New Emerging Chemokine Receptors: CCR5 or CXCR5 on Tumor Is Associated with Poor Response to Chemotherapy and Poor Prognosis in Locally Advanced Triple-Negative Breast Cancer.

BACKGROUND: We aim to investigate any possible associations between chemokine receptor expression and responses to neoadjuvant chemotherapy (NAC) along with outcomes in patients with triple-negative breast cancer (TNBC) with locally advanced disease. METHOD: Expressions of chemokine receptors were examined immunohistochemically after staining archival tissue of surgical specimens (n = 63) using specific antibodies for CCR5, CCR7, CXCR4, and CXCR5. RESULTS: Patients with high CCR5, CCR7, CXCR4, and CXCR5 expression on tumors and high CXCR4 expression on tumor-infiltrating lymphocytes (TILs) were less likely to have a pathological complete response (pCR) or Class 0-I RCB-Index compared to others. Patients with residual lymph node metastases (ypN-positive), high CCR5TM(tumor), and high CXCR4TM expressions had an increased hazard ratio (HR) compared to others (DFS: HR = 2.655 [1.029-6.852]; DSS: HR = 2.763 [1.008-7.574]), (DFS: HR = 2.036 [0.805-5.148]; DSS: HR = 2.689 [1.020-7.090]), and (DFS: HR = 2.908 [1.080-7.829]; DSS: HR = 2.132 (0.778-5.846)), respectively. However, patients without CXCR5TIL expression had an increased HR compared to those with CXCR5TIL (DFS: 2.838 [1.266-6.362]; DSS: 4.211 [1.770-10.016]). CONCLUSIONS: High expression of CXCR4TM and CCR5TM was found to be associated with poor prognosis, and CXCR5TM was associated with poor chemotherapy response in the present cohort with locally advanced TNBC. Our results suggest that patients with TNBC could benefit from a chemokine receptor inhibitor therapy containing neoadjuvant chemotherapy protocols.

Clinical factors predicting objective response to bevacizumab-based chemotherapies in advanced and recurrent epithelial ovarian cancer.

BACKGROUND: Bevacizumab-based chemotherapies are commonly administered in the treatment of patients diagnosed with epithelial ovarian cancer (EOC). The primary aim of this study was to assess the factors that predict the objective response to bevacizumab-based therapies in cases of advanced and recurrent EOC. METHODS: The retrospective data of 264 patients with EOC from the current study were collected between 2009 and 2022 at our clinic. Survival analyses were conducted utilizing the Kaplan-Meier method and the log-rank test. Binary logistic regression analysis was employed to assess the factors predicting the objective response. RESULTS: A predominant subset of patients (83%) presented with serous adenocarcinoma, exhibiting a high-grade differentiation at 87%. The vast majority (80%) of the cohort experienced disease recurrence. Three-fourths of the cases received bevacizumab in combination with platinum-based doublet chemotherapy. In the multivariate analysis, clinical factors such as a disease recurrence (P=0.031), upfront tumor debulking surgery before bevacizumab (P=0.009), doublet chemotherapy (P=0.003), and the presence of malignant pleural effusion (P=0.024) emerged as significant determinants influencing the Objective Response Rate (ORR) in patients undergoing bevacizumab-based therapy. The ORR was 67.5% (N.=178), comprising 15.2% complete responses (N.=40) and 52.1% partial responses (N.=138). The median Progression-Free Survival (PFS) and Overall Survival (OS) were estimated at 10.2 months (95% CI, 8.60-11.9) and 20.1 months (95% CI, 16.0-24.2), respectively. CONCLUSIONS: The responses to bevacizumab-based chemotherapies could be predict by the presence of malignant pleural effusion, disease recurrence, upfront tumor debulking surgery and doublet regimen of chemotherapy.

miR-3653-3p Expression in PBMCs: Unveiling the Diagnostic Potential for Ovarian Cancer.

