Faculty of Medicine

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Radiotherapy-induced thyroid dysfunction
(Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, 2025)
B Profka Haxhiu
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F Selimi
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I Kurtishi
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D Berberi
Aim:The aim of this paper was to evaluate the effects of radiotherapy on thyroid function in breast cancer patients, comparing those treated only on the chest wall with those who also received supraclavicular (SCV) nodal irradiation. Material and Methods: A total of 100 women with breast cancer treated with radiotherapy were analyzed. Blood samples were taken before radiotherapy and evaluated by measuring serum thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) levels. None of the women were on thyroid substitution therapy. Thyroid function, including TSH, fT3 and fT4 levels, was monitored in patients every 6 months after the completion of radiation. Results: The results revealed a significant impact on thyroid function, particularly an increased incidence of hypothyroidism in the SCV irradiation group. The study reported that after six months of radiotherapy, 35% of patients developed hypothyroidism, and this percentage decreased to 27% after twelve months. This suggests that while many patients may experience immediate thyroid dysfunction following radiotherapy, some may recover over time, though a substantial portion remains affected. Conclusions: The data presented highlight a concerning trend of increased hypothyroidism among breast cancer patients undergoing radiotherapy, particularly those receiving SCV irradiation. The study's findings indicate that a substantial proportion of patients may experience lasting thyroid dysfunction, necessitating vigilant monitoring and management.
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Pathologic and molecular subtypes characteristics of our breast cancer patients in Kosovo
(Macedonian Association of Anatomists and Morphologists, 2025)
B Profka Haxhiu
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L Abdullahu
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F Kurshumliu
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Aim: Тo classify breast cancer cases by molecular subtypes (luminal A, luminal B (HER2 positive), luminal B (HER2 negative), HER2 positive, triple negative). Secondly, to analyze the associations between the immunohistochemical markers, molecular subtype and known prognostic factors (stage, grade, age, location). Material and methods: In this study patients are enrolled prospectively from the oncology clinic 100 patients. All of them are breast cancer patients who have undergone different methods of treatment. Results: Radical mastectomy (RM) remains the cornerstone of surgery compared to breast conserving surgery (BCS) as we see from our result where 83% undergone to radical mastectomy and 16% BCS. All molecular subtypes have the primary treatment radical mastectomy plus lymph node dissection. Even in Luminal A subtype the ratio between BCS and RM is 1:3 Conclusion: Molecular subtypes correlate with tumor volume and disease stage, indicating differences in disease progression. Given that a significant portion of cases were diagnosed at locally advanced stages during initial presentation, mastectomy remained the preferred choice over breast-conserving surgery. This preference may be attributed to the need for more aggressive treatment approaches to address the advanced disease stage in the time of diagnosis.
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Breast microcalcifications on mammograms
(Здружение на Радиолошки Технолози на Македонија = Macedonian Association of Radiologists, 2023-11)
Breast calcifications are usually found by chance during screening mammograms or diagnostic mammograms. Early detection of breast calcifications through routine mammography is vital for timely intervention and effective treatment. Mammography is used worldwide to detect microcalcifications. Breast calcifications are very common, and they are usually benign and occur as a part of the aging process. Many fibroadenomas, breast cysts, injuries of the breast tissue, mastitis can also form microcalcifications. Additionally, calcifications can develop within the blood vessels of the breast. Some microcalcifications can be the only and early presenting sign of breast cancer. With the mammography we can not only diagnose breast cancer in a non palpable stage, but can also detect the extent of the disease. The knowledge of the various microcalcification patterns on mammography helps in correct interpretation and management of microcalcifications in breast. We will display numerous types of microcalcifications. The majority of presented microcalcifications are suspicious of malignancy. Also microcalcifications can be seen with no associated tumor mass.
