Prediction of recurrence risk in early breast cancer using human epidermal growth factor 2 and cyclin A2.

BACKGROUND: Human epidermal growth factor 2 (HER2) is one of the most important prediction factors, but only 25% - 30% of breast cancer patients HER2 are positive. It is unknown whether there are other molecular markers that could be used to predict prognosis and recurrence in HER2 negative patients. This study investigated correlations of cyclin A2 and HER2 levels with clinical outcomes in 281 patients with invasive breast cancer in order to identify whether cyclin A2 can serve as a prognostic factor in HER2 negative patients. METHODS: Immunohistochemical staining was used to detect cyclin A2 and HER2 expression in 281 patients. Cyclin A2 and HER2 gene amplifications were analyzed using gene analysis and RT-PCR in 12 patients. Risk and survival estimates were analyzed using Log-rank, Kaplan-Meier, and Cox regression analysis; cyclin A2 and HER2 consistency with survival were analyzed using Kappa analysis. RESULTS: Patients with higher cyclin A2 and HER2 expressions had significantly shorter disease-free survival periods (P = 0.047 and P = 0.05, respectively). Kappa analysis performed that cyclin A2 and HER2 showed a low Kappa index (kappa = 0.37), allowing us to conclude that cyclin A2 and HER2 detect different pathologies. Gene analysis and RT-PCR showed that cyclin A2 was upregulated in patients with early relapse; the average increase was 3.69 - 2.74 fold. CONCLUSIONS: Cyclin A2 and HER2 are associated with proliferation and high recurrence, particularly when combined. Cyclin A2 is easily detected by nuclear staining and might be a useful biomarker for recurrence risk in HER2 negative patients.

[Clinical study of aromatase inhibitors in advanced breast cancer].

OBJECTIVE: To assess the antitumor activity and safety of aromatase inhibitors in advanced breast cancer. METHODS: Fifty-two advanced and female breast cancer patients with measurable and /or bone valuable tumor lesions were observed from June 2003 to September 2006. They were treated by aromatase inhibitors for at least 24 weeks, of whom 11 were treated less than 24 weeks because of disease progress; their age range was from 37 to 75 years (median 58); 8 patients were pre-menopausal, 6 with ovarian ablation and 2 with Goserelin to suppress ovarian function. Thirty-six patients were treated with exemestane, 13 with anastrozole and 3 with letrozole. Major items were observed including objective response rate (ORR=CR+PR), clinical benefit rate (CBR=CR+PR+SD>or=24 weeks), time to progress (TTP), time to failure (TTF), safety and toxicity. RESULTS: CR were 6 cases (11.5%) , with 1 case going on for 152 weeks, 1 case for 96 weeks, and other 4 cases for longer than 60 weeks; PR were 19 cases (36.5%), lasting 32-96 weeks; 16 cases obtained SD>or=24 weeks(30.8%); and 11 cases PD (progress of disease)+SD<24 weeks (21.2%). ORR were 48%, CBR 78.8%, and TTP 78.87 weeks (95% CI 61.13%-96.61%); although the patients who did not achieve objective response (group B) were treated with chemotherapy, radiotherapy or another kind of aromatase inhibitor, but their survival time was significantly different from that of the patients who achieved objective response (group A) when defined by Kaplan-Meier survival estimate. The over survival was 92% in group A, and 81.5% in group B when patients follow up more than 24 weeks [Log Rank (Mantel-Cox) analysis, chi2=3.85, P=0.047]; side effects were observed such as arthralgia, sweating, hot flash, and 2 patients developed heart failure with uncertain related drug before recovery. CONCLUSION: The single agent effective rate of aromatase inhibitor was 48%. The patients had long term survival if they obtained CR or PR, and the side effects were well tolerated.

[FTIR spectroscopic characterization of freshly removed breast cancer tissues].

OBJECTIVE: To identify the FTIR spectroscopic characterization of breast cancer and explore the possibility of application of FTIR in differentiation of malignant and benign breast lesions. METHODS: FTIR spectra of surgically removed fresh breast tissues were measured by spectrometer equipped with mid-infrared fiber optics and an ATR probe. Peaks in the spectra were measured and relative intensity ratios were calculated and analyzed if there are significant differences between the spectra of malignant and benign breast lesions. RESULTS: There were significant differences (P < 0.05) between the spectra of malignant breast cancers and benign breast tissues in the relative intensity ratios of different peaks (I1640/ I1550 and I1160/I1120 for protein structures; I1640/I1460 and I1550/I1460 for relative content of protein and lipid; I1460/I1400 for lipid structures; I1310/I1240 for nucleic acid). CONCLUSION: FTIR spectroscopy could be a useful tool in clinical diagnosis of breast cancer.

[Expression of epidermal growth factor receptor-2 in Chinese breast cancer patients: a meta-analysis].

OBJECTIVE: To study the expression of cerbB-2 and its clinical biology value in Chinese breast cancer patients by evidence based medical analysis. METHODS: All the published studies about cerbB-2 and breast cancer for the last 10 years were reviewed and standard techniques of meta-analysis to combined with the results of these studies were used to produce a more precise estimate of the prognostic significance expression of cerbB-2. RESULTS: The mean of cerbB-2 positive expression was 50% (95% confidence interval 48%-54%), cerbB-2 positive expression was related with node metastasis, recurrence after surgery and survival time; the RR values were 1.71, 2.14 and 2.32 respectively; tumor size, nuclear grade and pathology type were also the important factors that were related with the expression of cerbB-2, while the expression was not related with age; cerbB-2 was a special and sensitive prognostic factor for breast cancer. CONCLUSION: cerbB-2 can be used as an independent molecular marker for definitive prognosis of breast cancer, as well as a reliable marker for choice of standard and individual therapy.

[FTIR spectroscopic explorations of clinical practice of breast cancer].

The authors detected ten normal breast tissue samples and eight breast cancer samples by FTIR spectroscopy with an ATR probe. Nineteen variables of thirteen bands in the spectra were compared using standard statistic methods. The results demonstrated that bands of protein, lipid, carbohydrate, and nucleic acid from cancerous samples were significantly different from those from normal ones: (1) The relative intensity of N-H band increased and amide I band shifted to lower wave number significantly; (2) Symmetric and antisymmetric vibrations of -CH2 group, C=O vibration, and relative intensity of (-CH2)n decreased; (3) The intensity of 1160 cm(-1) band was much weaker than that of 1120 cm(-1); (4) The band of P=O or P-O-C shifted toward lower wave number. The authors believe that FTIR spectroscopy has a promising future in breast cancer diagnosis.

Prevention and treatment of hepatitis B recurrence after liver transplantation.

OBJECTIVE: To study the efficacy of liver transplantation on end-stage hepatitis B related liver diseases, and the prevention and treatment strategies of hepatitis B recurrence after the transplantation. METHODS: The efficacy of combined treatment of lamivudine and hepatitis B immune globulin (HBIG) therapy on 24 patients who had received liver transplantation was retrospectively studied. RESULTS: All the 24 patients with end-stage hepatitis B-related liver diseases treated with lamivudine alone or combined therapy of lamivudine and HBIG showed normal liver function and 21 of them lost hepatitis B virus (HBV) markers. However, the remaining 3 patients became HBsAg positive again soon after liver transplantation. CONCLUSIONS: Liver transplantation is effective for patients with end-stage hepatitis B-related liver diseases. Combined treatment of lamivudine and HBIG may prevent the recurrence of hepatitis B after the operation.