The effect of internal mammary lymph node biopsy on the therapeutic decision and survival of patients with breast cancer.

BACKGROUND: The role of internal mammary lymph node biopsy (IMLNB) is still being discussed in breast cancer treatment. The aim of this study was to investigate the role of IMLNB on adjuvant therapy and survival of patients with breast cancer. PATEINTS AND METHODS: The data of 72 patients with clinically negative axilla and IMLNB were evaluated. IMLNB was performed either through a small separate intercostal incision or from the same incision for tumor resection or mastectomy by using both blue dye and radioisotope. Pathological analysis was performed on formalin-fixed paraffin-embedded tissues. RESULTS: Ten of the patients (14%) were IMLNB-positive. The axillary sentinel lymph node and IMLN were negative in most of the patients (52.8%). In one patient (1.4%), the axilla was negative but the IMLNB was positive. IMLNB changed the pathologic stage in eight patients (11%). Adjuvant internal mammary radiotherapy was added to the treatment protocol for 10 patients due to IMLNB positivity and adjuvant chemotherapy was added in for only one patient with negative axilla. The factors found to be related with IMLN positivity were SLN positivity (p = 0.033), mastectomy (p = 0.022), and the number of resected IMLN ≥2 (p = 0.040). The median follow-up time was 115.5 months (range, 30-162 months). The ten-year overall survival (OS) rate was 86%. Systemic metastasis (p = 0.007), SLNB positivity (p < 0.001), and IMLNB positivity (p = 0.005) were statistically related to overall survival. CONCLUSION: IMLNB positivity in patients with breast cancer changed the pathologic stage and adjuvant treatment modalities of patients and also adversely affected the overall survival.

Is there any diagnostic value of serum protease-activated receptor-1 (PAR1) levels on determination of epithelial ovarian carcinoma?

The role of molecular markers in ovarian cancer is still a matter of debate. Protease-activated receptor-1 (PAR1) might be a good marker in some types of malignant tumors and might provide useful information in diagnosis and prognosis. The objective of this study was to evaluate the serum levels of PAR1 in regard to diagnostic, predictive, and prognostic value in epithelial ovarian cancer (EOC) patients. Forty-four EOC patients were enrolled in this study. Serum PAR1 levels were determined by enzyme-linked immunosorbent assay (ELISA) method. Twenty-five age- and sex-matched healthy controls were included in the analysis. The median age of patients was 58 years old, ranging from 22 to 83 years, where most of them had advanced disease (stage III-IV) (n = 40, 91%). The median serum PAR1 values were significantly elevated in patients compared to healthy controls (1.52 ng/ml vs. 1.13 ng/ml) (p = 0.03), whereas any clinical variables including response to chemotherapy did not associate with serum assay (p > 0.05). Progression-free survival (PFS) and overall survival (OS) of patients who did not respond to chemotherapy nor had platinum resistance in relapsed disease were poorer in the analyses. On the other hand, serum PAR1 levels showed no significant adverse effect on either PFS or OS (p = 0.43 and p = 0.49, respectively). These results proved that baseline serum PAR1 levels of patients with EOC were significantly higher than those of healthy people. However, these assays suggested no predictive or prognostic value in this group of patients.

Phase II study of lapatinib in combination with vinorelbine in patients with HER2 positive recurrent or metastatic breast cancer: a multicentric Turkish Oncology Group (TOG) trial.

BACKGROUND: The aim of this explorative phase II study was to evaluate the activity and safety of lapatinib in combination with intravenous vinorelbine in women with HER2 positive metastatic or recurrent breast cancer. METHODS: Twenty-nine patients were enrolled. The primary objectives were response and clinical benefit (CB) rates, secondary objectives were toxicity, response duration and progression free survival. Patients received 1250 mg oral lapatinib continuously once daily and intravenous vinorelbine 20-25 mg/m(2) on days 1 and 8, every 3 weeks. RESULTS: Although 25 patients were evaluable for response, according to intend to treat analysis of 28 patients; 14% had confirmed partial response (PR) and 36% had stable disease more than 24 weeks with a CB rate of 50%. Sixty four percent of the patients suffered from grade 3-4 hematologic and 18% from grade 3 extra-hematologic toxicities. CONCLUSION: The results of this trial provide evidence to further investigate the potential of this combination for patients unsuitable for trastuzumab or who become refractory to trastuzumab.