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Ново дијагостицирана атријална фибрилација кај пациентка со активен карцином на дојка: тераписки предизвик - приказ на случај
(2023-10)
Breast cancer is the most common malignant disease in females. The specific cancer treatment protocol involves drugs with known cardiovascular toxicity. Patients with significant risk of cancer therapy-related cardiovascular toxicity (CRT-CVT) should be reported for cardiology referral. CASE REPORT: Seventy-year-old, obese patient with a previous history of hypertension and low normal left ventricular ejection fraction (LVEF) was diagnosed with breast cancer and scheduled for baseline assessment before initiating cardiotoxic cancer treatment protocol. Regular monitoring for an already high-risk patient for CRT-CVT was not enough for developing of first diagnosed, paroxysmal, asymptomatic atrial fibrilation after completing the 4 th cycle of anthracyclines and total cumulative dose of 208.3mg/m2. Transthoracic echocardiography did not reveal significant changes in LVEF and global longitudinal strain, so cancer therapy-related cardiac dysfunction was not the related diagnosis. Laboratory measurements of cardiac biomarkers did not confirm subclinical cardiac injury. Besides ACEinhibitors already prescribed for hypertension, drugs for rate control and anticoagulation therapy with both low-molecular-weight heparin and NOAC was the preferred therapeutic decision for successful completion of the oncological treatment. After a week, the electrocardiogram showed sinus rhythm. The patient also completed left-sided radiotherapy with total tumor dose of 41,25Gy, and six months after has stabile cardiac performances and normal sinus rhythm. CONCLUSION: CRT-CVT is the second leading cause of death in breast cancer patients. Management of the adverse effects is challenging and complex due to the imperative of completing the cancer therapy and frequent drug-drug interactions. Early detection, multidisciplinary approach and close monitoring are the cornerstone for overall good outcome in these patients.
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Breast cancer tumor characteristics and metastatic bone scintigraphy findings
(Department of Anaesthesia and Reanimation, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, R.N. Macedonia, 2023-10-09)
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Lazareva E
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Objectives: Bone scintigraphy (BS) is the gold standard for screening and initial diagnosis of bone metastases (BMs) in breast cancer (BC). The aim of this study was to analyze the correlation between multiple BMs diagnosed on BS with the tumor characteristics and molecular subtypes of the tumor in BC patients. Materials and Methods: We performed a retrospective, observational study of 66 BC patients (mean age 52.52±10.64 years) with multiple BMs confirmed on the first diagnostic BS, in the period 2013-2018. Data regarding the initial disease stage, tumor histological type, grade and molecular subtype were evaluated for correlation with BMs. Results: Sixteen patients (24%) presented with BMs at the time of BC. The metastasis-free period in the restaging group was 7.38±4.01 years and the same was significantly associated with the disease TNM stage (rs =-0.385; P=0.011). Ductal BC was more frequently associated with BMs than the lobular type (65% vs. 14%, respectively). ER+ were 86% of the cases, followed by PgR+ (74%) and HER2+ (35%) of the cases. A significant correlation was found between the HR+ status of BC patients and the presence of multiple BMs (P=0.021). BMs were mainly detected in the spine (predominantly the thoracic segment), the ribs and the pelvis (P= 0.013). Conclusion: Higher initial TNM stage reduces BMs free interval. HR positive status seems to be a significant predictor of BMs in BC.
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The highest frequency of BRCA1 c.3700_3704del detected among Albanians from Kosovo
(Greater Poland Cancer Centre, Poland, 2022)
Kostovska Maleva, Ivana
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Jakovchevska, Simona
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Özdemir, Milena Jakimovska
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Kiprijanovska, Sanja
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Kubelka-Sabit, Katerina
Background: The spectrum of BRCA1 and BRCA2 mutations varies among populations; however, some mutations may be frequent in particular ethnic groups due to the “founder” effect. The c.3700_3704del mutation was previously described as a recurrent BRCA1 variant in Eastern European countries. This study aimed to investigate the frequency of c.3700_3704del BRCA1 mutation in Albanian breast and ovarian cancer patients from North Macedonia and Kosovo. Materials and methods: A total of 327 patients with invasive breast and/or ovarian cancer (111 Albanian women from North Macedonia and 216 from Kosovo) were screened for 13 recurrent BRCA1/2 mutations. Targeted NGS with a panel of 94 cancer-associated genes including BRCA1 and BRCA2 was performed in a selected group of 118 patients. Results: We have identified 21 BRCA1/2 pathogenic variants, 17 (14 BRCA1 and 3 BRCA2) in patients from Kosovo (7.9%) and 4 (1 BRCA1 and 3 BRCA2) in patients from North Macedonia (3.6%). All BRCA1/2 mutations were found in one patient each, except for c.3700_3704del BRCA1 mutation which was observed in 14 unrelated families, all except one originating from Kosovo. The c.3700_3704del mutation accounts for 93% of BRCA1 mutation positive cases and is present with a frequency of 6% among breast cancer patients from Kosovo. Conclusions: This is the first report of BRCA1/2 mutations among breast and ovarian cancer patients from Kosovo. The finding that BRCA1 c.3700_3704del represents a founder mutation in Kosovo with the highest worldwide reported frequency supports the implementation of fast and low-cost screening protocol, regardless of the family history and even a pilot population-based screening in at-risk population.
