD-220066

Citation: Breast Disease, vol. 42, no. 1, pp. 101-114, 2023

Authors: Esmer, Ahmet Cem | Tazeoglu, Deniz | Dag, Ahmet

Article Type: Research Article

Abstract: BACKGROUND: Pseudoangiomatous stromal hyperplasia is a rare benign breast stromal proliferative lesion of the breast. Clinical presentation ranges from rapidly growing mass to incidental identification in routine screening. This difference in manifestation and its rarity makes it difficult to be a standard treatment protocol. Therefore, we aimed to share our clinical experience in Pseudoangiomatous stromal hyperplasia. METHODS: The files of patients who underwent core biopsy or surgical excision due to a breast mass and resulted in pseudoangiomatous stromal hyperplasia between January 2013 and December 2021 were included in the study. RESULTS: 17 patients with a median …age of 37 (22–68) were found Pseudoangiomatous stromal hyperplasia confirmed by surgical excision or core biopsy. Chosen treatment option was observation in 8 patients (47.1%), while surgical excision was used in 9 (52.9%) patients. The mean follow-up period was 55.24 ± 26.72 (13–102) months. None of the patients observed the Malignant transformation during the follow-up period. CONCLUSION: For Pseudoangiomatous Stromal Hyperplasia of the breast, surgical excision with clean margins or close follow-up after diagnosis confirmation by tissue biopsy is sufficient. Pseudoangiomatous Stromal Hyperplasia is not a risk factor for developing breast cancer. Show more

Keywords: Breast, core biopsy, pseudoangiomatous stromal hyperplasia, surgical excision

DOI: 10.3233/BD-220070

Citation: Breast Disease, vol. 42, no. 1, pp. 115-119, 2023

Authors: Afzal, Fatima | Aiman, Wajeeha | Zahoor, Hafsa | Bajwa, Ayfa Riaz | Kazmi, Syeda Hafsa | Anwar, Aqsa | Anwar, Muhammad Yasir | Rashid, Sana | Zubair, Hina | Kashif, Tooba | Ashar Ali, Muhammad

Article Type: Systematic Review

Abstract: Breast cancer (BC) is the 2nd most common cause of cancer-related deaths. Antibody-drug conjugates (ADCs) are monoclonal antibodies linked to cytotoxic agents and are directed towards a specific tumor protein. Therefore, they are more potent and can have relatively less toxicity. In this meta-analysis, we assessed the efficacy and safety of ADCs in breast cancer. We searched PubMed, Cochrane, Web of Science, and clinicaltrials.gov for relevant studies and included 7 randomized clinical trials (N = 5,302) and 7 non-randomized clinical trials (N = 658). R programming language software was used to conduct this meta-analysis. In 4 RCTs on HER-2 positive …BC (N = 2,825), the pooled HR of PFS and OS was 0.72 (95% CI = 0.61–0.84, I2 = 71%) and 0.73 (95% CI = 0.64–0.84, I2 = 20%), respectively in favor of ADCs versus chemotherapy. In RCT on triple negative BC (N = 468), HR of PFS and OS were 0.55 (95%CI = 0.51–0.61) and 0.59 (95% CI = 0.54–0.66), respectively, in favor of saci-gov versus chemotherapy. In RCT on HER-2 positive residual invasive BC, HR of recurrence/death was 0.61 (95% CI = 0.54–0.69) in favor of ADC versus chemotherapy. In an RCT (N = 524), the HR of PFS and OS were 0.28 (95% CI = 0.22–0.37) and 0.55 (95%CI = 0.36–0.86), respectively, in favor of trastuzumab-deruxtecan (T-der) as compared to trastuzumab-emtansine (T-DM1). Anemia, rash, diarrhea, fatigue, hypertension, thrombocytopenia, and elevated aminotransferases were the common ≥grade 3 adverse events reported in 4%, 1%, 2%, 1%, 2%, 9%, and 3% of the patients, respectively. ADCs were more effective than single and double agent chemotherapy in patients with HER-2 positive or triple negative BC. Among ADCs, T-der was more effective than T-DM1. Show more

Keywords: Breast cancer, antibody-drug conjugates, trastuzumab-emtansine, trastuzumab-deruxtecan, sacituzumab govitecan

DOI: 10.3233/BD-220052

Citation: Breast Disease, vol. 42, no. 1, pp. 121-136, 2023

Authors: Abbas, Yara | Hamdy, Omar

Article Type: Review Article

Abstract: Standard operative management for breast carcinoma has significantly shifted from extensive procedures to minor interventions. Although axillary dissection was a fundamental component of operative management, sentinel biopsy is an actual process for axillary staging. Axillary dissection may be postponed for cases that have negative SLNs or 1 or 2 infiltrated lymph nodes undergoing breast or axillary radiation. Contrarily, axillary dissection is still the conventional management for patients with clinically positive nodes. Arm lymphedema is a frequent and overwhelming complication of axillary dissection, with a worse impact on the patient’s life. Axillary reverse mapping was recently introduced to …map and conserve the lymph drain of the upper limb throughout axillary dissection or sentinel biopsy. A technique based on the theory that the breast’s lymphatic drainage differs from those that drain the arm, so preserving lymphatic drainage of the upper limb can prevent lymphedema, thereby not raising the risk of axillary recurrence. Therefore, this technique is the reverse of sentinel biopsy, which remove the lymph nodes that drain the breast. Show more

Keywords: Axillary reverse mapping, sentinel lymph node biopsy, lymphedema

DOI: 10.3233/BD-220040

Citation: Breast Disease, vol. 42, no. 1, pp. 137-146, 2023

Authors: Alikhassi, Afsaneh | Skarpathiotakis, Mia | Lu, Fang-l | Curpen, Belinda

Article Type: Review Article

Abstract: Pseudoangiomatous stromal hyperplasia (PASH) is a benign breast pathology, which most commonly presents incidentally along with other breast pathologies. The etiology and pathogenesis of PASH are still unknown; however, there is some evidence suggesting PASH is hormone dependent. The clinical history, presentation, and imaging appearance of PASH are variable. Clinically, PASH has a wide spectrum of presentations, from being silent to gigantomastia. On imaging, PASH demonstrates various benign to suspicious features. Here we summarize PASH’s clinical presentation, histopathology, imaging features, and management.

Keywords: Breast ultrasound, breast MRI, mammography, PASH

DOI: 10.3233/BD-220072

Citation: Breast Disease, vol. 42, no. 1, pp. 147-153, 2023

Authors: Patino-Hernandez, Daniela | Fernández-Ávila, Daniel G. | Mauricio Muñoz-Velandia, Óscar | del Socorro Moreno Luna, Isabel

Article Type: Research Article

Abstract: BACKGROUND: The Delphi technique is a consensus method aiming to obtain statistical estimations from a qualitative approach, through an iterative process that leads to consensus within experts. The main characteristics of the technique include iteration, anonymity, feedback, and consensus reaching. When high-quality, quantitative evidence on a particular topic is insufficient, the Delphi technique can be used for making decisions in clinical scenarios. However, the quality of studies on breast cancer conducted with this technique, has not been assessed. OBJECTIVE: We aim to evaluate the quality of studies on breast cancer which used the Delphi technique as their method. …METHODS: A quality assessment tool (Quali-D) was created through consensus among experts on the Delphi technique. Then, the tool was applied to studies on breast cancer which used the Delphi technique as their method. RESULTS: Studies conducted through the Delphi technique mainly assessed for quality indicators and expressed needs in patients with breast cancer. High-quality characteristics were reported in 63.89% of the studies. 98.61% used the Delphi technique due to lack of a more adequate method to solve their research question. 98.61% summarized and presented results in a clear way. In 91.67% of the studies, at least two rounds were conducted. 86.11% described the methods for expert selection in a complete manner. Only 54.17% of the studies reported an anonymous process and 4.17% of the studies disclosed conflicts of interest thoroughly. CONCLUSIONS: A variety of topics were assessed through the Delphi technique in cases where no other technique would have been more appropriate for assessing these issues. Significant limitations are present in terms of anonymity and full disclosure of conflicts of interest. We found that the quality of studies conducted with the Delphi technique regarding breast cancer is overall good. However, the limitations of each study must be considered when applying their results to clinical practice. Show more

