The efficacy and safety of palbociclib combined with endocrine therapy in patients with hormone receptor-positive HER2-negative advanced breast cancer: a multi-center retrospective analysis.

To explore the efficacy and safety of palbociclib combined with endocrine therapy (ET) in advanced breast cancer (ABC). We conducted a retrospective study involving patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) ABC who received palbociclib combined with ET in the first- to third-line at three centers in China between January 2018 and October 2020. A total of 151 patients were included in this study. The median age of the patients at palbociclib initiation was 56 years (range 30-86 years) with a median follow-up of 10.9 months (range 2.0-41.2 months). Among these patients, 88 patients received palbociclib combined with ET as first-line therapy, and achieved a median progression-free survival (mPFS) of 19.8 months and an objective response rate (ORR) of 40.9%, meanwhile, in the first-line setting, 62 patients received palbociclib at an initial dose of 125 mg, achieving a mPFS of 20.9 months and an ORR of 46.8%. There were 39 and 24 patients who received palbociclib combined with ET as second- and third-line therapy, the mPFS were 10.0 months and 6.1 months, respectively. The most common and serious adverse events (AEs) were leukopenia and neutropenia. A total of 64 patients (42.4%) underwent palbociclib dose reduction due to AEs. Palbociclib combined with ET is an effective therapeutic regimen for HR+/HER2- ABC, particularly in the first-line setting with palbociclib initial dose of 125 mg, and AEs were manageable.

Influence of Helicobacter pylori infection on PD-1/PD-L1 blockade therapy needs more attention.

BACKGROUND AND OBJECTIVE: The tumor microenvironment and tumor immunity are crucially involved in tumor therapy. Immune checkpoint inhibitors targeting PD-1/PD-L1 signal transduction have been widely used in tumor therapy and have shown ideal clinical efficacy. However, some kinds of cancers still do not respond to PD-1/PD-L1 blockade therapy effectively, including gastric cancer. The related factors should be explored. METHODS AND RESULTS: This review summarizes the recent progression of understanding the influence of Helicobacter pylori infection on PD-1/PD-L1 blockade therapy. Current pieces of evidence have indicated that H. pylori infection might affect the curative effect of tumor therapy associating with the induced immunomodulation. CONCLUSION: It is necessary to understand the overall integration of PD-1/PD-L1 blockade therapy, the tumor microenvironment, and H. pylori infection. Much attention on the influence of H. pylori infection on the efficacy of tumor immunotherapy should be paid.

Evaluation of cMET aberration by immunohistochemistry and fluorescence in situ hybridization (FISH) in triple negative breast cancers.

PURPOSE: To evaluate the incidence of cMET proto-oncogene aberration in a cohort of triple negative breast cancers using immunohistochemistry and fluorescence in situ hybridization (FISH) methods and correlated with patient outcome. PATIENTS AND METHODS: One hundred and six female patients with diagnosis of triple negative invasive breast carcinoma at The University of Texas-M D Anderson Cancer Center from 1983 to 2009 were included in the study. Expression of cMET was assessed by IHC using rabbit monoclonal anti-total cMET antibody (SP44 from Ventana). Staining intensity was scored on a scale of 0, 1+, 2+ and 3+. cMET overexpression was defined as at least moderate membranous/cytoplasmic staining in ≥50% of tumor cells (score ≥ 2+). FISH analysis was performed using MET (7q31) specific probe (BAC clone RP11-95i20, Abbott Molecular Inc.) and the centromere probe (CEP7/D7Z1, Abbott Molecular Inc.) as internal control. cMET amplification was defined as gene copy numbers ≥4 per cell or cMET/CEP7 ratio ≥ 2. cMET status was tested for correlation using Fisher's exact test with other clinicopathological parameters. The Kaplan-Meier product limit method was used to estimate the survival outcomes. Cox proportional hazards models were fit to determine the association of cMET status by IHC, or by FISH, or by copy number with survival outcomes after adjustment for other patient and disease characteristics. RESULTS: Medium follow up is 69.4 months (range 9-317 months). cMET was successfully evaluated by both IHC and FISH methods in ninety-six patients. There were 13 patients whose tumors overexpressed cMET was by IHC. Two patients had cMET amplification by FISH using definitive of cMET/CEP7 ratio of ≥2 and four patients had cMET copy number >4. Only one patient showed cMET/CEP7 ratio of 2.53 and one was positive for cMET overexpression by IHC. No significant association between cMET overexpression by IHC and by FISH using cut-off of with either cMET/CEP7 ratio of ≥2 or cMET copy number of >4 (P = 1.0). There was no significant correlation between the cMET overexpression and other clinicopathological characteristics, such as patient demographics, tumor grade, stage, or chemotherapy treatment history. cMET overexpression and gene amplification did not correlate with the prognosis of TNBC regarding OS or DFS. CONCLUSION: MET amplification is a rare incidence in TNBCs. cMET overexpression is infrequent in TNBCs and may not be driven by gene amplification. Neither have significant prognostic value nor do they correlate with other clinicopathological characteristics in this TNBC cohort.