Ovarian cancer is typically diagnosed at an advanced stage, recurs early and often, and currently lacks effective treatment. Therefore, overall survival and progression-free survival are relatively short for this disease. Sensitive and specific biomarkers for early diagnosis and follow-up for effective treatment of the disease are currently lacking. MicroRNA (miRNA/miR) expression studies are widely used in cancer research. Disruption or malfunction of miRNAs, a class of noncoding small RNAs, has been implicated in cancer progression in several publications. Of note, the expression of a series of miRNAs is known to differ in ovarian cancer. In cancer research, it is crucial to analyze expression patterns in both cancer patients and healthy individuals to identify cancer-specific biological markers and to understand their role in cancer. In the present study, the expression levels of miR-3653-3p in the peripheral blood mononuclear cells (PBMCs) of 150 patients with high-risk ovarian cancer were determined, including those with a family history of cancer or an early-age diagnosis of ovarian cancer, as well as 100 healthy individuals. The results were then compared between the two groups. The expression level of miR-3653-3p in the PBMCs of patients with ovarian cancer was determined to be 9.49-fold higher than that in the healthy control group, and this result was statistically significant (P < 0.001). In addition, receiver-operating characteristic curve analysis of PBMC showed statistical significance of miR-3653-3p in discriminating ovarian cancer patients from healthy subjects (P < 0.001). These results suggest that miR-3653-3p detected in peripheral blood may be used as a non-invasive biomarker for ovarian cancer.

The effect of parity, breastfeeding history, and duration on clinical and pathological characteristics of breast cancer patients.

Background/aim: The study is aimed to determine the relationship between the delivery and breastfeeding history of the patients and the clinicopathological properties of breast cancer. Materials and methods: A questionnaire was utilized for the study, which included the age of diagnosis, the number of children at the time of diagnosis, the age of the children, and the breastfeeding period of each child. Results: The study included 828 patients. The median age at diagnosis was 47 years for parous women and 42 years for nonparous women (p < 0.001). The tumor size of the patients diagnosed within the breastfeeding period was significantly larger compared to the other patients. Estrogen and progesterone receptor positivity were lower in patients diagnosed during breastfeeding. Additionally, the mean number of positive lymph nodes, dissected lymph nodes, and positive lymph node/dissected lymph node ratio in parous and breastfed patients with a nonmetastatic disease were statistically significantly higher in multivariable analysis than those patients who were nulliparous and have not breastfed. Conclusion: Breast cancer is seen at a later age in patients who are parous than those who have never given birth. Patients who are parous and have breastfed tend to present with a higher stage of the disease.

Outcomes of the patients with metastatic male breast cancer.

BACKGROUND: The goal of this research is to investigate the clinical characteristics and prognosis of men with metastatic breast cancer (mMBC). METHODS: A retrospective analysis of the data of 28 patients was conducted. Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS) and prognostic variables. RESULTS: At the time of diagnosis, the median age was 57 years (range 26-86). The most prevalent pathological subtype was invasive ductal carcinoma (92.6%). HER2 positivity was 21.6% in patients, with estrogen and progesterone receptor positivity at 96.4% and 71.4%, respectively. Bone-75%, lung-39.3%, brain-21.4%, and adrenal gland-10.7% were the most prevalent metastatic sites. Trastuzumab-based chemotherapy was given to six patients. During the study period, 14 patients (or half) died. All patients had a median OS of 42.6 months (range: 21.6-63.7). The OS rates after 1, 3, and 5 years were 95.7%, 54.2%, and 36.6%, respectively. The number of metastatic locations (P = 0.045), brain metastasis (P = 0.033), and a history of regular alcohol intake (P = 0.008) were all shown to be statistically significant factors affecting OS in univariate analysis. However, multivariate analysis did not support the findings. In addition, we discovered that trastuzumab-based therapy and de-novo metastatic disease had no effect on OS for mMBC. CONCLUSIONS: The data on mMBC is restricted because of its rarity. The prognosis of mMBC was shown to be poor in this investigation. Despite the small number of patients, we discovered that in univariate analysis, having brain metastases, the number of metastatic locations, and a history of alcohol intake may be prognostic factors.

Comparative analysis of doublet chemotherapy regimens plus bevacizumab in patients with recurrent ovarian cancer.

