COVID-19 Pandemic Effects on Breast Cancer Diagnosis in Croatia: A Population- and Registry-Based Study.

BACKGROUND: Our objective was to assess the effects of COVID-19 antiepidemic measures and subsequent changes in the function of the health care system on the number of newly diagnosed breast cancers in the Republic of Croatia. SUBJECTS, MATERIALS, AND METHODS: We performed a retrospective, population- and registry-based study during 2020. The comparator was the number of patients newly diagnosed with breast cancer during 2017, 2018, and 2019. The outcome was the change in number of newly diagnosed breast cancer cases. RESULTS: The average monthly percent change after the initial lockdown measures were introduced was -11.0% (95% confidence interval - 22.0% to 1.5%), resulting in a 24% reduction of the newly diagnosed breast cancer cases in Croatia during April, May, and June compared with the same period of 2019. However, during 2020, only 1% fewer new cases were detected than in 2019, or 6% fewer than what would be expected based on the linear trend during 2017-2019. CONCLUSION: It seems that national health care system measures for controlling the spread of COVID-19 had a detrimental effect on the number of newly diagnosed breast cancer cases in Croatia during the first lockdown. As it is not plausible to expect an epidemiological change to occur at the same time, this may result in later diagnosis, later initiation of treatment, and less favorable outcomes in the future. However, the effect weakened after the first lockdown and COVID-19 control measures were relaxed, and it has not reoccurred during the second COVID-19 wave. Although the COVID-19 lockdown affected the number of newly diagnosed breast cancers, the oncology health care system has shown resilience and compensated for these effects by the end of 2020. IMPLICATIONS FOR PRACTICE: It is possible to compensate for the adverse effects of COVID-19 pandemic control measures on breast cancer diagnosis relatively promptly, and it is of crucial importance to do it as soon as possible. Moreover, as shown by this study's results on the number of newly diagnosed breast cancer cases during the second wave of the pandemic, these adverse effects are preventable to a non-negligible extent.

Olaparib Outcomes in Patients with BRCA 1-2 Mutated, Platinum-Sensitive, Recurrent Ovarian Cancer in Croatia: A Retrospective Noninterventional Study.

Our objective was to assess the safety and efficacy of olaparib in maintenance therapy of BRCA 1-2 mutated, platinum-sensitive, recurrent ovarian carcinoma after the partial or complete response to the second or further lines platinum-based chemotherapy in a real-world setting. We performed a multicenter, real-world observational population-based cohort study on the whole population of Croatian patients initiated to olaparib maintenance therapy between 2016 and 2020. The primary endpoints were progression-free survival and the discontinuation of treatment because of adverse events. We enrolled the total population of 69 patients with the median (interquartile range; IQR) age of 53 (48-59), 56 (81%) of them with BRCA1 mutation. The median (IQR) follow-up was 16 (9-25) months. Treatment had to be discontinued because of toxicity in 2 (3%) and temporarily interrupted in 14 (20%), while dose was reduced because of toxicity in 18 (26%) of patients. Toxicity of any grade was observed in 61 (88%) patients and toxicity of grade 3 or 4 in 12 (17%). Median progression-free survival was 21 (95% CI 16-not calculable) months from the introduction of olaparib, and the median overall survival was not reached. Our study confirmed efficacy and safety of olaparib as the maintenance therapy of BRCA 1-2 mutated, platinum-sensitive, recurrent ovarian carcinoma. We observed the real-world efficacy and safety comparable to those observed in the randomized controlled trials. We found the interesting observation of better efficacy of 300 mg tablets, compared to 400 mg capsules, an issue that should be addressed on much larger real-world populations.

Efficacy and safety of palbociclib in heavily pretreated patients with HR+/HER2- metastatic breast cancer.