Keywords: Delphi technique, breast neoplasms, qualitative research

DOI: 10.3233/BD-220079

Citation: Breast Disease, vol. 42, no. 1, pp. 155-161, 2023

Authors: Abou Shousha, Seham | Baheeg, Suzan | Ghoneim, Hossam | Zoheir, Malak | Hemida, Mahmoud | Shahine, Yasmine

Article Type: Research Article

Abstract: Evasion of the immune system is the tumor’s key strategy for its maintenance and progression. Thus, targeting the tumor microenvironment (TME) is considered one of the most promising approaches for fighting cancer, where immune cells within the TME play a vital role in immune surveillance and cancer elimination. FasL is one of the most important death ligands expressed by tumor-infiltrating lymphocytes (TILs) and plays a vital role in eliminating Fas-expressing cancer cells via Fas/FasL pathway-induced apoptosis. However, tumor cells can express elevated levels of FasL inducing apoptosis to TILs. Fas/FasL expression is linked to the maintenance of cancer stem …cells (CSCs) within the TME, contributing to tumor aggressiveness, metastasis, recurrence, and chemoresistance. This study is considered the first study designed to block the overexpressed FasL on the tumor cells within TME mimicking tissue culture system using rFas molecules and supplementing the Fas enriched tissue culture system with blocked Fas - peripheral blood mononuclear cells PBMCs (using anti-Fas mAb) to protect them from tumor counterattack and augment their ability to induce tumor cell apoptosis and stemness inhibition. A significantly increased level of apoptosis and decreased expression of CD 44 (CSCs marker) was observed within the east tumor tissue culture system enriched with Fas molecules and anti-Fas treated PBMCs and the one enriched with Fas molecules only compared to the breast tumor tissues cultured alone (p < 0.001). Accordingly, we can consider the current study as a promising proposed immunotherapeutic strategy for breast cancer. Show more

Keywords: Stem cells, breast cancer, in vitro, cell therapy, apoptosis, immunotherapy

DOI: 10.3233/BD-220077

Citation: Breast Disease, vol. 42, no. 1, pp. 163-176, 2023

Authors: Raya, Indah | Kartina, Desy | Irfandi, Rizal | Sufiandi, Sandi | Wijaya, Ronald Ivan | Prihantono, Prihantono | Abdalrazaq, Eid A. | Kandeel, Mahmoud | Usman, Andi Nilawati

Article Type: Research Article

Abstract: OBJECTIVE: The new Mg(II) cysteindithiocarbamate complex drug has been synthesized by the in-situ method and tested for its anticancer activity in vitro. METHOD: Mg(II) cysteindithiocarbamate complexes were characterized using Ultra Violet Visible, Infra-Red, melting points, and molar conductivity. RESULTS: The UV-Vis data of cysteindithiocarbamate Mg(II), shows that at 296 nm and 385 nm was occurred the electronic transitions π → π * and n → π * for CS2 and N =C =S. Whereas the IR data at wavelengths in the 393–540 cm−1 shows that there has coordinated between Mg(II) with Sulfur (S), Nitrogen …(N), and Oxygen (O) atoms from cysteinedithiocarbamate ligands. CONCLUSION: The cytotoxicity test results showed that the Mg complex’s cytotoxicity was higher than that of the cytotoxicity of the Mg metal without ligands, which means that the Mg complex can be developed as a potential new anticancer drug. Show more

Keywords: Complex Mg(II), anticancer, breast disease, cytotoxicity

DOI: 10.3233/BD-239006

Citation: Breast Disease, vol. 42, no. 1, pp. 177-182, 2023

Authors: Wong, Chieng Bing | Mustapa, Aklimah | Matusin, Siti Nur Idayu | Abdullah, Muhammad Syafiq | Usman, Andi Nilawati | Haji Abdul Hamid, Mas Rina Wati

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the associations between breast cancer staging and body mass index (BMI), menopausal status, and family history of breast cancer, as well as to assess the expression of tumor markers in women with breast cancer in Brunei Darussalam. METHODS: A retrospective cross-sectional study was carried out at The Brunei Cancer Centre. Cases of women with breast cancer between 2000 and 2013 were retrieved from the medical records section and entered into a clinical proforma. These were reviewed and analyzed using appropriate statistical methods. RESULTS: Overall, the mean age at diagnosis was 53.6 years ± …9.83. The postmenopausal women had a significantly higher risk of being diagnosed with late-onset breast cancer than premenopausal women (P = 0.022). The expressions of PR (P = 0.034), Her2 (P = 0.046), and CatD (P = 0.004) were significantly different in breast cancer staging. Other factors did not have a statistically-significant association with breast cancer staging. CONCLUSION: While most of the factors studied were not significantly different in breast cancer staging, our findings showed that it is recommended that high-risk women perform regular breast screening after the age of 40 years old. A future study highly appreciates comparing breast cancer risk factors among the Bruneian and Western populations. Show more

Keywords: Breast cancer, body mass index, menopausal status, family history, tumor markers, breast cancer staging

DOI: 10.3233/BD-239001

Citation: Breast Disease, vol. 42, no. 1, pp. 183-189, 2023

Authors: Awaluddin, Awaluddin | Pieter Jr., John | Sampepajung, Elridho | Syamsu, Salman Ardi | Smaradhania, Nilam | Hamid, Firdaus | Prihantono, Prihantono | Laidding, Sachraswaty R. | Kusuma, Muhammad Ihwan | Faruk, Muhammad

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer (BC) is the second most frequent cancer-related death among women worldwide. Factors influencing BC patients’ survival include histopathological grade, histopathological type, stage, hormonal receptors, and number of mitotic images. OBJECTIVE: To compare the tumor size, histopathological grade, and molecular type of BC patients. METHODS: This was an observational analytic retrospective study. The population was BC patients at Dr. Wahidin Sudirohusodo Hospital from 2017 to 2021. The Kruskal–Wallis test was used to compare statistically between tumor size, histopathological grade, and molecular subtype. Significance was set at p < 0.05. RESULTS: The study …included 784 patients. Most were aged 50–59 years (34.8%), with tumor size 4c (37.0%) and moderate grade (66.1%), and the most common molecular subtype was luminal A (34.2%). Bivariate analysis using the Kruskal–Wallis test found no significant difference in molecular subtypes based on tumor size (p = 0.079), but significant differences existed in molecular subtype by histopathological grade (p = 0.005) and tumor size by histopathological grade (p < 0.001). CONCLUSIONS: Significant differences existed between histopathological grade by tumor size and molecular subtype. Early diagnosis and prompt treatment of BC patients are important to prevent morbidity and mortality. Show more

Keywords: Breast cancer, tumor size, molecular subtype, histopathological grade

DOI: 10.3233/BD-239000

Citation: Breast Disease, vol. 42, no. 1, pp. 191-195, 2023

Authors: Rezkallah, Emad M.N. | Elsaify, Andrew | Tin, Su M.M. | Dey, Debdeep | Elsaify, Wael M.

Article Type: Review Article

Abstract: BACKGROUND: Lymphoma of the breast can be classified as either primary breast lymphoma (PBL) or secondary to systemic lymphoma (SBL). PBL is a rare disease with Diffuse Large B cell Lymphomas (DLBCL) being the most common subtype. OBJECTIVES: In the current study, we represented eleven cases diagnosed with breast lymphoma in our trust; two of them had PBL and nine had SBL. We focused mainly on the clinical presentation, diagnosis, management and outcomes. METHODS: We did this retrospective review for all breast lymphoma patients who were diagnosed in our trust during the periods from 2011–2022. Patients’ …data were obtained from the hospital recording system. We followed up these patients thus far to identify the outcome of treatment in each patient. RESULTS: Eleven patients were included in our review. All patients were females. Average age of diagnosis was 66.1 ± 13 years of age. Eight patients were diagnosed with DLBCL, two patients were diagnosed with follicular lymphomas, and the last one had lymphoplasmacytic lymphoma. Chemotherapy +∕− radiotherapy was the standard treatment regimen in all patients. Four patients passed away within one year of chemotherapy, five patients achieved complete remission, one patient had two relapses and is still under treatment, while the last patient was diagnosed recently and still awaiting treatment. CONCLUSION: Primary breast lymphoma is an aggressive disease. The treatment for PBL is mainly systemic with chemoradiotherapy. The role of surgery is now limited to the diagnosis of the disease. Early diagnosis and proper treatment are crucial for the management of such cases. Show more

