Peng Yuan

Chongqing Cancer Hospital and Institute, Ch’ung-ch’ing-shih, Chongqing Shi, China

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Publications (45)65.41 Total impact

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    ABSTRACT: Concurrent use of anthracyclines and trastuzumab used to be avoided in the treatment of HER2-positive breast cancer due to the high risk of cardiac toxicity. However, several newly published studies challenged this view and demonstrated that concomitant use of the two agents significantly improved the clinical outcome without causing additional cardiac toxicity. This meta-analysis summarized available data to investigate the safety and efficacy of concurrent use of anthracyclines and trastuzumab. Eligible studies were identified through several search strategies and assessed for quality. Data were extracted from studies in terms of baseline characteristics and key statistics, which were utilized to calculate pooled effect size. Eight studies were included in the meta-analysis to evaluate the cardiac safety of concurrent use of anthracyclines and trastuzumab. It is demonstrated that concomitant administration was moderately associated with increased risk of cardiac-related adverse events (RR = 1.97, 95 % CI 1.49-2.60, P < 0.001) by fixed effect model. In addition, subgroup analysis showed combined use of anthracyclines and trastuzumab significantly increased the likelihood of cardiac toxicity in neo-adjuvant setting (RR = 1.51, 95 % CI 1.10-2.07, P = 0.01) as well as in palliative setting (RR = 3.92, 95 % CI 2.11-7.27, P < 0.001). Also, we found concurrent treatment as in neo-adjuvant treatment setting slightly increased pCR rate by randomized effect model with the pooled RR being 1.52 (95 % CI 1.05-2.20, P = 0.03). Concurrent use of anthracyclines and trastuzumab increased the risk of cardiac toxicity in both neo-adjuvant and metastatic settings, although moderately increased pCR rate as neo-adjuvant treatment.
    Medical Oncology 12/2014; 31(12):340. · 2.06 Impact Factor
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    ABSTRACT: Genetic variants have been shown to affect length of survival in cancer patients. This study explored the association between lung cancer susceptibility loci tagged by single-nucleotide polymorphisms (SNPs) identified in the genome-wide association studies and length of survival in small-cell lung cancer (SCLC). Eighteen SNPs were genotyped among 874 SCLC patients and Cox proportional hazards regression was used to examine the effects of genotype on survival length under an additive model with age, sex, smoking status and clinical stage as covariates. We identified 3 loci, 20q13.2 (rs4809957G >A), 22q12.2 (rs36600C >T) and 5p15.33 (rs401681C >T), significantly associated with the survival time of SCLC patients. The adjusted hazard ratio (HR) for patients with the rs4809957 GA or AA genotype was 0.80 (95% CI, 0.66-0.96; P = 0.0187) and 0.73 (95% CI, 0.55-0.96; P = 0.0263) compared with the GG genotype. Using the dominant model, the adjusted HR for patients carrying at least one T allele at rs36600 or rs401681 was 0.78 (95% CI, 0.63-0.96; P = 0.0199) and 1.29 (95% CI, 1.08-1.55; P = 0.0047), respectively, compared with the CC genotype. Stratification analyses showed that the significant associations of these 3 loci were only seen in smokers and male patients. The rs4809957 SNP was only significantly associated with length of survival of patients with extensive-stage but not limited-stage tumor. These results suggest that some of the lung cancer susceptibility loci might also affect the prognosis of SCLC.
