Yanxia Shi

To build a prognostic score model containing indispensible tumour markers for metastatic nasopharyngeal carcinoma in an epidemic area

BACKGROUND AND OBJECTIVEnThe survival outcomes of patients with metastatic nasopharyngeal carcinoma (NPC) differ significantly between individuals. The aim of this study is to build a prognostic score model (PSM) incorporating circulating tumour markers for metastatic NPC in an epidemic area.nnnMETHODSnSeven hundred and ninety-nine patients with disseminated NPC were analysed retrospectively. Univariate and multivariable analyses were conducted using the Cox proportion hazards model. Factors analysed included patients characteristics (gender, age group, performance status), circulating tumour-marker characteristics (Epstein-Barr virus (EBV) DNA level, EBV VCA-IgA level, lactate dehydrogenase (LDH) level, alkaline phosphatase (ALP) level), basic laboratory characteristics (leucocyte count, haemoglobin level, albumin level), and disease characteristics (presence of metastasis at presentation, disease-free interval, number of metastatic sites, specific metastatic sites). The PSM was built according to numerical score derived from the regression coefficients of each independent prognostic variable. The prognostic score of each patient was calculated by totalling up the scores of each independent variable.nnnRESULTSnIndependent prognostic factors included performance status, age, haemoglobin level, LDH level, ALP level and EBV DNA level. Three prognostic groups based on PSM were obtained: low risk (total score=0-4); intermediate risk (5-8); high risk (9-12). Median survivals of the three groups were 25.5, 15.1 and 7 months, respectively, (P<0.001).nnnCONCLUSIONnClinical and laboratory characteristics can help guide the prognostication of patients with metastatic NPC in epidemic areas.

Distribution, clinicopathologic features and survival of breast cancer subtypes in Southern China

Breast cancer research and treatment by different subtypes is an inevitable trend. We investigated the clinicopathologic features and outcomes of different breast cancer subtypes in Southern China. A total of 5809 patients with invasive ductal carcinomas were identified. Immunohistochemical (IHC) markers for estrogen receptor (ER), progesterone receptor (PR), Her2/neu, and Ki‐67 proliferation index were used to classify cases into five molecular subtypes. Clinicopathologic characteristics and survival rates were analyzed retrospectively. Of all patients, 31.1% were luminal A subtype, 30.4% luminal B (high Ki‐67), 13.1% luminal B (Her2/neu+), 9.0% Her2/neu and 16.5% triple negative subtype. Luminal B (high Ki‐67) presented primarily in premenopausal patients with the lowest average age (43.0 years). Her2/neu positive tumors were more closely associated with aggressive features including increased tumor size, positive lymph node status and lymphvascular invasion (LVI). Triple negative subtype was characterized by poorer histologic grade. Her2/neu positive cases had presented the worst 5‐year disease‐free survival (DFS) and overall survival (OS). Multivariate analyses of OS and DFS suggested that there were different negative prognostic factors for the five subtypes. The benefit of the cyclophosphamide, methotrexate, and 5‐fluorouracil (5FU) (CMF) regimen was equal to that of anthracycline‐based and Taxane‐based regimens for patients with luminal A subtype and triple negative subtype, but inferior to anthracycline‐based and Taxane‐based regimens for those with two luminal B subtypes and Her2/neu subtype. The prognostic significance of traditional markers may differ among subtypes. This study revealed the distinct clinicopathologic characteristics, systemic therapy benefits, prognostic factors and survival rate among different breast cancer subtypes.

