Efficacy of first-line CDK 4-6 inhibitors in premenopausal patients with metastatic breast cancer and the effect of dose reduction due to treatment-related neutropenia on efficacy: a Turkish Oncology Group (TOG) study.

The only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival. Our study is a multicenter, retrospective study, and factors affecting progression-free survival (PFS) were examined in patients diagnosed with metastatic premenopausal breast cancer from 29 different centers and receiving combination therapy containing palbociclib or ribociclib in the metastatic stage. 319 patients were included in the study. The mPFS for patients treated with palbociclib was 26.83 months, and for those receiving ribociclib, the mPFS was 29.86 months (p = 0.924). mPFS was 32.00 months in patients who received a reduced dose, and mPFS was 25.96 months in patients who could take the initial dose, and there was no statistical difference (p = 0.238). Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor. No new adverse events were observed. In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.

The efficacy of palbociclib and ribociclib in the first-line treatment of metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer in male patients: a Turkish oncology group (TOG) study.

INTRODUCTION: Male breast cancer, comprising approximately 1% of all breast cancer cases, often leads to the exclusion of male patients as a criterion in clinical trials. While the efficacy of Cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors has been established in metastatic hormone receptor-positive (HR +) and human epidermal growth factor receptor 2-negative (HER2 -) breast cancer in women, limited data exist on their effectiveness in male patients. We aimed to evaluate the efficacy and safety of palbociclib or ribociclib in male patients with breast cancer. METHODS: This study is a multicenter, retrospective study. We included male patients with HR + and HER2-metastatic breast cancer who received palbociclib or ribociclib as first-line treatment. Our primary endpoints were progression-free survival (PFS), overall response rates (ORR), and drug-related adverse effects. RESULTS: A total of 46 male patients from 27 institutions were enrolled. The median age at initiation of CDK 4/6 inhibitors was 63.64 ± 13.69 years, with a median follow-up of 21.33 (95% CI 14.92-27.74) months. The ORR were 84% for palbociclib and 76.2% for ribociclib. The mPFS for the entire cohort was 28.06 months (95% CI 18.70-37.42). No significant difference in PFS was observed between palbociclib and ribociclib (mPFS: 24.46 months (95% CI 11.51-37.42) vs 28.33 months (95% CI 14.77-41.88), respectively, p = 0.211). No new adverse events were reported. DISCUSSION: This study demonstrates that palbociclib and ribociclib are effective and safe options for first-line treatment in male patients with HR + /HER2 - metastatic breast cancer. However, further prospective studies are warranted to establish their efficacy in this population.

Successful treatment with carboplatin and paclitaxel in melanoma progression after immune-related adverse events.

The overall survival of melanoma patients has improved using antibodies targeting immune checkpoints (anti-PD-1, anti-CTLA-4 and anti-LAG-3). Systemic chemotherapy was administered in melanoma for many years with limited effectiveness. Here we report a case of a patient who experienced immune-mediated adverse effects from checkpoint blockade therapy and subsequently responded to chemotherapy. The patient presented with melanoma and paraneoplastic digital ischemia. She received a combination of ipilimumab/nivolumab and experienced G3 myocarditis, followed by melanoma progression after a steroid taper. This patient achieved a partial and durable response with platinum and taxane-based chemotherapy. This report suggests the possibility of a subset of patients who experience progression after immune-based side effects where chemotherapy may be effective in the modern age of melanoma treatment.

We describe a patient with a type of skin cancer called melanoma. At first, we tried to treat it with a medication that made the patient's body's defense system fight against it, but it caused problems with her heart so we had to stop it. Instead, we used another type of treatment called chemotherapy, which worked. The patient remains off therapy 4.5 years later. The lesson learned from this case is that chemotherapy is still helpful in certain situations. The initial treatment did not stop the melanoma growth. In addition, the patient had life-threatening toxicity.

Efficacy and toxicity of adjuvant radiotherapy in recurrent melanoma after adjuvant immunotherapy.

