In Romania, breast cancer (BC) is the most common malignancy in women. However, there is limited ... more In Romania, breast cancer (BC) is the most common malignancy in women. However, there is limited data on the prevalence of predisposing germline mutations in the population in the era of precision medicine, where molecular testing has become an indispensable tool in cancer diagnosis, prognosis, and therapeutics. Therefore, we conducted a retrospective study to determine the prevalence, mutational spectrum, and histopathological prediction factors for hereditary breast cancer (HBC) in Romania. A cohort of 411 women diagnosed with BC selected upon NCCN v.1.2020 guidelines underwent an 84-gene NGS-based panel testing for breast cancer risk assessment during 2018–2022 in the Department of Oncogenetics of the Oncological Institute of Cluj-Napoca, Romania. A total of 135 (33%) patients presented pathogenic mutations in 19 genes. The prevalence of genetic variants was determined, and demographic and clinicopathological characteristics were analyzed. We observed differences among BRCA and n...
Tumors act systemically to sustain cancer progression, affecting the physiological processes in t... more Tumors act systemically to sustain cancer progression, affecting the physiological processes in the host and triggering responses in the blood circulating cells. In this study, we explored blood transcriptional patterns of patients with two subtypes of HER2 negative breast cancers, with different prognosis and therapeutic outcome. Peripheral blood samples from seven healthy female donors and 29 women with breast cancer including 14 triple-negative breast cancers and 15 hormone-dependent breast cancers were evaluated by microarray. We also evaluated the stroma in primary tumors. Transcriptional analysis revealed distinct molecular signatures in the blood of HER2− breast cancer patients according to ER/PR status. Our data showed the implication of immune signaling in both breast cancer subtypes with an enrichment of these processes in the blood of TNBC patients. We observed a significant alteration of “chemokine signaling,” “IL-8 signaling,” and “communication between innate and adapt...
Background and aims. Breast cancer (BC) is the most frequently diagnosed cancer and the leading c... more Background and aims. Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer-related death among women worldwide. For locally advanced diseases and high-risk tumors, neoadjuvant therapy (NAT) is the treatment of choice. Some studies show that mammographic density (MD) tumor margins and the presence of microcalcifications play a prognostic role in BC patients. Hence, the objective of this retrospective study was to assess if MD could predict the response to NAT among different molecular subtypes of BC patients undergoing NAT at The “Prof. Dr I. Chiricuta” Oncology Institute of Cluj-Napoca, Romania (IOCN). Furthermore, the association between MD, tumor margins and the presence of microcalcifications with clinico-pathological data was analyzed. Methods. Eighty-four breast cancer patients diagnosed and treated at IOCN were included in this study. The morphological characteristics of the tumors were framed according to the BIRADS lexicon. The presence o...
Neo-adjuvant therapy (NAT) is increasingly used in the clinic for the treatment of breast cancer ... more Neo-adjuvant therapy (NAT) is increasingly used in the clinic for the treatment of breast cancer (BC). Pathological response to NAT has been associated with improved patients’ survival; however, the current techniques employed for assessing the tumor response have significant limitations. Small EVs (sEVs)-encapsulated miRNAs have emerged as promising new biomarkers for diagnosis and prediction. Therefore, our study aims to explore the predictive value of these miRNAs for the pathological response to NAT in BC. By employing bioinformatic tools, we selected a set of miRNAs and evaluated their expression in plasma sEVs and BC biopsies. Twelve miRNAs were identified in sEVs, of which, miR-21-5p, 221-3p, 146a-5p and 26a-5p were significantly associated with the Miller–Payne (MP) pathological response to NAT. Moreover, miR-21-5p, 146a-5p, 26a-5p and miR-24-3p were independent as predictors of MP response to NAT. However, the expression of these miRNAs showed no correlation between sEVs an...
