ABSTRACT
PURPOSE: The breast sarcoma induced by radiation therapy is rare but increasing, given the increased long-term survival of patients receiving radiation therapy. Fibrosarcoma, histiocytofibroma and angiosarcoma are the most common breast sarcoma. Angiosarcoma is the most common after breast cancer treated by radiation therapy, often diagnosed too late, with a severe prognosis and a high rate of recurrence. However, because of the low incidence of angiosarcoma associated with radiation therapy (AAR), the benefit of radiation therapy in breast cancer treatment outweighs the risk to develop angiosarcoma. The aim of this study is to evaluate these rare cases of AAR diagnosed in eastern Belgium in comparison to the data from the literature. PATIENTS AND METHODS: Nine cases of AAR after radiation for breast ductal carcinoma were included in this retrospective study. AAR was diagnosed according to Cahan criteria between January 2007 and December 2016. Latency, incidence, management and prognosis are comparable to the literature. RESULTS, CONCLUSION: The median latency was 10 (4-24) years, the incidence of AAR in the East Belgian area was 0.09% of the patients irradiated on the same period. Patients were treated by surgery with wide local excision with or without reconstructive surgery, without radiotherapy and chemotherapy treatment. Kaplan-Meier analysis showed median overall survival of 61.8 months, patient survival of 55.6% at one year and 29.6% at five years. With the constant progress of medicine and its technologies, it would be possible to limit the occurrence of AAR or to diagnose it at an earlier stage.
Subject(s)
Breast Neoplasms/etiology , Breast Neoplasms/radiotherapy , Carcinoma, Ductal, Breast/radiotherapy , Hemangiosarcoma/etiology , Neoplasms, Radiation-Induced/etiology , Neoplasms, Second Primary/etiology , Aged , Aged, 80 and over , Belgium/epidemiology , Breast Neoplasms/epidemiology , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/epidemiology , Carcinoma, Ductal, Breast/mortality , Female , Hemangiosarcoma/epidemiology , Hemangiosarcoma/mortality , Hemangiosarcoma/surgery , Humans , Incidence , Kaplan-Meier Estimate , Mastectomy , Middle Aged , Neoplasms, Radiation-Induced/epidemiology , Neoplasms, Radiation-Induced/mortality , Neoplasms, Radiation-Induced/surgery , Neoplasms, Second Primary/epidemiology , Neoplasms, Second Primary/mortality , Neoplasms, Second Primary/surgery , Rare Diseases/epidemiology , Rare Diseases/etiology , Rare Diseases/mortality , Rare Diseases/surgery , Retrospective Studies , Survival Analysis , Time Factors , Unilateral Breast Neoplasms/epidemiology , Unilateral Breast Neoplasms/etiology , Unilateral Breast Neoplasms/mortalityABSTRACT
Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as overexpressed in several cancers and shown to contribute to proliferation, migration and invasion of cancer cells. We have previously demonstrated that myoferlin regulates epidermal growth factor receptor activity in breast cancer. In the current study, we report a consistent overexpression of myoferlin in triple-negative breast cancer cells (TNBC) over cells originating from other breast cancer subtypes. Using a combination of proteomics, metabolomics and electron microscopy, we demonstrate that myoferlin depletion results in marked alteration of endosomal system and metabolism. Mechanistically, myoferlin depletion caused impaired vesicle traffic that led to a misbalance of saturated/unsaturated fatty acids. This provoked mitochondrial dysfunction in TNBC cells. As a consequence of the major metabolic stress, TNBC cells rapidly triggered AMP activated protein kinase-mediated metabolic reprogramming to glycolysis. This reduced their ability to balance between oxidative phosphorylation and glycolysis, rendering TNBC cells metabolically inflexible, and more sensitive to metabolic drug targeting in vitro. In line with this, our in vivo findings demonstrated a significantly reduced capacity of myoferlin-deficient TNBC cells to metastasise to lungs. The significance of this observation was further supported by clinical data, showing that TNBC patients whose tumors overexpress myoferlin have worst distant metastasis-free and overall survivals. This novel insight into myoferlin function establishes an important link between vesicle traffic, cancer metabolism and progression, offering new diagnostic and therapeutic concepts to develop treatments for TNBC patients.
Subject(s)
Calcium-Binding Proteins/metabolism , Membrane Proteins/metabolism , Muscle Proteins/metabolism , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Animals , Calcium-Binding Proteins/biosynthesis , Cell Line, Tumor , Cytoplasmic Vesicles/metabolism , Female , Glycolysis , Heterografts , Humans , Lipid Metabolism , Membrane Proteins/biosynthesis , Mice , Mice, Inbred NOD , Mice, SCID , Muscle Proteins/biosynthesis , Neoplasm Metastasis , Oxidative PhosphorylationABSTRACT
AIM: To measure the impact of MammaPrint on adjuvant treatment decisions and to analyze the agreement in treatment decisions between hospitals from 4 European countries for the same patient cohort. METHODS: Breast cancer patients were prospectively enrolled and MammaPrint was assessed. Patients' clinical data without and then with MammaPrint results were sent to the different multidisciplinary teams and treatment advice was provided for each patient. RESULTS: Using MammaPrint, chemotherapy treatment advice for ER+/HER2- breast cancer patients was changed in 37% of patients by the Dutch, 24% by the Belgian, 28% by the Italian and 35% by the Spanish teams. MammaPrint increased the inter-institutional agreement in treatment advice (chemotherapy or no chemotherapy) from 51% to 75%. CONCLUSION: The results of this study indicate that MammaPrint impacts adjuvant chemotherapy recommendation. MammaPrint can decrease inter-institutional and inter-country variability in adjuvant treatment advice for breast cancer patients.
