Diagnosis Rates Through Cancer Screening Programs in Patients with Breast Carcinoma.

AIM: This study investigated whether breast cancer patients had ever applied for Cancer Early Diagnosis Screening and Training Centers (KETEM). METHOD: This study, conducted from November 2020 to April 2021, adopts a cross-sectional research design and is planned as a survey study. The "Diagnosis Rates with Screening Programs in Breast Cancer Patients" survey was conducted on women over 45 who were diagnosed with breast cancer in the Medical Oncology Clinic of Izmir Katip Çelebi University Atatürk Education and Research Hospital. Further information about the cancer stage was gathered from the Medical Oncology outpatient clinic file records. Data obtained in the study were evaluated using the the Statistical Package for Social Sciences version 26.0 software (IBM Corp.; Armonk, NY, USA), using the number, percentage distribution, arithmetic mean, and chi-square test methods. RESULTS: It has been determined that most patients diagnosed did not receive a diagnosis through screening programs, were not aware of KETEM, and did not apply to KETEM. A positive relationship was found between the level of education and participation in screening programs. It was observed that women who knew about the KETEM's participated more often in the scans. CONCLUSION: The study discovered a lack of knowledge and inadequacy in screening programs for patients with breast cancer. We believe that it is essential to introduce and disseminate KETEMs so that cancers can be detected early through screening.

Clinicopathological analysis of invasive cribriform carcinoma of the breast, with review of the literature.

Invasive cribriform carcinoma (ICC) is a rare type of a primary breast carcinoma. It is subdivided into two groups as pure and mixed types. There are limited studies comparing the pure and mixed ICC at present. We aim to investigate the clinicopathological, radiological, prognostic features, and survival outcomes of two types with reviewing the published literature. 16 pure ICC and 26 mixed ICC cases were evaluated. The population consisted of 41 female and 1 male patients. The only male patient was a pure ICC case. The median age was for pure and mixed type, 46.5 and 54 years, respectively. All ICCs were ER positive. All ICCs except one mixed ICC, were positive for PR. Only one mixed ICC was accepted HER2 positive (3+). Pure ICCs showed more favorable features than mixed ICCs such as lesser axillary lymph node involvement, lower grade, and proliferation index. Twenty-five patients had one of the following imaging methods; ultrasonography (US), mammography (MG), and magnetic resonance imaging (MRI). Irregular shape, hypoechogenicity, and spiculated margins were the most common US findings. Similarly, irregular shape+spiculated margin is the most common MG findings. The median follow-up time for pure and mixed ICC was 88 and 56.5 months, respectively. One mixed ICC case developed bone metastasis. One death occurred in each group. Reasons of death were unknown. The 5-year OS for both ICC groups was 100%. 10-year OS for pure and mixed ICCs was 100% and 90%, respectively. 5-year DFS was 100% for pure ICC, and 94% for mixed ICC.

BCR-ABL1-Negative Chronic Myeloproliferative Neoplasms and Pulmonary Hypertension: A Prospective Long-Term Follow-up Study of the Impact of Pulmonary Hypertension on Survival.

PURPOSE: To assess the prevalence of PHT in patients with BCR-ABL1-negative CMPN and to evaluate impact of PHT on survival during long-term follow-up. PATIENTS AND METHODS: A total of 122 patients with BCR-ABL1-negative CMPN underwent transthoracic echocardiographic (TTE) evaluation at the beginning of study. Patients undergoing PHT on TTE examination were also evaluated by a pulmonologist. Patients were divided into 3 groups. Group A comprised patients with CMPN-related PHT; group B, patients with no PHT; and group C, patients with PHT due to secondary causes. Patients were evaluated again every 3 to 6 months. RESULTS: PHT was detected in 33 (27%) of 122 patients. Eight (6.5%) had CMPN-related PHT and the remaining 25 (20.5%) had non-CMPN-related PHT. Positivity for JAK2 V617F mutation in the study population was 72.9%. Groups were similar with respect to hematologic parameters and gender. Follow-up times were as follows: median (range) time from diagnosis to TTE and study end were 34 (1-158) months and 107 (16-251) months, respectively, and from TTE to study end was 88 (7-110) months. No significant differences found among the groups in terms of median time from diagnosis to TTE, follow-up, and overall survival. CONCLUSION: BCR-ABL1-negative CMPN patients had a lower prevalence of PHT compared to earlier studies. There was no statistically significant difference in median overall survival between patients with or without PHT. This may be because patients with PHT were asymptomatic and PHT was mild. The impact of PHT on survival was negligible.

Prognostic significance of androgen receptor expression in HER2-positive and triple-negative breast cancer.