Among all gynecological malignancies, ovarian cancer is the predominant cause of mortality. Hence, various chemotherapy protocols have been established for managing metastatic ovarian cancer cases. The present study aimed to assess and compare the efficacy of dual chemotherapy regimens plus bevacizumab in patients diagnosed with recurrent platinum-sensitive epithelial ovarian cancer. This was a retrospective observational study. Data on the clinical, pathological, radiological, and treatment characteristics of the patients were recorded. Survival analyses were performed using the Kaplan-Meier method. Moreover, multivariate Cox regression analysis was conducted. Data of a total of 198 patients with a median follow-up duration of 18.7 months after bevacizumab treatment were analyzed. Serous carcinoma was found to be the most common pathological subtype in the analyzed patients, accounting for 85.8% of all cases. In total, 46.5% (n = 92), 38.4% (n = 76) and 15.2% (n = 30) patients had received gemcitabine plus carboplatin, paclitaxel plus carboplatin (PC), and gemcitabine plus cisplatin combined with bevacizumab, respectively. The complete response rate was 18.7%, partial response rate was 56.1%, stable disease rate was 6.6%, and progressive disease rate was 18.7%. The patients received bevacizumab treatment at a median of 9 cycles and doublet chemotherapy at a median of 7 cycles. The median progression-free survival was 11.9 (95% CI: 9.2-14.5) months, and the median overall survival (OS) was 24.7 (95% CI: 19.9-29.4) months. The results showed that a history of surgery prior to bevacizumab treatment was a significant factor affecting OS (P = .006). Patients who had received gemcitabine plus carboplatin with bevacizumab (28 months) had significantly better OS than patients who had received paclitaxel plus carboplatin (20.1 months) and gemcitabine plus cisplatin (17 months) (P = .009). Doublet chemotherapy regimens plus bevacizumab are safe and effective against recurrent platinum-sensitive epithelial ovarian cancer. Gemcitabine plus carboplatin with bevacizumab was superior to other treatment regimens in terms of OS outcomes.

Germline mutational variants of Turkish ovarian cancer patients suspected of Hereditary Breast and Ovarian Cancer (HBOC) by next-generation sequencing.

Hereditary Breast and Ovarian Cancer (HBOC) syndrome is characterized by an increased risk of developing breast cancer (BC) and ovarian cancer (OC) due to inherited genetic mutations. Understanding the genetic variants associated with HBOC is crucial for identifying individuals at high risk and implementing appropriate preventive measures. The study included 630 Turkish OC patients with confirmed diagnostic criteria of The National Comprehensive Cancer Network (NCCN) concerning HBOC. Genomic DNA was extracted from peripheral blood samples, and targeted Next-generation sequencing (NGS) was performed. Bioinformatics analysis and variant interpretation were conducted to identify pathogenic variants (PVs). Our analysis revealed a spectrum of germline pathogenic variants associated with HBOC in Turkish OC patients. Notably, several pathogenic variants in BRCA1, BRCA2, and other DNA repair genes were identified. Specifically, we observed germline PVs in 130 individuals, accounting for 20.63% of the total cohort. 76 distinct PVs in genes, BRCA1 (40 PVs), BRCA2 (29 PVs), ATM (1 PV), CHEK2 (2 PVs), ERCC2 (1 PV), MUTYH (1 PV), RAD51C (1 PV), and TP53 (1PV) and also, two different PVs (i.e., c.135-2 A>G p.? in BRCA1 and c.6466_6469delTCTC in BRCA2) were detected in a 34-year-old OC patient. In conclusion, our study contributes to a better understanding of the genetic variants underlying HBOC in Turkish OC patients. These findings provide valuable insights into the genetic architecture of HBOC in the Turkish population and shed light on the potential contribution of specific germline PVs to the increased risk of OC.

Efficacy and outcomes of systemic chemotherapy in posttransplant and immunosuppression associated Kaposi sarcoma: Twenty years experience of a tertiary cancer center.

Kaposi sarcoma is a malignant angioproliferative disease, and human herpesvirus-8 plays a major role in its etiology. Iatrogenic Kaposi sarcoma (IKS) can occur in patients undergoing immunosuppressive therapy. The treatment strategy for patients with IKS is immunosuppressive therapy modification. However, it is unclear which chemotherapy drug is the most effective and safe in the treatment of IKS. Therefore, we investigated the efficacy and safety of systemic treatment in patients with IKS at our tertiary cancer center. This cross-sectional retrospective study analyzed the clinical data of 22 patients diagnosed with IKS between January 2000 and January 2020. The patients were divided into the following 2 groups according to the transplantation status: organ transplant recipient (OTR) group and non-organ transplant recipient (non-OTR) group. Of the 22 patients, 12 were included in the OTR group and 10 were included in the non-OTR group. The median patient age at diagnosis was 52.1 years in the OTR group and 68.1 years in the non-OTR group. The median overall survival (OS) was 65.4 months in the OTR group, while the median OS was not reached in the non-OTR group. There was no statistically significant difference in OS between the 2 groups (P = .45). The 5-year OS rate among all patients was 54%. In the OTR group, the objective response rate and disease control rate were 50% and 83%, respectively, and in the non-OTR group, the objective response rate and disease control rate were 60% and 90%, respectively. Chemotherapy was well tolerated in both groups. Hematological toxicities were the main dose-limiting adverse events. Grade III/IV leucopenia and neutropenia were observed in 5 and 4 patients, respectively; however, no patient experienced febrile neutropenia. No chemotherapy-related death occurred. Systemic chemotherapy is an effective treatment and can be considered for disease control in patients with an aggressive disease course, who do not experience regression with immunosuppressive therapy modification.

