Breast Disease - Volume 43, issue 1

Authors: Sahin, Seniha Irem | Balci, Serdar | Guler, Gulnur | Altundag, Kadri

Article Type: Research Article

Abstract: BACKGROUND: Male breast cancer (MBC) accounts for one percent of all breast cancers. Due to the lack of awareness and routine screening programs, most patients present with systemic disease at the time of diagnosis with low overall survival. OBJECTIVES: This study aims to investigate the prognostic factors of male breast cancer and its correlation with established prognostic parameters and patient outcomes. METHODS: Thirty-eight male breast cancer patients are identified from the MKA Breast Cancer Clinic database, and their corresponding clinical and pathological characteristics are obtained. Cut-off values of 1% and 10% are applied to further classify …ER and PR results. RESULTS: Older men are more likely to develop MBC than younger men and are more likely to have spread to axillary lymph nodes. Invasive ductal carcinoma is a more common histologic type in MBC. All the tested patients have ER and PR positivity. Distant metastasis developed in 17/38 (44.7%) patients. Bone metastasis is seen commonly in metastatic MBC. CONCLUSIONS: According to our cohort, MBC is seen in older males, presents in later stages, and shows hormone receptor positivity and a tendency to bone involvement. MBC is a heterogenous but distinct biological entity requiring a specific clinical and pathological approach. Show more

Keywords: Male, breast cancer, prognostic parameters, survival

DOI: 10.3233/BD-230050

Citation: Breast Disease, vol. 43, no. 1, pp. 1-8, 2024

Authors: Triki, Meriam | Zghal, Mouna | Ayed, Houda Ben | Makni, Saadia | Bouhamed, Maroua | Fendri, Semi | Charfi, Slim | Boudawara, Tahya | Mellouli, Manel

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer (BC) patients’ diagnosis and management was affected by a global reorganization after the Coronavirus disease 2019 (COVID-19). Our study aimed to assess the impact of the pandemic on the pathological stage of newly diagnosed patients with BC compared to pre-pandemic and to identify predictive factors of tumor advanced stage. METHODS: Pathological records of all consecutive newly operated BC patients between March 2020 and December 2021 were reviewed retrospectively. Clinical and pathological prognostic factors of BC were collected and compared between pre-pandemic and pandemic periods. Then, predictive factors of tumor advanced stage were identified. …RESULTS: Of the 225 cases included in the analysis, 98.7% were females and 1.3% were males. The median time from first histological diagnosis to first surgical treatment was enlarged by 42 days with a significant difference between the two periods (p = 0.002). Newly diagnosed BC patients during the COVID-19 pandemic were operated at a more advanced stage (54.1% vs 36.2%, p = 0.007), had a greater lymphovascular invasion (p = 0.002), lymph node metastasis (p = 0.015) and are more commonly of IBC NST histological type (p = 0.005). Moreover, multivariate analyses showed that the pandemic period (AOR = 2.28; p = 0.016) and the lympho-vascular invasion (p < 0.001) were independently associated with advanced stage of tumors. CONCLUSION: Our findings proved an increase in alarming rates of advanced stage BC associated with the COVID-19 crisis. These findings support recommendations for a quick restoration of BC screening at full capacity, with adequate prioritization strategies to mitigate harm. Show more

Keywords: Breast cancer, COVID-19, impact, pathology, Stage, Tunisia

DOI: 10.3233/BD-230051

Citation: Breast Disease, vol. 43, no. 1, pp. 9-17, 2024

Authors: Lim, Geok Hoon | Allen, John Carson | Lee, Yien Sien | Teo, Sze Yiun | Lau, Li Ching | Win, Thida | Leong, Lester Chee Hao