Keywords: Breast, lymphoma, presentation, diagnosis, management, outcome

DOI: 10.3233/BD-220051

Citation: Breast Disease, vol. 42, no. 1, pp. 197-205, 2023

Authors: Usman, Andi Nilawati | Manju, Budu | Ilhamuddin, Ilhamuddin | Ahmad, Mardiana | AB, Takko | Ariyandy, Andi | Budiaman, Budiaman | Eragradini, Athirah Rinandha | Hasan, Intan Idiana | Hashim, Sabarisah | Sartini, Sartini | Sinrang, Andi Wardihan

Article Type: Review Article

Abstract: BACKGROUND: Cancer is a type of disease caused by the uncontrolled growth of abnormal cells that can destroy body tissues. The use of traditional medicine naturally uses plants from ginger with the maceration method. The ginger plant is a herbaceous flowering plant with the Zingiberaceacea group. METHODS: This study uses the literature review method by reviewing 50 articles from journals and databases. RESULTS: A review of several articles, namely ginger has bioactive components such as gingerol. Ginger is used as a treatment in complementary therapies using plants. Ginger is a strategy with many benefits and functions …as a nutritional complement to the body. This benefit has shown the effect of anti-inflammatory, antioxidant, and anticancer against nausea and vomiting due to chemotherapy in breast cancer. CONCLUSION: Anticancer in ginger is shown by polyphenols associated with anti-metastatic, anti-proliferative, antiangiogenic, anti-inflammatory, cell cycle arrest, apoptosis, and autophagy. Therefore, consuming ginger regularly affects natural herbal therapy with the prevention and treatment of breast cancer and serves as a prevention against the effects of chemotherapy. Show more

Keywords: Ginger, prevention, treatment, cancer, breast

DOI: 10.3233/BD-239003

Citation: Breast Disease, vol. 42, no. 1, pp. 207-212, 2023

Authors: Usman, Andi Nilawati | Ahmad, Mardiana | Sinrang, Andi Wardihan | Natsir, Sartini | Takko, A.B. | Ariyandy, Andi | Ilhamuddin, Ilhamuddin | Eragradini, Athira Rinandha | Hasan, Intan Idiana | Hasyim, Sabarisah

Article Type: Review Article

Abstract: BACKGROUND: FOXP3 Tregs have been found in breast cancer patients, both humoral and tumor. Survival or prognosis of breast cancer patients seems to correlate with the increase and decrease in FOXP3 Treg. OBJECTIVES: This review aims to provide insights regarding the FOXP3 Tregs involved and their mechanisms in breast cancer prognosis. METHODS: The literature study method is used from primary and secondary libraries. The library search used online-based search instruments such as NCBI-PubMed, Google Scholar, and Elsevier. The data obtained were then arranged according to the framework, data on the relationship between FOXP3 Regulatory T Cells …and breast cancer, and writing a journal review was carried out according to the given format. Regulators (Tregs) can inhibit anti-tumor immunity and promote tumor growth. Tregs also play a role in inhibiting cytotoxic T lymphocyte cells by inhibiting the release of granules from CD8+ , where CD8+ is important in killing tumor cells. FOXP3 is a Treg-specific biomarker and plays an important role in the development and function of Tregs. RESULTS: Studies on the presence of FOXP3+ Tregs in tumors have shown controversial results. Studies in some tumors reported the presence of FOXP3+ , indicating a poor prognosis, whereas studies in other tumors found that FOXP3+ correlated with a good prognosis. CONCLUSION: Regulatory T lymphocytes and TILs in invasive breast carcinoma are still not established. Therefore, further research on the Effect of FOXP3 expression of regulatory T lymphocytes on breast cancer is still important. Show more

Keywords: Treg-regulatory T cells, FOXP3, breast cancer

DOI: 10.3233/BD-239002

Citation: Breast Disease, vol. 42, no. 1, pp. 213-218, 2023

Authors: Pankratjevaite, Lina | Igbokwe, Michelle Mistry | Benian, Cemil | Lelkaitis, Giedrius

Article Type: Case Report

Abstract: INTRODUCTION: Breast granular cell tumour (GCT) is a rare but usually benign lesion. PRESENTATION OF CASE: We report a case of a woman with breast GCT. CONCLUSION: Clinically and radiologically, GCT may mimic breast carcinoma. A conclusive diagnosis is made after a histopathological examination of the lesion. The treatment of choice is surgery.

Keywords: Granular cell tumor, rare breast disease, surgery, case report

DOI: 10.3233/BD-220063

Citation: Breast Disease, vol. 42, no. 1, pp. 219-222, 2023

Authors: Santana Valenciano, Ángela | Juez Sáez, Luz Divina | Pérez Mies, Belén | Moreno, Sara Corral | Fidalgo, Sonia Rivas | Montero, Jacobo Cabañas

Article Type: Brief Report

Abstract: BACKGROUND: Metastases from extramammary malignant neoplasms are very rare, accounting for less than 2% of all breast malignancies. OBJECTIVE: The aim of this study is to describe the clinicopathological features and prognosis of breast metastases from non-primary breast malignancies at our institution. METHODS: We performed a retrospective observational study, obtaining data from electronic medical records and pathology databases between January 1985 and December 2020 for patients diagnosed with breast metastasis from non-primary breast malignancies. Only patients diagnosed by biopsy were included. RESULTS: Fifteen patients diagnosed with breast metastases from non-primary breast malignancies were included, …13 women (86,67%) and 2 men (13,33%). The median age at time of initial diagnosis was 56 years (IQR 21–68). The most frequent primary malignancy was melanoma (9/15; 60%). The median time to diagnosis of breast metastases was 65 months (IQR 13–106). The most common diagnostic modality was CT-scan (10/15; 66,67%). The median follow-up was 96 months (IQR 29–136). Eight patients underwent surgery (53,3%), being the most common surgical intervention breast-conserving surgery (5/8; 62,5%). Mortality at the end of follow-up was 53,3% (8/15). On the survival analysis, we found no differences between patients undergoing surgery and those only receiving systemic treatment [41,5 months (IQR 17,5–57,5) versus 14 months (IQR 2–24), respectively; p = 0,161]. CONCLUSIONS: Breast metastases from non-primary breast malignancies are extremely rare and represent a diagnostic and therapeutic challenge, due to the poor prognosis of these patients. Thus, arriving at the correct diagnosis is crucial to avoid unnecessary treatment in this population. Show more

Keywords: Breast metastases, extramammary malignancies, diagnosis, treatment

DOI: 10.3233/BD-220056

Citation: Breast Disease, vol. 42, no. 1, pp. 223-228, 2023

Authors: da Costa Vieira, René Aloisio | Ching, An Wan | de Oliveira-Junior, Idam

Article Type: Brief Report

Abstract: Thoracoabdominal (TA) flaps are a good option for primary closure of small and medium defects after mastectomy for locally advanced breast tumours. Although they have a higher rate of necrosis than myocutaneous flaps, they can be easily performed by breast surgeons. Few studies on this procedure have been reported, and we have been unable to identify any prior publications reporting breast reconstruction with TA flaps.

Keywords: Breast cancer, surgical flaps, myocutaneous flaps, locally advanced tumors

DOI: 10.3233/BD-220057

Citation: Breast Disease, vol. 42, no. 1, pp. 229-232, 2023

Authors: Nadia, Shafa | Rivai, Fridawaty | Sidin, Indahwaty | Pasinringi, Syahrir A.