Safety and efficacy evaluation of personalized exercise prescription during chemotherapy for lung cancer patients.

BACKGROUND: To explore the safety and effectiveness of personalized exercise intervention during chemotherapy for lung cancer patients who were relatively weak and with compromised cardiopulmonary function. METHODS: Thirty-eight lung cancer patients treated with chemotherapy at Peking University Third Hospital were enrolled in this prospective study. The exercise group (N = 21) received individualized exercise guidance based on personal test results and exercised regularly, while the control group (N = 17) only received exercise education and planed exercise methods according to their own preferences. Both groups underwent three fitness tests and clinical indicator assessments at 0, 6, and 12 weeks after starting the exercise, and the differences in trends of various indicators between the two groups were compared. RESULTS: No exercise-related adverse events occurred during the 12-week exercise period. After 12 weeks of exercise training, in terms of fitness, the exercise group showed significant improvements in 6-min walk test (6MWT) (p < 0.001), peak oxygen consumption (VO2peak) (p = 0.005), muscle content (p < 0.001), muscle percentage (p < 0.001), and grip strength (p = 0.008) compared to the control group. In terms of clinical indicators, the exercise group showed significant improvements in vital capacity (p = 0.018), D-dimer (p = 0.031), and C-reactive protein (CRP) (p = 0.01), uric acid (p = 0.003), triglycerides (p < 0.001), functional average score (p < 0.001), and main symptom average score (p = 0.004) compared to the control group in trends over time. CONCLUSION: Rehabilitation exercises using individualized exercise prescriptions tailored by exercise prescription specialists during chemotherapy are safe for lung cancer patients. Adhering to exercise can achieve comprehensive improvements in physical fitness and quality of life at 12 weeks.

Clinical observation of peripheral nerve injury in 2 patients with cancer after radiotherapy.

AIM OF THE STUDY: This study aims to analyze the clinical manifestations and sequelae of peripheral nerve radiation damage of two cases of cancer patients after radiotherapy at the corresponding sites in clinical practice and to summarize experiences and lesions in order to provide a reference for future tumor radiotherapy. MATERIAL AND METHODS: Some data of two cases of patients, such as doses of radiotherapy, clinical manifestations and damage occurrence time, were collected and examinations were conducted to define diagnosis. Afterwards, therapies and follow-up were conducted. RESULTS: Case 1 (rectal cancer) was diagnosed as mild left lower extremity nerve damage. After the symptomatic treatment, the disease condition was improved, and there was no tumor recurrence sign. Case 2 (breast cancer) was diagnosed as left brachial plexus damage, and left upper extremity movement function was lost completely. While the analgesic treatment was conducted, anti-tumor relevant treatments were being carried out. CONCLUSIONS: Radiotherapy can cause different extents of radioactive nerve damage. In practice, it is necessary to constantly improve the radiotherapy technology level and actively prevent the occurrence of complications. Once symptoms appear, the diagnosis and treatment should be conducted as early as possible in order to avoid aggravating damage to cause dysfunction and cause lifetime pain to patients.

A Bibliometric Analysis on the Research Trend of Exercise and the Gut Microbiome.