Article Type: Research Article

Abstract: INTRODUCTION: Chemotherapy is conventionally offered to non-stage IV breast cancer patients with metastatic nodes. However, the RxPONDER trial showed that chemotherapy can be omitted in selected patients with 1–3 metastatic nodes if the 21-gene assay recurrence score is ≤25. We aimed to investigate if axillary ultrasound can identify this group of patients with limited nodal burden so that they can undergo upfront surgery followed by gene assay testing, to potentially avoid chemotherapy. METHODS: T1-3, node positive, hormone receptor-positive and HER2-negative breast cancer patients ≥50 years old with axillary lymph node dissection (ALND) were reviewed from 2 centres. Patients …with neoadjuvant chemotherapy and bilateral cancers were excluded. Number of ultrasound-detected abnormal axillary nodes, demographic and histological parameters were correlated with the number of metastatic nodes found on ALND. RESULTS: 138 patients were included, 59 (42.8%) and 79 (57.2%) patients had 1–3 and >3 metastatic nodes on ALND respectively. On logistic regression and ROC analysis, the number of ultrasound-detected abnormal nodes was significant (p < 0.001) for predicting limited nodal burden (ROC AUC = 0.7135). Probabilities of <4 metastatic nodes with ultrasound cut-offs of 5, 6 and 8 abnormal nodes were 0.057, 0.026 and 0.005 respectively, with 100% specificity. CONCLUSION: A cut-off of ≤5 ultrasound-detected abnormal nodes can distinguish between patients with limited versus high nodal burden, with high specificity. Hence, incorporating the number of abnormal ultrasound-detected nodes into clinical practice may prove useful in guiding between upfront surgery and gene assay testing or neoadjuvant chemotherapy in this group of patients. Show more

Keywords: Breast cancer, neoadjuvant chemotherapy, axillary ultrasound, genomic assay

DOI: 10.3233/BD-230032

Citation: Breast Disease, vol. 43, no. 1, pp. 19-23, 2024

Authors: Kashyap, Dharambir | Bhattacharya, Shalmoli | Irinike, Santosh | Khare, Siddhant | Das, Ashim | Singh, Gurpreet | Bal, Amanjit

Article Type: Research Article

Abstract: BACKGROUND: Tumour microenvironment (TME) contributes to resistance to anti-cancer drugs through multiple mechanisms including secretion of pro-survival factors by cancer associated fibroblasts (CAFs). In this study, we determined the chemotherapy resistance producing potential of CAFs in molecular subtypes of breast cancer. METHODS: The CAFs were isolated from fresh lumpectomy/mastectomy specimens of different molecular subtypes of breast cancer. The CAFs were cultured and secretome was collected from each breast cancer subtype. Breast cancer cell lines MCF-7, SK-BR3, MDA-MB-231, and MDA-MB-468 were treated with different doses of tamoxifen, trastuzumab, cisplatin, and doxorubicin alone respectively and in combination with secretome of …CAFs from respective subtypes. MTT assay was done to check cell death after drug treatment. Liquid chromatography–mass spectrometry (LCMS) analysis of CAF secretome was also done. RESULTS: MTT assay showed that anti-cancer drugs alone had growth inhibitory effect on the cancer cells however, presence of CAF secretome reduced the anti-cancer effect of the drugs. Resistant to drugs in the presence of secretome, was determined by increased cell viability i.e., MCF-7, 51.02% to 63.02%; SK-BR-3, 34.22% to 44.88%; MDA-MB-231, 52.59% to 78.63%; and MDA-MB-468, 48.92% to 55.08%. LCMS analysis of the secretome showed the differential abundance of CAFs secreted proteins across breast cancer subtypes. CONCLUSIONS: The treatment of breast cancer cell lines with anti-cancer drugs in combination with secretome isolated from molecular subtype specific CAFs, reduced the cytotoxic effect of the drugs. In addition, LCMS data also highlighted different composition of secreted proteins from different breast cancer associated fibroblasts. Thus, TME has heterogenous population of CAFs across the breast cancer subtypes and in vitro experiments highlight their contribution to chemotherapy resistance which needs further validation. Show more

Keywords: Breast cancer, tumor microenvironment, cancer associated fibroblast, secretome, therapy resistance

DOI: 10.3233/BD-230011

Citation: Breast Disease, vol. 43, no. 1, pp. 25-36, 2024

Authors: Abou Shousha, Seham | Osman, Eman M. | Baheeg, Suzan | Shahine, Yasmine

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer tumor microenvironment (TME) is a promising target for immunotherapy. Autophagy, and cancer stem cells (CSCs) maintenance are essential processes involved in tumorigenesis, tumor survival, invasion, and treatment resistance. Overexpression of angiogenic chemokine interleukin-8 (IL-8) in breast cancer TME is associated with oncogenic signaling pathways, increased tumor growth, metastasis, and poor prognosis. OBJECTIVE: Thus, we aimed to investigate the possible anti-tumor effect of neutralizing antibodies against IL-8 by evaluating its efficacy on autophagic activity and breast CSC maintenance. METHODS: IL-8 monoclonal antibody supplemented tumor tissue culture systems from 15 females undergoing mastectomy were used …to evaluate the expression of LC3B as a specific biomarker of autophagy and CD44, CD24 as cell surface markers of breast CSCs using immunofluorescence technique. RESULTS: Our results revealed that anti-IL-8 mAb significantly decreased the level of LC3B in the cultured tumor tissues compared to its non-significant decrease in the normal breast tissues. Anti-IL-8 mAb also significantly decreased the CD44 expression in either breast tumors or normal cultured tissues. While it caused a non-significant decrease in CD24 expression in cultured breast tumor tissue and a significant decrease in its expression in the corresponding normal ones. CONCLUSIONS: Anti-IL-8 monoclonal antibody exhibits promising immunotherapeutic properties through targeting both autophagy and CSCs maintenance within breast cancer TME. Show more

