Bone metabolism markers: Indicators of loading dose intravenous ibandronate treatment for bone metastases from breast cancer.

To investigate the changes in bone metabolism markers after second-line treatment with loading dose intravenous (i.v.) ibandronate in patients with bone metastases (BM) from breast cancer, 80 patients were enrolled in this study during January 2010 to April 2014. All the patients were treated with a second-line loading dose ibandronate for advanced breast cancer with BM and moderate-to-severe bone pain. Ibandronate (6 mg) was intravenously administered on three consecutive days followed by maintenance treatment every 3-4 weeks. Clinical data, including pain score, Karnofsky performance status (KPS) score, and changes in bone metabolism markers, were analyzed. Sixty-two patients were included in the final analysis. Compared with their pre-treatment scores, patients exhibited significantly increased KPS scores (P < .01) and a reduced dose of analgesic medication (oxycodone) (P < .01) after 3 and 6 weeks' post-treatment. The levels of serum bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRACP-5b), and cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were significantly reduced after 3 and 6 weeks' post-treatment (P < .001). Aside from a few adverse events, no liver or renal toxicity was observed. Bone metabolism markers decreased by varying degrees after treatment with a loading dose of ibandronate in patients with BM from breast cancer. It might be convenient using bone metabolism markers to potentially evaluate the efficacy of bisphosphonates treatment for bone metastasis.

[Clinical efficacy and safety of trastuzumab plus capecitabine as first-line therapy for HER-2 positive metastatic breast cancer].

OBJECTIVE: To evaluate the efficacy and safety of trastuzumab plus capecitabine as first-line therapy for HER-2-positive metastatic breast cancer patients who have previously received anthracyclines and taxanes. METHODS: The patients who have HER-2-positive breast cancer recurrence and metastasis after treated by anthracyclines and taxanes were enrolled in this study. The patients received trastuzumab (6 mg/kg every 21 days following a loading dose of 8 mg/kg on cycle 1) and capecitabine (2 000 mg/m², days 1 to 14 every 21 days). RESULTS: 38 patients were enrolled. The median PFS for trastuzumab plus capecitabine was 8.6 months. The objective response rate (ORR) was 31.6%. Clinical benefit rate (CBR) was 65.8%. The most serious adverse event was leucopenia in one patient. Relatively common hematology toxicity was grade I or II leucopenia and neutropenia. The most common nonhematologic toxicity was hand-foot syndrome (HFS), which observed in 8 patients (21%). The morbidity of grade II and III HFS were 8% and 3% respectively. CONCLUSION: Trastuzumab plus capecitabine is an effective and safe regimen as first-line treatment for HER-2-positive metastatic breast cancer patients whose cancer is resistant to treatment with anthracyclines and taxanes.

[PTEN loss correlates withthe clinical efficacy of lapatinib in HER2 positive metastatic breast cancer with trastuzumab-resistance].

OBJECTIVE: To discuss the indexes related to the efficacy of lapatinib after failure in trastuzumab in HER2-positive metastatic breast cancer (MBC) such as the status of PTEN, p-4EBP1 and clinical features. METHODS: Sixtymatched patients were included. Immunohistochemical (IHC) test of tissue specimens of metastatic lesions were applied to determine the status of PTEN and p-4EBP1. The correlation betweenclinical efficacy andthestatus of PTEN, p-4EBP1 and clinical features were analysed by long-rank test and Cox regression. RESULTS: In all patients, themedian progression free survival (PFS), ORR and CBR was 4.6 months, 36.7% and 50.0% respectively.Univariate analysis revealed that lapatinib-treated patients with PTEN loss (P = 0.015) and liver metastasis (P = 0.02) had significantly shorter median PFS. Multivariate analysis revealed that patients with PTEN lossandliver metastasis had higher risk of diseaseprogression (P = 0.005, 0.006, respectively). CONCLUSION: HER2-positive MBC with trastuzumab-resistance could benefit from lapatinib regimen. PTEN statusand liver metastasis couldpredict theclinical efficacyof subsequent lapatinib therapy. The detection ofrelated biomarkers could provide some referenceto optimize the personal treatment with HER2-positive breast cancer.