Glutathione S-transferase P1 polymorphisms are associated with time to tumor progression in small cell lung cancer patients.

PURPOSE: Many of commonly used chemotherapeutics in lung cancer treatment are metabolized by glutathione-S transferases (GSTs). The placental isoform of GST (GSTP1) is the most abundant isoform in the lung. Polymorphisms within the GSTP1 may result in alterations in enzyme activity and change sensitivity to platinum-based chemotherapy. We investigated whether the polymorphism within the exons 5 and 6 of GSTP1 gene may change response to therapy, time to tumor progression (TTP) and overall survival in small cell lung cancer (SCLC) patients. METHODS: Ninety-four histologically confirmed patients with SCLC were enrolled in this study during 1995-2006. GSTP1 Ile105Val polymorphism in exon 5 and GSTP1 Ala- 114Val polymorphism in exon 6 were determined by using PCR-RFLP techniques. Associations between the GSTP1 polymorphisms and treatment response were evaluated using the chi-square test. Associations between the GSTP1 polymorphisms and TTP and overall survival were compared using Kaplan-Meier survival curves. RESULTS: We found no significant associations between exon 5 and exon 6 GSTP1 gene polymorphisms and response to therapy or overall survival. Patients carrying both variant exon 5 (Ile/Val or Val/Val) and variant exon 6 (Ala/Val) genotypes had significantly shorter TTP (5 vs. 8 months, p = 0.04). Moreover, patients with heterozygote exon 6 variant had presented with extensive-stage disease. CONCLUSION: No individual effect of variant alleles was found in relation to chemotherapy response, median TTP and overall survival. The carriage of both types of variant alleles may predict worse outcome.

MAPK overexpression is associated with anthracycline resistance and increased risk for recurrence in patients with triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer is estimated to account for 15%-20% of all patients with breast cancer and is considered as a prognostically unfavorable subset. The aim of this study is to evaluate the prognostic impact of various molecular factors in patients with triple-negative breast cancer. PATIENTS AND METHODS: Tumor specimens from 109 patients with receptor-negative (estrogen receptor and progesterone receptor) breast cancer were analyzed for mitogen-activated protein kinase (MAPK), epidermal growth factor receptor (EGFR) and phosphoinositol-3-kinase (PI3K) expression by immunohistochemistry. The prognostic significance of these molecular factors, in addition to various prognostic variables, was investigated. RESULTS: Fifteen (13.8%), 38 (34.9%) and 33 patients (30.3%) had positive staining for EGFR, MAPK and PI3K, respectively. MAPK was associated with anthracycline resistance (P = 0.008) and lower MAPK score was significantly associated with shorter disease-free survival (P = 0.029). Survival following relapse was significantly worse for those with a higher MAPK score (P = 0.03). CONCLUSION: MAPK is a significant prognostic and predictive factor in patients with triple-negative breast cancer. Furthermore, the level of staining among those with a positive MAPK expression may play a prognostic role at different stages of relapse. Further translational research is required to elucidate molecular mechanisms of tumor proliferation in this subset of patients.

Prognostic factors and survival in patients with metastatic or recurrent carcinoma of the uterine cervix.

The aim of this study is to identify the impact of various prognostic factors on survival in patients with recurrent carcinoma of the uterine cervix. Fifty-two patients who were treated with platinum-based chemotherapy for recurrent or metastatic disease were retrospectively evaluated. Twenty-seven patients (90%) had received pelvic radiation as primary treatment. Out of 45 evaluable patients, two (4.4%) had complete response (CR), three (6.7%) had a continuous CR after additional surgical treatment and irradiation. Five patients (11.1%) had partial response (PR). The majority of patients had progressive response to treatment (22 patients, 48.9%). After a median follow-up period of 19 months, 31 patients (60%) had died. Progression-free survival after initial diagnosis was observed to have a significant association with response to chemotherapy for recurrent disease (Fisher two-sided P = 0.027). The median survival duration for relapsed disease was 11.8 months. Those with a longer disease-free interval ( 8 months vs.

Efficacy of cisplatin and cyclophosphamide combination for recurrent and metastatic carcinoma of the uterine cervix.