Article Type: Research Article

Abstract: BACKGROUND: Over the past two decades, patient-centered care has become internationally recognized as a dimension of high-quality health care. Recent research has shown that patient-centered care has many benefits, which are broadly categorized as patient experience and clinical and operational benefits. OBJECTIVE: The study aimed at analyzing the correlation between the application of patient-centered care (PCC) and length of stay, patient satisfaction, and clinical outcome of post-surgical breast cancer patients. METHODS: The study design was cross-sectional. A sample of 100 patients was determined and selected with the inclusion criteria. Data were collected using measuring tools comprising …patient-centered care and patient satisfaction questionnaires as well as medical records to evaluate the length of stay and clinical outcomes. Bivariate analysis was conducted to analyze the correlation between patient-centered-care and length of stay (LOS), patient satisfaction, and the clinical outcomes of inpatients. RESULTS: A correlation was found between patient-centered care (PCC) application and patient satisfaction (p  = 0.005), but no correlation was observed between PCC application and length of stay (LOS) (p  = 0.176) as well as clinical outcome (p  = 0.128). CONCLUSIONS: The application of patient-centered care can be attributed to patient satisfaction but is not correlated to length of stay and clinical outcome of post-surgical breast cancer patients. The hospital should create an accepted definition and commonly agreed set of dimensions used for the concept of operationalization and its measurement to implement PCC and improve overall patient satisfaction and clinical outcome and reduce the length of stay as expected. Show more

Keywords: Patient-centered care, patient satisfaction, length of stay, clinical outcome, breast cancer surgery

DOI: 10.3233/BD-239004

Citation: Breast Disease, vol. 42, no. 1, pp. 233-243, 2023

Authors: Hassan, Mohammad Jaseem | Ahmed, Saqib | Siddiqui, Bushra | Akhtar, Kafil | Anees, Afzal | Arif, Sayeedul Hasan | Hasan, Mahboob

Article Type: Case Report

Abstract: Development of a neoplasm in an ectopic breast is uncommon, while the development of phyllodes tumor in an ectopic breast in the axilla is even rarer. We report a rare case of a 51-year-old female who presented with a complain of swelling and pain in the right axilla with no associated complaints in other organs. Magnetic resonance imaging suggested a possibility of metastatic lymphadenopathy. Complete excision of the right axillary mass was performed and sent for histopathological examination which was examined thoroughly and sections were given. On microscopic examination, stromal proliferation in a leaf-like pattern with mild stromal atypia and …focal permeation of borders were seen, and a diagnosis of Ectopic borderline phyllodes tumor in axilla was made, which is extremely rare and needs to be differentiated from its close differentials like fibroadenoma and periductal stromal sarcoma. Show more

Keywords: Axillary ectopic breast, phyllodes tumor, accessory breast, axillary swelling

DOI: 10.3233/BD-230007

Citation: Breast Disease, vol. 42, no. 1, pp. 245-249, 2023

Authors: Sadeghi, Minoosh | Gholizadeh, Majid | Safataj, Neda | Tahmasebivand, Mahsa | Mohajeri, Gholamreza | Lotfi, Hajie | Bostanabad, Saber Yari | Safar, Behnaz | Salehi, Mansoor

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer (BC) is the most prevalent cancer in women, with increasing incidence and death rates in recent years. Disruptions of different signaling pathways partially cause breast cancer. Hence, different genes through particular pathways are involved in BC tumorigenesis. METHODS: In this study, we evaluated the expression level of GLIS2 and CCND1 genes in 50 patients. Also, in-silico analyses were used to enrich related signaling pathways involving the mentioned genes. RESULTS: The results showed an increased expression level of Cyclin D1 and decreased expression level of GLIS2 in BC patients. Moreover, a …relationship between aberrant expression levels of GLIS2 and CCND1 and BC development was determined. CONCLUSION: These observations could help uncover new therapeutic targets for treating patients with BC in the progressive stage. Show more

Keywords: Breast cancer, GLIS2 , CCND1 , signaling pathway

DOI: 10.3233/BD-220068

Citation: Breast Disease, vol. 42, no. 1, pp. 251-259, 2023

Authors: Usman, Andi Nilawati | Ahmad, Mardiana

Article Type: Systematic Review

Abstract: BACKGROUND: Breast cancer is a malignancy that occurs in cells in the breast tissue where cells in the breast divide and grow out of control, invade surrounding tissues, or spread (metastasize) to distant areas of the body. METHOD: This review was systematically carried out through PubMed, Scopus, ScienceDirect, and Google Scholar websites in English and Indonesian using the keyword content of the article, obtaining 21 selected articles. This review demonstrates honey’s promising mechanism of combined synergistic effect for breast cancer management. CONCLUSION: Antioxidants in honey intercept free radicals of phenolic compounds which are the main factors …responsible for the antioxidant activity of honey. The antimicrobial activity in most honey is due to the enzymatic production of hydrogen peroxide, and its anti-cancer properties are discussed in this section. Show more

Keywords: Honey, breast, cancer, phenolic

DOI: 10.3233/BD-239005

Citation: Breast Disease, vol. 42, no. 1, pp. 261-269, 2023

Authors: Ben Kridis, Wala | Lajnef, Mayssa | Bouattour, Faida | Toumi, Nabil | Daoud, Jamel | Khanfir, Afef

Article Type: Research Article

Abstract: BACKGROUND: Male breast cancer (MBC) is a rare malignancy presenting only 1% of all breast cancer. The purpose of this study was to analyze clinical and pathological prognostic factors of MBC. METHODS: This is a retrospective study including 32 men diagnosed and treated for a primary breast cancer at the department of medical oncology in Sfax between 2005 and 2020. RESULTS: The incidence of MBC was 1.3%. The median age of our patients was 55 years (range: 29–85 years). The average tumor size of 3.9 cm. Lymph nodes involvement was present in 18 cases (56.2%) with …capsular rupture in 52% cases. Tumor was grade II in 71.8 % of cases. The expression of hormonal receptors was founded in 100% of cases. Two patients had an overexpression of HER2 (6.2%). There was no case of triple negative MBC. The OS at 5 and 10 years was 67.8% and 30.8% respectively. Prognostic factors were T4 (p = 0.015), involved nodes (p = 0.035), M+ (p = 0.01), SBR III (p = 0.0001) and HER2+++ (p = 0.001). CONCLUSION: Contrary to breast cancer in women, our study showed that Tunisian MBC have positive hormone receptors in all cases. Although the overexpression of HER2 was low (8.33%) and there was no case of triple negative MBC, the prognosis was poor because of T4 stage, involved nodes, SBR III and distant metastases. Show more

Keywords: Male breast cancer, survival, prognosis

DOI: 10.3233/BD-220073

Citation: Breast Disease, vol. 42, no. 1, pp. 271-275, 2023

Authors: Hassan, Zaman Hussein | Auda, Ibtesam Ghadban | Mahdi, Likaa Hamied

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer is the most fatal type of cancer in women worldwide. Many chemotherapeutics targeted breast cancer however, they have frightening side effects. One method of controlling cancer cell growth is targeting apoptosis. OBJECTIVE: This study aimed to induce apoptosis in breast cancer cells by purifying L-asparaginase from human breast milk Lactobacillus reuteri isolates via inhibition of Caspases 8 and 9. METHODS: The best L. reuteri isolates producing L-asparagine with the highest enzyme activity were identified from human breast milk and chosen for L-asparaginase purification. The MTT cell viability assay used for measure the toxicity of …the enzyme. Breast cancer cell line was used to study the effect of the enzyme on the caspase 8 and caspase 9 gene expression. RESULTS: The MTT cell viability assay showed the inhibition rates ranged between 30% and 80%, of cell death, occurred when 3.125, 6.25, 12.5, 25, 50, and 100 μg/ml of the enzyme used and IC50 was 4.305 μg/ml. The breast cell lines were treated with the enzyme at a concentration of IC50 value. The Cas8 and Cas9 genes expression in L-asparagine treated breast cancer cell line at a concentration of IC50 value were upregulated (the fold of gene expression are 2.071 and 1.197 respectively). CONCLUSIONS: Breast milk L. reuteri L-asparaginase induces apoptosis via Cas8 and Cas9 upregulation in the breast cancer cell line. L. reuteri L-asparaginase treatment may be the hopeful approach for the management of breast cancer. Furthermore, the results may highlight the fact that the presence of L-asparaginase-producing L. reuteri isolates in human breast milk may aid in breast cancer improvement or even prevention. Show more

Keywords: Caspases 8, Caspases 9, L-asparagine, Lactobacillus reuteri , breast cancer cell line