    PLoS ONE 11/2014; 9(11):e113574. · 3.53 Impact Factor
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    ABSTRACT: Aims and background. Contralateral axillary lymph node metastasis (CAM) in breast cancer patients is uncommon and the source uncertain. Management is complicated when CAM occurs as the first event of relapse after treatment of the primary tumor, especially in the absence of metastatic disease elsewhere. Methods. We reviewed the records of all breast cancer patients treated during 1999-2012. All patients with pathologically confirmed metachronous CAM were included. The examined data were demographic characteristics, tumor features and management modalities. Data from an epidemiological report that described the pathological characteristics of breast cancer in China during 1999-2008 were employed to allow further comparison. Twenty-eight patients with CAM were included in the study; they comprised 0.81% of the total number of patients. The median patient age was 47 years (range, 27-60 years). Half of the initial breast cancers were located at inner and central sites. Initial cancers were generally locally advanced (stage III, 50%) and hormone receptor negative. Treatment modalities included axillary lymph node dissection (ALND), mastectomy, radiation, and chemotherapy (± targeted therapy). Results. After 29 months of follow-up, 25 patients had disease progression with a median progression-free survival of 10 months. Regional recurrence was most commonly seen at sites including bilateral breast, chest wall and superficial lymph nodes, accounting for 44% (n = 11) of patients who progressed. Median progression-free survival was prolonged in patients treated with radiotherapy (10 months vs 22 months). During the observation period, 13 patients died of disease progression. We found that CAM was associated with tumors with aggressive pathological features and had a poor prognosis. Conclusion. CAM is most likely to be distant metastasis from the initial breast cancer through lymphatic drainage rather than regional metastasis from a new occult breast cancer. Comprehensive treatment including chemotherapy and radiotherapy can provide better control; however, ANLD alone is insufficient treatment and mastectomy is not recommended.
    Tumori. 11/2014; 100(6):600-4.
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    ABSTRACT: The role of platinum-based chemotherapy (PBCT) in the treatment of triple-negative breast cancer (TNBC) is still undetermined. The aim of this study was to compare the efficacy of PBCT versus non-PBCT in patients with lung metastasis from TNBC. Clinical data on patients diagnosed and treated for lung metastasis from TNBC between 2004 and 2012 at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences, were retrospectively analyzed. Of the 79 patients identified, 34 received PBCT and 45 received non-PBCT. The median progression-free survival was 10 months [95% confidence interval (CI) 6.6-13.4 months] in the platinum-based group and 5 months (95% CI 3.7-6.3 months) in the nonplatinum group (P=0.002); overall survival was also significantly improved (32 vs. 21 months, P=0.002). In the multivariate analysis for the entire cohort, first-line PBCT (hazard ratio 0.425; 95% CI 0.251-0.720; P=0.001) and presentation of symptoms related to lung metastasis (hazard ratio 2.237; 95% CI 1.180-4.240; P=0.014) were associated independently with survival. Our results support the use of PBCT in the first-line treatment of lung metastasis from TNBC.
    Anti-Cancer Drugs 10/2014; 25(9):1089-1094. · 1.89 Impact Factor
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    ABSTRACT: To compare the effect of first-line treatment with platinum-based chemotherapy and non-platinum-based chemotherapy in patients with lung metastases from triple negative breast cancer (TNBC). Sixty-five eligible patients were divided into platinum-treated group and non-platinum-treated group according to the first-line therapy. Factors predicting the chemotherapeutic efficacy included overall survival (OS), progression-free survival (PFS) and objective response (OR). In the platinum-treated group of 32 patients, 2 cases (6.3%) achieved CR, 16 cases (50.0%) achieved PR, 11 (34.4%) cases achieved SD, and 3 patients (9.4%) achieved PD. In the non-platinum-treated group of 33 patients, 2 cases (6.1%) achieved CR, 6 cases (18.2%) achieved PR, 16 cases (48.5%) achieved SD, and 9 cases (27.3%) achieved PD. Median PFS was significantly longer in the platinum-treated group than in the non-platinum-treated group (10 months vs. 6.0 months, P = 0.012), and OS was also improved (32 months vs. 22 months, P = 0.006). Multivariate analysis of several factors including local-regional lymph node involvement, lung metastasis-related symptoms, first-line platinum-based chemotherapy, disease-free interval, size and number of lung lesions, showed that first-line platinum-based chemotherapy was an independent prognostic factor for TNBC patients with lung metastases. Compared with non-platinum-based chemotherapy, the first-line platinum-based chemotherapy can improve PFS and OS in TNBC patients with metastases confined to the lungs.
    Zhonghua zhong liu za zhi [Chinese journal of oncology] 10/2014; 36(10):788-92.