Keywords: Breast cancer, tumor microenvironment, autophagy, cancer stem cells, anti-IL-8 mab

DOI: 10.3233/BD-230052

Citation: Breast Disease, vol. 43, no. 1, pp. 37-49, 2024

Authors: Bouguerra, Fadoua | Belajouza, Samia Kanoun | Mziou, Emna | Zanzouri, Rym | Chahdoura, Hayfa | Tbessi, Sabrine | Bouzid, Nadia | Mrad, Sameh Tebra

Article Type: Research Article

Abstract: AIM: To retrospectively study the therapeutic modalities of primary breast sarcomas in view of the data of a local Tunisian experience. METHODS: It is a monocentric, descriptive, retrospective study including 13 cases of primary breast sarcoma treated over a period of 25 years (1995–2020) in the oncological radiotherapy department of a university hospital in Sousse, Tunisia. RESULTS: In our study, 13 cases of non-metastatic breast sarcomas that has been identified, divided into ten cases of phyllodes sarcomas and three cases of non-phyllodes sarcomas. Surgically, all our patients had a mastectomy. Among them, seven underwent a lymph …node procedure: five underwent axillary lymph node dissection, and two others had primary axillary lymph node biopsy. For the adjuvant treatment, all the patients included in our study received radiotherapy and seven received chemotherapy. Local recurrence occurred on the operative scar in one patient after completion of radiation therapy. Metastatic relapse was described in five patients. The time to onset of metastases varied between two months and five years. Nevertheless, a complete remission was noted in 6 patients with a follow-up varying from four years to 20 years. Two patients were lost to follow-up. CONCLUSION: Breast sarcomas remain a very rare entity of aggressive tumors. The therapeutic approach is poorly codified. For this reason, the therapeutic decision should always be discussed in a multidisciplinary assessment. Show more

Keywords: Sarcoma, breast, surgery, radiotherapy, chemotherapy

DOI: 10.3233/BD-230037

Citation: Breast Disease, vol. 43, no. 1, pp. 51-59, 2024

Authors: Rodriguez, Gabriella F. | Shah, Anuj | Maderal, Andrea D.

Article Type: Case Report

Abstract: BACKGROUND: Tucatinib is a tyrosine kinase inhibitor currently used in salvage therapy for human epidermal growth factor receptor 2 (HER2)-positive breast and colorectal cancer. The use of tucatinib alone or in combination with ado-trastuzumab emtansine (T-DM1) in the treatment of advanced HER2-positive cancers is rapidly expanding. OBJECTIVE/METHODS: We report the case of a 66-year-old female who presented to the dermatology clinic with a one-year history of widespread telangiectasias that began after initiation of combination chemotherapy with tucatinib and T-DM1 for metastatic HER2-positive invasive ductal carcinoma. RESULTS: The patient’s lesions regressed upon cessation of combination therapy and …reappeared in the setting of tucatinib re-initiation, with gradual improvement over the following four months following electrocautery to the affected regions. CONCLUSIONS: We postulate that telangiectasias may be a previously unreported dermatologic side effect of combination treatment with tucatinib and T-DM1. Electrocautery is a safe and effective procedure to reduce the appearance of telangiectasias and improve patient satisfaction during chemotherapy. Show more

Keywords: Tucatinib, trastuzumab, telangiectasia, breast cancer, chemotherapy, dermatology, cutaneous

