Genetic testing and counseling challenges in personalized breast cancer care: review article with insights from Türkiye.

According to current evidence, testing for germline BRCA pathogenic variants in newly diagnosed breast cancer (BC) patients has the potential to reduce the burden of the disease through targeted therapies and secondary prevention. A personalized approach to testing can lead to improved individual outcomes for patients. Despite the proven clinical utility and therapeutic impact of BRCA1/2 tests in shaping therapy for metastatic BC, awareness and access to these tests are limited in many developing countries, including Türkiye. This limitation impacts the healthcare economy as delayed or missed interventions can lead to increased long-term costs. The limited access is mainly due to fear of stigmatization among patients, country-specific legislation and costs, a lack of awareness, vagueness surrounding the tests and access restrictions. This review offers a perspective for policymakers and healthcare providers in Türkiye to establish pathways that integrate the patient experience into comprehensive care pathways and national cancer control plans.

Recent studies show that testing for a specific gene change in people newly diagnosed with breast cancer can help reduce the impact the disease has on their life as they can be given special treatments. When tests are tailored to each person, they can get better results. However, in many countries, including Türkiye, not many people know about or can get these tests. This is because of concerns about being judged, rules in the country, the cost, confusion about the tests and limited access. Not having these tests can make healthcare more expensive in the long run. This article suggests ways for Türkiye's leaders and health workers to make these tests a regular part of cancer care and planning.

The efficacy of immunotherapy and chemoimmunotherapy in patients with advanced rare tumors: A Turkish oncology group (TOG) study.

INTRODUCTION: The advances in immune checkpoint inhibitors (ICIs) were relatively slow in rare tumors. Therefore, we conducted a multi-center study evaluating the efficacy of ICI monotherapy and the combination of ICIs with chemotherapy (CT) in patients with advanced rare tumors. METHODS: In this retrospective cohort study, we included 93 patients treated with ICIs for NCI-defined rare tumors from the 12 cancer centers in Turkey. The primary endpoints were the overall response (ORR) and disease control rate (DCR). RESULTS: The cohort's median age was 56, and 53.8% of the patients were male. The most frequent diagnosis was sarcoma (29%), and 81.7% of the patients were previously treated with at least one line of systemic therapy in the advanced stage. The ORR and DCR were 36.8% and 63.2%, respectively. The germ cell tumors had the lowest ORR (0%), while the Merkel cell carcinoma had the highest ORR to ICIs (57.1%). Patients treated with ICI + ICI or ICI plus chemotherapy combinations had higher ORR (55.2% vs. 27.6%, p = 0.012) and DCR (82.8% vs. 53.4%, p = 0.008). The median OS was 13.47 (95% CI: 7.79-19.15) months, and the six and 12-month survival rates were 71% and 52%. The median duration of response was 16.59 months, and the 12-month progression-free survival rate was 66% in responders. The median time-to-treatment failure was 5.06 months (95% CI: 3.42-6.71). Three patients had high-grade irAEs with ICIs (grade 3 colitis, grade 3 gastritis, and grade 3 encephalitis in one patient each). CONCLUSION: We observed over 30% ORR and a 13-month median OS in patients with rare cancers treated with ICI monotherapy or ICI plus CT combinations. The response rates to ICIs or ICIs plus CT significantly varied across different tumor types. Responding patients had over 2 years of survival, highlighting a need for further trials with ICIs for patients with rare tumors.

The safety and efficacy of first-line atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma: A multicenter real-world study from Turkey.