AIM: CDK4/6 inhibitors in the first and second treatment line in patients with HR+/HER2- metastatic breast cancer (mBC) in combination with hormonal therapy improve progression-free survival. Role of CDK4/6 inhibitors in further treatment lines remains unclear. METHODS: Retrospective analysis of 24 HR+/HER2- heavily pretreated mBC patients is presented. RESULTS: A total of 58.3% patients achieved stable disease. No objective response was observed. Median progression-free survival was 4.8 months; median overall survival was 11 months. Treatment was well tolerated. CONCLUSION: Favorable toxicity profile and efficacy of palbociclib/aromatase inhibitors combination in heavily pretreated luminal mBC patients in this study emphasize the need for further investigation of such drugs in this population.

Bone health and adherence to vitamin D and calcium therapy in early breast cancer patients on endocrine therapy with aromatase inhibitors.

OBJECTIVES: Randomized trials involving aromatase inhibitors (AIs) in the adjuvant treatment of breast cancer patients have reported increased osteoporosis risk. Bone loss can be reduced with appropriate life style, vitamin D and calcium supplements, and with bisphosphonate therapy. The aim of this analysis was to investigate adherence to vitamin D and calcium in postmenopausal breast cancer patients receiving adjuvant non-steroidal AIs, and oncologists' adherence to the bone health guidelines. MATERIAL AND METHODS: This prospective study included 438 newly diagnosed patients and those who have already been receiving non-steroidal AIs for up to 3.5 years. Median endocrine therapy duration before recruitment in the study was 10.5 months (interquartile 4.8-26.6). RESULTS: Densitometry was performed on 142 patients (32.4%) before initiation of endocrine therapy, and on additional 38 (8.6%) patients at second study visit. Densitometry was not performed on 258 (59%) patients. Vitamin D and calcium were prescribed to 329/438 (75.1%) patients at some point during the study. Patients who took more than 80% of the prescribed dose were considered adherent. Self-reported adherence was 88.4%. Osteoporosis was diagnosed in 24 patients (5.5%) of the total study population, bearing in mind that 258/438 (59%) patients did not have densitometry. Bisphosphonates were prescribed to 54/438 (12.3%) patients, whilst only 19 (35.2%) of those had osteoporosis. CONCLUSION: In this analysis, lack of oncologists' adherence to the bone health guidelines was observed. In addition, a significant proportion of the patients did not adhere to the vitamin D and calcium.

[CLINICAL GUIDELINES FOR DIAGNOSIS, TREATMENT AND MONITORING OF PATIENTS WITH INVASIVE BREAST CANCER--CROATIAN ONCOLOGY SOCIETY]. / KLINICKE UPUTE HRVATSKOGA ONKOLOSKOG DRUSTVA ZA DIJAGNOZU, LIJECENJE I PRACENJE BOLESNICA/KA OBOLJELIH OD INVAZIVNOG RAKA DOJKE.

Breast cancer is the most common cancer in women. It can be diagnosed in early stage through screening, early detection and educational programs, and when diagnosed early it can be efficiently treated. Treatment modalities include surgery, chemotherapy, radiotherapy, hormonal therapy and targeted biologic therapy, according to the stage of the disease and patient condition. Treatment decisions should be made after multidisciplinary team discussion. Due to the significance of this disease it is important to define and implement standardized approach for diagnostic, treatment and monitoring algorithm as well. The following text presents the clinical guidelines in order to standardize the procedures and criteria for diagnosis, management, treatment and monitoring of patients with breast cancer in the Republic of Croatia.

Adjuvant Chemotherapy in Locally Advanced Cervical Cancer After Treatment with Concomitant Chemoradiotherapy--Room for Improvement?

BACKGROUND: The standard treatment for locally advanced cervical cancer (LACC) is concomitant chemoradiotherapy. In the majority of patients with LACC after properly executed concomitant chemoradiotherapy local control of the disease is achieved, and consequently distant relapse becomes the main cause of death for these patients. In an attempt to improve the outcome of patients with LACC, we designed a regimen of concomitant chemobrachyradiotherapy with cisplatin and ifosfamide followed by consolidation chemotherapy. PATIENTS AND METHODS: Between 1999 and 2012, 118 patients diagnosed with LACC, The International Federation of Gynecology and Obstetrics (FIGO) stages IB2-IVA, regardless of histology, were treated with concomitant chemobrachyradiotherapy and consolidation chemotherapy at our Institution. Chemotherapy consisted of two cycles of cisplatin and ifosfamide applied concomitantly with two intracavitary low-dose rate brachytherapy applications, and of four cycles of the same drug combination as an adjuvant/consolidation part of the treatment. The primary outcome in this analysis was distant disease-specific survival. RESULTS: A total of 18 patients had documented relapse of cervical cancer, with only three local recurrences observed; 15 patients developed only distant recurrence, and one patient developed both local and distant recurrence. The distant disease-specific survival after a median follow-up of 96 months was 86.4%. CONCLUSION: Consolidation or adjuvant chemotherapy that follows concomitant chemoradiotherapy has a potential role in further improving control of the disease, especially distant control of the disease.