Long-term outcomes and predictors of recurrence in node-negative early stage breast cancer patients.

BACKGROUND: We evaluated the outcomes, and risk factors for recurrence in patients with early stage node-negative breast cancer in this study. METHOD: Retrospective data analysis was done on patient treatment records from 1988 to 2018. The patient's demographic, clinical, pathological, and therapeutic characteristics were noted. To evaluate survival analysis and predictors of recurrence, we employed Kaplan-Meier analysis with the log-rank test. RESULTS: A total of 357 patients in all were enrolled in the research. At the time of diagnosis, the median age was 50 (with a range of 18-81). A total of 85.5% of patients had undergone a lumpectomy, while 14.5% had a mastectomy. 78.7% of patients had sentinel lymph node biopsy, and 21.3% had axillary lymph node dissection. In addition, the patients received adjuvant radiotherapy (88.7%), adjuvant endocrine therapy (82.1%), and adjuvant chemotherapy (48.5%). Recurrence of the tumor occurred in 31 (8.7%) patients (local recurrence 45.2% and metastatic disease 54.8%). Ten- and twenty-year recurrence-free survival rates were 92% and 77%. 19 (5.3%) patients had also developed contralateral breast cancer. Ten-year survival rates were 91.6%, and 20-year survival rates were 76.6%, respectively. Aged over 65 years (p = 0.004), necrosis (p = 0.002), mitosis (p = 0.003), and nuclear pleomorphism (p = 0.049) were found as statistically significant factors for recurrence in univariate analysis. In the ROC analysis, the largest size of the tumor (over 1.45 cm, p = 0.07) remained outside the statistical significance limit in terms of recurrence. CONCLUSIONS: Thirty-year outcomes in individuals with early stage, node-negative breast cancer were shown in this study. We found that the recurrence ratios between 10 and 20 years were more frequent than the first 10 years during the follow-up. Despite the small number of patients who experienced a recurrence, we demonstrated that, in univariate analysis, being older than 65 and having some pathological characteristics (nuclear pleomorphism, mitosis, and necrosis) were statistically significant factors for disease recurrence.

Survival results according to Oncotype Dx recurrence score in patients with hormone receptor positive HER-2 negative early-stage breast cancer: first multicenter Oncotype Dx recurrence score survival data of Turkey.

Background: The Oncotype Dx recurrence score (ODx-RS) guides the adjuvant chemotherapy decision-making process for patients with early-stage hormone receptor-positive, HER-2 receptor-negative breast cancer. This study aimed to evaluate survival and its correlation with ODx-RS in pT1-2, N0-N1mic patients treated with adjuvant therapy based on tumor board decisions. Patients and methods: Estrogen-positive HER-2 negative early-stage breast cancer patients (pT1-2 N0, N1mic) with known ODx-RS, operated on between 2010 and 2014, were included in this study. The primary aim was to evaluate 5-year disease-free survival (DFS) rates according to ODX-RS. Results: A total of 203 eligible patients were included in the study, with a median age of 48 (range 26-75) and median follow-up of 84 (range 23-138) months. ROC curve analysis for all patients revealed a recurrence cut-off age of 45 years, prompting evaluation by grouping patients as ≤45 years vs. >45 years. No significant difference in five-year DFS rates was observed between the endocrine-only (ET) and chemo-endocrine (CE) groups. However, among the ET group, DFS was higher in patients over 45 years compared to those aged ≤45 years. When stratifying by ODx-RS as 0-17 and ≥18, DFS was significantly higher in the former group within the ET group. However, such differences were not seen in the CE group. In the ET group, an ODx-RS ≥18 and menopausal status were identified as independent factors affecting survival, with only an ODx-RS ≥18 impacting DFS in patients aged ≤45 years. The ROC curve analysis for this subgroup found the ODx-RS cut-off to be 18. Conclusion: This first multicenter Oncotype Dx survival analysis in Turkey demonstrates the importance of Oncotype Dx recurrence score and age in determining treatment strategies for early-stage breast cancer patients. As a different aproach to the literature, our findings suggest that the addition of chemotherapy to endocrine therapy in young patients (≤45 years) with Oncotype Dx recurrence scores of ≥18 improves DFS.