This article aims to provide an overview of research hotspots and trends in exercise and the gut microbiome, a field which has recently gained increasing attention. The relevant publications on exercise and the gut microbiome were identified from the Web of Science Core Collection database. The publication types were limited to articles and reviews. VOSviewer 1.6.18 (Centre for Science and Technology Studies, Leiden University, Leiden, the Netherlands) and the R package "bibliometrix" (R Foundation: Vienna, Austria) were used to conduct a bibliometric analysis. A total of 327 eligible publications were eventually identified, including 245 original articles and 82 reviews. A time trend analysis showed that the number of publications rapidly increased after 2014. The leading countries/regions in this field were the USA, China, and Europe. Most of the active institutions were from Europe and the USA. Keyword analysis showed that the relationship between disease, the gut microbiome, and exercise occurs throughout the development of this field of research. The interactions between the gut microbiota, exercise, status of the host's internal environment, and probiotics, are important facets as well. The research topic evolution presents a trend of multidisciplinary and multi-perspective comprehensive analysis. Exercise might become an effective intervention for disease treatment by regulating the gut microbiome. The innovation of exercise-centered lifestyle intervention therapy may become a significant trend in the future.

ABSDELL Model: Development and Internal Validation of a Risk Prediction Model of LVEF Decline in Breast Cancer Patients Treated With Trastuzumab.

INTRODUCTION/BACKGROUND: This study aims to establish an integrated model for predicting trastuzumab-associated decline of Left ventricular ejection fraction (LVEF) during drug administration. METHODS: A retrospective study of 212 women who diagnosed with HER2-positive breast cancer and treated with chemotherapy and trastuzumab was conducted. Medical records were collected from 6 months before staring trastuzumab to 3 years afterwards. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to select variables, time-dependent receiver operating characteristic (ROC) curve and calibration plots were used to evaluate the model. The adjusted C-index and Brier scores were calculated using a bootstrap internal validation procedure. RESULTS: The median age of participants is 53.2 years old. The median length of follow-up was 336 days. There were 72 patients (33.96%) whose LVEF declined ≥ 10% (10 absolute percent points). Seven factors, namely age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), mitral peak E-wave velocity (E-wave), left ventricular end-systolic diameter (LVESD) and LVEF, were selected. The name of the ABSDELL model was formed by the initials of each predictor. The area under the curve (AUC) of the model was 0.802 in 1 year and 0.881 in 3 years. Calibration plots indicate the predicted and actual probabilities were highly consistent. In the internal validation, 1-year and 3-year adjusted C-index was 0.801 and 0.881, and adjusted Brier score was 0.118 and 0.091, separately. CONCLUSION: The ABSDELL model can effectively predicts the probability of LVEF decline in breast cancer patients treated with trastuzumab.

Corrigendum: Nitazoxanide, an antiprotozoal drug, reduces bone loss in ovariectomized mice by inhibition of RANKL-induced osteoclastogenesis.

[This corrects the article DOI: 10.3389/fphar.2021.781640.].

Successful immune checkpoint inhibitor-based rechallenge in a patient with advanced esophageal squamous cell cancer: A case report.

Immune checkpoint inhibitors (ICIs) have been shown to improve survival in patients with advanced or metastatic esophageal cancer. However, ICI-based rechallenges after recovery from fatal adverse events (AEs) are equivocal, especially in patients who have already undergone treatment-related AEs. In this study, we report the case of a patient with advanced esophageal squamous cell cancer (ESCC) who developed a treatment-related tracheoesophageal fistula (TEF) after two cycles of ICI administration, provided in combination with traditional chemotherapeutics. After spontaneous healing of the TEF, the patient was again treated with ICIs and achieved a durable clinical response without any signs of fistula recurrence. Successful ICI-based rechallenges after fistula healing have rarely been reported. Therefore, ICI-based rechallenge in patients with esophageal cancer having an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 after serious AEs may serve as a clinically viable treatment strategy that should be administered under close monitoring.

Advances in molecular biomarkers research and clinical application progress for gastric cancer immunotherapy.