[Clinical recommendations for diagnosis, treatment and monitoring of patients with cancer of unknown primary site]. / Klinicke preporuke za dijagnozu, lijecenje i pracenje bolesnika oboljelih od raka nepoznata primarnog podrijetla.

Cancer of unknown primary (CUP) site comprises very heterogeneous group of various malignant tumors presented in metastatic phase of the disease. Diagnosis is set when primary site remains unidentified after a thorough diagnostic evaluation in patients with histologically proven malignant metastatic disease. Despite poor prognosis in most patients, favorable prognostic clinical entities have been recognized constituting the most important group of patients for oncological treatment. The following text presents the clinical guidelines in order to standardize the diagnosis, treatment and follow-up of patients with cancer of unknown primary site in the Republic of Croatia.

Correlation Between E-cadherin Immunoexpression and Efficacy of First Line Platinum-Based Chemotherapy in Advanced High Grade Serous Ovarian Cancer.

To analyze correlation between immunoexpression of E-cadherin and efficacy of first line platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma. The expression of E-cadherin was analyzed immunohistochemically in formalin-fixed, paraffin-embedded samples from 98 patients with advanced-stage high-grade serous ovarian cancer and related to clinical features (stage according to the International Federation of Gynecology and Obstetrics (FIGO) and residual tumors after initial cytoreductive surgery), response to platinum-based chemotherapy (according to Response Evaluation Criteria in Solid tumors (RECIST 1.1 criteria)), platinum sensitivity (according to platinum free interval (PFI) as platinum-refractory, platinum-resistant and platinum-sensitive) and patients progression free survival (PFS) and overall survival (OS). E-cadherin immunostaining was positive in 74 and negative in 24 serous ovarian carcinomas. E-cadherin immunoreactivity was not associated with FIGO stage, residual tumor after initial cytoreductive surgery and number of chemotherapy cycles. Positive E-cadherin expression predict significantly better response to first line platinum-based chemotherapy (p < 0.001) and platinum sensitivity (p < 0.001). Moreover, positive E-cadherin expression predict significantly longer PFS (p < 0.001) and OS (p < 0.001). The multivariate analysis for OS showed that positive E-cadherin expression is predictor to platinum sensitivity (p < 0.001) and longer OS (p = 0.01). Positive E-cadherin expression seems to be a predictor of better response to first line platinum-based chemotherapy, platinum sensitivity and favorable clinical outcome in patients with advanced-stage serous ovarian cancer. Negative E-cadherin expression was shown to be significant, independent predictor of poorer PFS and OS. E-cadherin as a marker has predictive and prognostic value.

[Clinical recommendations for diagnosing, treatment and monitoring of patients with uterine cervical cancer -- Croatian Oncology Society and Croatian Society for Gynecology and Obstetrics as Croatian Medical Association units and Croatian Society of Gynecological Oncology]. / Klinicke upute za dijagnostiku, lijecenje i pracenje bolesnica oboljelih od raka vrata maternice hrvatskoga onkoloskog drustva i hrvatskog drustva za ginekologiju i opstetriciju hrvatskoga lije nickog zbora te hrvatskoga ginekoloskoonkoloskog drustva.