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    ABSTRACT: To analyze the clinical characteristics and survival depending on biological subtypes in breast cancer patients with brain metastases (BM). A retrospective analysis was performed on 152 breast cancer patients with BM admitted to the Cancer Institute & Hospital, Chinese Academy of Medical Sciences from January 2003 to December 2012. Depending on the biological characteristics, these patients were divided into three subtypes: Luminal, human epidermal growth factor receptor 2 (HER-2)-overexpressing, and triple-negative subtypes. The clinicopathological characteristics, recurrence status, and prognostic factors were analyzed at the initial diagnosis. The systemic therapy after BM was further studied. Among the 152 patients, the number of Luminal, HER-2-overexpressing, and triple-negative breast cancer (TNBC) subtypes were 60, 53, and 39 cases, respectively. The median time from first recurrence to BM of all patients was 7.3 months, the median time of Luminal, HER-2-overexpressing, and TNBC subtypes was 11.0 months, 9.6 months, and 5.5 months, respectively (P < 0.001). Compared with the TNBC subtype, BM occurred later in the HER-2-overexpressing subtype (P < 0.001). In the HER-2-overexpressing subtype, trastuzumab could delay the occurrence of BM in advanced breast cancer patients (17.1 vs. 1.7 months, P < 0.001, 95%CI 5.21-13.98). The median time of overall survival (OS) in the whole group was 56.5 months (7.5-240.2 months, 95%CI 52.6-60.4). The median survival time of Luminal, HER-2-overexpressing and TNBC subtypes was 70.9 months, 53.9 months, and 40.9 months, respectively (P = 0.013). The median survival time of after BM was 11.5 months in the whole group, and the median survival time of Luminal, HER-2-overexpressing and TNBC subtypes was 11.2 months, 12.7 months, and 11.6 months, respectively, with a difference of no statistical significance. Compared with non-BM as the first site, the patients with BM as the first site had a longer survival (14.8 months vs. 8.0 months, P = 0.001). Systemic therapy could prolong the survival after BM. The median survival of chemotherapy, chemotherapy in combination with trastuzumab, and without systemic therapy was 13.6 months, 19.0 months, and 6.5 months, respectively (P = 0.043). The survival after BM is influenced by biological subtypes. Compared with the Luminal subtype, brain meatastases occurr earlier in HER-2-overexpressing and TNBC subtypes. Trastuzumab can delay the occurrence of BM from advanced breast cancer, and systemic therapy can improve the survival of patients after brain metastasis.
    Zhonghua zhong liu za zhi [Chinese journal of oncology] 09/2014; 36(9):697-702.
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    ABSTRACT: The aim of this study was to look for predictive and prognostic factors in anthracycline-based neoadjuvant chemotherapy.
    The International journal of biological markers 07/2014; · 1.36 Impact Factor
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    ABSTRACT: To discuss the clinicopathological features and prognosis of metastases to the breast from extramammary solid tumors.
    Zhonghua zhong liu za zhi [Chinese journal of oncology] 06/2014; 36(6):453-6.
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    ABSTRACT: To evaluate the efficacy and safety of trastuzumab plus different chemotherapy regimens in treatment of patients with HER-2-positive advanced breast cancer.
    Zhonghua zhong liu za zhi [Chinese journal of oncology] 05/2014; 36(5):372-6.
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    ABSTRACT: To evaluate the clinical characteristics and prognosis of adrenal metastasis from breast cancer, and to explore methods to improve prognosis. Thirty-four breast cancer patients with adrenal metastasis were diagnosed and treated in our hospital from Jan. 1999 to Dec. 2010. SPSS 17.0 was used for survival analysis. During the Jan. 1999 to Dec. 2010 period, 13 595 patients with breast cancer were treated in our hospital. Among them, 34 cases had adrenal metastasis from breast cancer, with an incidence of 0.25%. The median time to progression (TTP) and overall survival of the 34 patients was 6.2 months (95%CI 3.1-9.3 months) and 21.4 months (95%CI 0-44.0 months), respectively. Eleven patients (34.4%) achieved partial response among 32 patients who received chemotherapy, and 10 (31.2%) achieved stable disease. Patients who achieved best response of PR or SD were superior in TTP and OS than patients with disease progression after chemotherapy (TTP: 18.1 months vs. 2.3 months, P < 0.001; OS: 35.2 months vs. 10.3 months, P = 0.003). Patients who received 1st or 2nd line chemotherapy were superior in TTP than patients who received over 2nd line chemotherapy (TTP: 15.7 months vs. 4.2 months, P = 0.005). The incidence of adrenal metastasis from breast cancer is low. Chemotherapy-based systemic therapy should be recommended to improve the prognosis for these patients.