EGFR expression correlates with decreased disease-free survival in triple-negative breast cancer: a retrospective analysis based on a tissue microarray

The aim of this study was to analyze the prognostic value of EGFR expression for patients with triple-negative breast cancer (TNBC). Clinical data of these patients were collected and analyzed, and immunohistochemical staining for EGFR was performed on tissue microarrays of operable breast cancer from 287 patients with TNBC, who were treated at Sun Yat-sen University Cancer Center from January 1995 to December 2008. EGFR expression was found in 36.2% of the cases with TNBC. A significant correlation was found between EGFR expression and disease-free survival (DFS). Univariated analysis indicated that EGFR expression had a significant prognostic value in TNBC patients, whereas multivariate analysis indicated that EGFR was a significant independent prognostic factor of DFS (Pxa0=xa00.011) in all patients. Our results suggested that EGFR was an independent prognostic factor of DFS in patients with TNBC. Therefore, EGFR could become a good therapeutic target in the treatment of TNBC.

Patients 35 years old or younger with operable breast cancer are more at risk for relapse and survival: A retrospective matched case–control study

It has long been suggested that younger women with breast cancer have less favorable prognostic factors and poorer outcomes. Our main objectives were to determine whether poor prognosis among young women was independent of other common clinicopathologic parameters. We retrospectively analyzed 551 young patients (≤ 35 years, Group I) and 551 older patients (36-50 years, Group II), matched for year of diagnosis, family history of breast cancer, pathologic stage, hormone receptor expression and application of adjuvant therapy. Patients in Group I had significantly shorter disease-free survival (DFS) than Group II (median 23.2 months vs. 28.4 months, P = 0.024). Five-year DFS rate(63.7% vs. 74.7%, P < 0.001) and overall survival (OS) rate (79.5% vs. 85.6%, P = 0.024) in Group I was inferior to those in Group II. Multivariate analysis showed that young age was a significantly negative predictor for DFS and OS. Our study thus shows that age (≤ 35 y/o) is an independent risk factor for prognosis in operable breast cancer.

Classical CMF regimen as adjuvant chemotherapy for triple-negative breast cancer may be more effective compared with anthracycline or taxane-based regimens

Patients suffering from triple-negative breast cancer (TNBC) have poor prognosis mainly because no standard treatment is currently available. Our objectives were to explore the prognostic factors for first relapse of patients with TNBC. A cohort of 687 patients with TNBC, diagnosed and treated between January 1995 and December 2008 at Sun Yat-sen University Cancer Center, were retrospectively analyzed. Cox proportional hazards models were fitted to explore factors that predict relapse development. Survival rate was computed using the Kaplan–Meier product limit method. The median age of the 687 patients was 46 (range 16–76xa0years), and 64.8% of the patients were pre-menopausal. The median follow-up time was 56xa0months (range 14–156xa0months), in which 194 patients had recurrence, and 115 died. The median recurrence-free time was 25xa0months (range 4–143xa0months), with 118 (60.8%) of the cases first relapsing at a single site. The three- and five-year disease-free survival rates were 79.7 and 72.6%, respectively. Primary tumor size at diagnosis, lymph node status, and type of regimen used in the (neo)adjuvant chemotherapy were considered independent predictors of first relapse. CMF-containing adjuvant chemotherapy significantly decreased recurrence compared with the anthracycline- or taxane-based regimens (RRxa0=xa00.66, 95%; CI 0.45–0.96; Pxa0=xa00.030). The median time from first relapse to death was 26xa0months (range 2–121xa0months). The two- and five-year survival rates were 60.6 and 36.6%, respectively. Liver metastasis at first recurrence and progression-free survival over 12xa0months after first-line therapy were two important factors that affected survival rate after recurrence. The median relapse time of TNBC was about 2xa0years after diagnosis. CMF regimens for TNBC patients may be more effective than anthracycline- or taxane-based regimens. Liver metastasis at first recurrence signifies unfavorable prognosis.