The aim of the study was to evaluate the real-world clinical outcomes of atezolizumab and bevacizumab (Atez/Bev) as the initial therapy for advanced hepatocellular carcinoma (HCC). We retrospectively analyzed 65 patients treated with Atez/Bev for advanced HCC from 22 institutions in Turkey between September 2020 and March 2023. Responses were evaluated by RECIST v1.1 criteria. The median progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Cox regression model was employed to conduct multivariate analyses. The median age was 65 (range, 22-89) years, and 83.1% of the patients were male. A total of 1.5% achieved a complete response, 35.4% had a partial response, 36.9% had stable disease, and 26.2% had progressive disease. The disease control rate was 73.8% and associated with alpha-fetoprotein levels at diagnosis and concomitant antibiotic use. The incidence rates of any grade and grade ≥ 3 adverse events were 29.2% and 10.7%, respectively. At a median follow-up of 11.3 (3.4-33.3) months, the median PFS and OS were 5.1 (95% CI: 3-7.3) and 18.1 (95% CI: 6.2-29.9) months, respectively. In univariate analyses, ECOG-PS ≥ 1 (relative to 0), Child-Pugh class B (relative to A), neutrophil-to-lymphocyte ratio (NLR) > 2.9 (relative to ≤ 2.9), and concomitant antibiotic use significantly increased the overall risk of mortality. Multivariate analysis revealed that ECOG-PS ≥ 1 (HR: 2.69, P = .02), NLR > 2.9 (HR: 2.94, P = .017), and concomitant antibiotic use (HR: 4.18, P = .003) were independent predictors of OS. Atez/Bev is an effective and safe first-line therapy for advanced-stage HCC in a real-world setting. The survival benefit was especially promising in patients with a ECOG-PS score of 0, Child-Pugh class A, lower NLR, and patients who were not exposed to antibiotics during the treatment.

Is there any prognostic significance in pleural involvement and/or effusion in patients with ALK-positive NSCLC?

PURPOSE: Anaplastic lymphoma kinase (ALK) mutations occurs in approximately 3-5% of patients with non-small cell lung cancer (NSCLC). Pleural involvement/effusion is common in ALK-positive patients with NSCLC at baseline. The aim of the study was to evaluate the characteristics of ALK-positive patients who have Ple-I/E. METHODS: In this multicenter study, patients with ALK-positive NSCLC who have Ple-I/E were retrospectively analyzed. Clinical and demographic characteristics of the disease, response rates, median progression-free survival (PFS), and overall survival (OS) were evaluated in 362 ALK-positive patients with NSCLC. RESULTS: Of the patients, 198 (54.7%) were male. The median age at the time of diagnosis was 54 (range 21-85) years. All patients' histology was adenocarcinoma (100%). At baseline, 57 (15.7%) patients had Ple-I/E. There was no association between Ple-I/E and gender, lung metastasis, or distant lymphadenopathy (LAP) metastasis. The frequencies of liver, brain, and bone metastases were significantly higher in ALK-positive patients without Ple-I/E compared to those with Ple-I/E (respectively 18.2% vs 4.8%, p = 0.008; 19.1% vs 4.8%, p = 0.001; 20.6% vs 8.9%, p = 0.002). The median PFS was longer in ALK-positive patients who had Ple-I/E (18.7 vs 10.6 months, p = 0.017). Similarly, the median OS was longer in ALK-positive patients who had Ple-I/E (44.6 vs 22.6 months, p = 0.051). CONCLUSION: Brain, liver, and bone metastases were lower in ALK-positive patients with Ple-I/E. Patients presented with Ple-I/E were prone to have better PFS and OS.

Safety of lorlatinib in ALK-positive non-small-cell lung cancer and management of central nervous system adverse events.

The use of tyrosine kinase inhibitors has made a breakthrough in the treatment of non-small-cell lung cancer (NSCLC). Recently, lorlatinib, a third-generation tyrosine kinase inhibitor, has demonstrated significant systemic and intracranial activity in both first-line and subsequent-line therapy in ALK-positive NSCLC patients. In this review, general characteristics of lorlatinib, its efficacy in the treatment of ALK-positive NSCLC patients and the safety of lorlatinib, particularly addressing central nervous system adverse events, are discussed. Management of central nervous system adverse events, which seem to be specific to lorlatinib therapy, is outlined.

Lung cancer is a common disease and affects patients badly. Lorlatinib is a new and useful drug for this disease. But this drug has also some undesirable effects for the brain. These effects are generally mild and can be treated. This article discusses the undesirable effects of this drug on the brain and how to cope with these effects.

Uncommon variants detected via hereditary cancer panel and suggestions for genetic counseling.