Gastric cancer is characterized by high morbidity and mortality worldwide. Early-stage gastric cancer is mainly treated with surgery, while for advanced gastric cancer, the current treatment options remain insufficient. In the 2022 NCCN Guidelines for Gastric Cancer, immunotherapy is listed as a first-line option for certain conditions. Immunotherapy for gastric cancer mainly targets the PD-1 molecule and achieves therapeutic effects by activating T cells. In addition, therapeutic strategies targeting other molecules, such as CTLA4, LAG3, Tim3, TIGIT, and OX40, have also been developed to improve the treatment efficacy of gastric cancer immunotherapy. This review summarizes the molecular biomarkers of gastric cancer immunotherapy and their clinical trials.

Starting dose selection of palbociclib in Chinese patients with breast cancer based on population kinetic-pharmacodynamic model of neutropenia.

Neutropenia is the most common adverse event (AE) of palbociclib, an oral CDK4/6 inhibitor for breast cancer. Neutropenia increases the risk of infection and is even life threatening. Asian patients generally suffer more severe neutropenia from palbociclib treatment, but the label does not recommend a reduction in the starting dose for Asian patients. Therefore, the study aimed to explore the exposure-response (E-R) relationship in Chinese patients and preliminarily generate a scale for starting dose selection of palbociclib in Chinese patients. After comparing the kinetic-pharmacodynamic (K-PD) and the pharmacokinetic/pharmacodynamic (PK/PD) model, a semi-mechanistic K-PD model was selected and developed on the basis of real-world data from 28 patients with breast cancer to describe the time course of longitudinal absolute neutrophil counts (ANC). The longitudinal ANC data were well described by the population K-PD model with reasonable parameters: mean transit time (MTT) of 198 h, feedback parameter (γ) of 0.317, baseline ANC level (Circ0) of 3.36 × 109 L-1, drug effect coefficient (kd) of 0.0349, and drug effect power (ß) of 0.383. No covariate was included in the final model. The model showed that palbociclib dose-dependently reduced ANC levels in a Chinese population, and lower baseline ANC level was associated with more severe neutropenia. The dose selection scale suggested that palbociclib 125 mg daily was appropriate for Chinese patients with Circ0 higher than 3.75 × 109 L-1. In summary, the K-PD model of palbociclib well described the longitudinal ANC in Chinese patients. Besides, the starting dose selection scale may provide reference for clinicians during individualized therapy.

Nitazoxanide and related thiazolides induce cell death in cancer cells by targeting the 20S proteasome with novel binding modes.

Nitazoxanide and related thiazolides are a novel class of anti-infectious agents against protozoan parasites, bacteria and viruses. In recent years, it is demonstrated that thiazolides can also induce cell cycle arrest and apoptotic cell death in cancer cells. Due to their fast proliferating nature, cancer cells highly depend on the proteasome system to remove aberrant proteins. Many of these aberrant proteins are regulators of cell cycle progression and apoptosis, such as the cyclins, BCL2 family members and nuclear factor of κB (NF-κB). Here, we demonstrate at both molecular and cellular levels that the 20S proteasome is a direct target of NTZ and related thiazolides. By concurrently inhibiting the multiple catalytic subunits of 20S proteasome, NTZ promotes cell cycle arrest and triggers cell death in colon cancer cells, either directly or as a sensitizer to other anti-tumor agents, especially doxorubicin. We further show that the binding mode of NTZ in the ß5 subunit of the 20S proteasome is different from that of bortezomib and other existing proteasome inhibitors. These findings provide new insights in the design of novel small molecular proteasome inhibitors as anti-tumor agents suitable for solid tumor treatment in an oral dosing form.

Maintenance Therapy with Pembrolizumab after Platinum-Doublet Chemotherapy Leading to Hyperprogression in a Patient with Metastatic Bladder Cancer.