BACKGROUND: In patients with stage III melanoma, despite surgical resection and adjuvant systemic therapy, locoregional recurrences still occur. The randomized, phase III Trans-Tasman Radiation Oncology Group (TROG) 02.01 trial demonstrated that adjuvant radiotherapy (RT) after complete lymphadenectomy (CLND) halves the incidence of melanoma recurrence within local nodal basins without improving overall survival or quality of life. However, the study was conducted prior to the current era of adjuvant systemic therapies and when CLND was the standard approach for microscopic nodal disease. As such, there is currently no data on the role of adjuvant RT in patients with melanoma who recur during or after adjuvant immunotherapy, including those that may or may not have undergone prior CLND. In this study, we aimed to answer this question. METHODS: Patients with resected stage III melanoma who received adjuvant anti-programmed cell death protein-1 (PD-1) (±ipilimumab) immunotherapy with a subsequent locoregional (lymph node and/or in-transit metastases) recurrence were retrospectively identified. Multivariable logistic and Cox regression analyses were conducted. Primary outcome was rate of subsequent locoregional recurrence; secondary outcomes were locoregional recurrence-free survival (lr-RFS2) and overall RFS (RFS2) to second recurrence. RESULTS: In total, 71 patients were identified: 42 (59%) men, 30 (42%) BRAF V600E mutant, 43 (61%) stage IIIC at diagnosis. Median time to first recurrence was 7 months (1-44), 24 (34%) received adjuvant RT and 47 (66%) did not. Thirty-three patients (46%) developed a second recurrence at a median of 5 months (1-22). The rate of locoregional relapse at second recurrence was lower in those who received adjuvant RT (8%, 2/24) compared with those who did not (36%, 17/47, p=0.01). Adjuvant RT at first recurrence was associated with an improved lr-RFS2 (HR 0.16, p=0.015), with a trend towards an improved RFS2 (HR 0.54, p=0.072) and no effect on risk of distant recurrence or overall survival. CONCLUSION: This is the first study to investigate the role of adjuvant RT in patients with melanoma with locoregional disease recurrence during or after adjuvant anti-PD-1-based immunotherapy. Adjuvant RT was associated with improved lr-RFS2, but not risk of distant recurrence, demonstrating a likely benefit in locoregional disease control in the modern era. Further prospective studies are required to validate these results.

Real life experience of patients with locally advanced gastric and gastroesophageal junction adenocarcinoma treated with neoadjuvant chemotherapy: a Turkish oncology group study.

Neoadjuvant chemotherapy (NACT) in gastroesophageal junction (GEJ) and gastric cancer (GC) was shown to improve survival in recent studies. We aimed to share our real-life experience of patients who received NACT to compare the efficacy and toxicity profile of different chemotherapy regimens in our country. This retrospective multicentre study included locally advanced GC and GEJ cancer patients who received NACT between 2007 and 2021. Relation between CT regimens and pathological evaluation were analysed. A total of 794 patients from 45 oncology centers in Turkey were included. Median age at the time of diagnosis was 60 (range: 18-86). Most frequent NACT regimens used were FLOT (65.4%), DCF (17.4%) and ECF (8.1%), respectively. In the total study group, pathological complete remission (pCR) rate was 7.2%, R0 resection rate 86.4%, and D2 dissection rate was 66.8%. Rate of pCR and near-CR (24%), and R0 resection (84%) were numerically higher in FLOT arm (p > 0.05). Patients who received FLOT had also higher chemotherapy-related toxicity rate compared to patients who received other regimens (p > 0.05). Median follow-up time was 16 months (range: 1-154 months). Estimated median overall survival (OS) was 58.4months (95% CI: 35.2-85.7) and disease-free survival (DFS) was 50.7 months (95% CI: 25.4-75.9). The highest 3-year estimated OS rate was also shown in FLOT arm (68%). We still do not know which NACT regimen is the best choice for daily practice.  Clinicians should tailor treatment regimens according to patients' multifactorial status and comorbidities for to obtain best outcomes. Longer follow-up period needs to validate our results.

Is adipose tissue metabolic activity a predictor of pathological responses to neoadjuvant treatment in breast cancer.