Poster: "EuroSafe Imaging 2017 / ESI-0002 / First Steps in Clinical Audit in Romania" b... more Poster: "EuroSafe Imaging 2017 / ESI-0002 / First Steps in Clinical Audit in Romania" by: "L. Bogdan1, M. Lesaru2, C. Lisencu3, A. R. Chiorean4, A. I. Ciurea4, C. A. Ciortea5; 1National Institute of Public Health, Regional Center Cluj-Napoca Cluj-Napoca/RO, 2'Fundeni' Institute Bucharest/RO, 3'Ion Chiricuta' Oncologic Institute Cluj-Napoca/RO, 4'Iuliu Hatieganu' University of Medicine and Pharmacy Cluj-Napoca/RO, 5Emergency County University Hospital Cluj-Napoca/RO"
Rezumat Carcinomul ductal in situ (CDIS) a devenit un subiect de interes după introducerea progra... more Rezumat Carcinomul ductal in situ (CDIS) a devenit un subiect de interes după introducerea programelor de screening mamografic. Aproape 90% din CDIS sunt detectate prin mamografie, în particular cea de screening, aceasta rămănând principala metodă imagistică pentru CDIS. Evaluarea mărimii tumorii realizată prin metode imagistice a ajutat chirurgul să utilizeze chirurgia conservatoare mai frecvent, comparativ cu mastectomia, cu rezultate oncologice sigure. În cele mai multe situaţii mamografia poate fi considerată suficientă pentru a determina corect extensia bolii. Totuşi, imagistica prin rezonanţă magnetică (IRM) s-a dovedit mai precisă în evaluarea extensiei bolii, în special la femeile tinere. Ecografia nu este metoda de elecţie pentru CDIS dar pare să îşi aducă contribuţia în detectarea semnelor specific ale diagnosticului şi ale extensiei tumorii. Revederea literaturii este trecută prin lumina propriei experienţe.
Breast cancer patients' response to treatment is highly dependent on the primary tumor molecular ... more Breast cancer patients' response to treatment is highly dependent on the primary tumor molecular features, with triple-negative breast tumors having the worst prognosis of all subtypes. According to the molecular features, tumors stimulate the microenvironment to induce distinct immune responses, baseline immune activation being associated with higher likelihood of pathologic response. In this study, we investigated the deconvolution of the immunological status of triple-negative tumors in comparison with luminal tumors and the association with patients' clinicopathological characteristics. Patients and methods: Gene expression of 84 inflammatory molecules and their receptors were analyzed in 40 peripheral blood samples from patients with Her2-primary breast cancer tumors. We studied the association of triple-negative phenotype with age, clinical stage, tumor size, lymph nodes, and menopausal status. Results: We observed that more patients with estrogen (ER)/progesterone (PR)-negative tumors had grade III, while more patients with ER/PR-positive tumors had grade II tumors. Gene expression analysis revealed a panel of 14 genes to have differential expression between the two groups: several interleukins: IL13, IL16, IL17C and IL17F, IL1A, IL3; interleukin receptors: IL10RB, IL5RA; chemokines: CXCL13 and CCL26; and cytokines: CSF2, IFNA2, OSM, TNSF13. Conclusion: The expression levels of these genes have been previously shown to be associated with reduced immunological status; indeed, the triple-negative breast cancer patients presented with lower counts of lymphocytes and eosinophils than the ER/PR-positive ones. These results contribute to a better understanding of the possible role of antitumor immune responses in mediating the clinical outcome.
Background: Breast cancer is the first leading cause of cancer death in women in Romania with an ... more Background: Breast cancer is the first leading cause of cancer death in women in Romania with an age-adjusted (world) mortality rate of 15.2 (GLOBOCAN 2012). The country completely lacked organized cancer screening programs until recently. An exception is attempted by the national cervical cancer screening program recently initiated (2012) and a breast cancer screening pilot study in Northwestern region of Romania that started in 2014 at the Oncology Institute from Cluj-Napoca, within Norway Grants framework, in collaboration with the Cancer Registry of Norway. The correct pathological classification plays a central role in order to avoid misdiagnosis, overdiagnosis and overtreatment. Method: We designed a database management system and a high resolution pathology dataset to ensure an optimum communication between clinician, radiologist and pathologist. Results: The first challenge was the lack of standardization and consistency in breast biopsy result-reporting. We designed the pat...
Most ductal carcinomas in situ are clinically occult; therefore, proper techniques must be used f... more Most ductal carcinomas in situ are clinically occult; therefore, proper techniques must be used for adequate diagnosis. Current guidelines recommend minimally invasive tissue sampling before surgical excisions of all breast malignancies. Regardless of the technique used, correctly performed biopsies that are geographically, dimensional and numerical representative are essential, and post-interventional markers can be placed at the site. Whenever possible, vacuum-assisted guided by mammography should be the first choice of biopsy for all nonpalpable lesions of the breast, especially for microcalcifications. Surgical excision is expected in most ductal carcinomas in situ; therefore, appropriate imaging-guided localization techniques must be deployed in the hope of aiding the surgeon to perform a free-margin cosmetically adequate procedure. No significant performance differences have been noticed by comparing wire localization to radio guided occult lesion localization or radioactive seed technique, while the choice of imaging guidance should consider the best visibility of the lesion or marker. In the current paper we review the main interventional procedures used for diagnosis in ductal carcinoma in situ, illustrated with images from the database of the
In Romania, breast cancer (BC) is the most common malignancy in women. However, there is limited ... more In Romania, breast cancer (BC) is the most common malignancy in women. However, there is limited data on the prevalence of predisposing germline mutations in the population in the era of precision medicine, where molecular testing has become an indispensable tool in cancer diagnosis, prognosis, and therapeutics. Therefore, we conducted a retrospective study to determine the prevalence, mutational spectrum, and histopathological prediction factors for hereditary breast cancer (HBC) in Romania. A cohort of 411 women diagnosed with BC selected upon NCCN v.1.2020 guidelines underwent an 84-gene NGS-based panel testing for breast cancer risk assessment during 2018–2022 in the Department of Oncogenetics of the Oncological Institute of Cluj-Napoca, Romania. A total of 135 (33%) patients presented pathogenic mutations in 19 genes. The prevalence of genetic variants was determined, and demographic and clinicopathological characteristics were analyzed. We observed differences among BRCA and n...