The anti-programmed cell death receptor 1 (anti-PD-1) immunotherapy has been recommended in several treatment scenarios of metastatic urothelial cancer (UC), including as a maintenance therapy after first-line chemotherapy. However, the PD-1 inhibitor accelerates tumor growth occasionally, causing hyperprogressive disease (HPD). We presented here a case of HPD in a 43-year-old male Chinese patient with bladder UC, metastasizing to liver and bone, and harboring amplification of Murine Double Minute gene 2, cyclin-dependent kinase 4, fibroblast growth factor receptor substrate 2, ERBB3, and Enhancer of Zeste Homolog 2. After achieving partial remission with the traditional platinum doublet chemotherapy, he sought PD-1 inhibitor (pembrolizumab) for maintenance therapy in another hospital. After 3 doses of pembrolizumab in <2 months, his liver metastasis dramatically increased both in size and number. Liver biopsy confirmed genuine progression. He died from liver failure 6 months later. This case alerted us about HPD again in the scenario of maintenance therapy, enhanced the importance of selecting appropriate patients.

Nitazoxanide, an Antiprotozoal Drug, Reduces Bone Loss in Ovariectomized Mice by Inhibition of RANKL-Induced Osteoclastogenesis.

Nitazoxanide (NTZ) is an FDA-approved anti-parasitic drug with broad-spectrum anti-infective, anti-inflammatory, and antineoplastic potential. However, its regulatory effects on osteoclastogenesis and the underlying mechanisms remain unclear. The present study found that NTZ potently inhibited osteoclast formation at the early stage of receptor activator of NF-κB ligand-induced osteoclastogenesis in a concentration-dependent manner at a non-growth inhibitory concentration. NTZ suppressed actin ring formation and decreased osteoclast marker gene expression, including TRAP, MMP9, and cathepsin K. NTZ significantly impaired the bone resorption activity of osteoclasts. In vivo, ovariectomized mice were treated with 50, 100 and 200 mg/kg/d NTZ for 3 months. NTZ (100 mg/kg/d) administration markedly reduced ovariectomy-induced bone loss by suppressing osteoclast activity. Mechanistically, osteoclastogenesis blockade elicited by NTZ resulted from inhibition of STAT3 phosphorylation, and reduction of the Ca2+ fluorescence intensity and NFATc1 expression. NTZ weakened the binding between STAT3 and the NFATc1 promoter region. Furthermore, enforced NFATc1 expression partly rescued the impaired osteoclast differentiation in NTZ-treated RAW264.7 cells. In summary, NTZ could inhibit osteoclastogenesis and bone loss through modulation of the receptor activator of NF-κB ligand-induced STAT3-NFATc1 signaling pathway, which might be a potential alternative treatment regimen against bone destruction-related diseases including osteoporosis.

Alisol A is potentially therapeutic in human breast cancer cells.

Recent developments in breast cancer therapy have significantly improved patient survival rate; however, recurrence remains a major problem. Systemic treatment of breast cancer with available therapies is not curative. Natural products can be potentially used for treating cancer. Recently, a wide range of pharmacological activities has been reported for Alismatis Rhizoma, a popular traditional Chinese medicine. However, the mechanisms via which its compounds act on breast cancer remain unclear. The present study aimed to investigate the potential of natural therapeutic agents from Alismatis Rhizoma for treating breast cancer. Human breast cancer MDA­MB­231 cells were treated with four main protostane triterpenes from Alismatis Rhizoma, including alisol A, alisol A 24­acetate, alisol B and alisol B 23­acetate. Among these, alisol A significantly inhibited cell viability. Alisol A induced cell apoptosis, G1 phase cell cycle arrest, autophagy, and intracellular reactive oxygen species (ROS) generation in MDA­MB­231 cells. The number of APE1­/γH2AX­/LC3­II positive cells was also significantly higher compared with that of negative control cells. All these results were dose­dependent. Cleaved caspase­3, cleaved caspase 9, Bcl­2, and p­p38 expression indicated cell apoptosis after alisol A treatment. The changes in cyclin A and cyclin D1 expression was associated with cell cycle arrest upon alisol A treatment. Furthermore, LC3­II expression upon alisol A treatment was indicative of autophagy. Alisol A treatment can induce autophagy­dependent apoptosis in human breast cancer cells via induction of ROS and DNA damage. Thus, Alisol A might serve as a new therapeutic agent against breast cancer.