    Zhonghua zhong liu za zhi [Chinese journal of oncology] 11/2013; 35(11):855-7.
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    ABSTRACT: Retrospective and prospective studies have shown that continuous administration of trastuzumab with different chemotherapy regimens resulted in better clinical outcomes than the administration of chemotherapy alone in women with HER2-positive, trastuzumab-refractory metastatic breast cancer (MBC). However, there are limited data to evaluate the activity of trastuzumab in patients progressed after other anti-HER2 therapies, e.g. lapatinib. The aim of the present study was to evaluate retrospectively the clinical value of trastuzumab in patients with lapatinib-resistant HER2-positive advanced breast cancer treated in our center. Patients with HER2-positive MBC who experienced progression after first-line lapatinib-based regimens were assigned to receive either conventional treatment without trastuzumab or in combination with trastuzumab as second-line therapy. The efficacy end points included progression-free survival (PFS) and overall survival (OS). Thirty-five eligible patients progressed after treatment with lapatinib-based regimens were collected. None of the patients had received prior trastuzumab in either the adjuvant or metastatic setting. Twenty-two patients were assigned to receive conventional treatment without trastuzumab as second-line therapy (non-T arm) and 13 patients received conventional treatment combined with trastuzumab (T arm). There were no significant differences in the main clinical factors between the two arms, such as age, PS status, ER/PR, metastatic status, etc. Both the two cases with no disease progression after the second-line therapy were trastuzumab-treated patients, and all the other 33 cases were patients with progression despite the second-line therapy. Twenty-seven patients died due to disease progression, and eight survived (six cases of the T-arm and two cases of the non-T arm). The median PFS was 3.3 months in the non-T arm and 10.0 months in the T arm (P = 0.001). The median OS was 7.0 months in the non-T arm and 31.1 months in the T arm (P = 0.015). Trastuzumab plus conventional treatment is superior to conventional treatment in women with lapatinib-resistant HER2-positive metastatic breast cancer. Continuous anti-HER2 management can provide survival benefit to patients with HER2-positive breast cancer.
    Zhonghua zhong liu za zhi [Chinese journal of oncology] 07/2013; 35(7):521-524.
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    ABSTRACT: Anthracycline-Taxane chemotherapy is widely used in neoadjuvant treatment for breast cancers. However, there is limited data reported in patients with triple negative breast cancer (TNBC). Here, we evaluated the pathologic responses and survival of neoadjuvant epirubicin and taxanes chemotherapy in patients with locally advanced TNBC to provide some useful information for clinical practice. A total of 43 patients with locally advanced TNBC were enrolled in this study. Patients were administered with epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2) or docetaxel 75 mg/m(2) every 3 weeks for at least 2 cycles. The primary endpoint was pathologic complete response (pCR), which was defined as no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node, while relapse-free survival (RFS) and overall survival (OS) were secondary endpoints. Thirty-nine (90.7%) patients were at clinical stages IIB-IIIC. Thirty-seven (86%) completed 4-6 cycles of preoperative chemotherapy, and objective response rate (ORR) was 81.4% (35/43). Forty-two patients underwent radical surgery subsequently. The pCR rate was 14.3% (6/42). The most common adverse events in neoadjuvant chemotherapy were nausea/vomiting (88.4%, 38/43) and neutropenia (88.4%). After a median follow-up period of 34.0 months, 3-year RFS and OS rate was 53.6% and 80.1%, respectively. All events of recurrence and death occurred in non-pCR patients, in whom the 3-year RFS and OS rates were 44.3% and 76.6%, respectively. This study suggest that neoadjuvant chemotherapy with epirubicin plus taxanes has a relatively low pCR rate and high early recurrence risk in locally advanced TNBC, which indicates the necessity for more efficacious treatment. Further study is needed to validate these results.