Tumors act systemically to sustain cancer progression, affecting the physiological processes in t... more Tumors act systemically to sustain cancer progression, affecting the physiological processes in the host and triggering responses in the blood circulating cells. In this study, we explored blood transcriptional patterns of patients with two subtypes of HER2 negative breast cancers, with different prognosis and therapeutic outcome. Peripheral blood samples from seven healthy female donors and 29 women with breast cancer including 14 triple-negative breast cancers and 15 hormone-dependent breast cancers were evaluated by microarray. We also evaluated the stroma in primary tumors. Transcriptional analysis revealed distinct molecular signatures in the blood of HER2− breast cancer patients according to ER/PR status. Our data showed the implication of immune signaling in both breast cancer subtypes with an enrichment of these processes in the blood of TNBC patients. We observed a significant alteration of “chemokine signaling,” “IL-8 signaling,” and “communication between innate and adapt...
Background and aims. Breast cancer (BC) is the most frequently diagnosed cancer and the leading c... more Background and aims. Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer-related death among women worldwide. For locally advanced diseases and high-risk tumors, neoadjuvant therapy (NAT) is the treatment of choice. Some studies show that mammographic density (MD) tumor margins and the presence of microcalcifications play a prognostic role in BC patients. Hence, the objective of this retrospective study was to assess if MD could predict the response to NAT among different molecular subtypes of BC patients undergoing NAT at The “Prof. Dr I. Chiricuta” Oncology Institute of Cluj-Napoca, Romania (IOCN). Furthermore, the association between MD, tumor margins and the presence of microcalcifications with clinico-pathological data was analyzed. Methods. Eighty-four breast cancer patients diagnosed and treated at IOCN were included in this study. The morphological characteristics of the tumors were framed according to the BIRADS lexicon. The presence o...
Neo-adjuvant therapy (NAT) is increasingly used in the clinic for the treatment of breast cancer ... more Neo-adjuvant therapy (NAT) is increasingly used in the clinic for the treatment of breast cancer (BC). Pathological response to NAT has been associated with improved patients’ survival; however, the current techniques employed for assessing the tumor response have significant limitations. Small EVs (sEVs)-encapsulated miRNAs have emerged as promising new biomarkers for diagnosis and prediction. Therefore, our study aims to explore the predictive value of these miRNAs for the pathological response to NAT in BC. By employing bioinformatic tools, we selected a set of miRNAs and evaluated their expression in plasma sEVs and BC biopsies. Twelve miRNAs were identified in sEVs, of which, miR-21-5p, 221-3p, 146a-5p and 26a-5p were significantly associated with the Miller–Payne (MP) pathological response to NAT. Moreover, miR-21-5p, 146a-5p, 26a-5p and miR-24-3p were independent as predictors of MP response to NAT. However, the expression of these miRNAs showed no correlation between sEVs an...