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Preoperative determination of DNA ploidy and hormone receptor status (ER and PgR) on cytologic material from breast cancer patients using image cytometry
(Karger, 1997-09)
Ivkovski, Ljube
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Zografski, George
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Yashar, Genghis
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Stavrik, George
OBJECTIVE: FNAB of breast masses is a commonly performed diagnostic test. DNA ploidy, along with estrogen (ER) and progesterone (PgR) receptors, is becoming increasingly useful as a prognostic adjunct to conventional staging and histologic grading. These prognostic parameters could be assessed preoperatively by using FNAB material. STUDY DESIGN: Sixty-three breast cancer aspirates were assayed for DNA distribution patterns and hormone receptor status with the CAS 200 Image Analyzing System. Consequently, their relations with well-established conventional prognostic factors in breast carcinoma (tumor size, lymph node status and histological grade) were analyzed. RESULTS:The majority of the primary invasive breast carcinomas were aneuploid (43/63). Most of the aneuploid tumors had histogram type IV (31/43). The data showed that breast carcinomas in which the DNA amounts of the tumor cells were euploid (histograms of types I and I1) were characterized by high levels of ER and PgR, while aneuploid types (histograms of types III and IV) had low levels of ER and PgR. Of the aneuploid breast carcinomas, 86.1% (37/43) had lymph node involvement, while only 40% (8/20) of the euploid carcinomas had lymph node involvement. The majority of the aneuploid carcinomas were of ductal type (29/43), while most of the lobular carcinomas were euploid (9/20). CONCLUSION: Our results strongly indicate a correlation between nuclear DNA distribution patterns, hormone receptor levels and postsurgical factors of prognosis in primary breast carcinomas. By determining the DNA ploidy and hormone receptor status preoperatively, the planning of treatment options available to breast cancer patients could be improved.
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Real-world data of cardiotoxicity during long-term therapy with trastuzumab in human epidermal growth factor receptor-2-positive metastatic breast cancer
(National Library of Serbia, 2022-12-16)
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Lazareva, Emilija
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Introduction/Objective. This study aims to investigate the cardiotoxicity of long-term therapy with trastuzumab in patients with HER2 positive metastatic breast cancer. Methods. A total of 48 patients with metastatic HER2 positive breast cancer were analyzed. The patients received long-term trastuzumab (time of application was longer than 20 months). The analyzed characteristics of the patients were: age, initial stage of the disease, application of anti-HER2 therapy and anthracyclines in the adjuvant setting, the number and type of applied systemic therapies concomitant with trastuzumab in the metastatic setting. Cardiac toxicity was assessed using left ventricular ejection fraction (LVEF) values at three time points: at the beginning, in the middle, and at the end of treatment period for each patient separately. Results. In 17 (35.4%) patients the trastuzumab treatment was temporary discontinued. The average time of trastuzumab therapy interval was 52.2 ? 23.5 months. The mean LVEF values were 66.73 ? 7.02%, 64.62 ? 5.7% and 63.44 ? 6.1%, respectively. The mean values of LVEF differed significantly in the observed three time points (F=4.9 p=0.009). Post hoc pairwise comparison, using Bonferonni correction, confirmed significantly lower mean LVEF values at the end point (at the end of treatment) compared with the mean LVEF values at the beginning of anti-HER2 treatment (p = 0.019), but within the reference range of LVEF ?50%. Conclusion. The data confirm good safety profile of long-term trastuzumab therapy in HER2 positive metastatic breast cancer patients considering cardiotoxicity.