DOI: 10.3233/BD-220074

Citation: Breast Disease, vol. 42, no. 1, pp. 277-283, 2023

Authors: Tuan, Hoang Thanh | Ngoc, Nguyen Anh | Ai, Luu Dang | Van Luat, Nguyen

Article Type: Case Report

Abstract: Breast deformities caused by silicone injections affect aesthetic results and cause irreversible complications in patients. In the treatment, it is necessary to entirely remove silicone particles and infiltrated and fibrous breast tissues. The maximal preservation of healthy breast tissues is also critical. This report presents a case of severe breast deformities as complications 20 years after silicone injections at an unreputable aesthetic center. During the surgery, the authors separately removed fluid (silicone) masses and reconstructed mammary glandular tissues. Breast reconstruction was performed by the anchor breast lift along with the functional preservation of the nipple-areola complex and the superomedial pedicle. …The surgery entirely addressed complications after injecting a large amount of silicone. 6 months postoperatively, the surgical outcomes were satisfactory. The surgical excision should be done to remove silicone-infiltrated tissues as much as possible before the reconstructive surgery. The combination of radical surgical excision and reconstructive surgery using the anchor breast lift as a single-stage procedure brought good aesthetic results. Show more

Keywords: Breast reconstruction, complications, deformity, gigantomastia, silicone injection, surgery

DOI: 10.3233/BD-230021

Citation: Breast Disease, vol. 42, no. 1, pp. 285-290, 2023

Authors: El Battioui, Fadoua | El Malki, Fatima | Barrijal, Said

Article Type: Research Article

Abstract: This article is a cross-sectional study of 216 women undergoing adjuvant hormone therapy for breast cancer in two oncology centers in northern Morocco. Quality of life (QoL) was assessed using the Functional Assessment of Cancer Therapy (FACT) questionnaire and its endocrine subscale (ES). The relationship between rural–urban status in our sample and QoL was assessed by linear regression analysis using sociodemographic and clinical variables as covariates. Our results show that physical and functional well-being are significantly (p < 0.001) higher in rural areas (24 and 29, respectively) than in urban areas (16 and 19, respectively), while social and emotional well-being …are significantly (p < 0.001) higher in urban areas (22 and 21, respectively) than in rural areas (15 and 16, respectively). However, there was no significant difference (p = 0.097) between rural and urban breast cancer survivors regarding endocrine symptom burden. Regarding the effect of sociodemographic and clinical factors on overall HRQOL of breast cancer survivors, hormone type was shown to have a significant effect on overall HRQOL (FACT-ES) of rural and urban breast cancer survivors (𝛽 = +0.849 and 𝛽 = +0.678, respectively). A similar effect was observed for ES (𝛽 = +0.896 and 𝛽 = +0.180, respectively). In contrast, other factors (age, marital status, economic status, menopausal status, type of surgery) did not have a significant effect on HRQOL (FACT-ES) or ES. The study highlighted the need for increased psychosocial supportive care efforts for rural breast cancer survivors to improve their QoL. Show more

Keywords: Urban, rural, quality of life, breast cancer, survivor, hormonal therapy

DOI: 10.3233/BD-230012

Citation: Breast Disease, vol. 42, no. 1, pp. 291-298, 2023

Authors: Yan, Zhiyan | Ngeow, Joanne | Allen, John | Lim, Geok Hoon

Article Type: Research Article

Abstract: INTRODUCTION: Ductal carcinoma in situ (DCIS) in young women is rare and not well studied. Since they do not qualify for mammographic screening, they are more likely to present with symptoms. Young women have also been associated with poorer outcomes, but it is unknown whether presentation mode affects outcome. We aimed to compare characteristics of DCIS patients <40 years of age presenting with symptoms versus those without, and determine whether presentation mode affects recurrence. METHODS: Pure DCIS patients aged <40 years were retrospectively analyzed. Clinical presentation, pathology and recurrence data were collected. Statistical analysis was performed …to investigate the correlation of presentation mode with outcomes. RESULTS: 40 patients with 41 cases were included. The mean age at diagnosis was 32.3 years (range 17–39). 73.2% and 26.8% presented with symptoms or abnormal imaging respectively. Of the cases who presented with symptoms, 86.7%, 10.0% and 3.3% had palpable lump, nipple discharge or breast pain, respectively. The average tumor size was 22.0 mm (range 2.0–86.9) and 12.2 mm (range 3–25) for patients who presented with symptoms and non-symptomatic group, respectively. Cases presenting with symptoms were statistically associated with higher grade (p = 0.0090). On median follow-up of 85 months, there were 3 (7.3%) recurrences, which were not statistically associated with presentation mode. CONCLUSION: Young women with DCIS tend to present with symptoms, with breast lump as the commonest symptom. Symptomatic patients tend to be associated with grade III tumours, compared to non-symptomatic patients. On long-term follow-up, mode of presentation was not statistically associated with recurrence. Show more

Keywords: Breast cancer, DCIS

DOI: 10.3233/BD-230018

Citation: Breast Disease, vol. 42, no. 1, pp. 299-303, 2023

Authors: Gozalishvilli-Boncheva, Anna | Gonzalez-Espinoza, Iván R. | Castro-Ponce, Abraham | Bravo-Gutiérrez, Omar A. | Juárez-Salazar, Gabriela | Montes-de-Oca-Moreda, Ricardo I. | Aguirre-Flores, Evelyn | Coyotl-Huexotl, Marisela | Orozco-Luis, Juan | Chiquillo-Domínguez, Mariana | Garibay-Díaz, Julio C. | Aranda-Claussen, Jorge E. | Ponce-de-León, Eric A. | Sánchez-Sosa, Sergio | Sabaté-Fernández, Mónica | García-Reyna, Juan C. | Cordero-Vargas, Carlos | González-Blanco, María J. | Aguilar-Priego, José M. | Sánchez-Fernández, Norberto J. | Cortés-García, Carlos A. | González-Lozada, Laura E. | Miguel-Cruz, Enrique | Ceja-Utrera, Francisco J. | Hernández-Garcia, Maria S. | Piña-Vazquez, Mirielly | Aguilar-Jiménez, Carmen

Article Type: Research Article

Abstract: Breast cancer is the most incidental and deadly neoplasm worldwide; in Mexico, very few epidemiologic reports have analyzed the pathological features and its impact on their clinical outcome. Here, we studied the relation between pathological features and the clinical presentation at diagnosis and their impact on the overall and progression-free survival of patients with breast cancer. For this purpose, we collected 199 clinical records of female patients, aged at least 18 years old (y/o), with breast cancer diagnosis confirmed by biopsy. We excluded patients with incomplete or conflicting clinical records. Afterward, we performed an analysis of overall and progression-free survival …and associated risks. Our results showed an average age at diagnosis of 52 y/o (24–85), the most common features were: upper outer quadrant tumor (32%), invasive ductal carcinoma (76.8%), moderately differentiated (44.3%), early clinical stages (40.8%), asymptomatic patients (47.8%), luminal A subtype (47.8%). Median overall survival was not reached, but median progression-free survival was 32.2 months (29.75–34.64, CI 95%) associated risk were: clinical stage (p < 0.0001) symptomatic presentation (p = 0.009) and histologic grade (p = 0.02). Therefore, we concluded that symptom presence at diagnosis impacts progression-free survival, and palpable symptoms are related to an increased risk for mortality. Show more

Keywords: Breast cancer, Mexican population, clinical presentation, prognostic impact

DOI: 10.3233/BD-230025

Citation: Breast Disease, vol. 42, no. 1, pp. 305-313, 2023

Authors: Chandra, Smita | Bhasin, Sanya | Saini, Sunil

Article Type: Case Report

Abstract: ER− /PR+ is a controversial subtype and is not formally recognised as molecular subtype of breast carcinoma. Few studies concluded that this subtype does not exist and is due to technical errors, however, in contrast others consider it to be distinct entity with different response to therapy and clinical outcome. It is also essential to know whether this subtype shows any distinct histomorphological features or prognosis. Therefore, the present two cases of controversial subtype ER− /PR+ breast cancer is being reported with both the cases showing neuroendocrinal differentiation.