Delanzomib, a novel proteasome inhibitor, sensitizes breast cancer cells to doxorubicin-induced apoptosis.

BACKGROUND: Delanzomib, a novel proteasome inhibitor, has demonstrated promising efficacy and antitumor ability in human multiple myeloma cell lines and patient-derived cells. However, the potential therapeutic effects of delanzomib on breast cancer remain unknown. In this study, we show that delanzomib has antitumor effects and synergizes with doxorubicin (Dox) in human breast cancer cell lines. METHODS: Cell proliferation assay and flow cytometry were used to evaluate cell viability and apoptosis in eight human breast cancer cell lines after treatment with delanzomib or Dox. Essential molecules of the p53, MAPK, and apoptosis signaling pathways were analyzed by Western blotting. RESULTS: Delanzomib induced cell death and demonstrated synergism with Dox in all tested breast cancer cell lines. In addition, delanzomib enhanced the Dox-induced phosphorylation of p38/JNK and the expression of transcriptional target proteins of p53, such as p21, p27, NOXA, and PUMA. CONCLUSION: The combined regimen of the proteasome inhibitor delanzomib with Dox chemotherapy may become an effective strategy for breast cancer therapy.

The deregulation of miR-133b is associated with poor prognosis in bladder cancer.

BACKGROUND: MicroRNAs (miRNAs) are single-stranded, endogenous, non-coding RNAs that are increased or decreased in almost all cancer types, and they paly crucial roles in the tumorigenesis as well as development. MATERIALS AND METHODS: 90 patients diagnosed with bladder cancer were enrolled in the present study. The bladder cancer tissues or adjacent normal tissues were obtained from the tumor area or adjacent normal zone. The expression level of miR-133b was examined by quantitative real-time polymerase chain reaction assay (qRT-PCR). Survival curves were displayed by the Kaplan-Meier method, and differences between two survival curves were calculated by the log-rank test. RESULTS: The expression levels of miR-133b in bladder tissues were significantly decreased when compared with the matched adjacent normal bladder tissues (P < 0.05). Moreover, miR-133b expression levels are significantly associated with lymphatic invasion (P = 0.026), distant metastasis (P = 0.025), tumor grade (P = 0.038), as well as the muscle invasion status (P < 0.001). The log-rank test indicated that patients with decreased miR-133b expression underwent poorer overall survival (P = 0.007). Furthermore, multivariate Cox regression analysis showed that the expression level of miR-133b (P = 0.024) was an independent factor for predicting the overall survival in patients with bladder cancer. CONCLUSIONS: The present study showed that miR-133b might be associated with bladder cancer progression, and its down-regulation might be a biomarker for poor prognosis of bladder cancer.

MELK is a novel therapeutic target in high-risk neuroblastoma.

Maternal embryonic leucine zipper kinase (MELK) is known to modulate intracellular signaling and control cellular processes. However, the role of MELK in oncogenesis is not well defined. In this study, using two microarray datasets of neuroblastoma (NB) patients, we identified that MELK expression is significantly correlated to poor overall survival, unfavorable prognosis, and high-risk status. We found that MELK is a direct transcription target of MYCN and MYC in NB, and MYCN increases MELK expression via direct promoter binding. Interestingly, knockdown of MELK expression significantly reduced the phosphorylation of target protein Retinoblastoma (pRb) and inhibited NB cell growth. Furthermore, pharmacological inhibition of MELK activity by small-molecule inhibitor OTSSP167 significantly inhibited cell proliferation, anchorage-independent colony formation, blocked cell cycle progression, and induced apoptosis in different NB cell lines including a drug-resistant cell line. Additionally, OTSSP167 suppressed NB tumor growth in an orthotopic xenograft mouse model. Overall, our data suggest that MELK is a novel therapeutic target for NB and its inhibitor OTSSP167 is a promising drug for further clinical development.

[Clinical study of aromatase inhibitors in advanced breast cancer].