INTRODUCTION AND OBJECTIVE: Prediction of the pathologic response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer is essential for optimal treatment strategy. The current approach of adjuvant or neoadjuvant treatment is based on the molecular subtype. Obesity may have affected chemotherapy response. This study aims to evaluate the relationship between metabolic activity of adipose tissue (AT) and pathological responses to NAC. And to define the association with body mass index (BMI) and metabolic parameters of standardized uptake value (SUV) of adipose tissue measured by positron emission computed tomography (PET/CT). MATERIAL AND METHODS: One-hundred and sixteen consecutive patients with stage II and III breast cancer who underwent PET/CT before receiving NAC, were evaluated in the study. Metabolic parameters of visceral adipose tissue (VAT-SUV), subcutaneous adipose tissue (SAT-SUV), and calculated SUV of visceral-to-subcutaneous ratio (V/S-ratio) were regarded. The relationship between SUV of AT and pathologic response was evaluated from medical records retrospectively. RESULTS: Univariate-analysis revealed that good pathological response was significantly associated with clinical stage (P<.001), HER-2 positivity (P<.001), VAT-SUV (P=.037), VAT-density (P=.043) and V/S-ratio (P=.003). In multivariate-analysis clinical stage, HER-2 positivity and V/S-ratio were found to have statistically effect on pathological response. VAT-volume (P<.001), VAT-SUV (P=.016), SAT-volume (P<.001) and SAT-SUV (P<.001) has positive correlation with BMI value. On the other hand, V/S-ratio (P=.039) and SAT-density (P=.003) has negative correlation with BMI. CONCLUSION: Metabolic activity of AT is associated with BMI and effected chemotherapy responses. LowV/S ratio was associated with high BMI and poor pathological response to NAC. V/S ratio may be a useful marker for the prediction of NAC responses.

Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group).

BACKGROUND: Perioperative FLOT regimen is a standard of care in locally advanced operable gastric and GEJ adenocarcinoma. We aimed to determine the efficacy, prognostic factors of perioperative FLOT chemotherapy in real-life gastric and GEJ tumors. METHODS: The data of patients who were treated with perioperative FLOT chemotherapy were retrospectively analyzed from 34 different oncology centers in Turkey. Baseline clinical and demographic characteristics, pretreatment laboratory values, histological and molecular characteristics were recorded. RESULTS: A total of 441 patients were included in the study. The median of age our study population was 60 years. The majority of patients with radiological staging were cT3-4N(+) (89.9%, n = 338). After median 13.5 months (IQR: 8.5-20.5) follow-up, the median overall survival was NR (95% CI, NR to NR), and median disease free survival was 22.9 (95% CI, 18.6 to 27.3) months. The estimated overall survival at 24 months was 62%. Complete pathological response (pCR) and near pCR was achieved in 23.8% of all patients. Patients with lower NLR or PLR have significantly longer median OS (p = 0.007 and p = 0.033, respectively), and patients with lower NLR have significantly longer median DFS (p = 0.039), but PLR level did not affect DFS (p = 0.062). The OS and DFS of patients with better ECOG performance scores and those who could receive FLOT as adjuvant chemotherapy instead of other regimens were found to be better. NLR was found to be independent prognostic factor for OS in the multivariant analysis. At least one adverse event reported in 57.6% of the patients and grade 3-4 toxicity was seen in 23.6% patients. DISCUSSION: Real-life perioperative FLOT regimen in operable gastric and GEJ tumors showed similar oncologic outcomes compared to clinical trials. Better performance status, receiving adjuvant chemotherapy as same regimen, low grade and low NLR and PLR improved outcomes in real-life. However, in multivariate analysis, only NLR affected OS.

Is the benefit of using adjuvant capecitabine in patients with residual triple-negative breast cancer related to pathological response to neoadjuvant chemotherapy?

BACKGROUND: Triple-negative-breast-cancer (TNBC) has a poor prognosis if pathologic complete response (pCR) cannot be achieved following neoadjuvant chemotherapy (NAC). The group of patients that benefit most from adjuvant capecitabine remains unclear. MATERIALS AND METHODS: We analyzed data of 160 consecutive patients with residual TNBC from eight cancer-center. Pathologic response was defined into two groups as having good-pathologic-response (MillerPayneGrading (MPG) IV-III) or poor-pathologic-response (MPG I-II). The characteristics of patients were compared regarding adjuvant capecitabine usage. RESULTS: Univariate-analysis revealed that age, histology, clinical-stage, tumor-size, lymph-nodes number, menopausal status, and pathological-stage were significantly different between two groups. In multivariate-analysis, menopausal status (p = 0.043) and residual tumor-size (p < 0.001) were found to be independent prognostic factors for pathological response. The hazard-ratio for disease recurrence and death in the poor-response group with adjuvant capecitabine was 2.94 (95% confidence-interval (CI), 1.21 to 7.10; p = 0.016) and 4.080 (95% CI, 1.22 to 13.64; p = 0.022), respectively. DFS (p = 0.58) and OS (p = 0.89) improvements with adjuvant capecitabine were not demonstrated in good-response groups. CONCLUSION: This multicenter-study suggested that only the poor-response group to NAC achieved benefit from adjuvant capecitabine. Postmenopausal status and residual tumor-size were related to poor prognosis.

