Peng Yuan

Efficacy of oral Etoposide in pretreated metastatic breast cancer: a multicenter phase 2 study.

AbstractNo standard chemotherapy has been defined for metastatic breast cancer (MBC) patients pretreated with anthracyclines and taxanes. A multicenter phase 2 study was conducted to evaluate the safety and efficacy of oral etoposide in patients with MBC.Eligible patients were treated with repeated cycles of oral etoposide (60u200amg/m2/d on days 1–10, followed by 11 days of rest). The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate, clinical benefit rate (CBR), and toxicity profiles.Seventy-five women with MBC were enrolled at 10 centers in China. Seven (9.3%) patients achieved partial response (PR) and 29 (38.7%) had stable disease (SD). Nine patients (12%) had SD for >24 weeks and the CBR was 21.3% (16/75). The median PFS was 4.5 (range, 1.3–7.7) months. Of the 38 patients who received ≥3 regimens prior to this study, 2 (5.3%) had PR and 3 (7.9%) had SD for >24 weeks, with a CBR of 13.2%. The reported grade 3/4 adverse events included leukopenia (13.3%, nu200a=u200a10), neutropenia (17.9%, nu200a=u200a14), anemia (2.7%, nu200a=u200a2), vomiting (2.6%, nu200a=u200a2), and alopecia (1.3%, nu200a=u200a1).Oral etoposide was effective and well tolerated in Chinese women with pretreated MBC.

Value of Breast Cancer Molecular Subtypes and Ki67 Expression for the Prediction of Efficacy and Prognosis of Neoadjuvant Chemotherapy in a Chinese Population.

AbstractThe aim of the study was to determine the predictive role of breast cancer subtypes in the efficacy and prognosis of neoadjuvant chemotherapy (NCT) regimens combining taxanes and anthracyclines.Data from 240 patients with breast cancer who received surgery after 4 to 6 weeks of NCT were retrospectively analyzed. The patients were classified into luminal A, luminal B, HER2 overexpression, and triple negative breast cancer (TNBC) as well as low Ki67 (⩽ 14%) and high Ki67 (> 14%) expression groups using immunohistochemistry. NCT outcome parameters were pathological complete response (pCR), clinical complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) 4 weeks after surgery. Long-term outcome parameters were disease-free survival (DFS) with a follow-up time of 3 to 56 months.pCR rates were 1.6%, 13.4%, 22.6%, and 23.8% in patients with luminal A, luminal B, HER2, and TNBC cancers, respectively. High pCR rates correlated with high Ki67 expression (> 40%) (Pu200a<u200a0.001, HRu200a=u200a0.17, 95% CI: 0.074–0.37) and negative estrogen receptor (ER) status (Pu200a<u200a0.001, HRu200a=u200a3.74, 95% CI: 1.71–8.12) in a multivariate analysis. However, the DFS rate of luminal A breast cancer was the highest compared to all other groups, but only significantly higher compared to luminal B (Pu200a=u200a0.035, HRu200a=u200a1.480, 95% CI: 1.060–1.967) patients and correlated with Ki67 expression > 40% (Pu200a=u200a0.005).Luminal A type patients derived the least benefit from neoadjuvant chemotherapy but had better long-term prognoses. ER status and Ki67 expression served as efficacy predictors for NCT, whereas only Ki67 expression > 40% correlated with long-term treatment outcomes.

Unfavorable pathological complete response rate of neoadjuvant chemotherapy epirubicin plus taxanes for locally advanced triple-negative breast cancer.

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/m2 plus paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 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.SummaryAnthracycline-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/m2 plus paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 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.