Diverging prognostic effects of CD155 and CD73 expressions in locally advanced triple-negative breast cancer.

Background: Immune checkpoint inhibition, combined with novel biomarkers, may provide alternative pathways for treating chemotherapy-resistant triple-negative breast cancer (TNBC). This study investigates the expression of new immune checkpoint receptors, including CD155 and CD73, which play a role in T and natural killer (NK) cell activities, in patients with residual TNBC after neoadjuvant chemotherapy (NAC). Methods: The expression of biomarkers was immunohistochemically examined by staining archival tissue from surgical specimens (n = 53) using specific monoclonal antibodies for PD-L1, CD155, and CD73. Results: Of those, 59.2% (29/49) were found to be positive (>1%) for PD-L1 on the tumour and tumour-infiltrating lymphocytes (TILs), while CD155 (30/53, 56.6%) and CD73 (24/53, 45.3%) were detected on tumours. Tumour expressions of CD155 and CD73 significantly correlated with PD-L1 expression on the tumour (p = 0.004 for CD155, p = 0.001 for CD73). Patients with CD155 positivity ≥10% were more likely to have a poor chemotherapy response, as evidenced by higher MDACC Residual Cancer Burden Index scores and Class II/III than those without CD155 expression (100% vs 82.6%, p = 0.03). At a median follow-up time of 80 months (range, 24-239), patients with high CD73 expression showed improved 10-year disease-free survival (DFS) and disease-specific survival (DSS) rates compared to those with low CD73 expression. In contrast, patients with CD155 (≥10%) expression exhibited a decreasing trend in 10-year DFS and DSS compared to cases with lower expression, although statistical significance was not reached. However, patients with coexpression of CD155 (≥10%) and low CD73 were significantly more likely to have decreased 10-year DFS and DSS rates compared to others (p = 0.005). Conclusion: These results demonstrate high expression of CD73 and CD155 in patients with residual tumours following NAC. CD155 expression was associated with a poor response to NAC and poor prognosis in this chemotherapy-resistant TNBC cohort, supporting the use of additional immune checkpoint receptor inhibitor therapy. Interestingly, the interaction between CD155 and CD73 at lower levels resulted in a worse outcome than either marker alone, which calls for further investigation in future studies.

Termination of trastuzumab in HER2-positive metastatic breast cancer patients who received trastuzumab beyond progression.

The purpose of the study was to assess the prognosis of HER2-positive metastatic breast cancer patients who received trastuzumab beyond progression and investigate the predictors of complete response. HER2-positive metastatic breast cancer patients who received long-term trastuzumab were included in the study. Predictors of complete response were analyzed with binary regression analysis. The prognosis of patients who had their trastuzumab-based treatment terminated was assessed. Eighty patients were involved in the study. The patients were received with trastuzumab for a median of 62 months (12-191). A complete response was observed in 60 (75%) patients. The median duration to development of complete response was found as 14.8 months (2.4-55). In logistic regression analysis: using endocrine therapy with trastuzumab (p = 0.04), menopausal status (p = 0.03), and the number of metastatic sites (p = 0.01) were found to be statistically significant factors for a complete response. Trastuzumab-based therapy of fifteen patients was terminated, six (40%) patients continued to receive an aromatase inhibitor, and nine (60%) patients were followed up without treatment. After termination of trastuzumab, at a median follow-up of 32 months (11-66), recurrence was detected in two (13.3%) patients. We detected that menopausal status, the number of metastatic sites, and using endocrine therapy with trastuzumab were predictors of complete response in HER2-positive metastatic breast cancer patients who received long-term trastuzumab-based therapy. We observed that HER2-positive metastatic breast cancer patients may be completely cured with trastuzumab-based therapy. There are no defined criteria for termination of trastuzumab treatment in this selected patient group. It is necessary to confirm our data with multicenter studies involving a large number of patients.

Prognostic Factors Influencing Progression-Free Survival in HER2-Positive Metastatic Breast Cancer Patients Who Were Treated With A Combination of Lapatinib and Capecitabine.