The efficacy of a combination of cyclophosphamide and cisplatin in patients with metastatic and recurrent carcinoma of the cervix, was tested. Thirty patients were included in the study. Initially, 27 patients (90%) had received pelvic radiation and intracavitary boost and one patient was additionally given paraaortic radiation. Cisplatin was given at 75 mg/m2 followed by cyclophosphamide at 750 mg/m2 on day 1 with three weekly intervals for a maximum of six cycles. All patients received a median of four cycles of chemotherapy. The overall response rate for all eligible patients was 20% (continuous CR: 1, CR: 1, PR: 4 patients). Overall response rate and progressive response in patients with relapse within the previous radiation field were 9.5% and 66.7%, respectively; while for patients who had recurrent disease outside any irradiated area both were 44.4%. Eighteen patients (60%) had early withdrawal from the planned schedule, which was due to patient incompliance in seven patients (23.3%), disease progression in ten (33.3%) and early death after the first cycle in one patient (3.3%). Anemia was the most frequent toxicity, necessiating 24 transfusions in nine patients (30%). WHO grade 3 and 4 toxicity were anemia: 13 (43.3%), leucopenia: one (3.3%), thrombocytopenia: two (6.6%), renal: one, emesis: nine (30.0%) patients. The median survival duration for all eligible patients was 11 months. Univariate analysis revealed that progressive response to chemotherapy was the only prognostic factor for survival (7.1 vs 16.8 months, p = 0.003). The combination of cisplatin and cyclophosphamide did not appear to be more active than single agent cisplatin in this patient group with a relatively poor prognosis. Further studies are required to determine a better therapeutic approach for patients with relapsed carcinoma of the cervix.

An atypical presentation of metastatic gestational choriocarcinoma with maxillary sinus and subcutaneous involvement; report of a case with literature review.

Extragonadal germ cell tumors are rare neoplasms with histologic features comparable to those of gonadal origin. In this case report we present a 21-year-old female patient with an atypical localization of metastatic gestational choriocarcinoma. She was admitted to our hospital with recurrent epistaxis, abnormal vaginal bleeding, rectal bleeding, subcutaneous nodules on both thighs and forearms and left maxillary mass with intranasal cavity invasion. Laboratory analysis revealed significant elevation in serum beta-human chorionic gonodotropin (beta-HCG) level. Abdominal computerized tomography (CT) revealed left renal and retroperitoneal masses and thoracic CT displayed multiple bilateral lung metastases. Histopathological evaluation of the biopsy specimen obtained from the maxillary sinus showed choriocarcinoma. Based on WHO criteria she was classified as high-risk metastatic choriocarcinoma and treated with combination chemotherapy. We believe that in young women with recurrent epistaxis, gross abnormal vaginal and rectal bleeding and atypical maxillary sinus tumor with multiple lung metastases, choriocarcinoma should be included in the differential diagnosis and previous history of pregnancy or abortion should be obtained.

Thymidine labeling index in epithelial ovarian cancer.

OBJECTIVE: The aim of this study is to determine the thymidine labeling index and its prognostic role in patients with ovarian cancer. METHODS: Tumor cell proliferation in 32 patients with primary ovarian cancer admitted to Istanbul Medical Faculty, Department of Obstetrics and Gynecology, between 1993 and 1997 was investigated using the [3H]thymidine labeling index (TLI). TLI results were compared with other clinical and histopathologic prognostic parameters. RESULTS: The mean and median TLI values of the patients were 9.3+/-6.2% and 9.20% (range: 0.4-23.0%), respectively. Sixteen patients showed high proliferation rates (mean TLI: 14.3%). These patients had an overall survival rate of 46.7% at 3 years. The mean TLI level and overall survival at 3 years in the low proliferation rate group were 4.4 and 68.8%, respectively. Patients with a high TLI had a significantly shorter survival compared to those with a low TLI (P<0.01). There was tendency towards a higher TLI with advanced stage (P>0.05). However, there was no statistically significant correlation between TLI and other prognostic parameters. CONCLUSION: TLI may have a predictive value in determining the outcome of patients with ovarian cancer. Further larger scale studies are needed before definite conclusions can be made about its role as a prognostic factor in this disease.

5-fluorouracil-induced balanitis in a patient with oesophageal carcinoma.

We have reported the case history of a patient with balanitis, who was treated with 5-FU. Although 5-FU has a wide toxicity profile, balanitis has not been reported in association with this therapy.