Pin Zhang

A Nation-Wide multicenter 10-year (1999-2008) retrospective clinical epidemiological study of female breast cancer in china

BackgroundAccording to the very limited cancer registry, incidence and mortality rates for female breast cancer in China are regarded to be increasing especially in the metropolitan areas. Representative data on the breast cancer profile of Chinese women and its time trend over years are relatively rare. The aims of the current study are to illustrate the breast cancer profile of Chinese women in time span and to explore the current treatment approaches to female breast cancer.MethodsThis was a hospital-based nation-wide and multi-center retrospective study of female primary breast cancer cases. China was divided into 7 regions according to the geographic distribution; from each region, one tertiary hospital was selected. With the exception of January and February, one month was randomly selected to represent each year from year 1999 to 2008 at every hospital. All inpatient cases within the selected month were reviewed and related information was collected based on the designed case report form (CRF). The Cancer Hospital/Institute, Chinese Academy of Medical Sciences (CICAMS) was the leading hospital in this study.ResultsFour-thousand two-hundred and eleven cases were randomly selected from the total pool of 45,200 patients and were included in the analysis. The mean age at diagnosis was 48.7 years (s.d. = 10.5 yrs) and breast cancer peaked in age group 40-49 yrs (38.6%). The most common subtype was infiltrating ductal carcinoma (86.5%). Clinical stage I & II accounted for 60.6% of 4,211 patients. Three-thousand five-hundred and thirty-four cases had estrogen receptor (ER) and progestin receptor (PR) tests, among them, 47.9% were positive for both. Two-thousand eight-hundred and forty-nine cases had human epidermal growth factor receptor 2(HER-2) tests, 25.8% of them were HER-2 positive. Among all treatment options, surgery (96.9% (4,078/4,211)) was predominant, followed by chemotherapy (81.4% (3,428/4,211). Much less patients underwent radiotherapy (22.6% (952/4,211)) and endocrine therapy (38.0% (1,599/4,211)).ConclusionsThe younger age of breast cancer onset among Chinese women and more advanced tumor stages pose a great challenge. Adjuvant therapy, especially radiotherapy and endocrine therapy are of great unmet needs.

Phase I Study and Biomarker Analysis of Pyrotinib, a Novel Irreversible Pan-ErbB Receptor Tyrosine Kinase Inhibitor, in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer

Purpose This phase I study assessed the safety, tolerability, pharmacokinetics, antitumor activity, and predictive biomarkers of pyrotinib, an irreversible pan-ErbB inhibitor, in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Patients and Methods Pyrotinib was administered continuously, orally, once per day to patients who did not have prior exposure to tyrosine kinase inhibitors of HER2. Planned dose escalation was 80, 160, 240, 320, 400, and 480 mg. For pharmacokinetic analysis, timed blood samples were collected on day 1 and day 28. Next-generation sequencing was performed on circulating tumor DNA and genomic DNA from tumor samples. Results Thirty-eight patients were enrolled. The dose-limiting toxicity was grade 3 diarrhea, which occurred in two patients administered 480 mg of pyrotinib; thus, the maximum tolerated dose was 400 mg. Common pyrotinib-related adverse events included diarrhea (44.7% [17 of 38]), nausea (13.2% [five of 38]), oral ulceration (13.2% [five of 38]), asthenia (10.5% [four of 38]), and leukopenia (10.5% [four of 38]). The only grade 3 adverse event was diarrhea. Pharmacokinetic analyses indicated that pyrotinib exposure was dose dependent. The overall response rate was 50.0% (18 of 36), and the clinical benefit rate (complete response + partial response + stable disease ≥ 24 weeks) was 61.1% (22 of 36). The median progression-free survival was 35.4 weeks (95% CI, 23.3 to 40.0 weeks). The overall response rate was 83.3% (10 of 12) in trastuzumab-naive patients and 33.3% (eight of 24) in trastuzumab-pretreated patients. Preliminary results suggest that PIK3CA and TP53 mutations in circulating tumor DNA ( P = .013) rather than in archival tumor tissues ( P = .474) may predict the efficacy of pyrotinib. Conclusion Continuous once-per-day pyrotinib was well tolerated and demonstrated promising antitumor activity in HER2-positive patients with metastatic breast cancer. The maximum tolerated dose was established as 400 mg. Diarrhea was the dose-limiting toxicity. The promising antitumor activity and acceptable tolerability of pyrotinib warrant its further evaluation in a phase II study.