Keywords: Breast carcinoma, ER−, PR+, molecular subtype

DOI: 10.3233/BD-230039

Citation: Breast Disease, vol. 42, no. 1, pp. 315-318, 2023

Authors: Valente, Maria Stella Vasconcelos Sales | Mota, Fábio Augusto Xerez | Ricciardi, Bárbara Bezerra | de Carvalho Borges, Bárbara Matos | de Lucena Feitosa, Enzo Studart | de Aquino, Pedro Lucena | Valente, Paulla Vasconcelos

Article Type: Case Report

Abstract: INTRODUCTION: Desmoid fibroma (DF) is a disorder characterized by strong clonal proliferation of myofibroblasts and fibroblasts. We describe a case of DF that mimicked a breast tumor, along with a review of the literature on the clinical manifestation, diagnostic process, and course of therapy for this combative disease. CASE REPORT: A 34-year-old female patient with breast lump at the junction of the upper quadrants of the left breast. After the diagnosis of DF, it was decided to perform a sectorectomy of the left breast associated with post-quadrant reconstruction, with immunohistochemistry and findings compatible with DF. DISCUSSION: …Clinically manifests as a solid mass that is often painless and occasionally adherent to the chest wall. A treatment strategy should be idealized for each patient. Thus, there is the possibility of performing radical surgery for resection and/or radiotherapy, and surgery may be followed by radiotherapy. Show more

Keywords: Breast, desmoid fibroma, neoplasms

DOI: 10.3233/BD-230028

Citation: Breast Disease, vol. 42, no. 1, pp. 319-323, 2023

Authors: Brouwer de Koning, I.M. | van Heusden, H.C. | Mol, S.J.J. | Rots, M.L. | Draaisma, W.A. | Bosscha, K.

Article Type: Case Report

Abstract: BACKGROUND: Fibroadenomas are the most common benign breast lesions in women. They present as a unilateral mass and can rapidly enlarge in size through hormonal changes. Fibroadenomas could be classified as small or giant, and as simple or complex. They are classified as ‘giant’ when the size exceeds 5 cm and/or weight 500 gram; and as ‘complex’ if one of the following characteristics is present: cysts with a size >3 mm, epithelial calcifications, sclerosing adenosis and papillary apocrine metaplasia. Giant fibroadenomas can cause compression of surrounding breast tissue or breast asymmetry, requiring surgical excision in order to preserve a normal …breast shape. CASE: A 26-year-old pregnant woman was referred with a palpable mass of her right breast. The mass rapidly increased in size to a diameter of 13 cm during the second trimester of her pregnancy. A tru-cut biopsy confirmed a fibroadenoma. The rapid growth and compression of normal breast tissues indicated a lumpectomy during her pregnancy. The mass was easily excised without any consequences for the pregnancy. Pathological examination showed a complex giant fibroadenoma. CONCLUSION: A unique case of a pregnant woman with rapid progression of a fibroadenoma that met the criteria of a complex and giant fibroadenoma, was presented. This case emphasizes the importance of timely surgical intervention, even during pregnancy, to prevent permanent breast tissue damage. Show more

Keywords: Breast, giant fibroadenoma, complex fibroadenoma, pregnancy, phyllodes tumor

DOI: 10.3233/BD-230030

Citation: Breast Disease, vol. 42, no. 1, pp. 325-330, 2023

Authors: van den Biggelaar, Yannick J.P.G. | Kuiper, Josephina G. | van der Sangen, Maurice J.C. | Luiten, Ernest J.T. | Siesling, Sabine | van Herk-Sukel, Myrthe | Voogd, Adri C. | Mesters, Ilse

Article Type: Research Article

Abstract: BACKGROUND: Hormonal receptor (HR) positive breast tumors are common. Adjuvant hormonal therapy (AHT) with tamoxifen or Aromatase Inhibitors (AIs) is beneficial depending on the stage of the tumor. Despite the fact that AHT has been shown to improve survival and recurrence, Dutch adherence rates, which were mostly dependent on Tamoxifen prescriptions until 2006, plummeted from 80% after one year to 50% after five years. Nonadherence with AHT reduces its effectiveness. This research presents more recent adherence statistics (from 2006 to 2016), on a larger sample (7,996 vs 1,451), as well as factors that influence AHT adherence. In addition to tamoxifen …data, AIs are now included. OBJECTIVE: As low use of adjuvant endocrine therapy is a potentially important and modifiable risk factor for poor outcome, it is important to monitor the rate as an indicator of women’s burden of disease and the direction of adherence trends. METHODS: The Netherlands Cancer Registry (NCR) was used to find women with early-stage breast cancer who started AHT within a year of surgery and were linked to the PHARMO Database Network (n = 8,679). The Kaplan-Meier approach was used to measure AHT adherence five years after treatment was started, with a 60-day gap between refills as our primary outcome. Furthermore, the Medication Possession Rate (MPR) was determined using a cutoff of ≥80%. Analysis was performed on influential factors of adherence. RESULTS: The proportion of persistent women declined over time to reach 46.6% at the end of the fifth year and 53.3% of the women had a MPR ≥80% during the fifth year. Older and being diagnosed in 2006-2010 were associated with AHT adherence. CONCLUSION: Dutch 5-year AHT adherence appears to remain poor. Improving AHT adherence in HR+ breast cancer survivors is a critical medical need. Show more

Keywords: Breast cancer, compliance, survival, survival analysis, adjuvant hormonal therapy

DOI: 10.3233/BD-230024

Citation: Breast Disease, vol. 42, no. 1, pp. 331-339, 2023

Authors: Dharmarajan, Adarsh | Gopinath, Vipin | Keloth Nayanar, Sangeetha | Velandi Kunnummal, Sobhith | Balasubramanian, Satheesan | Roshan Valiyaparambil Gopi, Deepak

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer is the most common cancer among females, with an incidence of 6,41,000 cases annually. The genetic makeup of the individuals, ethnicity, geographical location, lifestyle, and BMI are some well-described factors associated with breast cancer. It is well known that pathogenic variants in BRCA1 and BRCA2 are associated with a majority of hereditary breast cancer. Genome-wide association studies (GWAS) have identified more than 80 germline susceptibility loci responsible for hereditary breast cancer. METHODS: In the present study, analysis of 94 genes associated with hereditary cancer was performed using next generation sequencing (NGS) in twelve patients having …breast cancer and suspected with hereditary association. RESULTS: Four out of twelve (33%) patients harbored pathogenic mutation of the BRCA1 gene. Two patients was identified p. E23Vfs*17 mutation in BRCA1, one patient had p.Glu1580Gln in BRCA1, and a novel frameshift variant p.T1456Ifs*9(c.4367Cdel) in one patient. CONCLUSION: In the present study, out of four detected mutations in the BRCA1 gene, three were known and one was a novel BRCA1 mutation. It is advised to perform NGS-based genome sequencing to identify the genetic predisposition in breast cancer patients. Show more

Keywords: Hereditary breast Cancer, BRCA1, NGS

DOI: 10.3233/BD-220002

Citation: Breast Disease, vol. 42, no. 1, pp. 341-347, 2023

Authors: Fernández-Laguna, Clara Luz | Maray, Ivan | Macia-Rivas, Lola | Álvarez-Asteinza, Cristina | Fernández-Lastras, Sergio | Velasco Durántez, Veronica | Carbajales Álvarez, Mónica | Lozano-Blázquez, Ana

Article Type: Research Article

Abstract: BACKGROUND: Metastatic breast cancer (MBC) is incurable. Systemic therapy is the standard treatment; however, an optimal sequence of chemotherapy has not been established. OBJECTIVE: Evaluating effectiveness and safety of eribulin in MBC treatment and comparing the results obtained with published literature. METHODS: Observational, descriptive and retrospective study of patients with MBC treated with eribulin from 01/12/2015 to 30/10/2021. Effectiveness was analysed using Kaplan–Meier-survival-curves, for the overall number of patients treated and stratified by treatment line. Safety was measured according to adverse events (AE) based on CTCAE v5.0. Data analysis was performed using R v4.0.1. …RESULTS: They were included in this study 53 women who received eribulin (median age 58 years). Comparison of median survival from this study versus published data were: progression-free-survival (PFS) 3 (IC95%: 3–4) versus 3.7 months and overall-survival (OS) 8 (IC95%: 3–4) versus 13.2 months for the overall number of patients. For the 1–3 line treatment group, PFS was 6 (IC95%: 3-NA) and OS was 15 (IC95%: 6-NA). There were 322 AEs, the most frequent being blood disorders 16% (52), general disorders 12% (38), and gastrointestinal disorders 12% (38). CONCLUSIONS: The median PFS was similar to that reported previously, with lower OS. There was a tendency to achieve better results when eribulin was used earlier. Eribulin is a less well-tolerated drug than published literature. Show more

Keywords: Eribulin, metastatic breast cancer, effectiveness, safety, Real world data