2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial.

BACKGROUND: Trastuzumab has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. The standard of care is 1 year of adjuvant trastuzumab, but the optimum duration of treatment is unknown. We compared 2 years of treatment with trastuzumab with 1 year of treatment, and updated the comparison of 1 year of trastuzumab versus observation at a median follow-up of 8 years, for patients enrolled in the HERceptin Adjuvant (HERA) trial. METHODS: The HERA trial is an international, multicentre, randomised, open-label, phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard neoadjuvant chemotherapy, adjuvant chemotherapy, or both in 5102 patients with HER2-positive early breast cancer. The primary endpoint was disease-free survival. The comparison of 2 years versus 1 year of trastuzumab treatment involved a landmark analysis of 3105 patients who were disease-free 12 months after randomisation to one of the trastuzumab groups, and was planned after observing at least 725 disease-free survival events. The updated intention-to-treat comparison of 1 year trastuzumab treatment versus observation alone in 3399 patients at a median follow-up of 8 years (range 0-10) is also reported. This study is registered with ClinicalTrials.gov, number NCT00045032. FINDINGS: We recorded 367 events of disease-free survival in 1552 patients in the 1 year group and 367 events in 1553 patients in the 2 year group (hazard ratio [HR] 0·99, 95% CI 0·85-1·14, p=0·86). Grade 3-4 adverse events and decreases in left ventricular ejection fraction during treatment were reported more frequently in the 2 year treatment group than in the 1 year group (342 [20·4%] vs 275 [16·3%] grade 3-4 adverse events, and 120 [7·2%] vs 69 [4·1%] decreases in left ventricular ejection fraction, respectively). HRs for a comparison of 1 year of trastuzumab treatment versus observation were 0·76 (95% CI 0·67-0·86, p<0·0001) for disease-free survival and 0·76 (0·65-0·88, p=0·0005) for overall survival, despite crossover of 884 (52%) patients from the observation group to trastuzumab therapy. INTERPRETATION: 2 years of adjuvant trastuzumab is not more effective than is 1 year of treatment for patients with HER2-positive early breast cancer. 1 year of treatment provides a significant disease-free and overall survival benefit compared with observation and remains the standard of care. FUNDING: F Hoffmann-La Roche (Roche).

Schlafen-11 sensitizes colorectal carcinoma cells to irinotecan.

Schlafen-11 (SLFN11) showed a highly significant positive correlation with the response of topoisomerase inhibitors in cancer cell lines derived from prostate, lung, etc. However, this finding has not been validated in colorectal cancers (CRCs). Although irinotecan (CPT-11), a topoisomerase inhibitor, is one of the most important drugs in the treatment of advanced and/or metastatic CRC, resistance is a critical drawback to its clinical effectiveness. The present study aimed to investigate the mechanism of SLFN11 in the response of CRC cell lines to SN-38 (an active CPT-11 metabolite) treatment. Western blotting was used to measure protein expression levels of SLFN11 in human CRC cell lines. Then, SLFN11 expression was modulated by transfecting human CRC cell lines with vectors carrying the SLFN11 gene or specific SLFN11 small interfering RNAs. The effects of SN-38 treatment on CRC cells with different SLFN11 expression levels were detected, including inhibition of cell growth, induction of apoptosis, and cell cycle arrest. This study showed that SLFN11 expression varied between the CRC cell lines and high-level SLFN11 expression promoted SN-38-induced antiproliferative activity, apoptosis, and cell cycle arrest. Our results suggest that SLFN11 plays a key role in cell cycle arrest and/or induction of apoptosis in response to exogenous SN-38-induced DNA damage and might be used as a new predictive biomarker for CRC treatment.

[Clinical observations of ductal carcinoma in situ and early stage breast cancer with invasive depth less than 1 cm].