HER2-positive breast cancer patients receiving trastuzumab treatment obtain prognosis comparable with that of HER2-negative breast cancer patients

Purpose The efficacy of trastuzumab in Chinese breast cancer (BC) patients has rarely been reported. This study was designed to compare the clinical outcomes of HER2-positive BC patients receiving or not receiving trastuzumab treatment and HER2-negative BC patients. Patients and methods This study involved three groups of patients. The first group was 115 human epidermal growth factor receptor 2 (HER2)-positive BC patients treated with trastuzumab who were enrolled at Sun Yat-sen University Cancer Center between January 2002 and July 2010; the second group was a matched control group of 115 HER2-positive patients who did not receive trastuzumab treatment; the third group was a matched group of 115 HER2-negative patients who received conventional therapy in the adjuvant setting. The primary endpoint was 3-year and 5-year disease-free survival (3-DFS and 5-DFS, respectively). The Kaplan–Meier method, log-rank test, and multivariate Cox proportional hazard regression model were used for survival analysis. The differences in survival rates among the three groups were also analyzed according to two different periods: 2002–2006 and 2007–2010. Results The median duration of follow-up was 36 months (range, 12–111 months). The 3-DFS rates in the HER2-negative group, the HER2-positive group who received trastuzumab treatment, and the HER2-positive group who did not receive trastuzumab treatment were 82.6%, 89.6%, and 67.0%, respectively. The 3-DFS rate for the total study population was statistically significant (P < 0.001). Further analysis indicated a statistically significant difference in 3-DFS between either of the first two groups and the third group (P < 0.01), but the difference between the first two groups was not statistically significant (P = 0.157). Among the three groups, the 3-DFS rates during 2002–2006 did not have a significant difference compared with that during 2007–2010. Conclusion This study has further confirmed the efficacy of trastuzumab for HER2-positive operable BC in Chinese patients. It has also demonstrated that the 3-DFS and 5-DFS rates between HER2-positive patients receiving trastuzumab treatment and HER2-negative patients are comparable.

Efficacy and tolerability of toremifene and tamoxifen therapy in premenopausal patients with operable breast cancer: a retrospective analysis

BACKGROUNDnGiven the use of tamoxifen as standard treatment for hormone receptor-positive breast cancer, the use of toremifene as an adjuvant endocrine therapy has not been widely examined. The present retrospective study compared the efficacy and safety of toremifene and tamoxifen in the treatment of operable hormone receptor-positive breast cancer in premenopausal women.nnnMETHODSnPremenopausal patients with hormone receptor- positive operable breast cancer were eligible. Enrolled patients (n = 1847) received either 60 mg toremifene (n = 396) or 20 mg tamoxifen (n = 1451) daily for a minimum of 5 years after surgery. Disease-free survival (dfs) was the primary endpoint. Overall survival (os) and time to distant recurrence were secondary endpoints.nnnRESULTSnTreatment with toremifene and tamoxifen resulted in no between-group differences in dfs (p = 0.659) or os (p = 0.364). Mean dfs was 10.3 years for both groups. Mean os was 11.2 years for the toremifene group and 11.1 years for tamoxifen group. The 5-year dfs rate was 87.0% in the toremifene group and 85.0% in the tamoxifen group. The 5-year survival rate was 94.3% in the toremifene group and 93.5% in the tamoxifen group. Adverse events rates were similar in the two groups, with the exception of irregular menses, which occurred at a higher rate in the tamoxifen group than in the toremifene group (10.0% vs. 6.3%, p = 0.025).nnnCONCLUSIONSnIn this retrospective study, the efficacy and safety profiles of toremifene and tamoxifen for the treatment of operable hormone receptor-positive breast cancer in premenopausal women were similar.

Clinicopathologic characteristics and prognostic factors for HER2-positive patients with metastatic breast cancer in southern China