    Journal of Huazhong University of Science and Technology 04/2013; 33(2):262-265. · 0.78 Impact Factor
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    ABSTRACT: Triple-negative breast cancer (TNBC) is defined by the lack of the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). It is characterized by aggressive behavior, poor prognosis and lack of targeted therapies. MicroRNA (miRNA) as a novel modulator of gene expression has played an important regulatory role in the malignancy. Dysregulation and/or mutation of the miRNAs may also contribute to the TNBC susceptibility since it is associated with the expression of ER, PR and HER2. Single nucleotide polymorphisms (SNPs) in miRNAs may be extremely relevant for TNBC. We tried to validate the hypothesis that genetic variations in miRNA are associated with TNBC development, and identify candidate biomarkers for TNBC susceptibility and clinical treatment. We screened the genetic variants in all miRNA genes listed in the public database miRBase and NCBI. A total of 23 common SNPs in 22 miRNAs, which tagged the known common variants in the Chinese Han people with a minor allele frequency greater than 0.05, were genotyped. This case-control study involved 191 patients with TNBC and 192 healthy female controls. Frequencies of SNPs were compared between cases and controls to identify the SNPs associated with TNBC susceptibility. No significant association was found between TNBC risk and the SNPs in the miRNA genes in the Chinese Han people (P>0.05), but this warrants further studies.
    PLoS ONE 03/2013; 8(3):e60195. · 3.53 Impact Factor
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    ABSTRACT: To analyze the clinicopathological features and prognostic factors of breast cancer patients with inguinal lymph node metastases. Seventeen breast cancer patients with inguinal lymph node metastases were treated from January 1999 to December 2010 in our cancer center. All of the patients had a history of breast cancer without other primary cancer. Their clinicopathological characteristics and prognostic factors were surveyed. The frequency of breast cancer cases with inguinal lymph node metastaseis consisted of 0.11% of the total number of breast cancer patients in the same period. Two patients (11.8%) had inguinal lymph node metastasis only, and multi-site metastases were observed in the remaining 15 (88.2%) patients. The number of ER- and/or PR-positive and negative were 10 (58.8%) and 7 (41.2%) cases, respectively, and among the 13 cases who underwent HER-2 test, the number of HER-2-positive was 4 (30.8%). For the 16 patients who underwent surgery, 9 patients were detected with metastatic axillary lymph nodes equal or greater than 4. All of the 17 patients were treated with chemotherapy.The median follow-up time was 156 months. The 5-year overall survival rate was 49.9%. Univariate analysis revealed that metastatic axillary lymph nodes ≥ 4, ER- and(or) PR-negative, adjuvant chemotherapy ≤ 6 cycles, disease stage as III/IV at diagnosis and the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis ≤ 36 months were predictors of shorter PFS (P < 0.05). Metastatic axillary lymph nodes ≥ 4, ER- and(or) PR-negative, adjuvant chemotherapy ≤ 6 cycles, primary recurrence as multiple distant metastases, the period from diagnosis of breast cancer to the occurrence of inguinal lymph nodes metastasis ≤ 36 months and pleural effusion were predictors of shorter OS (P < 0.05). Multivariate analysis revealed that the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis was an independent prognostic factor concerning PFS (P < 0.05). The prognostic factors of breast cancer patients with inguinal lymph node metastases include the number of metastatic axillary lymph nodes, ER and(or) PR status, the cycles of adjuvant chemotherapy, type of primary recurrence, the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis and pleural effusion. Regular and complete physical examination after surgery as well as prompt intensive treatment for high-risk patients may have positive significance in the treatment of such type of patients. However, a type of more reasonable and individualized treatment is warranted in future studies.
    Zhonghua zhong liu za zhi [Chinese journal of oncology] 03/2013; 35(3):207-11.