DOI: 10.3233/BD-230031

Citation: Breast Disease, vol. 42, no. 1, pp. 349-360, 2023

Authors: Bagher Hosseini, Najmeh | Moosapour, Sara | Fakhar, Haniyeh Bashi Zadeh | Nazari, Afshin Ryan | Hasehmi, Maryam Omrani | Hadavand, Fatemeh | Seraj, Mohammad | Akbari, Mohammad-Esmaiel

Article Type: Systematic Review

Abstract: INTRODUCTION: Studies in recent years have shown that parental environmental experiences can affect their offspring’s risk of breast cancer (BC). We assessed the effect of different paternal factors on BC risk in offspring by reviewing the existing literature. METHOD: This systematic review followed the Joanna Briggs Institute’s (JBI) method for systematic reviews of qualitative evidence. The primary keywords were searched in reliable databases such as PubMed, Google Scholar, Elsevier, SID, and Wiley in English until 31 December 2021. Two authors independently examined the articles in terms of inclusion criteria and quality assessment of the articles. RESULTS: …Of the 438 studies, 19 met the inclusion criteria of this systematic review and were included in the study. Paternal factors investigated in these studies included age at delivery, diet, occupational exposures, occupation type and education. The reported relationships between these factors and breast cancer varied among different studies. CONCLUSION: Studies considered in this article show that fathers’ age at the time of delivery of the child, dietary habits, overweight and occupational factors can affect the incidence of BC risk in the next generation. Show more

Keywords: Paternal, breast cancer, environmental factors, offspring

DOI: 10.3233/BD-220062

Citation: Breast Disease, vol. 42, no. 1, pp. 361-374, 2023

Authors: Ng, Ruey Pyng | Allen, John C. | Chia, Yen-Yen | Lim, Geok Hoon

Article Type: Research Article

Abstract: INTRODUCTION: In breast cancer patients undergoing mastectomy without reconstruction, an external breast prosthesis could aid patients’ recovery, improve body image and confidence by helping to regain a symmetrical chest appearance when dressed. However, external breast prosthesis preferences among Asian breast cancer patients were not widely studied. We aimed to compare patients’ experience with the conventional commercially manufactured standard-sized (small, medium, large, extra-large) bra and prosthesis versus customized hand-knitted external breast prosthesis with patient’s bra after unilateral mastectomy at a tertiary hospital. This is the first such study in Asian women, to our knowledge. METHODS: In this prospective study, …participants used the conventional bra-prosthesis followed by the customized one consecutively, each for at least 3 months before they were administered an identical questionnaire at 3 and 6 months respectively. The questionnaire assessed the patients’ experience with the prosthesis on the aspects of comfort, body image and satisfaction etc. Patients were also invited for in-depth interviews. RESULTS: Of 155 eligible patients, 148 patients participated with a response rate of 95.5%. 99 (67%) participants preferred the customized prosthesis, while 38 (25.7%) did not. 11 (7.4%) participants were undecided. Seventeen participants underwent in-depth interviews until data saturation on major qualitative themes was achieved. More patients experienced excessive sweating (p  < 0.0001), greater discomfort (p  = 0.0195) and higher rates of prosthesis dislodgement (p  = 0.0269) with the conventional bra-prosthesis. CONCLUSION: Customized external breast prostheses could be an alternative to the conventional ones for breast cancer patients with mastectomy, with additional benefits of less sweating, more comfort and less dislodgement perceived. Show more

Keywords: Body image, breast cancer, breast prosthesis, mixed method evaluation, post-mastectomy, satisfaction

DOI: 10.3233/BD-230040

Citation: Breast Disease, vol. 42, no. 1, pp. 375-382, 2023

Authors: Patrianagara, Arga | Hwei, Lie Rebecca Yen

Article Type: Systematic Review

Abstract: BACKGROUND: Endoscopy-assisted breast conserving surgery (E-BCS) was developed over 10 years ago as a method for breast cancer treatment with the potential advantage of less noticeable scarring. However, the evidence supporting its superiority over conventional breast conserving surgery (C-BCS) remains unclear. OBJECTIVE: This study aims to compare the outcomes of E-BCS and C-BCS for the treatment of early breast cancer. METHODS: A comprehensive search for relevant articles was performed using specific keywords in Medline, Scopus, ClinicalTrials.gov, and Cochrane Library PubMed up to October 17th, 2022. Clinical trials that compared E-BCS with C-BCS in early breast cancer …patients were collected. RESULTS: Our analysis of nine studies revealed that E-BCS was associated with shorter incision length [Mean Difference (MD) −6.50 cm (95% CI −10.75, −2.26), p = 0.003, I 2 = 99% ] and higher cosmetic score [MD 2.69 (95% CI 1.46, 3.93), p < 0.0001, I 2 = 93% ] compared with C-BCS. However, E-BCS had a longer operation time [MD 35.95 min (95% CI 19.12, 52.78), p < 0.0001, I 2 = 93% ] and greater drainage volume [MD 62.91 mL (95% CI 2.55, 123.27), p = 0.04, I 2 = 79% ]. There was no significant difference in blood loss volume (p = 0.06), drainage duration (p = 0.28), postoperative complications (p = 0.69), or local recurrence (p = 0.59) between the two groups. CONCLUSION: Our study suggests that E-BCS offers a shorter incision length and better cosmetic outcome compared with C-BCS in the treatment of early breast cancer. However, E-BCS requires a longer operation time and has greater drainage volume. Further studies are needed to confirm these findings. Show more

Keywords: Endoscopy, minimal-invasive, surgery, breast cancer, oncology

DOI: 10.3233/BD-230023

Citation: Breast Disease, vol. 42, no. 1, pp. 383-393, 2023

Authors: Jha, Chandan Kumar | Sinha, Upasna | Sinha, Mainak | Singh, Prashant Kumar

Article Type: Case Report

Abstract: Lymphedema (LE) in a breast cancer patient usually results from axillary lymph node dissection, sentinel lymph node biopsy, and/or axillary radiotherapy. Although lymphatic obstruction and consequent LE can occur due to axillary lymph node involvement, such presentation in breast cancer patients has rarely been reported. This report describes the case of a 50-year-old lady with right breast carcinoma who presented with right upper limb lymphedema. Surprisingly, she did not have any bulky axillary lymphadenopathy that could have accounted for lymphedema of the upper limb, but a suspicious breast mass was present on clinical examination. Diagnosis of breast cancer on clinical …examination can be challenging in such patients due to breast edema and careful imaging of the breast and axilla with appropriate imaging tools (mammogram, ultrasound, MRI, PET mammography) should be resorted to before excluding malignancy. Lymphoscintigraphy confirmed the findings of lymphedema in the right upper limb and revealed uptake in the epitrochlear lymph nodes of the contralateral limb suggesting that she might had pre-existing widespread “subclinical lymphedema” which presented as “clinical lymphedema” in right upper limb after axillary lymph node/lymphatic involvement by right breast carcinoma. Show more

Keywords: Breast carcinoma, lymphedema of the upper limb, axillary lymphadenopathy, lymphoscintigraphy

DOI: 10.3233/BD-230022

Citation: Breast Disease, vol. 42, no. 1, pp. 395-399, 2023

Authors: Khaldi, Oumeima | Ghalleb, Montassar | Jallali, Amani | Fenniche, Insaf | Somai, Mehdi | Daoud, Fatma | Boussema, Fatma | Kammoun, Salma | Hamza, Khadija | Ayadi, Med Ali | Dhieb, Tarek

Article Type: Case Report

Abstract: BACKGROUND: Amyloidosis is an uncommon disorder characterized by the extracellular deposition of amorphous and insoluble proteins in an abnormal fibrillary configuration. Mammary amyloidosis is an unusual and easily overlooked diagnosis with an ambivalent presentation that could mimic breast cancer. CASE REPORT: We here report the case of 60-year-old Caucasian woman who presented to our surgical oncology department for clinically and radiologically suspicious breast mass. A fine needle biopsy was irrelevant, so we performed a lumpectomy. Final histology revealed an amyloid deposit and further workup was consistent with nodular cutaneous and breast AL amyloidosis associated with Sjögren’s syndrome. …CONCLUSION: Although rare, an awareness of the clinicopathologic characteristics of this easily overlooked entity is of great importance for breast surgeons. Show more