OBJECTIVE: To assess the antitumor activity and safety of aromatase inhibitors in advanced breast cancer. METHODS: Fifty-two advanced and female breast cancer patients with measurable and /or bone valuable tumor lesions were observed from June 2003 to September 2006. They were treated by aromatase inhibitors for at least 24 weeks, of whom 11 were treated less than 24 weeks because of disease progress; their age range was from 37 to 75 years (median 58); 8 patients were pre-menopausal, 6 with ovarian ablation and 2 with Goserelin to suppress ovarian function. Thirty-six patients were treated with exemestane, 13 with anastrozole and 3 with letrozole. Major items were observed including objective response rate (ORR=CR+PR), clinical benefit rate (CBR=CR+PR+SD>or=24 weeks), time to progress (TTP), time to failure (TTF), safety and toxicity. RESULTS: CR were 6 cases (11.5%) , with 1 case going on for 152 weeks, 1 case for 96 weeks, and other 4 cases for longer than 60 weeks; PR were 19 cases (36.5%), lasting 32-96 weeks; 16 cases obtained SD>or=24 weeks(30.8%); and 11 cases PD (progress of disease)+SD<24 weeks (21.2%). ORR were 48%, CBR 78.8%, and TTP 78.87 weeks (95% CI 61.13%-96.61%); although the patients who did not achieve objective response (group B) were treated with chemotherapy, radiotherapy or another kind of aromatase inhibitor, but their survival time was significantly different from that of the patients who achieved objective response (group A) when defined by Kaplan-Meier survival estimate. The over survival was 92% in group A, and 81.5% in group B when patients follow up more than 24 weeks [Log Rank (Mantel-Cox) analysis, chi2=3.85, P=0.047]; side effects were observed such as arthralgia, sweating, hot flash, and 2 patients developed heart failure with uncertain related drug before recovery. CONCLUSION: The single agent effective rate of aromatase inhibitor was 48%. The patients had long term survival if they obtained CR or PR, and the side effects were well tolerated.

[Observation and clinical significance of adjuvant chemotherapy-induced amenorrhea in premenopausal breast cancer patients].

OBJECTIVE: A retrospective analysis of 160 pre-menopausal breast cancer patients was carried out to elucidate the the menstrual outcome in those cases who had undergone adjuvant chemotherapy after surgery, and evaluate the relationship between chemotherapy-induced amenorrhea (CIA) and recurrence of the disease. METHODS: 160 pre-menopausal breast cancer patients were collected, 62/159 (39.0%) of them were node positive, 91/158 (57.6%) were ER positive, and 95/155 (61.3%) were PR positive. 111 cases had infiltrative ductal carcinoma, 26 cases had infiltrative lobular carcinoma, and 22 cases with others. In 152 cases data were collected by face-to-face interview and 8 cases by phone conversation. Types and cycles of chemotherapy regimen as well as menstrual abnormalities were recorded before, during, and after chemotherapy completion. Follow up duration was 12-72 months after chemotherapy completion for all patients. RESULTS: 107 (66.9%) developed CIA, 24 cases returned to normal menses (22.4%), 83 cases continued CIA during more than 12-month follow up (77.6%). The rate of CIA increased with age (P < 0.01). During the follow up, disease free survival (DFS) rate was 85.9% in CIA group and 79.2% in non-CIA group, with no statistically significant difference. But in hormonal receptor positive patients, DFS was 80.0% in non-CIA and 90.1% in CIA, respectively (P = 0.04), showing a significant difference. Because of the small number of died cases, no analysis of the overall outcome was carried out. CONCLUSION: Adjuvant chemotherapy causes ovarian function suppression, and may further leading to amenorrhoea. Women who experienced amenorrhoea after chemotherapy had a significantly better disease-free survival (DFS) rate showed by univariate analysis than women who continued normal menstruation. Chemotherapy is insufficient therapy for very young patients who are in high risk with hormone responsive disease, particularly when chemotherapy fails to induce amenorrhea. Further research is needed to evaluate interventional chemotherapy to improve the quality of life in women with early stage breast cancer who experienced ovarian toxicity. The post-chemotherapy menstruation status is a clinically valuable, objective and salient marker for sufficient endocrine effect of chemotherapy in ER/PR-positive premenopausal patients.