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Correlation between PD-L1 expression and clinicopathological characteristics in triple-negative breast cancer patients
(Springer, 2020-12)
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Ognenoska-Jankovska, Biljana
Background & objectives: While immunotherapy is emerging as an effective treatment option for advanced triple-negative breast carcinoma (TNBC) patients, the clinicopathological significance of PD-L1 expression in TNBC remains unclear. Our objective was to investigate the association between PD-L1 expression and clinicopathological characteristics in TNBC. Methods: The study group comprised 47 TNBC patients in which PD-L1 status was evaluated by immunohistochemistry with SP142 assay on the Ventana BenchMark. All PDL1(+) tumour-associated immune cells (IC) were quantified as % of the tumour area. Tumours were classified as PDL1(+)(>=1%) or PD-L1(-)(<1%). The statistical significance of the correlation between PD-L1 status and clinicopathological characteristics was determined by chi-square test. Results: PD-L1(+) were 24(51.1%) of the 47 TNBC patients whose median age at diagnosis was 59 (range, 39-79). 53.5% (23/43) of the primary and 25%(1/4) of the metastatic TNBC cases were PD-L1(+). 21(87.5%) of the PD-L1(+) TNBC had IC1( 1 and <5%), 2(8.3%) had IC2( 5 and <10%), and 1(4.2%) had IC3( 10) score. The PD-L1(+) status significantly associated with high histological grade (G3, P=0.022), and higher proliferative index (Ki-67>35%, P=0.004), while the correlation with larger tumour size (>2 cm, P=0.055) did not reach statistical significance. No significant relationship was found between PD-L1 status and other variables such as patients` age, postoperative stage, tumour status, lymph nodal status, tumour type, vascular invasion, and p53 expression. Conclusion: Our preliminary results suggest that PD-L1 expression is associated with several high-risk clinicopathological parameters in TNBC patients. Further larger studies are warranted to clarify the clinical relevance of PD-L1 expression in TNBC patients.
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Correlation between clinico-pathological characteristics, Ki67 and p53 expression in triple negative and non-triple negative breast cancer – A single center experience
(Klinicko bolnicki centar Zemun - Beograd, 2016)
Ognenoska-Jankovska, Biljana
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Stojkoska, Elena
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Qerimi, Adelina
Aim: The aims of our study were to compare clinicopathological characteristics, Ki-67 and p53 expression between triple-negative (TN) and non-TN invasive breast carcinomas. Introduction: TN breast cancer is associated with a higher histologic grade, shorter survival, and a higher recurrence rate. TN tumors usually express high levels of p53 and Ki67 that is currently considered prognostic markers for patients with breast cancer. Materials and Methods: A total of consecutive 189 breast carcinoma cases analyzed in our department in 2013 were included in this study. Clinicopathological characteristics such as age, tumor (pT), nodal status (pN), and grade, and Ki-67 and p53 expression were compared between the TN and non-TN groups using Pearson's chi-square and Student's t-test. Results: Mean age for the two groups was 59 years, and vary between 36 and 84, and there was no significant difference in the groups. There was no significant difference in the pT between TN and non-TN group. G (p<0.05) and pN (p<0.01) were significantly higher than that in the non-TN group. Ki-67 expression in the TN group was significantly higher than that in the non-TN group (p<0.01), and significantly correlated with the G (p<0.01), but not with pT and pN. p53 expression in the TN group was significantly higher (p<0.01), but was not significantly correlated with pT, pN and G. Conclusions: TN breast carcinomas have higher grade and nodal status, and they are associated with significantly higher expression of Ki-67 and p53 compared with non-TN tumors.

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