Poster: "EuroSafe Imaging 2017 / ESI-0002 / First Steps in Clinical Audit in Romania" b... more Poster: "EuroSafe Imaging 2017 / ESI-0002 / First Steps in Clinical Audit in Romania" by: "L. Bogdan1, M. Lesaru2, C. Lisencu3, A. R. Chiorean4, A. I. Ciurea4, C. A. Ciortea5; 1National Institute of Public Health, Regional Center Cluj-Napoca Cluj-Napoca/RO, 2'Fundeni' Institute Bucharest/RO, 3'Ion Chiricuta' Oncologic Institute Cluj-Napoca/RO, 4'Iuliu Hatieganu' University of Medicine and Pharmacy Cluj-Napoca/RO, 5Emergency County University Hospital Cluj-Napoca/RO"
Rezumat Carcinomul ductal in situ (CDIS) a devenit un subiect de interes după introducerea progra... more Rezumat Carcinomul ductal in situ (CDIS) a devenit un subiect de interes după introducerea programelor de screening mamografic. Aproape 90% din CDIS sunt detectate prin mamografie, în particular cea de screening, aceasta rămănând principala metodă imagistică pentru CDIS. Evaluarea mărimii tumorii realizată prin metode imagistice a ajutat chirurgul să utilizeze chirurgia conservatoare mai frecvent, comparativ cu mastectomia, cu rezultate oncologice sigure. În cele mai multe situaţii mamografia poate fi considerată suficientă pentru a determina corect extensia bolii. Totuşi, imagistica prin rezonanţă magnetică (IRM) s-a dovedit mai precisă în evaluarea extensiei bolii, în special la femeile tinere. Ecografia nu este metoda de elecţie pentru CDIS dar pare să îşi aducă contribuţia în detectarea semnelor specific ale diagnosticului şi ale extensiei tumorii. Revederea literaturii este trecută prin lumina propriei experienţe.
Breast cancer patients' response to treatment is highly dependent on the primary tumor molecular ... more Breast cancer patients' response to treatment is highly dependent on the primary tumor molecular features, with triple-negative breast tumors having the worst prognosis of all subtypes. According to the molecular features, tumors stimulate the microenvironment to induce distinct immune responses, baseline immune activation being associated with higher likelihood of pathologic response. In this study, we investigated the deconvolution of the immunological status of triple-negative tumors in comparison with luminal tumors and the association with patients' clinicopathological characteristics. Patients and methods: Gene expression of 84 inflammatory molecules and their receptors were analyzed in 40 peripheral blood samples from patients with Her2-primary breast cancer tumors. We studied the association of triple-negative phenotype with age, clinical stage, tumor size, lymph nodes, and menopausal status. Results: We observed that more patients with estrogen (ER)/progesterone (PR)-negative tumors had grade III, while more patients with ER/PR-positive tumors had grade II tumors. Gene expression analysis revealed a panel of 14 genes to have differential expression between the two groups: several interleukins: IL13, IL16, IL17C and IL17F, IL1A, IL3; interleukin receptors: IL10RB, IL5RA; chemokines: CXCL13 and CCL26; and cytokines: CSF2, IFNA2, OSM, TNSF13. Conclusion: The expression levels of these genes have been previously shown to be associated with reduced immunological status; indeed, the triple-negative breast cancer patients presented with lower counts of lymphocytes and eosinophils than the ER/PR-positive ones. These results contribute to a better understanding of the possible role of antitumor immune responses in mediating the clinical outcome.
Background: Breast cancer is the first leading cause of cancer death in women in Romania with an ... more Background: Breast cancer is the first leading cause of cancer death in women in Romania with an age-adjusted (world) mortality rate of 15.2 (GLOBOCAN 2012). The country completely lacked organized cancer screening programs until recently. An exception is attempted by the national cervical cancer screening program recently initiated (2012) and a breast cancer screening pilot study in Northwestern region of Romania that started in 2014 at the Oncology Institute from Cluj-Napoca, within Norway Grants framework, in collaboration with the Cancer Registry of Norway. The correct pathological classification plays a central role in order to avoid misdiagnosis, overdiagnosis and overtreatment. Method: We designed a database management system and a high resolution pathology dataset to ensure an optimum communication between clinician, radiologist and pathologist. Results: The first challenge was the lack of standardization and consistency in breast biopsy result-reporting. We designed the pat...
Most ductal carcinomas in situ are clinically occult; therefore, proper techniques must be used f... more Most ductal carcinomas in situ are clinically occult; therefore, proper techniques must be used for adequate diagnosis. Current guidelines recommend minimally invasive tissue sampling before surgical excisions of all breast malignancies. Regardless of the technique used, correctly performed biopsies that are geographically, dimensional and numerical representative are essential, and post-interventional markers can be placed at the site. Whenever possible, vacuum-assisted guided by mammography should be the first choice of biopsy for all nonpalpable lesions of the breast, especially for microcalcifications. Surgical excision is expected in most ductal carcinomas in situ; therefore, appropriate imaging-guided localization techniques must be deployed in the hope of aiding the surgeon to perform a free-margin cosmetically adequate procedure. No significant performance differences have been noticed by comparing wire localization to radio guided occult lesion localization or radioactive seed technique, while the choice of imaging guidance should consider the best visibility of the lesion or marker. In the current paper we review the main interventional procedures used for diagnosis in ductal carcinoma in situ, illustrated with images from the database of the
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