OBJECTIVE: To explore the clinical characteristics and prognosis of ductal carcinoma in situ (DCIS) and early stage ductal breast cancer with invasive depth ≤ 1 cm. METHODS: Follow-up analyses were performed for the clinical data of 57 patients with DCIS, 46 with pT(1mic) and 74 with pT(1a-b) breast cancer treated or consulted at our hospital. Single factor analysis was used to examine their prognostic factors. RESULTS: Among them, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2(HER-2) positive rate and visual tumor size (2.0(0.1-7.0) vs 2.0(0.5-10.0) vs 2.0(0.3-10.0) cm)had no statistical differences between 3 groups (all P > 0.05). After median follow-up periods of 63, 38, 59 months, 12 patients suffered recurrence and metastasis and the rate of each group had no statistical differences. For pT(1a-b) patients with positive hormone receptor, endocrine therapy markedly reduced the risk of recurrence and metastasis (P = 0.024) . pT(1mic), pT(1a-b) patients on chemotherapy had higher or comparable recurrence rate versus those without. And DCIS patients on chemotherapy had a much higher recurrence rate (P = 0.016) . In pT(1a-b) group, HER-2 positive patients had higher recurrence and metastasis rates. Yet there was a decreasing tendency after Herceptin treatment. CONCLUSIONS: Chemotherapy without proper indications may not improve the prognosis of DCIS, pT(1mic) and pT(1a-b) patients. Endocrine therapy is the crucial prognostic factor of patients with positive hormone receptor. Use of Herceptin for HER-2-positive patients is probably significant.

[Serum HER2 ECD level and its clinical significance in advanced breast cancer patients with different molecular subtypes].

OBJECTIVE: To evaluate the serum HER2 ECD level and its significance in advanced breast cancer patients with different molecular subtypes. METHODS: A total of 322 advanced breast cancer patients were enrolled. The serum HER2 ECD concentrations were quantitatively detected by enzyme-linked immunosorbent assay(ELISA). Its relationship with clinicopathological characteristics and clinical significance were analyzed. RESULTS: It was found that 55.9% (19/34)Luminal A, 42.7% (44/103) Luminal B-HER2(-), 70.6% (60/85) Luminal B-HER2(+), 73.8% (45/61)HER2-enriched and 23.1% (9/39) triple-negative patients had serum concentrations of HER2 ECD at least 15 ng/ml respectively. The prevalence of elevated ECD level in patients of different molecular subtypes differed significantly (P < 0.001). Tissue HER2 status, number of metastatic sites, visceral metastasis, CA15-3 and carcinoembryonic antigen(CEA) levels exhibited statistically significant correlations with the prevalence of elevated serum HER2 ECD level. The serum concentrations of HER2 ECD decreased after effective targeted therapy in tissue HER2-positive patients. CONCLUSION: The prevalence of elevated serum levels of HER2 ECD differed significantly in advanced breast cancer patients with different molecular subtypes. The serum HER2 ECD level may reflect both histological HER2 status and tumor load. And the dynamic changes of ECD concentrations are somewhat correlated with the efficacies of targeted treatment.

[Detection of circulating tumor cells and its clinical value for different stages and various subtypes of breast cancer].

OBJECTIVE: To explore the prognostic value of applying a semi-automated detection system for detecting circulating tumor cells (CTC) for different stages and various subtypes of breast cancer. METHODS: Immunomagnetic separation and immunofluorescent staining were employed to detect the expressions of CTC and CTC HER-2. Chi-square test, univariate and multivariate analyses were used to examine the correlations between CTC and clinical characteristics. RESULTS: CTC was detected in 57.5% (138/240) of metastatic breast cancer (MBC). CTC enumeration, HER-2 status, number of metastasis and bone metastasis were relevant (P < 0.05). CTC was detected in 23.1% (6/26) of early-stage breast cancer (EBC). CTC enumeration, pathological type, estrogen receptor (ER), progesterone receptor (PR), Ki-67, tumor size and lymph node metastasis were irrelevant (P > 0.05). HER-2-positive MBC detected less CTC than HER-2-negative (χ(2) = 12.296, P < 0.001) . CTC HER-2 expression was different between HER-2-positive and negative patients in 99 MBC cases (χ(2) = 8.082, P = 0.004). CONCLUSION: CTC enumeration is different for various stages and different subtypes of breast cancer. CTC enumeration and bone metastasis are relevant. CTC detection in EBC may predict tumor relapse. And CTC HER-2 expression is different between HER-2-positive and negative MBC patients.

