Value of UGT2B7-161 Single Nucleotide Polymorphism in Predicting the Risk of Cardiotoxicity in HER-2 Positive Breast Cancer Patients Who Underwent Pertuzumab Combined with Trastuzumab Therapy by PSL.

Objective: To explore the value of uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7)-161 single nucleotide polymorphism in predicting the occurrence of cardiotoxicity in Chinese human epidermal growth factor 2 (HER-2) positive breast cancer patients who underwent pertuzumab combined with trastuzumab Therapy. Methods: Fifty patients with HER-2 positive breast cancer who planned to receive trastuzumab and pertuzumab therapy for more than four cycles were enrolled in this study, and blood samples were collected. Thirty healthy volunteers of matching ages were selected as the control group. Myocardial parameters such as global work index, global effective work, and global wasted work were measured before treatment (M0) and at the end of four cycles of treatment month three (M3). Blood samples were collected from patients at the M0 stage, and polymorphisms of the UGT2B7-161 gene were detected to evaluate the predictive ability of different gene phenotypes on the myocardial drug toxicity injury. Results: There were 35 myocardial work decreased events among 50 patients. There were 24 (47.3%), 15 (40.8%), and 11 (11.8%) patients carrying UGT2B7-161 CC, CT, and TT genotypes, respectively. The occurrence of myocardial work decreased was decreased in UGT2B7-161 TT and CT genotypes (12.5%) compared with CC genotype (41.7%) with statistical significance (P < 0.001). Multivariate logistic regression model analysis exhibited that UGT2B7-161 genotypes, body mass index, and cardiac troponin I were independent factors influencing the risk of cardiotoxicity. Conclusion: UGT2B7-161 single nucleotide polymorphism is a potential predictive factor for cardiotoxicity in HER-2 positive breast cancer patients receiving trastuzumab and pertuzumab dual-targeted drug therapy.

[Relationship between metastasis or recurrence of hepatocellular carcinoma and hepatitis B virus DNA or double mutation at 1762/1764 in the basic core promoter].

OBJECTIVE: To study the relationship between metastasis or recurrence of hepatocellular carcinoma (HCC) and hepatitis B virus (HBV) DNA load or the presence of double mutation at 1762/1764 in the basic core promoter (BCP). METHODS: One-hundred-and-fifty-seven patients with HCC were included in the study. Events of tumor metastasis or recurrence were recorded during 120 weeks of clinical follow-up after treatment by surgery or transarterial chemoembolization (TACE). The 1-year follow-up included monthly alpha fetoprotein (AFP) measurement and abdominal ultrasonography (US), as well as helical computed tomographic (CT) scan performed every 3 months. Follow-up beyond 1-year (surveillance) included AFP measurement and abdominal US every 2 months and helical CT scan every 6 months. Suspected metastasis or recurrence was investigated by hepatic angiography and confirmed according to the combined imaging findings. Serum HBV DNA level was measured by real-time PCR. HBV genotypes were determined by PCR-restriction fragment length polymorphism analysis. RESULTS: Of the 157 HCC cases 110 experienced tumor metastasis or recurrence; the cumulative probability of post-treatment HCC metastasis or recurrence was 4 (2.55%) at week 12, 14 (8.92%) at week 24, 28 (17.83%) at week 48, 64 (40.76%) at week 72, 92 (58.60%) at week 96, and 110 (70.06%) at week 120. Multivariate analysis indicated that both the BCP 1762/1764 double mutations and HBV DNA levels were risk factors for HCC recurrence or metastasis. In particular, the incidence of HCC recurrence or metastasis increased with baseline serum HBV DNA levels in a dose-response manner, ranging from 8/19 (42.1%) for less than 3 log10 copies/ml HBV DNA to 35/61 (57.3%) for 3-5 log10 copies/ml and 67/77 (87.0%) for more than 5 log10 copies/ml. After adjusting for potential confounders, serum HBV DNA level remained independently associated with HCC metastasis or recurrence. HCC recurrence or metastasis occurred in 22/43 (51.2%) of patients without BCP 1762/1764 mutations and 88/114 (77.2%) of patients with BCP 1762/1764 mutations. The adjusted odds ratio for patients infected with BCP 1762/1764 double mutation HBV, compared with those infected with non-BCP 1762/1764 mutation HBV, was 5.264 (95% CI: 1.436-12.574, P less than 0.05). CONCLUSION: Infection with HBV carrying the BCP 1762/1764 double mutation and presence of high HBV DNA load are independent risk factors for developing HCC metastasis or recurrence after surgery or TACE.

[Clinical characteristics and prognosis of different subtypes of breast cancer].