Triple-negative breast cancer (TNBC) and HER2-positive breast cancer are more aggressive than other subtypes of breast cancer. Due to the limited number of treatment alternatives and the absence of target receptors in TNBC, and because of progression in the HER2-positive group despite targeted treatments, new treatment targets and therapeutic combinations are required. In this context, the present study aims to evaluate the prognostic importance of immunohistochemical androgen receptor (AR) expression in HER2-positive breast cancer and TNBC subtypes. AR nuclear staining density was evaluated immunohistochemically. A total of 111 operated patients with breast cancer were included in the study; 44 (39.6%) belonged to the HER2-positive breast cancer subgroup and 67 (60.4%) belonged to the TNBC subgroup. AR expression was 34.3% and 79.5% in TNBC and HER2-positive groups, respectively. The 5-year overall survival (OS) was 76% and 58% for the group with an AR-expression > 7.5% and AR-expression < 7.5%, respectively, in the TNBC subgroup (p = 0.042). In the HER2-positive patient group, the subgroups characterised by an AR-expression > 7.5% and AR-expression < 7.5% had 5-year OS rates of 57.6% and 63.5%, respectively (p = 0.91). Including the assessment of AR expression in the routine pathological examination will contribute to our understanding of the relevance of AR in the biology and prognosis of breast cancer.

Treatment choice in metaplastic breast cancer: A report of 5 cases.

Metaplastic breast carcinoma (MBC) is a general term defining a heterogeneous group that includes biphasic lesions, with both malignant epithelial and mesenchymal tissue components. Although its clinical findings are similar to those present in invasive ductal carcinoma, it rarely presents with the findings of inflammatory breast cancer. It is generally seen in the fifth decade. MBC spreads via lymph and blood circulation. Most common distant metastasis areas include lungs and the bone. Although the treatment generally relies on the same principles applied in invasive ductal carcinoma, a more aggressive treatment should be employed in at-risk groups due to higher rates of local recurrence. In this study, we aimed to discuss clinicopathological features and treatment approach in 5 women with MBC.

PDGFRA and KIT Mutation Status and Its Association With Clinicopathological Properties, Including DOG1.

Most of the gastrointestinal stromal tumors (GISTs) have gain-of-function mutations in the KIT gene, which can be used as a prognostic marker for the biological behavior of tumors, predictive marker for the response of tyrosine kinase inhibitors, and diagnostic marker. Researchers have focused on PDGFRA mutations because of both their prognostic and predictive potential and DOG1 positivity for diagnosis on GISTs. The aim of this study is to investigate the effect DOG1, PDGFRA, and KIT mutations on the prediction of the outcome for GIST management. Polymerase chain reaction was performed for KIT gene exons 9, 11, 13, and 17 and PDGFRA gene exons 12 and 18 with the genomic DNA of 46 GIST patients, and amplicons were sequenced in both directions. Immunocytochemical stainings were done by using primary antibodies. Molecular analysis revealed that the KIT mutation was observed in 63% of all cases, while the PDGFRA mutation was observed in 23.9% of cases. Significant relationships were found between age and KIT mutation, tumor location and KIT mutations, and tumor location and PDGFRA mutations (p ≤ 0.05). DOG1 positivity was detected in 65.2% of all GISTs and DOG1-positive cells had a higher KIT mutation ratio than DOG1-negative cells (p ≤ 0.05). KIT gene exon 11 mutations in DOG1-positive cells was higher than DOG1-negative cells (p ≤ 0.05). Conversely, KIT gene exon 13 mutations were higher in DOG1-negative cells than DOG1-positive cells (p ≤ 0.05). In this study, KIT mutation frequency was found similar with the European population; conversely, PDGFRA mutation frequency was similar with an Asian-Chinese-based study. KIT/PDGFRA mutations and tumor location can be used for the prediction of tumor behavior and the management of disease in GISTs. DOG1 positivity might be a candidate marker to support KIT and PDGFRA mutations, due to the higher DOG1 positivity in KIT exon 11 mutant and stomach- and small intestine-localized GISTs.

Cytopathological features of matrix-producing carcinoma of the breast.

Matrix producing carcinoma (MPC) of the breast is a very rare subtype of metaplastic carcinoma with heterelogous elements, which comprises <0.1% of invasive breast carcinomas. There are very few reports describing the cytological features of MPC. In this article, we aimed to discuss cytological, histopathological and immunohistochemical features of this rare entity in a 59-year-old woman.

Prognostic value of mesothelin expression in patients with triple negative and HER2-positive breast cancers.