OBJECTIVE: Hereditary cancer syndromes constitute 5-10% of all cancers. The development of next-generation sequencing technologies has made it possible to examine many hereditary cancer syndrome-causing genes in a single panel. This study's goal was to describe the prevalence and the variant spectrum using NGS in individuals who were thought to have a hereditary predisposition for cancer. MATERIAL AND METHOD: Analysis was performed for 1254 who were thought to have a familial predisposition for cancer. We excluded 46 patients who were carrying BRCA1/2 variants in this study, for focusing on the rare gene mutations. Sequencing was performed using the Sophia Hereditary Cancer Solution v1.1 Panel and the Qiagen Large Hereditary Cancer Panel. The Illumina MiSeq system was used for the sequencing procedure. The software used for the data analyses was Sophia DDM and QIAGEN Clinical Insight (QCITM) Analyze. The resulting genomic changes were classified according to the current guidelines of ACMG/AMP. RESULTS: Pathogenic/likely pathogenic variants were detected in 172 (13.7%) of 1254 patients. After excluding the 46 BRCA1/2-positive patients, among the remaining 126 patients; there were 60 (4.8%) breast cancer, 33 (2.6%) colorectal cancer, 9 (0.7%) ovarian cancer, 5 (0.4%) endometrium cancer, 5 (0.4%) stomach cancer, 3 (0.2%) prostate cancer patients. The most altered genes were MUTYH in 27 (2.1%) patients, MMR genes (MLH1, MSH6, MSH, MSH2, PMS2 and EPCAM) in 26 (2%) patients, and ATM in 25 (2%) patients. We also examined the genotype-phenotype correlation in rare variants. Additionally, we identified 11 novel variations. CONCLUSION: This study provided significant information regarding rare variants observed in the Turkish population because it was carried out with a large patient group. Personalized treatment options and genetic counseling for the patients are therefore made facilitated.

Treatment efficacy of ribociclib or palbociclib plus letrozole in hormone receptor-positive/HER2-negative metastatic breast cancer.

Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods: The authors report retrospective real-life data for 600 patients with estrogen receptor- and/or progesterone receptor-positive and HER2-negative metastatic breast cancer who were treated with ribociclib and palbociclib in combination with letrozole. Results & conclusion: The results demonstrated that the combination of palbociclib or ribociclib with letrozole has similar progression-free survival and overall survival benefit in real life for the patient group with similar clinical features. Specifically, endocrine sensitivity may be a factor to be considered in the treatment preference.

Impact of adding pertuzumab to trastuzumab plus chemotherapy in neoadjuvant treatment of HER2 positive breast cancer patients: a multicenter real-life HER2PATH study.

AIM: To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting. METHODS: A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR. RESULTS: Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p < 0.001) and lower relapse (4.5 vs. 12.2%, p < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p < 0.001) and NCT-HP (41.5 vs. 32.1%, p < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p = 0.008) significantly predicted the pCR. CONCLUSIONS: This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time.

External Validation of a Novel Risk Model in Patients With Favorable Risk Renal Cell Carcinoma Defined by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC): Results From the Turkish Oncology Group Kidney Cancer Consortium (TKCC) Database.

BACKGROUND: A novel prognostic model was recommended for patients with metastatic RCC (mRCC) by the International mRCC Database Consortium (IMDC). In this study, we aimed to externally validate a novel risk model for the IMDC-favorable risk group in patients with mRCC. METHODS: The Turkish Oncology Group Kidney Cancer Consortium (TKCC) is a multicenter registry that includes 13 cancer centers in Turkey. As described by Schmidt et al., 3 parameters (ie, time from diagnosis to systemic therapy <3 vs. ≥3 years, Karnofsky Performance Status [KPS] 80 vs. >80, and the presence of brain, liver, or bone metastasis) were used to divide the IMDC favorable risk group into 2 new categories: very favorable and favorable risk groups. The primary endpoint was overall survival (OS). Time to treatment failure (TTF) and objective response rate (ORR) in the very favorable and favorable risk groups were the secondary endpoints. RESULTS: A total of 545 patients with mRCC from all IMDC risk groups and 112 patients from the favorable risk group were included in this study. According to the novel classification model, 44 (39.3%) and 68 (60.7%) patients with former favorable risk were categorized into very favorable and favorable risk groups, respectively. The median OS (55.8 months vs. 34.2 months, P = .025) and TTF (25.5 months vs. 15.5 months, P = .010) were longer in the very favorable risk group than in the favorable risk group. The concordance index of the new IMDC model in all patients was 0.65 for OS. Despite the higher ORR in the very favorable risk group than in the favorable risk group, the difference between the groups was not statistically significant (52.4% vs. 44.7, P = .573). CONCLUSIONS: This was the first study to externally validate the novel IMDC risk model presented in the American Society of Clinical Oncology Genitourinary Cancers Symposium 2021.