A Nation-Wide Multicenter 10-Year (1999-2008) Retrospective Clinical Study of Endocrine Therapy for Chinese Females with Breast Cancer

Endocrine therapy (ET) is one of the main systemic treatments for patients with breast cancer. To our knowledge, few studies have addressed the performance of ET or relevant influencing factors in cancer treatment in China. By retrospectively analyzing the clinicopathological data on breast cancer collected from representative hospitals of 7 traditional areas in China in one random month from each year between year 1999 and 2008, we found that: 1) The rate of the use of hormone receptor (HR) testing was 83.8% (3529/4211), with the estrogen receptor-positive (ER+) rate and/or the progesterone receptor-positive (PR+) rate being 67.9% (2395/3529), and the ER-PR rate being 32.1% (1134/3529). 2) Of the 1599 patients who had received ET, 999 patients (58.3%) were premenopausal while 600 (41.7%) were postmenopausal; 1598 patients received adjuvant hormonal therapy (AHT), whereas only 1 patient received palliative therapy. The medications mainly administered to patients were anti-estrogen agents (80.3% [1283/1598]), followed by AIs (15.5% [248/1598]). Of the 1598 patients receiving AHT, 1416 patients (88.6%) were positive for ER and/or PR, while 75 (4.7%) were negative for both and 108 patients (6.7%) had unknown HR status. The ratio of the use of endocrine therapy for breast cancer patients with ER+ and/or PR+ status was 60.0% (1416/2395). 3) Results from the logistic regression analysis revealed that geography, occupations, and history of chemotherapy and surgery were dependent factors affecting the application of ET in breast cancer treatment in China (P<0.001). In conclusion, the use of ET on Chinese women with breast cancer is increasingly and gradually accounted into the standardized process. Economic status, occupations, and history of chemotherapy and surgery were key factors affecting the application of ET. People residing in developed areas, engaging in mental labour, having history of chemotherapy and surgery are susceptible to accept ET.

Body Mass Index and Breast Cancer Defined by Biological Receptor Status in Pre-Menopausal and Post-Menopausal Women: A Multicenter Study in China

Background Few studies have investigated the association between body mass index (BMI) and breast cancer with consideration to estrogen/progesterone/human epidermal growth factor type 2 receptor status (ER/PR/HER2) in the breast tissue among Chinese pre- and post-menopausal women. Methods Four thousand two hundred and eleven breast cancer patients were selected randomly from seven geographic regions of China from 1999 to 2008. Demographic data, risk factors, pathologic features, and biological receptor status of cases were collected from the medical charts. Chi-square test, fisher exact test, rank-correlation analysis, and multivariate logistic regression model were adopted to explore whether BMI differed according to biological receptor status in pre- and post-menopausal women. Results Three thousand two hundred and eighty one eligible cases with BMI data were included. No statistically significant differences in demographic characteristics were found between the cases with BMI data and those without. In the rank-correlation analysis, the rates of PR+ and HER2+ were positively correlated with increasing BMI among post-menopausal women (rs BMI, PR+ = 0.867, P = 0.001; rs BMI, HER2+ = 0.636, P = 0.048), but the ER+ rates did not vary by increasing BMI. Controlling for confounding factors, multivariate logistic regression models with BMI<24 kg/m2 as the reference group were performed and found that BMI≥24 kg/m2 was only positively correlated with PR+ status among post-menopausal breast cancer cases (adjusted OR = 1.420, 95% CI: 1.116–1.808, Wald = 8.116, P = 0.004). Conclusions Post-menopausal women with high BMI (≥24 kg/m2) have a higher proportion of PR+ breast cancer. In addition to effects mediated via the estrogen metabolism pathway, high BMI might increase the risk of breast cancer by other routes, which should be examined further in future etiological mechanism studies.

Epidemiologic study of radiotherapy use in China in patients with breast cancer between 1999 and 2008.