FOLFIRINOX versus gemcitabine plus nab-paclitaxel as the first-line chemotherapy in metastatic pancreatic cancer.

Pancreas cancer (PCa) is one of the mortal cancer types with ranking as fourth leading cancer death in both sexes together. FOLFIRINOX (FFX) and Gemcitabine plus nab-paclitaxel (GNP) are approved as first-line metastatic treatment in PCa. The aim of this study was to compare the clinical outcomes, treated with FFX and GNP as first-line metastatic PCa. Medical records of patients diagnosed with metastatic PCa, from January 2010 to December 2020 were analyzed. This study was a retrospective cohort, multi-institution analysis. The focus of the present study was to compare the efficiency of FFX and GNP chemotherapy combinations in the first-line treatment of PCa. Efficacy had been measured by progression-free survival (PFS) and overall survival (OS). 182 patients diagnosed with PCa receiving metastatic first-line treatment were retrospectively analyzed. Patients were divided into two groups one hundred and three (56.6%) patients treated with FFX and seventy-nine (43.4%) patients treated with GNP. Patients in the FFX group were younger and had a better ECOG performance status. Overall response rate (ORR) was 69.9% in FFX and 37.9% in GNP group (p: 0.000). Disease control rate (DCR) was 73.7% in patients treated with FFX and 39.2% in GNP group (p: 0.000). The median PFS was 8.3 months (FFX 9.1 vs. GNP 6.7, HR = 0.25, 95% CI: 0.16-0.38) the median OS was 12.2 months (FFX 14.1 vs. GNP 9.6, HR = 0.48, 95% CI: 0.31-0.72). Guidelines recommend both FFX and GNP regimens as a first-line treatment of metastatic PCa. In clinical routine, it is still unclear which regiment is more effective. The present study showed increased survival parameters with FFX versus GNP with similar toxicity profiles.

Role of tumor location on high-grade serous ovarian cancer prognosis.

OBJECTIVES: Ovarian cancer is associated with the highest mortality of gynecologic cancers. Epidemiological and genetic factors of ovarian cancer development are clearly defined but prognostic factors have not been adequately identified. Right and left ovarian cancers seem to act different behaviors at high-grade serous ovarian cancer (HGSOC) prognosis. The aim of this study is to explain this prognostic role of its sidedness. The aim of this study is to explain this prognostic role of its sidedness. MATERIAL AND METHODS: We reviewed 160 consecutive patients with Figo stage 1-3 HGSOCs and undergone surgery at two high-volume hospitals. Prognostic effects of primary tumor location onset were evaluated in terms of 5-year disease free survival and overall survival rate. RESULTS: One hundred-sixty patients with ovarian cancer records were analyzed using the Kaplan-Meier method, that demonstrated a significant difference in the 5-year disease-free survival rates between right and left-sided cancers for all stages (44.6% vs 78.5%, p < 0.001). Also, there was significant difference in the 5-year overall survival rates between the two groups (71.1% vs 91.9%, p = 0.020). CONCLUSIONS: Tumor location within the HGSOC seems to be a compelling prognostic factor ovarian cancer. Further prospective studies are needed in order to support our hypothesis.

Initial Ca 125 Value as a Predictive Marker for High-grade Serous Ovarian Cancer.

OBJECTIVE: To determine the relevance between the cut-off level of cancer antigen 125 (CA 125) level and long-term prognosis in high-grade serous ovarian cancer (HGSCs). STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Departments of Oncology, Medeniyet University Goztepe Education and Research Hospital, and Kartal Lutfi Kirdar Education and Research Hospital, Istanbul, Turkey, from January 2017 to June 2019. METHODOLOGY: Medical records of 230 women with HGSC were reviewed randomly from two Oncology Clinics. Descriptive analysis and CA 125 marker levels were evaluated with five years of disease-free survival rate (DFS) and overall survival rate (OS). Patients were divided into groups of high and low initial CA 125 levels (cut-off ≥385U/ml). The ability of initial serum CA 125 levels in predicting the presence of marker-recurrence of ovarian cancer were analysed using ROC (Receiver operating characteristics) curve analysis. RESULTS: Statistically significant predictive value of initial CA 125 level was calculated as 385U/ml (p=0.008). The 5-year DFS of high and low CA 125 levels for all stages in HGSC was statistically significant (p<0.001). The sub-group analysis demonstrated that the significant survival difference was especially in FIGO stage III. Patients with HGSC <385 U/ml had a significantly improved 5-year DFS and OS rates within stage III disease: 5-year DFS (p = 0.008) and 5-year OS (p = 0.004) according to the stratification of CA 125 level. CONCLUSION: Initial CA 125 level appeared to be of beneficial clinical predictive value for HGSC. Key Words: Initial CA 125, Tumor marker, High-grade serous ovarian cancer, Disease-free survival, Overall survival, Predictive value.