Keywords: Breast amyloidosis, cutaneous amyloidosis, Sjögren syndrome, breast cancer

DOI: 10.3233/BD-230006

Citation: Breast Disease, vol. 42, no. 1, pp. 401-405, 2023

Authors: Luís, Carla | Fernandes, Rute | Dias, João | Pereira, Deolinda | Firmino-Machado, João | Baylina, Pilar | Fernandes, Rúben | Soares, Raquel

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer (BC) and obesity are two closely associated pathologies with increasing incidence and mortality rates. Bilateral Breast Cancer (BBC) displays a low incidence rate within BC and obesity represents a major risk factor. OBJECTIVE: The aim of this study is to analyzed BBC clinicopathological features distribution and determine the potential influence of obesity in BBC in these same features and overall survival. METHODS: Clinicopathological information was obtained from 42 cases of women with BBC diagnosed in IPO-Porto. To evaluate the frequency distribution of the clinicopathological data, a chi-square goodness of fit test was performed …for BBC cases. A chi-square test of independence was applied for BMI stratification. Cox regression was performed for overall survival. Statistical significance was set at p -value < 0.05. RESULTS: Distribution of BBC clinicopathological features was found to be statistically significant in family history (p -value < 0.001), BBC type (p -value < 0.001), stage (p -value = 0.005), differentiation grade (p -value < 0.001), receptor expression (p -value < 0.001) and histological type (p -value = 0.031). In comparison to the statistical expected results, we observed an increased cases of absence of family history and less cases of metachronous BBC. Histological types between tumours of BBC were mostly concordant. All cases presented concordant receptor expression. Analysis stratified by BMI revealed that obese women were diagnosed later, although without statistical significance. All obese women presented poor differentiation grade (n = 6). Overweight patients display a tendency to a better overall survival with lower tumour stages and lower differentiation grades. CONCLUSIONS: Our results reveal the same receptor expression between contralateral tumours. Also, most tumours share the same histological type. When stratified by BMI, we observed a tendency for overweight women to have improved overall survival. Show more

Keywords: Bilateral breast cancer, obesity, obesity paradox, BMI, retrospective study

DOI: 10.3233/BD-230014

Citation: Breast Disease, vol. 42, no. 1, pp. 407-414, 2023

Authors: van Cappellen-van Maldegem, Sandra J.M. | Hoedjes, Meeke | de Boer, Michiel R. | Nijman, Inge L. | van Valenberg, Henrike M.W. | Seidell, Jacob C. | van de Poll-Franse, Lonneke V. | Buffart, Laurien M. | Mols, Floortje | de Rooij, Belle H.

Article Type: Research Article

Abstract: BACKGROUND: As physical inactivity and poor sleep quality may impose additional risk for cancer recurrence and overall mortality in postmenopausal breast cancer (PMBC) survivors, it is important to gain insight into the effect of the COVID-19 pandemic on their physical activity (PA) and sleep level. OBJECTIVE: This study aimed to assess the course of their physical activity (PA) and sleep throughout governmental measures against COVID-19 during 12 months of the COVID-19 pandemic. METHODS: PMBC survivors (n = 96) wore an ActiGraph wGT3X-BT for seven consecutive days at 12 and 18 months after diagnosis and additional …measurements were taken after onset of the second (partial) COVID-19 lockdown. Longitudinal data was categorized into four timepoints: before onset of COVID-19 (T1), during the initial lockdown (T2), in between initial and second lockdown (T3), and during the second lockdown (T4). General linear mixed effects models assessed differences in moderate-to-vigorous physical activity (MVPA) per day, total minutes of PA per day, average acceleration, intensity gradient, sleep efficiency, and sleep duration over time. RESULTS: Levels of MVPA per day before COVID-19 were low (Median = 20.9 min/day (IQR = 10.8;36.2)), and time spent physically active was most often in light intensity, which remained stable throughout the pandemic. Sleep duration (Median = 442.8 min/night (IQR = 418.3;478.0)) and efficiency (85.9% (IQR = 79.6;88.4)) was sufficient before COVID-19 and showed stability over time. CONCLUSIONS: Low levels of PA with mostly light intensity, and adequate sleep efficiency and duration were observed before COVID in PMBC survivors. This was not further affected by COVID-19 governmental measures. Show more

Keywords: Physical activity, sleep, breast cancer survivors, COVID-19, accelerometer

DOI: 10.3233/BD-230049

Citation: Breast Disease, vol. 42, no. 1, pp. 415-427, 2023

Authors: Nicolau, Pau | Masó, Paula | Argudo, Núria | Jiménez, Marta | Martínez, Ana Isabel | Vázquez, Ivonne | Comerma, Laura | Vernet-Tomás, Maria

Article Type: Research Article

Abstract: BACKGROUND: The p53 mutation in breast cancer confers a worse prognosis and is usually associated with p53 overexpression (p53+) on immunohistochemistry. Previous studies have shown that p53+ tumors could be associated with low axillary tumor burden (ATB). OBJECTIVE: We aimed to evaluate the association between p53+ and ATB in a large series of breast cancers as an aid to personalizing axillary surgical treatment. METHODS: We retrieved 1762 infiltrating breast carcinomas from our database that were treated with upfront surgery in Hospital del Mar from 2004 to 2018. We compared p53+ and p53-negative (p53-) tumors in terms …of the percentage of cases with high ATB and overall survival. This comparison was made overall and for each immunophenotype. RESULTS: Overall, 18.7% of breast tumors were p53+. High ATB was less common in p53+ tumors than in p53- tumors in the luminal B-Her2-negative immunophenotype (6.2% versus 16.9%, respectively, P = 0.025), but not in the other immunophenotypes or overall. Overall survival was worse in patients with p53+ breast cancer (P = 0.002). CONCLUSION: p53+ breast cancers were associated with worse overall survival. However, low ATB was more common in these tumors than in p53- tumors in the luminal B-Her2-negative subtype. Information on p53 expression could be of use to predict ATB in some breast cancer tumors. Show more

Keywords: p53, axillary tumor burden, breast cancer, immunophenotypes

DOI: 10.3233/BD-230013

Citation: Breast Disease, vol. 42, no. 1, pp. 429-435, 2023

Authors: Goldoost, Solmaz | Zarredar, Habib | Asadi, Milad | Shirvaliloo, Milad | Raeisi, Mortaza

Article Type: Research Article

Abstract: AIM: In the present study, we sought to explore potential differences in the expression and promoter methylation of mitogen-activated protein kinase 1 (MAPK1) between tumor and marginal cells of breast cancer lesions. METHODS: A total of 50 randomly selected patients with breast cancer (BCa) undergoing needle biopsy were enrolled. Clinical specimens containing both tumor and marginal cells were collected and preserved. After DNA extraction using specific primers, MAPK1 mRNA and promoter methylation were measured with spectrophotometry at 260/280 nm absorption wavelengths. To deliver a comparative analysis, data from The Cancer Genome Atlas (TCGA) program regarding breast cancer (BRCA), …were downloaded from Xena Functional Genomics Explorer and separately analyzed. The suitability of MAPK1 expression and promoter methylation as biomarkers for BCa was analyzed with receiver operating characteristic (ROC) curves. RESULTS: We found a positive correlation between tumor stage and MAPK1 expression (P -value: 0.029) in BCa. Likewise, MAPK1 expression was significantly associated with lymph node metastasis (P -value: 0.018). There was a significant difference in the expression of MAPK1 mRNA between tumor and marginal cells of BCa and BRCA (P -value < 0.001). However, we did not find any statistically significant difference in MAPK1 promoter methylation between tumor and marginal cells of both BCa and BRCA. With an area under the curve (AUC) of 0.71, the diagnostic accuracy of MAPK1 expression in BCa and BRCA was validated. However, MAPK1 promoter methylation was not found to be a suitable biomarker. CONCLUSION: Our findings suggest that while MAPK1 expression, might be a promising biomarker for evaluating oncogenic activity in patients suspected of BCa. We were not able to detect a prognostic/diagnostic role for MAPK1 promoter methylation. Show more

Keywords: Breast cancer, mitogen-activated protein kinase 1, MAPK1, ERK2, promoter methylation

DOI: 10.3233/BD-230001

Citation: Breast Disease, vol. 42, no. 1, pp. 437-445, 2023