[Analysis of the factors affecting pathologic complete response to neoadjuvant chemotherapy in breast cancer patients].

OBJECTIVE: To analyze the factors affecting pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: A retrospective cohort study was carried out to analyze the clinical data of 141 breast cancer patients treated with neoadjuvant chemotherapy. The factors affecting pCR and the changes of tumor receptor status before and after treatment were analyzed. RESULTS: Among all the 141 patients, 21 patients (14.9%) achieved pCR. The rate of pCR achieved by regimens of anthracycline combined with taxane was higher (16.8%, 19/113) than that by anthracycline-containing regimens (7.1%, 1/14). The dose intensity of anthracycline had a significant correlation with pCR rate (P < 0.05). The pCR rate in the relative dose intensity of taxane ≥ 0.85 arm was higher than that of < 0.85 arm (P = 0.02). Eighty patients (56.7%) had completed more than 4 cycles of chemotherapy and the median time to achieve pCR was 6 (3 to 10) cycles. The pCR rate had a significant difference between patients < 6 and ≥ 6 cycles (7.1% vs. 22.5%,P = 0.01). Multivariate analysis showed that tumor size measured by palpation ≤ 5 cm and ≥ 6 chemotherapy cycles were significantly related with pCR rate (P < 0.05). In all the 21 pCR patients, the pre-treatment ER(-), PR(-), HER-2(-) statuses were in 14, 14 and 17 patients, respectively. The status of ER, PR, HER-2 of most patients (74.2%, 69.7% and 87.7%, respectively) was not changed after treatment. Among the patients with changes in receptor status, ER changed from negative to positive was in the majority (37.1%, 13/35 vs. 12.9%, 4/31, P < 0.05), and the percentage of changes in PR and HER-2 status had no significant differences. CONCLUSIONS: The regimens of anthracycline combined with taxane can achieve a higher pCR rate. The lymph node and receptor status before therapy have no significant correlation with pCR. Patients who have primary tumor size ≤ 5 cm, ≥ 6 chemotherapy cycles and enough dose intensity are easier to achieve pCR. The receptor status before and after therapy should be determined, and according to any positive results, physicians can chose HER-2 targeted therapy and/or endocrine therapy after surgery to benefit the patients.

[Clinical observation of sunitinib treatment for refractory advanced breast cancer ulcer].

OBJECTIVE: To observe the preliminary efficacies and adverse events of sunitinib in the treatment of metastatic breast cancer ulcer. METHODS: From December 2008 to May 2010, patients with advanced breast cancer ulcer took a single sunitinib. The dosage was adjusted on the basis of adverse events. And clinical response was evaluated. RESULTS: Nine patients with advanced breast cancer ulcer finished the treatment. The objective response and the clinical benefit time to progression of sunitinib were 3 and 7 patients with metastatic breast cancer ulcer, and the median time to progression (TTP) was 2.0 months. The most common adverse events included fatigue, hand-foot syndrome, neutropenia, thrombocytopenia and hypertension. CONCLUSION: Single-agent sunitinib treatment of refractory advanced breast cancer ulcer has marked efficacies. However, neutropenia, thrombocytopenia and hypertension are the major dose-limited toxicities.

[Efficacy and prognostic analysis of retreatment with trastuzumab-based therapy after multi-line targeted therapy resistance in HER2-positive metastatic breast cancer].