PURPOSE: Mesothelin is a cell surface glycoprotein that is overexpressed in various malignancies. Recent studies have revealed that mesothelin plays an oncogenic role in tumor growth and drug resistance through the Wnt/NF-κB/PI3K/Akt signaling pathways. Herein, the expression of mesothelin in HER2-positive and triple-negative breast cancer (TNBC) has been correlated with prognosis. METHODS: A total of 430 patients with breast cancer treated between 2006 and 2013 were retrospectively reviewed; of these, 123 cases were considered TNBC (n=71; 58%) or were positive for HER2 (n=52; 42%). Mesothelin expression was assessed by immunohistochemistry. RESULTS: Of the patients with TNBC, 30 (42.3%) were positive for mesothelin expression, compared to only two (3.8%) of the HER2-positive cases. As most HER2-positive tumors were negative for mesothelin staining, statistical analysis was not performed. Median overall survival (OS) was 70.1 months for patients with TNBC, whereas median OS was 70.1 months, in the mesothelin-positive group and 74.5 months in mesothelin-negative group, respectively. Strong correlation was seen between mesothelin expression and tumor grade in patients with TNBC (P<0.005). In a multivariable Cox proportional hazards model, mesothelin expression was not independently associated with OS in patients with TNBC. CONCLUSIONS: Expression of mesothelin was observed in 42.3% of patients with TNBC and demonstrated a strong association with tumor grade. However, its expression was not correlated with prognosis.

Do the derived neutrophil to lymphocyte ratio and the neutrophil to lymphocyte ratio predict prognosis in breast cancer?

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with cancer. Similarly, a study in a large series has shown that the newly defined derived NLR (dNLR; neutrophil/leukocyte-lymphocyte ratio) also has prognostic value. The present study retrospectively evaluates the prognostic significance of NLR and dNLR in breast cancer. METHODS: Hematological parameters and clinicopathological data during diagnosis were retrospectively recorded for 1,527 patients diagnosed with breast cancer at Izmir Katip Celebi University Ataturk Research and Training Hospital from January 2006 to December 2011. The cut-off values were determined by calculating the NLR and dNLR of the patients. RESULTS: The cut-off values were determined as 4 and 2 for NLR and dNLR, respectively. The association between NLR and dNLR assessed by Spearman's rank correlation analysis was 0.935 (P < 0.001). There was a significant difference regarding disease free survival (DFS) and overall survival (OS) in patients with NLR <4 and NLR ≥4 (respectively, P < 0.00, P < 0.001). Similarly, there was a significant difference regarding DFS and OS in patients with dNLR <2 and dNLR ≥2 (respectively, P < 0.001, P < 0.001). Furthermore, NLR and dNLR demonstrated a significant association with the American Joint Committee on Cancer (AJCC) staging (P < 0.001). Assessment using the Cox proportional multivariate model showed that high NLR, pN, pT, luminal A-like, luminal B-like (HER2 positive), basal-like, and AJCC staging are independent prognostic factors. DISCUSSION: NLR was shown to be better than dNLR in terms of predicting prognosis in patients with breast cancer. However, large prospective studies are required to further demonstrate the prognostic significance of these two values.

Primary mucinous cystadenocarcinoma of the breast with amplification of the HER2 gene confirmed by FISH - case report and review of the literature.

Fifty five-years-old woman was presented to the general surgery upon the palpation of a mass in her left breast. In the excisional biopsy performed, partially cystic tumor of 2 × 1 cm with solid areas was macroscopically observed. After through microscopic examination, the patient was diagnosed as invasive mucinous cystadenocarcinoma and the tumor was found to be ER- and PR-negative and C-erbB2 (2+). In the fluorescent in situ hybridization, HER2/neu gene amplification was observed. Here, we present the clinical, cytological, morphological and immunohistochemical features of a very rare type of breast carcinoma, mucinous cystadenocarcinoma of the breast, with the review of the relevant literature.

The prognostic significance of bone marrow metastases: evaluation of 58 cases.

BACKGROUND: Bone marrow biopsy is widely used method for diagnosis, follow-up and staging of hemato-oncologic diseases. This procedure is also used for determining the bone marrow metastasis in patients with solid tumors. In this study, clinical, hematological, and pathological features of 58 patients with bone marrow metastases diagnosed by bone marrow biopsies were examined retrospectively MATERIALS AND METHODS: Among 3345 bone marrow biopsies performed in our hospital between January 2006 and August 2013, 58 cases with solid tumor metastasized to bone marrow were included in this study. RESULTS: Among 58 cases with solid organ carcinoma metastasis in bone marrow, mean age was 59.9. Thirty-nine cases were found to have a known primary tumor focus. The most common tumors metastasized to bone marrow were breast carcinomas (23 patients, 59%), gastric carcinomas (6 patients, 15.3%), prostate carcinomas (4 patients, 10,2%), and lung carcinomas (3 patients, 7.7%), respectively. Nineteen patients were firstly diagnosed from bone marrow biopsies as metastatic carcinomas. The median overall survival after bone marrow metastasis was 28 days (95% confidence interval: 7.5-48.4). The median overall survival difference was not statistically significant between patients with primary known and unknown tumor (P = 0.973). Statistically significant difference was observed between the survival of breast cancer and gastric cancer (P = 0.028). The most common hematologic symptom was the coexistence of anemia and thrombocytopenia (31%), thrombocytopenia (27.6%) and anemia (20.7%) alone. The median overall survival difference was statistically significant between patients who have anemia and thrombocytopenia (P < 0.005). CONCLUSION: Bone marrow biopsy is an easily accessible, easily applied, a useful procedure for diagnosing metastatic diseases in patients with hematologic symptoms such as anemia and thrombocytopenia besides being an uncomfortable procedure for patients. Furthermore, it is useful in predicting the prognosis and short survey after diagnosing bone marrow metastasis.