Objective: The aim was to assess the prognostic variables in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer patients receiving lapatinib plus capecitabine. Materials and Methods: Retrospective data on HER2-positive metastatic breast cancer patients who received lapatinib and capecitabine were analyzed. Survival outcome was obtained with Cox regression analysis and the Kaplan-Meier method. Results: The study included 102 patients. Forty-four (43.1%) patients had de novo metastatic disease. The most frequent metastatic sites were, in order, bone (61.8%), brain (57.8%), liver (35.3%), and lung (34.3%). All of the patients had previously received chemotherapy based on trastuzumab. With combined lapatinib and capecitabine, complete response was observed in 7.8%, partial response in 30.4%, and stable disease in 24.5%. Progression-free survival was 8 (95% confidence interval, 5.1-10.8) months. In multivariable analysis, endocrine therapy (p = 0.02), de novo metastatic disease (p = 0.02), and age (p = 0.02) were prognostic factors for progression-free survival. However, the number of chemotherapy cycles with trastuzumab, palliative radiotherapy, history of breast surgery, and the number of metastatic sites were not significant in this respect. Conclusion: These results have demonstrated the effectiveness of lapatinib plus capecitabine in metastatic HER2-positive breast cancer patients. Furthermore, unfavorable prognostic factors for progression-free survival were shown to be hormone-negative tumor, de novo metastatic disease, and young age.

Demographic and Clinical Features of Patients with Metastatic Breast Cancer: A Retrospective Multicenter Registry Study of the Turkish Oncology Group.

This multicenter registry study aims to analyze time-related changes in the treatment patterns and outcome of patients with metastatic breast cancer (MBC) over a ten-year period. Correlations between demographic, prognostic variables and survival outcomes were carried out in database aggregates consisting of cohorts based on disease presentation (recurrent vs. de novo) and the diagnosis date of MBC (Cohort I: patient diagnosed between January 2010 and December 2014; and Cohort II: between January 2015 and December 2019). Out of 1382 patients analyzed, 52.3% patients had recurrent disease, with an increased frequency over time (47.9% in Cohort I vs. 56.1% in Cohort II, p < 0.001). In recurrent patients, 38.4% (n = 277) relapsed within two years from initial diagnosis, among which triple-negative BC (TNBC) was the most frequent (51.7%). Median overall survival (OS) was 51.0 (48.0-55.0) months for all patients, which was similar across both cohorts. HER2+ subtype had the highest OS among subgroups (HER2+ vs. HR+ vs. TNBC; 57 vs. 52 vs. 27 months, p < 0.001), and the dnMBC group showed a better outcome than recMBC (53 vs. 47 months, p = 0.013). Despite the lack of CDK inhibitors, luminal A patients receiving endocrine therapy had a favorable outcome (70 months), constituting an appealing approach with limited resources. The only survival improvement during the timeframe was observed in HER2+ dnMBC patients (3-year OS Cohort I: 62% vs. Cohort II: 84.7%, p = 0.009). The incorporation of targeted agents within standard treatment has improved the outcome in HER2+ MBC patients over time. Nevertheless, despite advances in early diagnosis and treatment, the prognosis of patients with TNBC remains poor, highlighting the need for more effective treatment options.

Is Breast Conserving Surgery Efficacious in Breast Cancer Patients with BRCA1 or BRCA2 Germline Mutation?

Background: The optimal surgical therapy for newly diagnosed breast cancer with germline mutations in susceptibility genes is still uncertain for many physicians. In this study, we aimed to determine the efficacy of breast conserving surgery (BCS) in breast cancer patients with BRCA1 or BRCA2 mutation by assessing its outcomes and locoregional recurrence (LR) rates. Materials and Methods: Seventy-five patients operated with BCS or mastectomy for breast cancer between 2006 and 2017 and had BRCA1 or BRCA2 mutation were included in the study. Effects of the performed breast surgery and clinicopathological characteristics on surgical outcomes, LR rates and survival were analyzed with showing the distribution of BRCA1 and BRCA2 germline mutations. Results: The median age of the patients was 42 years (20-77). BRCA1 mutations were found in 46 (61.3%) patients and BRCA2 mutations in 29 (38.7%) patients. Compared to BRCA2 carriers, BRCA1 carriers were more likely to have higher tumor grade (84.8% vs 44.8%; p = 0.001) and non-luminal subtype tumors (67.4% vs 13.8%; p = 0.001). A total of 44 (58.7%) patients underwent unilateral mastectomy and 31 (41.3%) patients underwent BCS. At a median follow-up time of 60 (12-240) months, LR was observed in 6 patients equally divided in both BCS and mastectomy groups. LR rates were slightly higher after BCS versus mastectomy (9.7% and 6.8%, respectively). Additionally, there were no statistically significant differences in disease-free survival (DFS) and disease-specific survival (DSS) rates after 10 years in the BCS group versus the mastectomy group (p = 0.117 and 0.109, respectively), but in fact, the rates were better in the BCS group. Conclusion: Our findings indicate that BCS may serve as an efficacious alternative to mastectomy for breast cancer patients with BRCA1 or BRCA2 mutation. Additionally, tumor size, lymph node positivity, and TNM stage should be taken into consideration for a better surgical decision-making.