Merkel cell carcinoma in Turkey: A multicentric study.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin. In this study, we aimed to evaluate the clinicopathologic characteristics, treatment outcomes, and survival of MCC cases in Turkey. MATERIALS AND METHODS: The patients diagnosed with MCC between 1999 and 2018 at twenty different centers in Turkey were included in the study. Patient and tumor characteristics and adjuvant and metastatis treatment outcomes were analyzed retrospectively. RESULTS: The median age of totally 89 patients was 70 (26-93). The most common primary location was lower limbs (n = 29, 32.5%). Immunohistochemically, CK20 positivity was present in 59 patients (66.3%). Only two patients had secondary malignancy. The majority of the patients (n = 76, 85.4%) were diagnosed at the localized stage. Surgery was performed for all patients in the early stage, and adjuvant radiotherapy or/and chemotherapy was applied to 52.6% (n = 40) of nonmetastatic patients. The median follow-up was 29 months. Recurrence developed in 21 (27.6%) of the 76 patients who presented with local or regional disease. Two-year disease-free survival (DFS) was 68.1% and 5-year DFS was 62.0% for localized stage. The 5-year DFS was similar for patients receiving adjuvant treatment (chemotherapy, radiotherapy, or sequential chemoradiotherapy) and without adjuvant therapy (P > 0.05). Two-year overall survival in patients who presented with localized disease was 71.3% and 18.5% in metastatic patients (P < 0.001). In the metastatic stage, platinum/etoposide combination was the most preferred combination regimen. Median progression-free survival (PFS) in first-line chemotherapy was 7 months (95% confidence interval: 3.5-10.5 months; standart error: 1.78). CONCLUSIONS: Although MCC is rare in Turkey, the incidence is increasing. Gender, CK20 status, tumor size, lymph node involvement, and adjuvant treatment were not associated with recurrence.

Pan-cancer landscape of CD274 (PD-L1) rearrangements in 283,050 patient samples, its correlation with PD-L1 protein expression, and immunotherapy response.

BACKGROUND: Immune checkpoint inhibitors (ICIs) benefit patients with multiple cancer types, however, additional predictive biomarkers of response are needed. CD274 (programmed cell death ligand-1, PD-L1) gene rearrangements are positively associated with PD-L1 expression and may confer benefit to ICI, thus a pan-cancer characterization of these alterations is needed. METHODS: We analyzed 283,050 patient samples across multiple tumor types that underwent comprehensive genomic profiling for activating CD274 rearrangements and other alterations. The DAKO 22C3 Tumor Proportion Scoring (TPS) method was used for PD-L1 immunohistochemistry (IHC) testing in a small subset with available data (n=55,423). A retrospective deidentified real-world clinico-genomic database (CGDB) was examined for ICI treatment outcomes. We also report a detailed case of CD274-rearranged metastatic rectal adenocarcinoma. RESULTS: We identified 145 samples with functional rearrangements in CD274. There were significant enrichments for PIK3CA, JAK2, PDCD1LG2, CREBBP, and PBRM1 co-mutations (ORs=2.1, 16.7, 17.8, 3.6, and 3.4, respectively, p<0.01). Genomic human papillomavirus (HPV)-16, Epstein-Barr virus, and mismatch repair genes also co-occurred (OR=6.2, 8.4, and 4.3, respectively, p<0.05). Median tumor mutational burden (TMB) was higher compared with CD274 wild-type samples (7.0 vs 3.5 mutations/Mb, p=1.7e-11), with disease-specific TMB enrichment in non-small cell lung, colorectal, unknown primary, and stomach cancers. PD-L1 IHC skewed toward positivity (N=39/43 samples with ≥1% positivity). Of eight patients from the CGDB, three remained on ICI treatment after 6 months. Separately, one patient with metastatic rectal adenocarcinoma experienced a pathologic complete response on chemoimmunotherapy. CONCLUSIONS: CD274 gene rearrangements are associated with increased PD-L1 IHC scores, higher TMB, and potential clinical benefit in ICI-treated patients with cancer.