JAK2 V617F mutation status of 232 patients diagnosed with chronic myeloproliferative neoplasms.

INTRODUCTION/BACKGROUND: The aim of this study was to investigate the presence of Janus kinase 2 (JAK2) V617F mutation in patients with break point cluster region-abelson negative chronic myeloproliferative neoplasms (CMPNs) in our center. PATIENTS AND METHODS: We compared patients with and without the mutation, and also patients with the homozygous and heterozygous mutation, in terms of different clinical and laboratory features. RESULTS: The JAK2 V617F mutation was detected in 77 (95%), 88 (68%), and 17 (77%) of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) patients, respectively. Among JAK2 V617F-positive patients, the homozygous genotype was found in 39 (50.6%) of the 77 PV, 23 (26.1%) of the 88 ET, and 11 (64.7%) of the 17 PMF patients. Bleeding was seen in 14 (6%) of all patients. Upper gastrointestinal bleeds were the most common, seen in 11 patients. Out of 232 CMPN patients, 44 (19%) had thrombosis. The most common thrombotic event was transient ischemic attack (52%). Progression to myelofibrosis was seen in 1 (1.2%) PV and 3 (2.3%) ET patients, and progression to acute leukemia was seen in 2 (2.5%) PV and 3 (2.3%) ET patients. Three patients with PV (3.7%), 3 with ET (2.7%), and 5 with PMF (2.7%) died during follow-up. CONCLUSION: JAK2 V617F mutation frequencies in our PV and ET patients were similar to those reported previously. JAK2 V617F mutation frequency in our PMF patients was greater than in previous reports. All of our PV patients with thrombosis and most of our ET patients with thrombosis (76.1%) were JAK2 V617F mutation-positive. This mutation seems to be correlated with thrombosis risk.

Prognostic Significance of Bcl-2 and p53 Protein Expressions and Ki67 Proliferative Index in Diffuse Large B-cell Lymphoma.

OBJECTIVE: Diffuse large B-cell lymphoma (DLBCL) is a high-grade neoplasm that has heterogeneous properties in clinical, morphological, and immunophenotypic aspects. In the present study the effects of p53, Bcl-2, and Ki67 on prognosis and their relationships with clinical parameters were examined. MATERIALS AND METHODS: Thirty-five patients who had been diagnosed with nodally located DLBCL at Izmir Atatürk Training and Research Hospital between January 1999 and June 2006 were included in the study. The Ann Arbor classification system was used to determine the stage of the patients. The patients were evaluated according to age, sex, stage, B symptoms, extranodal involvement, and lactate dehydrogenase (LDH) level as well as immunohistochemically. P53 protein and Bcl-2 oncoprotein expressions and Ki67 proliferation index were assessed immunohistochemically. RESULTS: High Bcl-2 expression was found in 9 patients (25.7%), high p53 expression was found in 10 patients (28.6%), and high Ki67 was observed in 23 patients (65.7%). There was no significant correlation between p53 expression, Bcl-2 expression, or Ki67 proliferation index and age, sex, stage, B symptoms, extranodal involvement, LDH level, and overall survival (p>0.05). We did not find a relationship among p53 expression, Bcl-2 expression, Ki67 proliferation index, and prognosis (p>0.05). There was no significant relationship between overall survival and age, sex, stage, B symptoms, extranodal involvement, or LDH level (p>0.05). Our results revealed that Bcl-2 and p53 protein expressions and Ki67 proliferation index have no effect on overall survival of patients with DLBCL. CONCLUSION: The prognostic importance of p53 and Bcl-2 protein expressions and Ki67 proliferation index in DLBCL, which has biological and clinical heterogeneity, can be understood in a large series of studies that have subclasses and immunohistochemical markers with optimal cut-off values. CONFLICT OF INTEREST: None declared.