Abstract P3-14-07: Carboplatin plus paclitaxel compared with epirubicin plus paclitaxel as neoadjuvant chemotherapy for triple-negative breast cancer - A phase II clinical trial

Background Combination anthrathyclin-taxane regimens are the most widely-used neoadjuvant chemotherapy for triple negative breast cancer (TNBC), with objective response rates (ORR) of approximately 80% but poor pathologic complete response rates (pCR, 10%-25%) and survival. More effective chemotherapy regimens are needed. Several small clinical trials have suggested cisplatin- or carboplatin-containing chemotherapy can achieve higher pCR rates. However, no studies have compared the efficacy of platinum combination chemotherapy with a traditional anthrathyclin-taxane regimen. The objective of this study is to compare carboplatin plus paclitaxel with epirubicin plus paclitaxel in the neoadjuvant setting to determine the better choice for TNBC. Methods This is a single centre, open label, two-arm phase II clinical trial (NCT01276769). Patients with ER/PR/Her-2 negative breast cancer by immunohistochemistry from core needle biopsy were enrolled. All had indication for neoadjuvant chemotherapy. Patients were stratified according to clinical stage (II/III), and then randomized to receive paclitaxel (175 mg/m2, d1) and carboplatin (AUC = 5, d2), every 3 weeks for 4-6 cycles (PC arm) or epirubicin (75mg/m2, d1) plus paclitaxel (175 mg/m2, d2), every 3 weeks for 4-6 cycles (EP arm). The primary endpoint was pCR, which was defined as no residual invasive cancer in both the excised breast and axillary lymph node, or only carcinoma in situ. The secondary endpoints included ORR, safety, RFS (relapse-free survival) and OS (overall survival). Results A total of 91 patients were recruited (PC 47 patients, EP 44 patients) from April 2006 to December 2012. Median age was 47 years (range 24-73); 65% patients were premenopausal; 66% were at stage III; CK5/6 and EGFR positive rates were 63.01% (46/73), and 79.73% (59/74), respectively. 77.03% (57/74) had Ki-67 scores ≥ 20%. The proportion of patients with basal-like subtype (defined as CK5/6 or EGFR positive) in the two arms was 97.30% vs. 91.67 (p = 0.358). Eighty-five percent of patients completed 4-6 cycles of chemotherapy. ORR in the PC and EP arm was similar (89.4% vs. 79.6%, P = 0.195), but the pCR rate in the PC arm was significantly higher compared to the EP arm (38.6% vs. 14.0%, p = 0.016). The main G3/4 adverse event in both arms was neutropenia (72.3% vs. 63.6%, p = 0.500). Median follow-up period was 37 months (range 3-78 months), and 8 and 17 RFS events occurred in the PC and EP arms, respectively. Eighty-eight percent (22/25) of death events occurred in the first 3 years after diagnosis. Four-year RFS in the PC and EP arms were 71.1% vs. 52.8%, respectively (p = 0.080), and 4-year OS were similar (70.1% vs. 72.5% respectively, p = 0.980). For the whole group, pCR patients had significantly better 4-year RFS (90.9% vs. 50.1%, p = 0.001) and 4-year OS (100% vs. 64.9%, p = 0.002) compared with non-pCR patients. Conclusion Compared with the most widely-used EP chemotherapy, the PC regimen could significantly improve pCR rate for TNBC, and the 4- year RFS showed a trend towards improvement. Overall, pCR patients’ prognosis was much better than non-pCR patients. PC chemotherapy could be the preferred choice for TNBC neoadjuvant treatment. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-07.

The relationship between the CYP2D6 polymorphisms and tamoxifen efficacy in adjuvant endocrine therapy of breast cancer patients in Chinese Han population

Variants of the CYP2D6 gene may lead to a poor prognosis of tamoxifen (TAM)‐treated patients. Our study validated the association between the CYP2D6 genotype and outcomes of patients receiving TAM in adjuvant endocrine therapy. A total of 778 breast cancer patients who received adjuvant TAM (nu2009=u2009325) or aromatase inhibitors (AIs) (nu2009=u2009453) at the National Cancer Center were analyzed. Nine single nucleotide polymorphisms (SNPs) in the CYP2D6 gene were selected from online databases. The associations of each SNP genotype with disease‐free survival (DFS) and clinicopathological characteristics were analyzed. A total of 167 (21.5%) patients carried the CYP2D6*10 (c.100C>T) T/T genotype. Among the 325 patients who received TAM, the 5‐year DFS rate was considerably lower in CYP2D6*10 T/T genotype patients than C/C or C/T patients (54.9% vs. 70.9%, pu2009=u20090.007). The T/T genotype for CYP2D6*10 was a significant prognostic marker for DFS in multivariate analysis (hazard ratiou2009=u20091.87; pu2009=u20090.006). The CYP2D6*10 genotype in women who received AIs was not significantly associated with DFS (pu2009=u20090.332). Other SNPs were not related to the survival of patients who received TAM. Our finding showed patients with CYP2D6*10 T/T received less benefit from TAM adjuvant treatment. This conclusion may optimize the individualized treatments for this subgroup of patients.