OBJECTIVE: To evaluate the predictive factors for efficacy and prognosis of retreatment trastuzumab in the patients with HER2 positive metastatic breast cancer (MBC) developing successive resistance to multi-line targeting therapies. METHODS: The data of 29 patients with HER2 positive MBC were collected from July 2008 to July 2010 at our department. All patients were treated with trastuzumab, lapatinib and retreated with trastuzumab sequentially. Twenty-one patients progressed during the initial trastuzumab therapy. All patients were treated with lapatinib to disease progression and retreated with trastuzumab to disease progression or death subsequently. A Log-rank test was used for univariate analysis and a Cox regression model was employed for multivariate analysis. RESULTS: The efficacy showed no significant difference between the patients with progression or those without progression during the initial trastuzumab therapy. The time-to-progression (TTP) of prior lapatinib therapy was an influencing factor of median progression-free survival (PFS) (P < 0.0001) and the duration from discontinuation of lapatinib to trastuzumab retreatment an influencing factor of median overall survival (OS) (P = 0.008) of trastuzumab retreatment in our univariate analysis. The median PFS of trastuzumab retreatment for patients with TTP of lapatinib therapy > 12 weeks (hazard ratio (HR) = 0.02, P = 0.003) or whose duration of double trastuzumab treatment ≤ 1 year (HR = 0.26, P = 0.03) was significantly prolonged in multivariate analysis. Meanwhile, the death risk of patients whose duration from discontinuation of lapatinib to trastuzumab retreatment ≤ 4 weeks decreased 89% as compared with trastuzumab retreatment (HR = 0.11, P = 0.004). CONCLUSION: TTP of prior lapatinib therapy and the duration of double trastuzumab treatment are two predictive factors of PFS of trastuzumab retreatment. And the duration from discontinuation of lapatinib to trastuzumab retreatment is an important independent prognostic factor for trastuzumab retreatment. The patients with HER2 positive MBC should be treated continually with anti-HER2 targeted therapy.

Single-agent capecitabine maintenance therapy after response to capecitabine-based combination chemotherapy in patients with metastatic breast cancer.

We performed an analysis of the efficacy of capecitabine monotherapy as maintenance treatment for metastatic breast cancer (MBC) after response to capecitabine-based chemotherapy [capecitabine plus docetaxel (XT) or vinorelbine (XN)] as a first-line or a second-line treatment. Sixty-four Chinese patients with histologically confirmed MBC received capecitabine maintenance therapy after disease stabilization or maximal response to capecitabine-based combination chemotherapy. Single-agent capecitabine was administered at a dose of 1000 mg/m(2) twice daily for 14 days, followed by a 7-day rest period, every 3 weeks. The median time to progression, the primary endpoint of the study, was 4.4 months (95% confidence interval, 3.4-5.4 months). Fifty-nine patients were evaluable for response. Capecitabine maintenance therapy produced an objective response rate of 5.1% (95% confidence interval, 3.9-6.3%). The incidence of grade 3/4 leukopenia (3.1%) and neutropenia (4.7%) was significantly lower (P<0.001) with capecitabine monotherapy than with combination chemotherapy (46.9 and 54.7%, respectively). Conversely, the incidence of grade 3 hand-foot syndrome was higher with capecitabine maintenance therapy than with combination therapy (14.1 vs. 0%, respectively; P=0.003). Capecitabine monotherapy is an effective maintenance treatment after response to capecitabine-based combination chemotherapy in MBC with a favorable safety profile.

Multicenter, randomized study of genetically modified recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in cancer patients receiving chemotherapy.