BACKGROUND To investigate the use of radiotherapy (RT) in China in patients with breast cancer over a 10-year period. A hospital-based, nationwide, multicenter, retrospective epidemiologic study of women with primary breast cancer was conducted. PATIENTS AND METHODS Patients were selected randomly in 7 hospitals from 1999 to 2008. Data on overall RT, postmastectomy RT (PMRT), RT after conservative breast surgery (PBRT) and palliative RT (PRT) were recorded. RT use was analyzed, and differences were compared by using the Cochran-Armitage trend test and the χ(2) test. A total of 3732 patients were included: 1009 (27%) received RT, including 688 (18.4%) PMRT, 170 (4.6%) PBRT, 86 (2.3%) PRT, 47 (1.3%) both PMRT and PRT, and 18 (0.5%) other RT. RESULTS Overall use of RT increased significantly from 1999 to 2008 (2P < .001). There was a slight but significant increase in PMRT (2P = .012) and a 10-fold increase in PBRT (2P < .001); use of PRT was relatively constant (2P = .777). There was a significant difference among regions in the use of RT, PMRT, PBRT, and PRT (2P < .01). Of patients with stage III disease, 51.6% and of those with node-positive stage II disease treated by radical mastectomy, 21% had received PMRT. In patients treated by using breast conservative surgery, 83.7% received PBRT, which was not affected by stage. CONCLUSION In summary, in China, the overall use of RT in patients with breast cancer was quite low, but there was an increasing trend in those treated between 1999 and 2008.

Epidemiologic study of compliance to postmastectomy radiation therapy guidelines in breast cancer patients in China between 1999 and 2008

PURPOSE To evaluate compliance with postmastectomy radiation therapy (PMRT) guidelines in breast cancer patients in China over a 10-year period. METHODS AND MATERIALS A hospital-based, nationwide, multicenter retrospective epidemiologic study of primary breast cancer in women was conducted. Seven first-class, upper-level hospitals from different geographic regions of China were selected. One month was randomly selected to represent each year from 1999-2008 in every hospital. All inpatient cases within the selected months were reviewed and demographic, clinical, and pathologic characteristics and treatment patterns were collected. Patients enrolled in this study had to meet the following inclusion criteria: (1) treated with mastectomy and axillary dissection; (2) information regarding whether or not they received postmastectomy radiation therapy was available; and (3) information about staging was available. Patients were divided into 3 groups based on National Comprehensive Cancer Network guidelines. Utilization of PMRT in each group was analyzed and compared between different years and different hospitals. RESULTS A total of 2310 patients were analyzed. There were 643 (27.8%) patients in the PMRT recommended group, 557 (24.1%) patients in the controversial group, and 1110 (48.1%) patients in the nonrecommended group. PMRT was used in 48.8% of patients in the recommended group, 15.6% in the controversial group, and 5.7% in the nonrecommended group. There was a trend toward increasing use of radiation therapy in the recommended and controversial groups from 1999-2008. The use of PMRT in the nonrecommended group remained relatively stable from 1999-2008. Fewer positive nodes and nonreceipt of chemotherapy or hormone therapy were associated with underuse of PMRT in the recommended group. In the controversial group, a higher ratio of positive nodes was associated with use of PMRT. CONCLUSIONS There is an apparent underuse of PMRT in the PMRT recommended group. Efforts should be made to improve the compliance to PMRT guidelines.

A nation-wide multicenter 10-year (1999–2008) retrospective study of chemotherapy in Chinese breast cancer patients