Prognostic Significance of Single Progesterone Receptor Positivity: A Comparison Study of Estrogen Receptor Negative/Progesterone Receptor Positive/Her2 Negative Primary Breast Cancer With Triple Negative Breast Cancer.

AbstractSingle progesterone receptor positive (PgR+), especially in form of ER−/PgR+/HER2−, is a nonnegligible phenomenon. Little is known about the characteristics and the role of single PgR positive in this phenotype. Therefore, we explore the significance of single PgR positivity by comparing ER−/PgR+/HER2− breast cancers with triple negative breast cancers (TNBCs).Three thousand nine hundred sixty-six cases of primary invasive breast carcinoma operated consecutively from January 2005 to May 2008 in Cancer Hospital, Chinese Academy of Medical Sciences were examined. Two hundred forty (6%) cases were identified as ER−/PgR+/HER2− breast cancers and 348 (8.8%) cases as TNBCs. Clinicopathological characteristics and survivals were analyzed respectively and then compared between 2 subtypes.Compared with patients with TNBCs, ER−/PgR+/HER2− tumor tended to have lower tumor grade (Grade 3: 45.7% vs. 37.5%, Pu200a=u200a0.051) and smaller tumor size (Pu200a=u200a0.036). However, no differences were found between ER−/PgR+/HER2− and TNBC patients in relapse-free survival (RFS) and OS. The 5-year RFS rates were 80.7% and 77.4%, respectively (Pu200a=u200a0.330) and the 5-year OS rates were 88.0% and 85.2%, respectively (Pu200a=u200a0.290). ER−/PgR+/HER2− patients receiving adjuvant endocrine treatment had better RFS (Pu200a=u200a0.016) and overall survival (OS) (Pu200a<u200a0.0001) than patients receiving no endocrine therapy.This exclusive analysis of patients with ER−/PgR+/HER2− breast cancers showed that this subtype exhibited an aggressive behavior as TNBC, suggesting that it should also be regarded as biologically distinctive group and single PgR positive itself is not a good prognostic factor. However, adjuvant endocrine therapy could still benefit this group of patients. Further investigations should be done to elucidate the underlying mechanism.

Vinorelbine Plus Platinum in Patients with Metastatic Triple Negative Breast Cancer and Prior Anthracycline and Taxane Treatment.

AbstractCurrently, there is no preferred standard chemotherapy regimen available for patients with metastatic triple negative breast cancer (mTNBC) and no cohort studies on the efficacy of vinorelbine plus platinum (NP) regimen in patients with mTNBC who failed to anthracyclines and/or taxanes have been reported. We present the single-center, retrospective experience of NP regimen in a total of 41 patients with mTNBC.All patients were treated with NP regimen, main combination used was vinorelbine-cisplatin in 34 patients (82.9%).The median follow-up was 36.8 months. Objective response rate was 34.1% (nu200a=u200a14) in the whole study group. Three patients experienced complete response (7.3%), 11 patients acquired partial response (26.8%), stable disease was observed in 14 patients (34.1%), and 10 patients (24.4%) had progressive disease. Response evaluation was not applicable in 3 patients who received the treatment of NP regimen after surgical removal of the metastatic lesions. The median overall survival and progression-free survival were 18.9 months (95% confidence interval, 15.6–22.1 months) and 6.7 months (95% confidence interval, 2.9–10.5 months), respectively. The main adverse events were grade 3/4 neutropenia (nu200a=u200a20, 48.8%) and grade 1/2 gastrointestinal toxicity (nu200a=u200a20, 48.8%).NP regimen is active and tolerable in patients with mTNBC pretreated with anthracyclines and/or taxanes. Therefore, among other chemotherapy regimens, NP combination may provide a rational treatment option for this patient subset.