Introduction The aim of the study was to analyze clinicopathologic characteristics and survival and to identify prognostic factors for Chinese patients with HER2-positive metastatic breast cancer. Material and methods A total of 243 patients with HER2-positive metastatic breast cancer, treated during the period 2002 to 2009, were followed up from initial disease diagnosis to death or date of last follow-up (December 2011). Cumulative survival curves were created using Kaplan-Meier analysis with the log-rank test. Prognostic factors were analyzed by univariate and multivariate Cox proportional hazards regression analysis. Results During follow-up, 205 patients died, with a median OS of 27 months (95% CI: 23.5, 30.5 months), and the 1-, 3-, and 5-year survival rates were 84.4%, 38.6%, and 18.1%, respectively. The median OS of HR+ patients was significantly higher than that of HR– patients (p < 0.001). Surgery (hazard ratio = 0.60, p = 0.002), endocrine therapy (hazard ratio = 0.53, p < 0.01), and anti-HER2 therapy (hazard ratio = 0.63, p = 0.003) were favorable independent prognostic factors for patients with HER2-positive metastatic breast cancer. Conclusions These results indicated that surgical intervention, endocrine therapy, and anti-HER2 therapy were good for these HER2 positive patients with metastatic breast cancer, but ECOG performance status < 1 and metastasis to brain were unfavorable independent prognostic factors. HR status was not an independent prognostic factor.

Comparison of overall survival between the early use and delayed use of Trastuzumab therapy groups: a retrospective analysis of 128 patients with HER-2-positive advanced breast cancer

Trastuzumab has been the standard treatment in first-line treatment of HER-2-positive advanced breast cancer (H2ABC). This study explored whether the delayed and repeated use of trastuzumab could influence overall survival (OS). A total of 128 patients with H2ABC who had received at least one line of trastuzumab-based regimens were included. The primary endpoint was OS defined as from the date of first diagnosis of H2ABC to death. The median OS of initiating trastuzumab in first-line group (nxa0=xa056), in the second-line group (nxa0=xa032), and the third- or more-line group (nxa0=xa040) was 40.6xa0m, 39.5xa0m, and 38xa0m, respectively (Pxa0=xa00.867). For patients who had received over one line of trastuzumab (nxa0=xa046), the median OS was 44xa0m, and for those receiving only one line (nxa0=xa067), it was 27.6xa0m (Pxa0=xa00.059). The delayed use of trastuzumab has no negative effect on the OS of patients with H2ABC. There is a trend of improved OS over the repeated use of trastuzumab.

Selective Estrogen Receptor Modulator-Associated Nonalcoholic Fatty Liver Disease Improved Survival in Patients With Breast Cancer: A Retrospective Cohort Analysis

AbstractSelective estrogen receptor modulator (SERM)-associated nonalcoholic fatty liver disease (NAFLD) might be related to treatment efficacy in patients with breast cancer because of circulating estrogen antagonism.The aim of the study was to investigate the relationship between NAFLD and survival outcomes in patients with breast cancer who were treated with tamoxifen or toremifene.This single-center, retrospective, cohort study included 785 eligible patients who received tamoxifen or toremifene, after curative resection for breast cancer, at the Sun Yat-sen University Cancer Center between January 2005 and December 2009. Data were extracted from patient medical records. All patients underwent abdominal ultrasonography, at least once, at baseline and at the annual follow-up. Patients who were diagnosed with NAFLD on ultrasonography were classified into the NAFLD or the non-NAFLD arm at the 3-year follow-up visit. Univariate and multivariate Cox regression analyses were conducted to evaluate any associations between NAFLD and disease-free survival (DFS) or overall survival (OS).One hundred fifty-eight patients were diagnosed with NAFLD. Patients who developed NAFLD had better DFS and OS compared with those who did not. Univariate analyses revealed that the 5-year DFS rates were 91.56% and 85.01% for the NAFLD and non-NAFLD arms, respectively (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.37–0.96; log-rank Pu200a=u200a0.032). The 5-year OS rates were 96.64% and 93.31% for the NAFLD and non-NAFLD arms, respectively (HR, 0.39; 95% CI, 0.16–0.99; log-rank Pu200a=u200a0.039). Multivariate analysis revealed that NAFLD was an independent prognostic factor for DFS, improving the DFS rate by 41% compared with that in the non-NAFLD arm (HR, 0.59; 95% CI, 0.36–0.96; Pu200a=u200a0.033).SERM-associated NAFLD was independently associated with improved DFS and might be useful for predicting treatment responses in breast cancer patients treated with SERMs.