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    ABSTRACT: To investigate the relationship between genetic variantions of circadian clock genes and risk of breast cancer. A case-control study including 406 breast cancer patients and 412 controls was conducted and genes Clock (rs2070062) and Per2 (rs2304672, rs2304669, rs934945) were genotyped by TaqMan real-time PCR. Unconditional logistic regression model was used to analyze the association between the genetic polymorphisms and breast cancer. Individuals with the rs2304669-TT genotype showed significantly increased breast cancer risk with the OR of 2.33 when compared with the individuals with rs2304669-CC and CT genotypes (P = 0.001). In addition, the three haplotypes containing the risk T allele of rs2304669 were identified to be associated with increased breast cancer risk. However, it was found that rs2304672, rs2070062 and rs934945 polymorphisms were not related with breast cancer risk. The locus rs2304669 on Per2 gene is associated with breast cancer risk. Genetic variation of circadian clock genes may increase the susceptibility to breast cancer. Therefore, it may become an important biomarker of susceptibility to breast cancer.
    Zhonghua zhong liu za zhi [Chinese journal of oncology] 03/2013; 35(3):236-9.
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    ABSTRACT: To explore the effects of polysomy 17 on human epidermal growth factor receptor-2 (HER-2) testing and study its clinicopathologic significance. We retrospectively analyzed the HER-2 status by fluorescence in situ hybridization (FISH) and HER-2 protein expression by immunohistochemistry (IHC) in a cohort of 619 patients with invasive breast cancer. The relationship between polysomy 17 and various clinicopathologic parameters was assessed. Polysomy 17 was observed in 31.8% of cases, but more frequently in the IHC(3+) (41.9%) than in the IHC(2+)(27.7%) and IHC(1+/0) (11.1%) subgroup (P = 0.001). There was no significant correlation between the frequency of polysomy 17 and HER-2 status in each IHC subgroup (P > 0.05). Among the cases without gene amplification by FISH, 9 of 15 IHC(3+) cases showed polysomy 17. As compared with the amplified group, unamplified polysomy 17 patients were associated with such good prognostic indicators as greater hormone receptor positivity (P < 0.001) and lower Ki-67 index (P = 0.003) with a trend towards those with neither amplification or polysomy. The frequency of polysomy 17 is partially correlated with HER-2 protein expression but not HER-2 amplification. And polysomy 17 is a major factor in strong HER-2 protein overexpression in 3+ nonamplified cases. Tumors displaying unamplified polysomy 17 resemble more HER-2-negative than HER-2-positive counterparts.
    Zhonghua yi xue za zhi 01/2013; 93(2):84-8.
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    ABSTRACT: OBJECTIVE: To explore the therapeutic outcomes of various first-line regimens and prognostic factors for hormone receptor positive (HR+) breast cancer (BrCa) patients with bone-only metastases. METHODS: A total of 139 HR+ BrCa patients with bone-only metastases between January 1, 2005 and October 31, 2010 were retrospectively reviewed. Their clinicopathologic characteristics, various treatment regimens and clinical survival factors were analyzed. Furthermore, the effects of various therapeutic regimens on skeletal-related events (SREs) were explored. RESULTS: In this cohort, 99 patients received first-line chemotherapeutic regimens and 40 had first-line endocrine drugs. Their median overall survival time was 61 months. No significant difference was noted in 5-year overall survival rate between first-line chemotherapy group (49.4%) and first-line endocrine group (44.3%) (hazard ratio (HR) 0.687, 95% confidence interval (CI) 0.307 - 1.539, P = 0.362). Furthermore, interval of disease-free survival > 3 years and number of positive lymph nodes < 10 were favorable prognostic factors by univariate analyses (HR = 0.333, 95%CI 0.138 - 0.803, P = 0.014; HR = 0.239, 95%CI 0.102 - 0.562, P = 0.001); they were also independent favorable prognostic factors by multivariate Cox-regression analyses. The proportion of patients with SREs decreased in the first-line chemotherapy group compared with the first-line endocrine group (45/99 (45.4%) vs 25/40 (62.5%)). Nonetheless, the difference was insignificant (P = 0.092). CONCLUSION: Interval of disease-free survival > 3 years and number of positive lymph nodes < 10 are independent favorable prognostic factors. The overall survival of HR+ BrCa patients with bone-only metastases is not significantly different between two groups. First-line chemotherapy may lower the incidence of SREs. Both endocrine therapy and chemotherapy are effective for HR+ BrCa patients with bone-only metastases and they should be individualized.