Cervical cancer, in comparison with other gynecological malignancies, mainly affects younger women. It can be prevented trough educational programs, screening and early detection. It also can be efficiently treated when it appears. Treatment modalities include surgery, chemotherapy and radiotherapy, according to the stage of the disease and patient condition. Treatment decisions should be made after multidisciplinary team discussion. Due to the significance of this disease it is important to define and implement standardized approach for diagnostic, treatment and monitoring algorithm as well. The following text presents the clinical guidelines in order to standardize the procedures and criteria for the diagnosis, management, treatment and monitoring of patients with uterine cervical cancer in the Republic of Croatia.

P53, MAPK, topoisomerase II alpha and Ki67 immunohistochemical expression and KRAS/BRAF mutation in ovarian serous carcinomas.

BACKGROUND: We investigated the immunohistochemical expression of p53, MAPK, topoisomerase II alpha (topoII alpha) and Ki67 in ovarian serous carcinomas (OSCs) along with mutational analysis for KRAS and BRAF. METHODS: Eighty one cases of OSCs were reviewed and examined immunohistochemically using antibodies against p53, MAPK, topoII alpha and Ki67. Staining was evaluated as a percentage of immunopositive cells with cut-off levels at 10% for p53 and topoII alpha, and 5% for MAPK. The Ki67 immunoexpression was assessed by means of Olympus Image Analysis System as a percentage of immunopositive cells in 1000 tumor cells. KRAS and BRAF mutational analysis was performed on 73 available microdissected samples. RESULTS: Of 81 cases of OSCs 13.6% were of low-grade and 86.4% were of high-grade morphology. In the high-grade group there was a significantly higher immunoexpression of p53 (P < 0.001) and topoII alpha (P = 0.001), with Ki67 median 56.5 vs. 19 in low-grade group (P < 0.001). The difference in immunoexpression of active MAPK between low- and high-grade group was also significant (P = 0.003). MAPK positive immunostaining was detected in 63.6% of low-grade vs. 17.1% of high-grade OSCs. The frequency of KRAS mutation was significantly higher in low-grade as compared to high-grade group (P = 0.006). None of the samples had BRAF mutation. In addition, we detected positive MAPK immunoexpression in 13/59 samples with wild-type KRAS, suggesting that activation of MAPK pathway is not ultimately related either to KRAS or BRAF mutation. Seven morphologically high-grade samples (11.7%) showed both KRAS mutation and p53 immunopositivity. CONCLUSIONS: Although this study is limited by its humble number of low-grade samples, our data fit the proposed dualistic pathway of ovarian carcinogenesis. Mutational analysis for KRAS and BRAF discloses some possible interactions between different tumorigenic pathways of low- and high-grade carcinomas. Immunohistochemical staining for MAPK was not sufficiently sensitive, nor specific, to precisely predict the KRAS mutation. However, it appears to be quite reliable in ruling out a KRAS mutation if the staining is negative. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9283563368804632.

[Clinical recommendations for diagnosis, treatment and monitoring of patients with invasive breast cancer]. / Klinicke upute za dijagnozu, lijecenje i pracenje bolesnika oboljelih od invazivnog raka dojke.

Breast cancer is the most common malignancy in women. Preventive measures, early diagnosis and development of all treatment modalities (surgery, radiotherapy, chemotherapy, hormonal and targeted biologic therapy) led to improvement in survival and quality of life of the patient. In order to standardize and optimize the approach, following good clinical practice standards, we bring consensus guidelines for diagnosis, treatment and monitoring of breast cancer patients as a result of consensus of a multidisciplinary team of experts for breast cancer.

Long-lasting control of triple-negative metastatic breast cancer with the novel drug combination ixabepilone and capecitabine--case report.

BACKGROUND: The optimal duration of ixabepilone and capecitabine chemotherapy combination is currently not known and will most likely be patient-specific based on efficacy, toxicity, quality of life, and patient preference. CASE REPORT: We report an extremely long duration of chemotherapy with ixabepilone and capecitabine (42 cycles) in a patient with triple-negative metastatic breast cancer previously treated with anthracyclines and taxanes. Partial remission was achieved, and acceptable toxicity was observed. CONCLUSIONS: This report adds to the pool of knowledge regarding the use of this important new metastatic breast cancer regimen, especially with respect to the optimal duration of its use.