Mechanisms of Resistance to BRAF-Targeted Melanoma Therapies.

About half of all cutaneous melanomas harbor activating mutations in the BRAF oncogene. Dependence on this pathway makes the tumors vulnerable to BRAF (and downstream MEK) inhibition, and three drug combinations are approved to target this vulnerability in advanced melanomas with BRAFV600 mutations. Responses to BRAF/MEK inhibitors are usually fast, but durability of response can be limited. Five-year data from BRAF/MEK inhibitors show long-term survival benefit for a third of the patients. There is a wide variety of known mechanisms of resistance to BRAF/MEK inhibition, such as mitogen-activated protein kinase reactivation, activation of parallel pathways, alterations in cell-cycle regulation, and non-genetic resistance mechanisms. Strategies that have been explored to overcome these mechanisms include alternative dosing regimens, addition of another kinase inhibitor, and use of anti-PD-1 immunotherapy either in combination or post-relapse on BRAF/MEK inhibitor therapies.

Is the duration of castration resistance predictive for sequential treatment responses in the metastatic castration-resistant prostate cancer setting?

OBJECTIVE: Prostate cancer is the second leading cause of cancer death in men. Androgen deprivation therapy (ADT) has been the primary therapeutic approach for treatment of prostate cancer. However,nearly all patients develop the castration-resistant disease . We evaluated real-world data with abiraterone and enzalutamide treatment. By this data, we aimed to analyze whether that prior short response to ADT could predict response to subsequent therapy with androgen receptor axis targeted agent (ARATA). MATERIAL AND METHOD: We collected data from two cancer centers, 151 consecutive patients with treated abiraterone or enzalutamide in the first line of metastatic castration resistant prostat cancer (mCRPC) setting were included. The patients who received docetaxel in castration naive setting is also included. Time to castration resistance (TTCR) was defined as the duration from the initial to failure of primary ADT. RESULTS: Patients with treated ARATA were divided into two groups according to the time to castration resistance (TTCR). Patients who became resistant to ADT up to one year had a median PFS of 6.6 months, compared to median PFS of 13.3 months for patients who responded ADT for more than 1 year. (p = 0.002). In the post-docetaxel setting, median PFS is 12.6 months of patients with treated ARATA who had TTCR for more than one year, and median PFS is 6.6 months in those who had TTCR less than one year (p = 0.007).Univariate and multivariate analyses were performed to determine the clinical factors on ARATA outcomes. Eastern Cooperative Oncology Group (ECOG) performance status(PS), median prostate-specific antigen(PSA) and time to CRPC were significantly predicted outcomes of ARATA on multivariate analysis. CONCLUSION: TTCR is also a predictor for PFS of the patients who were treated ARATA both whole cohort and post-docetaxel.

Prognostic Factors and Tumor Infiltrating Lymphocytes in Triple Negative Breast Cancer.

OBJECTIVE: Triple-negative-breast-cancer (TNBC) is a very heterogenous disease some of which are very aggressive and have poor prognosis. No targeted therapy is available. Immune response and tumor-infiltrating lymphocytes (TIL) can be related to longer disease-free survival (DFS) and overall survival (OS) in TNBC. Family history of cancer can be related poor prognosis, irrespective of genetic mutation. MATERIALS AND METHODS: Pathology reports and files of 167 patients operated for TNBC were assessed retrospectively. The effects of lymphocyte infiltration, family history of cancer and other tumor characteristics on prognosis were evaluated. Data of 137 patients was included in statistical analysis. RESULTS: Univariate-analysis revealed that stage, size of tumor, histological subtype, number of infiltrated axillary lymph-nodes, lymphatic and vascular invasion, choice of adjuvant/neoadjuvant chemotherapy, family history of cancer has a statistically significant effect on DFS. Increase in density of lymphocyte infiltration of tumor has also better a prognostic effect on DFS (p=0.02). In multivariate-analysis, only tumor size and choice of adjuvant/neoadjuvant chemotherapy are found to have statistically significant effect. CONCLUSION: Tumor lymphocyte infiltration was found to have a statistically significant better prognostic effect on DFS but not on OS of patients with operated TNBC. This result can be due to variability of therapies administered after recurrence and other confounding factors that may have an effect on OS.