Outcomes and Prognostic Factors in HER2-Positive Metastatic Breast Cancer Patients Who Had Developed Brain Metastasis in the Treatment Process.

INTRODUCTION: Patients with HER2-positive metastatic breast cancer are at risk for developing brain metastases. Different anti-HER2 treatments can be used in the management of the disease. In this study, we aimed to evaluate the prognosis and the factors affecting the prognosis in brain metastatic patients with HER2-positive breast cancer. METHODS: Clinical and pathological features of HER2-positive metastatic breast cancer patients and magnetic resonance imaging features at the onset of brain metastasis were recorded. Survival analyses were performed using Kaplan-Meier and Cox regression methods. RESULTS: Analyses of the study were performed by including 83 patients. The median age was 49 (25-76). All patients had HER2 receptor-positive tumors. Thirty-five (42.2%) patients had a hormone-positive disease. Thirty-two (38.6%) patients had de novo metastatic disease. Brain metastasis sites were found to be bilateral - 49.4%, right brain - 21.7%, left brain - 12%, and unknown - 16.9%, respectively. The median brain metastasis largest size was 16 mm (range 5-63). The median follow-up time from the post-metastasis period was 36 months. Median overall survival (OS) was found as 34.9 months (95% CI, 24.6-45.2). In multivariate analysis for factors affecting OS, estrogen receptor status (p = 0.025), number of chemotherapy agents used with trastuzumab (p = 0.010), number of HER2-based therapy (p = 0.010), and the largest size of brain metastasis (p = 0.012) were found to be statistically significant. CONCLUSIONS: In this study, we demonstrated the prognosis in brain metastatic patients with HER2-positive breast cancer. When the factors affecting the prognosis were evaluated, we determined that the largest size of brain metastasis, estrogen receptor positivity, and the use of TDM-1 and lapatinib plus capecitabine consecutively during the treatment process affected the prognosis of the disease.

Central nervous system metastasis in gynecologic cancers: Seeking the prognostic factors.

OBJECTIVE: Central nervous system (CNS) metastasis originating from gynecological cancer is a very rare and late manifestation of the disease. Therefore, there is still limited data on prognostic factors for survival. The objective of the present study is to identify prognostic factors for survival in patients with CNS metastasis originating from gynecological cancer. STUDY DESIGN: The present retrospective study analyzed the patients with gynecological cancers who were treated due to CNS metastases between January 1999 and December 2019 at Istanbul University Hospital. RESULTS: Forty-seven patients with CNS metastasis of gynecological origin were included in the study. The median age at the time of CNS metastasis was 59 (range 34-93). The median time from initial cancer diagnosis to CNS metastasis was 24.9 (range: 0-108.2) months. Most patients had epithelial ovarian cancer (EOC) (76.6%), followed by endometrial cancer (EC) (14.8%), cervical cancer (CC) (4.3%), and vulvar cancer (VC) (4.3%). By multivariate analysis, the presence of extracranial metastasis (HR: 5.10; 95% CI: 1.71-15.18), Eastern Cooperative Oncology Group (ECOG) performance status ≥3 (HR: 2.92; 95% CI: 1.36-6.26), palliative care only for the treatment of CNS metastasis (HR: 1.47; 95% CI: 0.58-4.11), and treatment-free interval (TFI) <6 months (HR: 2.74; 95% CI: 1.23-6.08) were independent factors that associated with worse survival. CONCLUSION: Patients with CNS metastasis who have favorable prognostic factors are considered to be appropriate candidates for aggressive and long-term treatment strategies. Extracranial metastasis, ECOG performance status, treatment history of CNS metastasis, and TFI were determined as independent prognostic factors that improved survival. TFI might be taken into account as a prognostic factor for patients with CNS metastasis in gynecological cancer.