Nivolumab in metastatic renal cell carcinoma: results from the Turkish Oncology Group Kidney Cancer Consortium database.

Aim: The authors present real-world data on the efficacy and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Methods: The Turkish Oncology Group Kidney Cancer Consortium (TKCC) database includes patients with mRCC from 13 cancer centers in Turkey. Patients with mRCC treated with nivolumab in the second line and beyond were extracted from the TKCC database. Results: A total of 173 patients were included. The rates of patients treated with nivolumab in the second, third, fourth and fifth lines were 47.4%, 32.4%, 14.5% and 5.7%, respectively. The median overall survival and progression-free survival were 24.2 months and 9.6 months, respectively. Nivolumab was discontinued owing to adverse events in 11 (6.4%) patients. Conclusion: Nivolumab was effective in patients with mRCC and no new safety signal was observed.

Lay abstract Nivolumab is an immune checkpoint inhibitor (ICI) that blocks the communication between T cells and cancer cells and instead activates T cells to fight against cancer. Metastatic renal cell carcinoma (mRCC) is one of the most susceptible tumors to ICIs. The Checkmate 025 trial showed the efficacy of nivolumab in patients with previously treated mRCC. In this real-world study, 173 patients with mRCC were treated with nivolumab in the second line and beyond. Nivolumab was effective in the real-world setting without additional safety concerns.

Comparison of real-life data of abiraterone acetate and enzalutamide in metastatic castration-resistant prostate cancer.

To compare enzalutamide (E) and abiraterone acetate (AA) in terms of efficacy, survival and to characterize prognostic factors affecting survival in metastatic castration-resistant prostate cancer (mCRPC) patients. A total of 250 patients treated with E or AA in 5 centers were included. The number of patients with no prostate specific antigen (PSA) decline was higher in the AA group than that in the E group, and the proportion of patients with a PSA decline of ≥ 50% was higher in the E group (p = 0.020). Radiological progression free survival (rPFS) and overall survival (OS) were significantly longer in the E group when compared to that in the AA group (p < 0.001 and p = 0.027, respectively). In the E group, rPFS was significantly longer than that in the AA group in both pre- and post-docetaxel settings (p = 0.010 and p = 0.003, respectively). OS was similar in the pre-docetaxel setting; but in the post-docetaxel setting, E group had a significantly longer OS than the AA group (p = 0.021). In the multivariate analysis performed in the whole patient group, we found that good prognostic factors for rPFS were E treatment, being ≥ 75 years and a PSA decline of ≥ 50% while there was no factor affecting OS. With longer OS and PFS, E seems to be more suitable for mCRPC patients in the post-docetaxel setting than AA.

The association between antibiotic use and survival in renal cell carcinoma patients treated with immunotherapy: a multi-center study.

BACKGROUND: Immunotherapy improves overall survival (OS) in the second and later lines of renal cell carcinoma (RCC) treatment. Recent studies have suggested that antibiotic (ATB) use either shortly before or after the start of immunotherapy could lead to decreased OS. Herein, we evaluate the impact of ATB use on OS in RCC patients treated with nivolumab in a multi-center cohort from Turkey. METHODS: The data of 93 metastatic RCC patients treated with nivolumab in the second line or later were retrospectively collected from 6 oncology centers. Previous treatments, sites of metastases, International Metastatic RCC Database Consortium risk classification, and ATB use in the three months before (-3) or three months after (+3) the start of immunotherapy were recorded together with survival data. The association of clinical factors with OS and progression-free survival (PFS) was analyzed with univariate and multivariable analyses. RESULTS: The median age was 61 (interquartile range 54-67), and 76.3% of the patients were male. The median OS of the cohort was 23.75 ± 4.41, and the PFS was 8.44 ± 1.61 months. Thirty-one (33.3%) patients used ATBs in the 3 months before (-3) or 3 months after (+3) nivolumab initiation. In the multivariable analyses, ATB exposure (HR: 2.306, 95% confidence interval [CI]: 1.155-4.601, P = 0.018) and the presence of brain metastases at the baseline (HR: 2.608, 95% CI: 1.200-5.666, P = 0.015) had a statistically significant association with OS, while ATB exposure was the only statistically significant parameter associated with PFS (HR: 2.238, 95% CI: 1.284-3.900, P = 0.004). CONCLUSION: In our study, patients with ATB exposure in the 3 months before or 3 months after the start of immunotherapy had shorter OS. Our findings further support meticulous risk-benefit assessments of prescribing ATBs for patients who are either receiving or are expected to receive immunotherapy.