PURPOSE: The aim of this study is to evaluate the efficacy and safety of genetically modified recombinant human IL-11 (mIL-11), using original IL-11 as an active control, in a multicenter randomized trial involving 88 cancer patients undergoing chemotherapy METHODS: Eighty-eight subjects who had platelets ≤ 75 × 10(9)/L during the prior chemotherapy were randomized to the MR or RM group. Cohort MR consists of subcutaneous injection of mIL-11 (7.5 µg/kg/day) for 10 days, beginning 72 h after chemotherapy for a 21-day chemotherapy cycle (cycle-1) followed by that of recombinant human interleukin-11 (rhIL-11) (25 µg/kg/day) for another 10 days (cycle-2). Cohort RM represents the reverse sequence. Intent-to-treat populations of mIL-11 (n = 73) or rhIL-11 (n = 80) were analyzed to evaluate the safety. RESULTS: The incidence of drug-related adverse events of mIL-11 (32.9%) was lower than that of rhIL-11 (51.3%) (p = 0.033). There were no unexpected ≥ grade-3 adverse events, and no subject developed antibodies to the mIL-11 protein. Sixty-two subjects were analyzed for efficacy by measuring average platelet levels. Both mIL-11 and rhIL-11 increased nadir platelet levels (62.6 ± 34.9 × 10(9)/L for mIL-11 vs. 60.2 ± 31.7 × 10(9)/L for rhIL-11) as compared with the untreated control group (41.2 ± 17.7 × 10(9)/L) (p < 0.0001). There was no statistical difference in average platelet levels and platelet recovery rate between mIL-11 and rhIL-11. CONCLUSIONS: This study shows that mIL-11 is well tolerated and has thrombopoietic activity equivalent to one third of the clinical dose of rhIL-11, indicating the potential of mIL-11 for use in the treatment of CIT.

[A clinical study of reasonable doses of docetaxel salvage therapy for patients with metastatic breast cancer].

OBJECTIVE: To evaluate the correlation of clinical effects and reasonable doses of docetaxel salvage therapy for patients with metastatic breast cancer. METHODS: We reviewed retrospectively the clinical records of patients with metastatic breast cancer treated with docetaxel and statistically analyzed the correlation between clinical effects and reasonable doses of docetaxel. RESULTS: The objective response rate and clinical benefit rate of docetaxol in patients with metastatic breast cancer were 27.0% and 35.0%, respectively, and the median progression free survival (PFS) was 5.0 (3.8 - 6.3) months. In the analysis at a single dose level, the clinical benefit rate and PFS of the ≥ 90.0 mg/m(2) docetaxel group were superior to that of the < 90.0 mg/m(2) group (P = 0.008, P = 0.045). Multi-dose level group stratified analysis showed that the docetaxel < 75.0 mg/m(2) group was better than the 75.0 - 84.9 mg/m(2) PFS group (P = 0.018), and the ≥ 95.0 mg/m(2) group was better than the 75.0 - 84.9 mg/m(2) group (P = 0.048). In patients who received >third line treatment or previously received paclitaxel adjuvant therapy, the PFS of the ≥ 94.9 mg/m(2) docetaxel group was 6.0 months, better than the 3.0 months of the 75.0 ∼ 84.9 mg/m(2) group (P = 0.031; P = 0.021). CONCLUSION: There is a clear correlation between clinical effects and reasonable doses of docetaxel salvage therapy in patients with metastatic breast cancer.

[Analysis of chemotherapeutic efficacies in metastatic triple-negative breast cancer].

OBJECTIVE: To explore the chemotherapeutic efficacies and prognostic factors of metastatic triple-negative breast cancer. METHODS: The clinicopathologic data of 151 patients with metastatic triple-negative breast cancer were collected from September 1994 to November 2011 and their clinicopathologic characteristics, recurrence and survival were analyzed. RESULTS: Platinum plus taxol or vinorelbine was significantly higher than others for these patients (42.1% vs 23.1%, P = 0.022). The median overall survivals of those on first-line chemotherapy with partial remission, stable disease and progressive disease were 29.6, 24.7 and 13.1 months respectively. The differences were statistically significant (P = 0.045). Two or three-line chemotherapy showed no obvious statistical relationship with total overall survival. Simple factor analysis showed that the number of metastasis, visceral metastases and the efficacies of first-line chemotherapy were correlated with overall survival (all P < 0.05). Multivariate Cox regression showed that disease-free survival and the efficacies of first-line chemotherapy were the independent prognostic factors of metastatic triple-negative breast cancer. CONCLUSION: The combined chemotherapy of platinum may achieve better efficacies in the treatment of metastatic triple-negative breast cancer. And the efficacies of first-line chemotherapy are closely correlated with survival.

[Chinese HER2 positive early breast cancer trastuzumab adjuvant therapy: preliminary outcomes].