DOI: 10.3233/BD-230053

Citation: Breast Disease, vol. 43, no. 1, pp. 61-64, 2024

Authors: González Mariño, Mario Arturo

Article Type: Research Article

Abstract: BACKGROUND: Sentinel lymph node biopsy in breast cancer is considered the standard of staging in cases of clinically negative lymph nodes. Its omission in favor of axillary dissection generates significant morbidity. OBJECTIVE: To determine the total number of sentinel node biopsy procedures in breast cancer in Colombia from 2017 through 2020, model and analyze them as if they were performed only in stage I breast cancer patients, and integrate their results into the concepts of quality of medical care. METHODS: Search in a database of the Ministry of Health and Social Protection of Colombia with sentinel …lymph node biopsy codes, and filters of breast cancer and year. Their results are contrasted with the number of cases in stage I of breast cancer. RESULTS: Breast cancer TNM staging was reported in 22154 cases, 3648 stage I. In the same time frame, the number of sentinel lymph node biopsies for breast cancer in Colombia was 1045, 28.64% of the total cases reported in stage I. CONCLUSIONS: Colombia is far from complying with the standard indicator of sentinel lymph node biopsy. It is recommended to concentrate breast cancer cases in hospitals that provide the conditions for its performance. Show more

Keywords: Breast, neoplasms, procedures and techniques utilization, axilla, lymph node excision

DOI: 10.3233/BD-230059

Citation: Breast Disease, vol. 43, no. 1, pp. 65-69, 2024

Authors: Amansyah, Fitran | Prihantono, Prihantono | Hamid, Firdaus | Syamsu, Salman Ardi | Pieter Jr., John | Faruk, Muhammad

Article Type: Research Article

Abstract: BACKGROUND: Molecular subtyping of breast cancer cells is increasingly being developed as an initial step in selecting therapy and predicting the prognosis of breast cancer patients. During breast cancer, the molecular subtype of cancer cells can change. This study aimed to analyze the relationship between changes in the intrinsic subtype of breast cancer with metastasis and progression-free survival in breast cancer patients. METHODS: This was a retrospective cohort study of patients diagnosed with breast cancer from 2016 to 2021. The molecular subtypes from the immunohistochemical examination results were recorded twice, and metastasis and progression-free survival (PFS) were recorded. …The data were analyzed using the chi-square test and SPSS 26. RESULTS: Of the 44 patients, 19 (43.2%) experienced a change in molecular subtype, and 25 (56.8%) did not. No significant relationship existed between changes in molecular subtype and metastasis (p = 0.405). No significant relationship existed between changes in molecular subtype and PFS (p = 0.900). A significant relationship was found between changes in the molecular subtype and PFS in the patients with changes in the molecular subtype (p = 0.022). CONCLUSIONS: Changes in the intrinsic subtype were associated with PFS in breast cancer patients. Patients with an intrinsic subtype that changed to triple-negative showed worse PFS. Show more

Keywords: Breast cancer, metastasis, molecular subtype, progression-free survival

DOI: 10.3233/BD-249000

Citation: Breast Disease, vol. 43, no. 1, pp. 71-78, 2024

Authors: Syamsu, Salman Ardi | Faruk, Muhammad | Smaradania, Nilam | Sampepajung, Elridho | Pranoto, Agung Sindu | Irsandy, Febie | Tammasse, Iin Fadhilah Utami

Article Type: Review Article

Abstract: INTRODUCTION: Immunotherapy has shown encouraging outcomes in breast cancer (BC) treatment in recent years. The programmed cell death ligand 1 (PD-L1) transmembrane protein is suggested to function as a co-inhibitory factor in the immune response, where it collaborates with programmed cell death protein 1 (PD-1) to stimulate apoptosis, suppress cytokine release from PD-1 positive cells, and limit the growth of PD-1 positive cells. Furthermore, in many malignancies, PD-L1 reduces the immune system’s response to neoplastic cells. These observations suggest that the PD-1/PD-L1 axis plays a vital role in cancer therapy and the regulation of cancer immune escape mechanisms. This review …aimed to provide an overview of the functions of PD-1 and PD-L1 in BC cancer therapy. METHODS: This research design is a literature review. The style is a traditional review on topics or variables relating to the PD-1/PD-L1 pathway. A literature search was carried out using three online databases. RESULTS: The search using the keywords yielded a total of 248 studies. Each result was filtered again according to the inclusion and exclusion criteria, resulting in a final total of 4 studies to be included in the literature review. CONCLUSIONS: The combination of PD-1/PD-L1 is essential for many malignancies. According to the evidence presented, this combination presents both an opportunity and a challenge in cancer treatment. Since many solid cancers, especially BC, express high levels of PD-1/PD-L1, cancer treatment mainly involves targeted therapies. Show more

Keywords: Breast cancer, programmed cell death receptor, programmed cell death 1 ligand 1, immune system

DOI: 10.3233/BD-249006

Citation: Breast Disease, vol. 43, no. 1, pp. 79-92, 2024