Clinicopathologic characteristics and prognostic factors in patients with male breast cancer: A single tertiary center experience.

BACKGROUND: The goal of this study was to assess the clinicopathologic characteristics and prognostic variables in men with breast cancer (BC). METHODS: Clinical features, pathological characteristics, stage at diagnosis, and therapy data were noted. Survival analysis was performed using the log-rank technique and Cox regression model. RESULTS: Eighty patients were included in the study. In 31% of the individuals, BRCA (BReast CAncer genes 1 and 2) mutations were identified. The estrogen receptor (ER) positivity ratio was 93.6%, whereas the progesterone receptor (PR) positivity ratio was 74.4%. In 16.9% of the cases, HER2 overexpression was found. The median survival time was 120.9 months (70.3-171.5), and the five-year overall survival (OS) ratio was 74.9%. In univariate analysis, BRCA mutation status had no effect on OS (P = 0.50). CA15-3 levels (P = 0.03) at diagnosis and history of smoking (P = 0.03) were significantly linked with OS. However, the multivariate analysis could not confirm these results. CONCLUSIONS: We found that BRCA mutation, body mass index, a history of smoking, and alcohol consumption did not affect the OS in this research.

Predictors of response in EGFR-mutant metastatic non-small cell lung cancer patients treated with tyrosine kinase inhibitors.

BACKGROUND: The goal of the study was to evaluate the efficacy of tyrosine kinase inhibitors in patients with epidermal growth factor receptor (EGFR)-mutant metastatic non-small cell cancer and to determine the factors that predict objective response. MATERIALS AND METHODS: In the study, data from metastatic non-small cell lung cancer patients with EGFR mutations treated with tyrosine kinase inhibitors were retrospectively reviewed. Factors predicting objective response were evaluated with logistic regression analysis. RESULTS: The study evaluated the data of 105 patients. The most common EGFR mutations detected in patients were exon 19 (56.2%) and exon 21 (23.8%). The median progression-free survival (PFS) associated with EGFR tyrosine kinase inhibitors was 20.1 (95% confidence interval [CI], 13.4-26.7) months. The median overall survival (OS) in the post-metastasis period was found to be 30.8 (95% CI, 20.2-41.4) months. Five- and seven-year OS was determined as 28.7% and 22.9%, respectively. Factors predicting the objective response were analyzed. Presence of drug-related toxicity (P = 0.02), histopathologic type (P = 0.01), metastasis burden (P = 0.03), and EGFR mutation type (P = 0.04) were found to be statistically significant in multivariate analysis. CONCLUSIONS: In our study, we found that EGFR tyrosine kinase inhibitors are effective and safe. Better response to EGFR inhibitors was observed in the presence of drug-induced toxicity, adenocarcinoma histology, low metastasis burden, and exon 19 mutation.

Comparison of Clinical, Pathological, and Prognostic Features in BRCA Mutant and Wild-Type Male Breast Cancer Patients.

Objective: Published studies on male breast cancer (MBC) and BRCA mutations are scarce and usually include, a small number of patients. The clinicopathological characteristics of BRCA mutant and wild-type MBC patients were compared in more than forty patients in this study. Materials and Methods: A retrospective review of MBC patients' clinical and histopathological data was conducted. To compare the patients' characteristics, chi-square test and Fisher's Exact test were utilized. Kaplan-Meier analysis was used to examine the survival analysis. Results: In total 43 cases were reviewed. The average duration of follow-up was 35.8 months. BRCA mutations were found in 11 (25.6%) of the patients. BRCA1 mutations were found in four patients (9.3%), BRCA2 mutations in six patients (14%), and BRCA1 and BRCA2 mutations in one patient (2.3%). The median age at diagnosis was 58 years old, and there was no statistically significant difference between groups (p = 0.7). Tumor location (p = 0.3), human epidermal growth factor receptor 2 overexpression (p = 0.5), estrogen receptor status (p = 0.05), progesterone receptor status (p = 0.6), tumor stage (p = 0.9), lymph node positivity (p = 0.5), tumor histology (p = 0.06), and recurrence status (p = 0.6) were similar between BRCA-wild type and -mutated patients. Overall survival averaged 115.6 months (range: 76.0-155.3), with no statistically significant differences between groups (p = 0.6). Conclusion: This study investigated clinical and pathological characteristics and prognoses of BRCA wild and mutant-type MBC and these were similar in all groups studied.