    Zhonghua yi xue za zhi 12/2012; 92(46):3279-3282.
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    ABSTRACT: To evaluate the efficacy, safety and survival of combination of carboplatin plus paclitaxel as neoadjuvant chemotherapy (NACT) for patients with locally advanced triple-negative breast cancer (TNBC), and explore an optimal regimen for TNBC. Patients with core needle biopsy confirmed pathological diagnosis of IIA ∼ IIIC invasive breast cancer, negative for estrogen and progesterone receptors and HER2 by immunohistochemistry, and with indication for NACT were eligible in this study. The biopsy tumor tissues were tested for CK5/6, CK14, EGFR and Ki67. The patients received paclitaxel 175 mg/m(2) on day 1, carboplatin at an area under the curve 5 mg×min/ml on day 2 of every 21 days. The clinical response was evaluated every 2 cycles according to Standard RECIST 1.0 criteria and surgery was done after four to six cycles. Pathological complete remission (pCR) was defined if absence of invasive tumor in the breast and axillary lymph nodes samples or residual carcinoma in situ only. Overall, thirty-one patients were enrolled from January 2008 to November 2010. The median age was 51 years and 83.9% of the patients were diagnosed as stage IIB to IIIC diseases. 30 Patients completed chemotherapy as planed while one patient changed regimen due to paclitaxel allergy. Twenty-eight patients could be evaluated for clinical efficacy, of which CR, PR, SD, PD were achieved in 4, 20, 3 and 1 women, respectively. The objective response rate was 85.7%. The expression rate of CK5/6, CK14 and EGFR were 88.9% (24/27), 59.3% (16/27) and 63% (17/27), respectively. Among 27 patients who received modified radical mastectomy or breast-conserving surgery, 11 patients obtained pCR, with a pCR rate of 40.7% (95%CI 22.2% - 59.3%). Five of six CK5/6- and CK14-positive patients achieved pCR. All the 31 patients could be evaluated for toxicity according to the NCI-CTC v3.0 criteria. The major toxicities were neutropenia (93.5%), vomiting (45.2%) and ALT/AST increase (32.3%), and grade 3-4 toxicities accounted for 74.2%, 3.2%, 0, respectively. Until December 2011, at a median follow-up of 28.9 months (range 5 - 47.9), eight patients developed recurrence including 5 patients died. Among 11 patients with pCR, one suffered from lung metastasis at 45 months after diagnosis and survived with tumor until now. The other ten were alive and disease free. The 3-year DFS and OS were 62% and 74.7%, respectively. As a neoadjuvant treatment for triple-negative breast cancer, carboplatin plus paclitaxel regimen achieves notable higher objective response rate and pCR rate compared with the anthracycline plus paclitaxel regimen reported in the literature, and is well tolerable. It is an optimized regimen for TNBC.
    Zhonghua zhong liu za zhi [Chinese journal of oncology] 10/2012; 34(10):770-4.
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    ABSTRACT: Anthracycline is a DNA topoisomerase 2-α (TOP2A) inhibitor and its concomitant over expression with Human Epidermal Growth Factor Receptor 2 (HER2) was investigated of being predictive for the response to anthracycline-based chemotherapies in breast cancer. 309 early and local advanced breast cancer patients were treated with anthracycline-based neoadjuvant chemotherapies in intense dose dense (IDD) (CE, Cyclophosphamide + Epirubicin) or conventional (TE, Paclitaxel + Epirubicin) regimens. HER2 proteins were qualitatively analyzed by immunohistochemistry (IHC) of primary tumor core biopsies, and TOP2A gene amplification levels of HER2 over-expressing cases were quantified by quantitative real-time polymerase chain reaction (qRT-PCR). Overall pathological complete response rate (pCR) was achieved in 14.3 %. HER2 was over expressed in 80/309 (25.9 %) cases, of which 61/80 cases have been tested for their TOP2A status. Over expression of HER2 was significantly positively correlated with higher pCR rates compared to low HER2 expression (27.5 % vs. 9.6 %, P < 0.001). Concurrent high TOP2A amplification led to a significantly higher pCR rate compared to low or no TOP2A amplification (56.3 % vs. 13.8 %, P = 0.001). HER2 over expression was associated with a significantly higher pCR rate only when TOP2A was also amplified (56.3 % vs. 9.6 %, P < 0.001), but not when it was deleted or normal (13.8 % vs. 9.6 %, P = 0.183) compared to HER2 low-expressing tumors. The interaction between HER2 or TOP2A and anthracycline-based regimen was observed in IDD and conventional neoadjuvant chemotherapies. The TOP2A amplification is related to anthracycline-based neoadjuvant chemotherapy sensitivity, and TOP2A should be included in future studies in breast cancer as a predictive marker.