OBJECTIVE: To evaluate the efficacy and safety of 1-year adjuvant trastuzumab (herceptin) versus 1-year non-trastuzumab observation in Chinese patients with HER2-positive early breast cancer during a median follow-up of 1 year. METHODS: The HERA trial was an international, multicenter, randomized, open-label, phase III trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard adjuvant chemotherapy, radiotherapy or both in patients with HER2-positive node-positive or high-risk node-negative early breast cancer. The primary endpoint was disease-free survival. Secondary end points included recurrence-free survival, distant disease-free survival, overall survival and cardiac safety. The first planned interim analysis comparing the efficacy and safety of treatment with trastuzumab for 1 year versus observation were completed in April 2005. Only the outcomes of recruited Chinese patients were reported. RESULTS: A total of 122 Chinese patients from 8 participating centers were included for planned interim analysis. And they were divided into trastuzumab (n = 68) and observation (n = 54) groups. Three and eight disease-free survival events were observed in the trastuzumab and observation groups respectively. Two-year disease-free survival rates were 92.9% and 81.4% respectively (P = 0.0489); 2-year recurrence-free survival and distant disease-free survivals were 98.1% vs 81.4% (P = 0.0064) and 98.1% vs 83.3% (P = 0.0117) respectively. Trastuzumab was generally well-tolerated with a decent safety profile. Severe cardiotoxicity was not observed. CONCLUSION: One-year treatment with adjuvant trastuzumab improves disease-free survival, recurrence-free survival and distant disease-free survival in Chinese patients with HER2-positive early breast cancer.

Evaluation of treatment response for breast cancer: are we entering the era of "biological complete remission"?

Breast cancer is one of the most common malignancies in women. The post-operative recurrence and metastasis are the leading causes of breast cancer-related mortality. In this study, we tried to explore the role of circulating tumor cell (CTC) detection combination PET/CT technology evaluating the prognosis and treatment response of patients with breast cancer; meanwhile, we attempted to assess the concept of "biological complete remission" (bCR) in this regard. A 56-year-old patient with breast cancer (T(2)N(1)M(1), stage IV left breast cancer, with metastasis to axillary lymph nodes and lungs) received 6 cycles of salvage treatment with albumin-bound paclitaxel plus capecitabine and trastuzumab. Then, she underwent CTC detection and PET/CT for efficacy evaluation. CTC detection combination PET/CT is useful for the evaluation of the biological efficacy of therapies for breast cancer. The bCR of the patient appeared earlier than the conventional clinical imaging complete remission and promised the histological (pathological) complete remission. The integrated application of the concepts including bCR, imageological CR, and histological CR can achieve the early and accurate assessment of biological therapeutic reponse and prognosis of breast cancer.

Gene expression profiling for breast cancer prognosis in Chinese populations.

To investigate a quantitative reverse transcription polymerase chain reaction (QRT-PCR) assay different from 21-gene assay which can be used to prognosticate the risk of recurrence in patients with estrogen receptor (ER) positive, lymph node (LN) negative breast cancer. To accurately determine the relationship between the Recurrence Score (RS) derived from our assay and the risk of distant recurrence in Chinese patients with LN negative and positive breast cancer through the analysis of paraffin tissues. We obtained archival paraffin-embedded tissues from patients with invasive breast cancer and varying axillary lymph node involvement. QRT-PCR reaction was performed by using the method of SYBR Green I dye with primers. Expression of the 21-genes was converted to RS by a prespecified algorithm. We then assessed the probability of the test to accurately predict distant recurrence-free survival in this retrospective cohort. Ninety-three patients were eligible based on gene expression profiles. In our population, most breast cancer patients were premenopausal (82.6%), at early stage (93.6%) and ER positive (91.4%). Median follow-up was 65.9 months. The 5-year recurrence-free survival rate for the group was 58.8%. The concordance between the reverse transcription-PCR and immunohistochemical (IHC) measurement for ER, progesterone receptor (PgR), and HER-2 determinations was high and comparable. High RS was predictive of an elevated risk of relapse (p < 0.001). In subgroups of patients, RS had significantly predictive performance both in node-negative (p = 0.009) and node-positive patients (p = 0.038). Multivariable analysis showed that nodal status, adjuvant hormonal therapy and RS were significantly related to prognosis. RS category is a better predictor than the other risk assessment criteria or clinicopatholic features, with which we can determine more accurately the risks for recurrence of various patients. We have established an easy and economical QRT-PCR assay and validated in concordance with IHC measurements for ER, PgR, and HER-2. RS was associated with distant recurrence among Chinese patients with hormone receptor (HR) positive breast cancer. This study may promote the use of RS estimated from the expression of the 21-gene set for prognostication and routine clinical diagnostic application in Chinese populations.