National consensus in China on diagnosis and treatment of patients with advanced breast cancer

The recently available guidelines on the management of advanced breast cancer (ABC) organized by Chinese Anti-Cancer Association, Committee of Breast Cancer Society (CACA-CBCS) do not elucidate ABC in details. To instruct clinicians in treatment of ABC, a Chinese expert consensus meeting on diagnosis and treatment of ABC was held in June 2014 and a consensus is developed. The following consensus provides the level of evidence and supporting documents for each recommendation, and introduces research topics to be urgently addressed. Notably, the consensus on diagnosis and treatment of ABC in China is developed to be applied nationwide. In different areas, multidisciplinary treatment (MDT) tailored to the each patient and the disease itself should be applied based on the basic principles of modern oncology.

Interpreting Advanced Breast Cancer Consensus Guidelines for Use in China

Abstract 58Background:In 2011, an international panel of breast cancer experts developed the first Advanced Breast Cancer (ABC) Consensus Guidelines to provide standards and improved care for the multidisciplinary care of patients with this common disease. We sought to adapt the ABC guidelines for China, incorporating cultural standards and available Chinese resource, and identifying suitable formed guideline.Methods:We organized the Chinese Consensus Guidelines Conference for ABC (CABC) yearly from 2013 through 2015 in Beijing as a joint effort between the China Medical Womens Association, the Organization of Beijing Sunshine Great Wall Oncology Program, Peking University, The panel included 50 breast oncology and surgery experts from 20 provinces, as well as two external consultant oncologists from the U.S. and Singapore. Permission was obtained from the ABC Chair to use the guidelines as a basis for our discussion. All questions were presented and discussed in detail, including a review of current app...

Abstract P5-08-19: A single-nucleotide polymorphism in the 3'-UTR region of the adipocyte fatty acid binding protein 4 gene is associated with prognosis of triple negative breast cancer

Objective Triple negative breast cancer (TNBC) is a subtype with poor prognosis and high heterogeneity. The aim of this study was to screen single nucleotide polymorphisms (SNPs) associated with the prognosis of TNBC patients and to explore the potential mechanism. Methods We selected SNPs(MAF≥1%) located on the 39 untranslated region (39UTR) of differentially expressed genes in breast cancer through databases (Nextbio,ensemble,NCBI,MirSNP). We investigated the possible associations between 111 SNPs and progression risk among 323 TNBC patients using two-step case-control study with discovery cohort (n=162) and validation cohort (n=161). The Benjamini Hochberg false discovery rate (FDR) method was used to assess the statistical significance after correction for multiple comparisons. Kaplan-Meier analysis was applied in order to assess the association between disease free survival (DFS) and positive SNPs, as well as Body Mass Index(BMI). We also investigated the expression of FABP4 in adipocytes adjacent to TNBC tissues (n=35) using immunohistochemistry. The integrated optical density (IOD) was measured as an approximation of FABP4 expression. Mann-Whitney U test was used in an attempt to assess the correlations among SNPs in FABP4, FABP4 expression and TNBC prognosis. Results SNPs in FABP4, KRAS and NTRK2 genes associated with the recurrence risk of TNBC throughout the discovery cohort and validation cohort, while the statistical significance was retained after multiple comparisons only for FABP4 rs1054135. The G allele of rs1057035 was associated with decreased risk of disease progression (aHR 0.14, 95%CI0.03-0.66), as well as an increased DFS (P Conclusions Our study found a lipid metabolism related gene and an important SNP in the 39UTR of FABP4 associated with TNBC prognosis, which may aid the screening of high-risk patients with TNBC recurrence and the development of novel chemotherapeutic agents. Citation Format: Yuan P, Wang W, Wu C, Lin D, Xu B. A single-nucleotide polymorphism in the 39-UTR region of the adipocyte fatty acid binding protein 4 gene is associated with prognosis of triple negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-19.