Clinical Outcomes and Prognostic Factors in HER-2 Positive Breast Cancer with Brain Metastasis: A Single-centre Experience.

OBJECTIVE:  To determine the characteristics and prognosis of brain metastasised HER-2 positive breast cancer (BC) patients. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Ankara Oncology Training and Research Hospital, Turkey between 2000 and 2019. METHODOLOGY: HER-2 positive BC patients were analysed retrospectively and 105 patients were included in the study. Age 18 years and over, HER-2 positive BC, with BM (brain metastases) were the inclusion criteria. Patients with secondary malignancies, those with missing data, and irregular follow-up were excluded from the study. The age, type of treatment, Eastern Cooperative Oncology Group Performance Status (ECOG PS) score, BM date, and the last contact date of the patients were obtained from the hospital records. The Kaplan-Meier method was used to determine the time to BM and OS. Independent factors affecting OS and time to BM were determined using the Cox regression model. RESULTS: Patients with ECOG PS score of 0-1 at the time of the BM had 19 months median overall survival (OS), while patients with ECOG PS score of 2 had 8 months (p <0.01). Median OS after BM was 32 and 14 months for patients with one BM and patients with multiple BM, respectively (p <0.01). Multivariate cox regression analyses revealed that time to progression of BM was shorter in patients with high-grade tumors compared to patients with low-grade tumors (p= 0.048), and in patients with de-novo metastasis compared to patients without de-novo metastasis (p= 0.003). Conclusion: Tumor grade and de-novo metastasis (extracranial metastasis at the time of diagnosis) are independent predictive factors that may cause the earlier occurrence of BM and affect mortality in BC patients. Key Words: Brain metastasis, Breast cancer, HER-2 positive, Metastasis.

The Effect of Primary Surgery in Patients with De Novo Stage IV Breast Cancer with Bone Metastasis Only (Protocol BOMET MF 14-01): A Multi-Center, Prospective Registry Study.

BACKGROUND: More evidence shows that primary surgery for de novo metastatic breast cancer (BC) prolongs overall survival (OS) in selected cases. The aim of this study was to evaluate the role of locoregional treatment (LRT) in BC patients with de novo stage IV bone only metastasis (BOM). METHODS: The prospective, multicenter registry study BOMET MF14-01 was initiated in May 2014. Patients with de novo stage IV BOM BC were divided into two groups: those receiving systemic treatment (ST group) and those receiving LRT (LRT group). Patients who received LRT were further divided into two groups: ST after LRT (LRT + ST group) and ST before LRT (ST + LRT group). RESULTS: We included 505 patients in this study; 240 (47.5%) patients in the ST group and 265 (52.5%) in the LRT group. One hundred and thirteen patients (26.3%) died in the 34-month median follow-up, 85 (35.4%) in the ST group and 28 (10.5%) in LRT group. Local progression was observed in 39 (16.2%) of the patients in the ST group and 18 (6.7%) in the LRT group (p = 0.001). Hazard of death was 60% lower in the LRT group compared with the ST group (HR 0.40, 95% CI 0.30-0.54, p < 0.0001). CONCLUSION: In this prospectively maintained registry study, we found that LRT prolonged survival and decreased locoregional recurrence in the median 3-year follow-up. Timing of primary breast surgery either at diagnosis or after ST provided a survival benefit similar to ST alone in de novo stage IV BOM BC patients.

Tolvaptan treatment in hyponatremia due to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH): effects on survival in patients with cancer.