Little information is available on the evolvement of chemotherapeutic regimens administered to Chinese females with breast cancer. We retrospectively analyzed demographic, pathological and chemotherapeutic data of 4211 breast cancer patients, who were randomly selected from representative hospitals of 7 traditional areas in China between 1999 and 2008. A total of 3271 cases (77.7%) received adjuvant chemotherapy, 558 (13.3%) received neoadjuvant chemotherapy, and 392 (9.3%) received chemotherapy for metastatic disease. In the adjuvant setting, higher percentage of patients with younger age, advanced stage, hormone receptor (HR) negative or HER2 positive disease received chemotherapy (P<0.001). The use of CMF (cyclophosphamide, methotrexate and 5-fluorouracil) in adjuvant chemotherapy decreased significantly from 1999 to 2008, while the use of anthracycline-based (without taxanes) regimens increased in the first 5 years, followed by increased use of regimens containing both anthracyclines and taxanes. Women with locally advanced disease received more neoadjuvant chemotherapy. The percentage of neoadjuvant regimens containing anthracyclines and taxanes increased during this period. In first-line chemotherapy of metastatic disease, 87.5% of cases received combined chemotherapy, and platinum-based regimens were also major choices aside from anthracyclines and taxanes. In second-line chemotherapy, 80.3% received combined chemotherapy, and the combination of taxane and platinum was the most common choice. In conclusion, major changes have taken place in breast cancer chemotherapy in China during this 10-year interval, which reflected the incorporation of key evidence and guidelines into Chinese medical practice.Little information is available on the evolvement of chemotherapeutic regimens administered to Chinese females with breast cancer. We retrospectively analyzed demographic, pathological and chemotherapeutic data of 4211 breast cancer patients, who were randomly selected from representative hospitals of 7 traditional areas in China between 1999 and 2008. A total of 3271 cases (77.7%) received adjuvant chemotherapy, 558 (13.3%) received neoadjuvant chemotherapy, and 392 (9.3%) received chemotherapy for metastatic disease. In the adjuvant setting, higher percentage of patients with younger age, advanced stage, hormone receptor (HR) negative or HER2 positive disease received chemotherapy (P<0.001). The use of CMF (cyclophosphamide, methotrexate and 5-fluorouracil) in adjuvant chemotherapy decreased significantly from 1999 to 2008, while the use of anthracycline-based (without taxanes) regimens increased in the first 5 years, followed by increased use of regimens containing both anthracyclines and taxanes. Women with locally advanced disease received more neoadjuvant chemotherapy. The percentage of neoadjuvant regimens containing anthracyclines and taxanes increased during this period. In first-line chemotherapy of metastatic disease, 87.5% of cases received combined chemotherapy, and platinum-based regimens were also major choices aside from anthracyclines and taxanes. In second-line chemotherapy, 80.3% received combined chemotherapy, and the combination of taxane and platinum was the most common choice. In conclusion, major changes have taken place in breast cancer chemotherapy in China during this 10-year interval, which reflected the incorporation of key evidence and guidelines into Chinese medical practice.

Phase I safety and pharmacokinetic study of cipatinib, an original dual tyrosine kinase inhibitor: Phase I clinical trial of cipatinib

Cipatinib is a novel tyrosine kinase inhibitor against both EGFR and HER2/neu. This phase I trial was conducted to assess the safety, dose‐limiting toxicities (DLTs), and maximum‐tolerated dose of cipatinib in HER2‐positive patients with advanced breast cancer.

Toremifene, rather than tamoxifen, might be a better option for the adjuvant endocrine therapy in CYP2D6*10T/T genotype breast cancer patients in China: Toremifene is a better option for the adjuvant endocrine therapy

Toremifene (TOR) is a valid and safe alternative to tamoxifen (TAM) for adjuvant endocrine therapy in breast cancer patients with a metabolic pathway that differs from that of TAM. TOR might have a therapeutic advantage in certain subgroups of patients, such as Chinese women with the CYP2D6 *10 (c.100C > T) T/T genotype, who would get less benefit when receiving adjuvant TAM treatment. A total of 230 breast cancer patients who received adjuvant TAM (n = 115) or TOR (n = 115) at the National Cancer Center were analyzed. The CYP2D6 *10 genotype was not significantly associated with DFS in patients who received TOR (p = 0.737). Patients treated with TOR had a higher 5‐year disease‐free survival (DFS) rate than those treated with TAM (89.6% vs. 80.9%, p = 0.009). TOR treatment remained an independent prognostic marker of DFS in multivariate analysis compared with TAM (hazard ratio = 0.51; p = 0.014). For all of the 50 CYP2D6 *10 T/T genotype patients, TOR treatment group had a significantly higher 5‐year DFS rate than TAM group (90.9% vs. 67.9%, p = 0.031). For the remaining 170 CYP2D6 *10 C/C or C/T genotype patients, there was no significant difference between the 5‐year DFS rates of the TOR and TAM groups (89.2% vs. 85.1%, p = 0.188). The advantage of adjuvant TOR over TAM in Chinese breast cancer patients might be caused by the significant benefit obtained by the CYP2D6 *10 T/T patients, who accounted for one‐fifth of the overall population. TOR might be a good option for adjuvant endocrine therapy in this subgroup of patients in China.

Timing of paclitaxel treatment in pre-operative or post-operative does not affect survival in breast cancer patients

Two epirubicin and paclitaxel‐based neoadjuvant chemotherapy regimens were compared in breast cancer patients.