Long-lasting response with polycythemia to third-line axitinib treatment in metastatic renal cell carcinoma: Very rare case presentation.

INTRODUCTION: Clear cell renal cell carcinoma is characterized by mutation or inactivation of Von Hippel-Lindau suppressor gene. The mutation of Von Hippel-Lindau mechanism is associated with the upregulation of the hypoxia-inducible factor protein, inducing the overexpression of proteins including erythropoietin and vascular endothelial growth factor. Vascular endothelial growth factor receptor-targeted tyrosine kinase inhibitors are widely used in treatment of metastatic renal cell carcinoma. In paradoxical hematological effect with tyrosine kinase inhibitor therapies, hemoglobin level may be increased, but polycythemia requiring phlebotomy is very rare. CASE DESCRIPTION: We present here a case of renal cell carcinoma who received successive treatment with sunitinib, everolimus, and axitinib. While he had a normal hemoglobin level with prior sunitinib treatment, on the sixth week of axitinib treatment, he developed polycythemia and treatment response was seen after axitinib-associated polycythemia. CONCLUSION: Progression-free survival (PFS) was 30 months in our case with third-line treatment axitinib. Higher hemoglobin levels may be associated with longer survival. Polycythemia was the first response to treatment of axitinib in our patient. It may be an indicator of persistent treatment response.

Prognostic value of aldehyde dehydrogenase 1 (ALDH1) in invasive breast carcinomas.

Aldehyde dehydrogenase 1 (ALDH1) has been identified as a marker of cancer stem cells in breast cancer (BC). Recent studies showed that ALDH1 expression is correlated with poor prognostic parameters and worse clinical outcome in BC. We evaluated ALDH1 expression by immunohistochemistry in a series of 217 invasive BCs and investigated the correlation between ALDH1 expression and clinicopathological parameters, molecular subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 [HER2] type, and triple-negative BC [TNBC]), and patient survival. There was a significant association between ALDH1 expression and tumor grade (p < 0.001), i.e., the expression of ALDH1 was higher in high-grade tumors. ALDH1 expression was significantly associated with estrogen and progesterone receptor (ER and PR) negativity (p < 0.001) and HER2 positivity (p = 0.001). ALDH1 expression ratios were higher in HER2 type and TNBC. There was a statistically significant correlation between ALDH1 negativity and luminal A subtype (p < 0.001). The overall and disease free survival were shorter in ALDH1+ tumors, although without statistical significance. We confirm that ALDH1 is a potentially important, poor prognostic factor in BC, associated with high histological grade, ER/PR negativity and HER2 positivity. For more accurate results, ALDH1 expression should be evaluated in larger case series including various types/subtypes of BC.

Pleural tuberculosis in a patient with untreated type 1 Gaucher disease.

Gaucher disease (GD) is an autosomal recessive glycolipid storage disorder, due to deficiency of the lysosomal enzyme glucocerebrosidase, leading to accumulation of the substrate glucocerebroside in the cells of the macrophage-monocyte system. Patients with GD have alteration in their immune system and impaired microbicidal capacity of mononuclear phagocytes. It has also been demonstrated that monocyte dysfunction may correlate with the plasma glucocerebrosidase concentrations. Tuberculosis (TB) is a major public health problem in developing countries. Pleural TB is one of the most common forms of extra-pulmonary TB. Since immune system can be impaired due to the deficiency of glucocerebrosidase in various ways, TB can be observed in patients with GD especially when left untreated. Cytopenia(s) is also general finding in untreated Gaucher patients, and they may be observed most frequently due to the infiltration of the bone marrow with Gaucher cells together with the additional factor of splenomegaly. We herein present a case of an adult patient with heterozygous untreated GD1, who developed pleural TB complicated by ipsilateral pulmonary fibrosis. Before his admission to our clinic, pleurectomy operation was performed and 4-drug combination anti-TB therapy was initiated including isoniazid, rifampicin, ethambutol and pyrazinamide. Fever complaint was disappeared with anti-TB treatment but he also had fatigue and pain. After initiation of enzyme replacement therapy in addition to anti-TB treatment, clinical and hematological improvement was observed. To our knowledge, this is the first reported case of GD1 with pleural TB.