PURPOSE: To investigate the clinical outcomes of patients with hyponatremia who received supportive treatment or tolvaptan plus supportive treatment and the effects of treatment and other variables on overall survival METHODS: This study included oncology patients who were hospitalized at two oncology centers between January 1, 2016 and December 31, 2019 for hyponatremia (sodium levels < 135 mEq/L) and who received tolvaptan plus supportive treatment (n = 22) or supportive treatment only (n = 42). RESULTS: The median age of all the patients was 59 years (range 26-85) and 64.1% of the patients were male. There was no statistically significant difference between patients in the tolvaptan plus supportive treatment (TpST) group and the supportive treatment only (ST) group in terms of gender and age (p > 0.05). In the TpST group, recovery days of the hyponatremia after treatment and the length of hospital stay was shorter and hyponatremia symptoms and hospital complications were less frequent compared to the ST group (p < 0.05). There was no significant difference between the TpST group and the ST group in terms of overall survival (OS). OS was shorter in men who were non-responders to hyponatremia treatment and had recurrent hyponatremia. Multivariable analysis showed that normal sodium levels after treatment decreased the risk of death. CONCLUSION: In the treatment of hyponatremia in cancer patients, TpST was found to have more positive effects on blood sodium levels, length of hospital stay, hospital complications, and hyponatremia symptoms compared to ST. A decreased risk of death was observed in patients with normal sodium levels after treatment.

Clinical features of metaplastic breast carcinoma: A single-center experience.

AIM: Metaplastic breast cancer (MBC) is a rare subtype with unusual clinical features. We aimed to analyze treatment results and define patients' characteristic features in our large MBC patient series. MATERIALS AND METHODS: Fifty-six patients with early MBC who received adjuvant radiotherapy (RT) in our center were included in the study. The age, sex, subtypes of MBC, histopathology, hormone and nodal status, tumor size, and types of treatment were retrospectively provided from hospital records. RESULTS: The median tumor size was 4 (1.3-16.5) cm, and triple-negative MBC cases were 38 (67.8%) of all patients. Axillary nodal involvements were present in 25 (44.6%) patients. The median follow-up time was 45.8 (4.9-130) months; the overall survival (OS) and disease-free survival (DFS) for 5 years were 67% and 64%, respectively. While distant metastases were seen in 15 (26.7%) patients, local recurrences were seen in only 4 patients. The median OS and DFS were higher in patients with ≤5.2 cm tumor than >5.2 cm ([130 vs. 49 months, P = 0.01] and [130 vs. 30 months, P = 0.009], respectively). Nodal involvement, hormone receptor status, surgical treatment, and type of RT had no effect on survival. In multivariate analysis, tumor size was not an independent prognostic factor for OS (P = 0.068; hazard ratio [HR]: 3.4, 95% confidence interval [CI] = 0.91-12.8), whereas age >65 years was found an independent poor prognostic factor for OS ([HR: 4.25, 95% CI: 0.23-0.78, P = 0.021] and DFS [HR: 3.1, 95% CI: 0.02-0. 87; P = 0.04], respectively). CONCLUSIONS: Distant metastasis is at the forefront rather than local recurrence in MBC patients. More studies are needed to determine the factors that affect survival independently in MBC.

Does a Secure Attachment Style Predict High Psychological Resilience in Patients With Cancer Receiving Chemotherapy?

Introduction To investigate the level of psychological resilience and the impact of attachment styles on the degree of resilience to distress in patients with cancer receiving chemotherapy. Methods Patients with cancer receiving chemotherapy were included in the study. Participants were requested to complete the Relationship Scales Questionnaire (RSQ), Resilience Scale for Adults (RSA), and a personal information form during the data collection phase. One-way analysis of variance (ANOVA) was used to compare that parameter among the attachment styles. Logistic regression analysis was carried out to identify independent factors affecting resilience. Results A total of 384 individuals were included in this study (mean age 53.5 ± 12.1, 27.1 % male). The RSQ results showed that the attachment styles of 190 (49.5%) participants were secure, whereas 194 (50.5%) subjects had an insecure attachment. The median RSA score of participants with a secure attachment was significantly higher than that of patients with insecure attachment (133.15 ± 16.6 vs. 127.0 ± 20.0, p=0.001). Patients with the RSA score of >130 were more educated, were in better economic condition, had better perceived social support, and had a higher frequency of secure attachment than those defined as low resilient. Logistic regression analysis revealed that poor and medium perceived social support and insecure attachment style independently predicted low resilience (RSA≤130). Conclusion This study demonstrates that the secure attachment style in patients with cancer improves stress resilience as compared to the insecure attachment style. Our findings also show that insufficient perceived social support is likely a negative factor in resilience.