    Breast Cancer Research and Treatment 08/2012; 135(2):531-7. · 4.47 Impact Factor
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    ABSTRACT: Triple-negative [estrogen receptor (ER)-/progesterone receptor (PR)-/HER2-] breast cancer (TNBC) accounts for ∼ 15% of overall breast cancer and associated with a poor prognosis. There is a short of standard adjuvant chemotherapy regimens for TNBC. A number of studies have shown that TNBC might be sensitive to cisplatin and carboplatin on the basis that dysfunction of BRCA1 and its pathway is associated with a specific DNA-repair defect, but data of adjuvant setting about this is limited. From January 2010 to September 2011, 95 early triple-negative breast cancer patients confirmed by pathology were randomly assigned to receive TP (docetaxel 75 mg/m², carboplatin AUC = 5, day 1, 21 days a cycle for 6 cycles) or EC-T (epirubicin 90 mg/m², cyclophosphamide 600 mg/m², d1, 21 days a cycle for 4 cycles, followed by docetaxel 80 mg/m², d1, 21 days a cycle for 4 cycles) chemotherapy. Adjuvant radiation therapy was given selectively after chemotherapy. Here we report a preliminary safety analysis with the chi-square test. Seventy-six out of the 95 patients had completed the chemotherapy and could be assessed for the safety profiles of the regimens. Thirty-seven of them were in the EC-T group with a median age of 47 years, and 21 out of these 37 patients were premenopausal (56.8%). Another 39 patients came from the TP group with a median age of 46 years, and 22 out of these 39 patients were premenopausal (56.4%). All of the 37 patients in EC-T group completed the planned treatment whereas 2 patients of the 39 cases in TP group did not because of bone marrow suppression. During the treatments, 9 patients had dose adjustment in each group. Adverse events of grade 1/2 were common. Specific incidence of adverse events with grade 3/4 in each group was as follows: alopecia, 29.7% vs. 10.3% (P = 0.033), vomiting 21.6% vs. 7.7% (P = 0.085), leukopenia 54.1% vs.25.6% (P = 0.011) and neutropenia 51.4% vs. 35.9% (P = 0.174). Other grade 3/4 toxicities were rare. All the adverse events (except peripheral neuropathy and pigmentation) recovered within 1 month after the chemotherapy. Both EC-T and TP regimens as adjuvant chemotherapy are safe and tolerable for the treatment of triple-negative breast cancer patients, while the TP regimen has advantages with less grade III/IV alopecia and leukopenia.
    Zhonghua zhong liu za zhi [Chinese journal of oncology] 06/2012; 34(6):465-8.

Publication Stats

198 Citations
65.41 Total Impact Points

Institutions

  • 2011–2014
    • Chongqing Cancer Hospital and Institute
      Ch’ung-ch’ing-shih, Chongqing Shi, China
  • 2012
    • Fuda Cancer Hospital
      Shengcheng, Guangdong, China
  • 2011–2012
    • China Academy of Chinese Medical Sciences
      • Department of Medical Oncology
      Peping, Beijing, China
  • 2003–2012
    • Peking Union Medical College Hospital
      Peping, Beijing, China
  • 2008–2011
    • Chinese Academy of Medical Sciences
      Peping, Beijing, China
  • 2010
    • Huazhong University of Science and Technology
      • Key Laboratory of Environment and Health, MOE
      Wuhan, Hubei, China