[Efficacy and safety of regimens of capecitabine-based chemotherapy in the treatment of advanced breast cancer].

OBJECTIVE: To evaluate retrospectively the efficacy and toxicity of capecitabine-based chemotherapy in the treatment of advanced breast cancer. METHODS: Three hundred and seventy-six patients with advanced breast cancer were treated with capecitabine-based chemotherapy regimens in our department from Sep 2002 to Sep 2009. They were divided into 3 groups. The group 1 was treated with capecitabine 1000 mg/m(2) orally twice daily on d1-d14, repeated every 3 weeks. The group 2 was treated with capecitabine as group 1, and combined with docetaxel 60 - 75 mg/m(2) intravenous infusion on d1, repeated every 3 weeks. The group 3 was treated with capecitabine as group 1, and combined with vinorelbine 25 mg/m(2) intravenous infusion on d1 and d8, repeated every 3 weeks. The median treatment period of treatment was 3 cycles. RESULTS: Among the 376 patients, 218 patients were evaluable for response. In the group 1 the objective response rate (ORR) was 12.8% and the clinical benefit rate (CBR) was 21.6%. The CBR but not ORR of first line therapy with capecitabine was 35.2%, significantly higher than that of more than first line therapy (17.1%, P < 0.01). The ORRs for group 2 and group 3 were 53.8% and 36.4%, respectively. In the group 2 there was no significant difference in the ORR between the first line therapy and more than first line therapy. In the group 3 the ORR of first line therapy of NX regimen was 36.4%, significantly higher than that of more than first line therapy (16.7%, P < 0.01). CONCLUSIONS: The capecitabine-based chemotherapy is effective and tolerable, and can be used not only in first line but also more than first line therapy. The single agent maintenance chemotherapy after response to combined chemotherapy can prolonge the duration of treatment for patients with metastatic breast cancer.

Antisense oligodeoxynucleotide targeting HER2 mRNA sensitized docetaxel in breast cancer treatment.

CONTEXT: Human epidermal growth factor receptor 2 (HER2) is one of the oncogenes closely associated with the development and prognosis of breast carcinoma. Down-regulation of HER2 mRNA by antisense oligodeoxynucleotide (ASO) HER2 has been suggested to be a feasible treatment for patients with breast carcinoma. OBJECTIVE: The antitumor effects of ASO HA6722 were investigated in vitro and in vivo. MATERIALS AND METHODS: In this study, SK-BR-3, a HER2-overexpressing breast carcinoma cell line, was used as the model for in vitro experiments. Inhibitory effects of the ASO HA6722 were detected by methyl-thiazoldiphenyl tetrazolium (MTT) assay. Meanwhile, HER2 mRNA levels were monitored by reverse transcription polymerase chain reaction (RT-PCR). The in vivo antitumor effects were evaluated in nude mice xenograft model. RESULTS: Our results showed that HA6722 alone could inhibit the growth of SK-BR-3 cells in a dose-dependent manner with the IC(50) value of 41.8 ± 8.1 nM. In addition, the antitumor effect of docetaxel (TXT) could be sensitized by low dose of HA6722 both in vitro and in vivo, suggesting that ASO HA6722 could inhibit the growth of breast cancer cells and enhance the cytotoxic effects of TXT. DISCUSSION AND CONCLUSION: The combination treatment of TXT and HA6722 could be a more effective approach for breast cancer treatment. The future study should focus on the antitumor effect in other models.