OBJECTIVE: To investigate the clinical characteristics and prognosis of patients with different subtypes of breast cancer: basaloid, HER-2 and luminal types, and try to find the evidence of individualized treatment for the patients. METHODS: 1280 histologically and immunohistochemically proven patients with resectable breast cancer were treated, and the clinical data including characteristics, relapse and survival of the patients with different subtypes of breast cancer were analyzed retrospectively. RESULTS: Of the 1280 breast cancer patients, basaloid, HER-2 and luminal types accounted for 20.9%, 23.2% and 55.9%, respectively. Basaloid type was more likely to be found in younger patients frequently with a family history of breast cancer. HER-2 type usually had a tumor of larger size with more advanced stage disease and more metastatic lymph nodes. Luminal type was likely to occur in aged patients with an earlier stage disease. The recurrence rates in basaloid, HER-2 and luminal types were 25.0%, 27.9% and 11.7%, respectively. Patients with basaloid or HER-2 type were found to have a significantly higher recurrence rate than the patients with luminal type breast cancer (P < 0.001), but no significant difference was observed between the basaloid and HER-2 types. However, patients with basaloid type breast cancer were more likely to develop lung metastasis than HER-2 type (13.4% vs. 7.1%, P = 0.017). Up to December 2006, the 5-year disease-free survival (DFS) rates for patients with basaloid, HER-2 and luminal types were 72.2%, 68.2% and 86.2% (P < 0.001), respectively. The overall 5-yr survival (OS) rates of the three groups were 88.6%, 83.8% and 95.8% (P < 0.001) , respectively. Of the patients with luminal type breast cancer, HER2-negative patients had a higher DFS (86.2% vs 57.0%, P < 0.001) and OS (95.8% vs 87.7%, P = 0.0001) compared with those with HER2-positive. The results of Multivariate Cox Regression showed that tumor size and lymph node state were the most important factors influencing the prognosis. CONCLUSION: Each subtype of breast cancer has somewhat its own specific clinical features in terms of recurrence pattern and prognosis, therefore, individualized treatment regimen may be required.

[Primary non-Hodgkin's lymphoma of the paranasal sinuses: a report of 14 cases].

BACKGROUND & OBJECTIVE: Primary paranasal sinus lymphoma (PPSL) is a rare presentation of extranodal non-Hodgkin's lymphoma with a natural history distinct from other lymphomas. This study was to evaluate the clinical and pathologic characteristics, treatment outcomes and prognosis of PPSL. METHODS: The records of 14 PPSL patients, treated at Cancer Center of Sun Yat-sen University from 1994 to 2006, were analyzed. RESULTS: The primary involvement sites included the maxillary sinus (11 cases), ethmoid sinus (2 cases), and sphenoid sinus (1 case). All patients were at stage I-II (Ann Arbor system). According to the AJCC TNM staging system, most patients had advanced T3-T4 disease. Of the 14 patients, 12 had B-cell PPSL, 1 had T-cell PPSL, and 1 had unclassified PPSL. The most common type was diffuse large B-cell PPSL (6 cases, 42.9%). Two patients underwent total maxillectomy and 12 underwent local excision or biopsy. All patients received chemotherapy and 6 received radiotherapy after chemotherapy. Both 5-year overall and event-free survival rates were 78.6%, with a median survival of 59.5 months(range, 2-192 months). CONCLUSIONS: PPSL is an uncommon presentation of lymphoma characterized by bulky local disease. Diffuse large B-cell lymphoma is the most common histologic type and the maxillary sinus is the most common original site of PPSL. A combined-modality approach with systemic chemotherapy and local-regional radiation is recommended for PPSL patients. The prognosis of PPSL is relatively good.

[Retrospective analysis of 98 cases of breast cancer with liver metastasis].

BACKGROUND & OBJECTIVE: The prognosis of breast cancer patients with liver metastasis is poor. How to improve treatment efficacy and prolong survival of these patients is a challenge in clinic. This study was to explore the efficacy of chemotherapy and transcatheter arterial chemoembolization (TACE) on breast cancer patients with liver metastasis, and analyze prognostic factors. METHODS: Clinical data of 98 breast cancer patients with liver metastasis, treated from 1996 to 2005 in Cancer Center of Sun Yat-sen University, were analyzed retrospectively. The prognostic factors correlated to clinical features and treatment approaches were determined using Cox multivariate model. RESULTS: The total response rate was 45.9% for all patients, 48.6% for the 74 patients received systemic chemotherapy, 23.1% for the 13 patients received TACE, and 54.6% for the 11 patients received chemotherapy plus TACE. At a median follow-up of 17 months (3-56 months), the 1-, 2-, 3-, and 4-year survival rates were 36%, 19%, 13%, and 3%, respectively; the median survival was 17 months (3-56 months), and the progression-free survival was 6 months (0-50 months). CONCLUSION: The combination of systemic chemotherapy and TACE may prolong the survival of breast cancer patients with liver metastasis.

[Blocking enhancive effect of vascular endothelial growth factor on proliferation of rhabdomyosarcoma cell line RH4 by avastin].

BACKGROUND & OBJECTIVE: Vascular endothelial growth factor (VEGF) signal pathway is a hot spot in recent tumor research, but its role in rhabdomyosarcoma (RMS) has rarely been reported, and its mechanism is unclear. This study was to investigate the expression of VEGF and its receptors (VEGFR) in RMS cell line RH4 to reveal the mechanism of VEGF signal pathway, and explore the therapeutic value of Avastin in RMS in vitro. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of VEGF, VEGFR1, VEGFR2, and VEGFR3 mRNA in RH4 cells. ELISA was used to detect the concentration of VEGF in supernatant. Western blot was used to detect the expression of VEGFR1 protein. The effects of VEGF and Avastin on RH4 cell growth were evaluated by direct cell counting. RESULTS: RH4 cells expressed VEGF at a high level and secreted VEGF to culture media. RH4 cells only expressed VEGFR1, did not express VEGFR2 and VEGFR3. VEGF promoted the growth of RH4 cells in a dose-dependent manner within a concentration range of 0-100 ng/ml, this effect could be blocked by 10-40 microg/ml Avastin. CONCLUSION: VEGF can promote the growth of RMS cell through VEGFR1, and this effect can be blocked by Avastin.