Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.
Female ; Humans ; Anthracyclines/therapeutic use* ; Antibiotics, Antineoplastic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Chemotherapy, Adjuvant ; Hormones/therapeutic use* ; Neoadjuvant Therapy ; Paclitaxel/therapeutic use* ; Prospective Studies ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/drug therapy*

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.
Female ; Humans ; Anthracyclines/therapeutic use* ; Antibiotics, Antineoplastic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Chemotherapy, Adjuvant ; Hormones/therapeutic use* ; Neoadjuvant Therapy ; Paclitaxel/therapeutic use* ; Prospective Studies ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/drug therapy*

Objective: To evaluate the efficacy and survival outcomes of dose-dense (biweekly) carboplatin plus paclitaxel (PC) as neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), and to explore an optimal neoadjuvant chemotherapy regimen for TNBC. Methods: Patients diagnosed as TNBC(cT1-4N0-3M0) in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Between January 2008 and September 2018 who received dose-dense PC and standard 3-weekly PC as NAC were 1∶1 matched using propensity score matching (PSM) to compare the efficacy, safety and survival outcomes. Results: One hundred of TNBC patients were enrolled (50 patients were divided in dose-dense group, 50 patients in standard group). The objective response rate (ORR) of dose-dense group and standard group were both 90.0% (45/50). The grade 3-4 neutropenia in dose-dense group was less than that of standard group (32.7% vs. 68.0%, P=0.001), while the rate of ALT/AST elevation in dose-dense group was higher than that of standard group (57.1% vs. 32.0%, P=0.012). The pathological complete response (pCR) rates were 34.0% (17/50) in dose-dense group and 38.0% (19/50) in standard group, without statistically significance (P=0.677). The median follow-up time was 55 months (3-150 months). The 5-year recurrence-free survival (RFS) in dose-dense group and standard group were 83.5% and 75.2%, respectively the 5-year overall survival (OS) in dose-dense and standard group were 87.9% and 84.5% the difference were not statistically significant (P=0.322 and 0.647, respectively). Patients with residual disease (tumor size≥1 cm or lymph node positive) had poor prognosis, the 5-year RFS and OS were 59.3% and 68.5%, respectively. Conclusions: Dose-dense PC has similar efficacy with standard 3-weekly PC and has a good safety profile. Since dose-dense regimen can shorten the duration of therapy, it can be an alternative in TNBC.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carboplatin/therapeutic use* ; Humans ; Neoadjuvant Therapy/adverse effects* ; Paclitaxel/therapeutic use* ; Treatment Outcome ; Triple Negative Breast Neoplasms/pathology*

In this work,a highly sensitive electrochemical biosensor for the detection of trace adenosine triphosphate (ATP) was proposed.The biosensor was based on porous anodic alumina (PAA) and SiO2 nanoparticles combining with several oligonucleotides to construct sandwich structure.It was characterized by scanning electron microscopy,fluorescence microscopy,differential pulse voltammetry and electrochemical impedance spectroscopy,which conformed to the reliability of the biosensor fabrication and the feasibility of the detection.In the presence of ATP,the sandwich structures could be destroyed.The variation of the current was directly corresponding to the amount of the ATP.The application of SiO2nanoparticles could effectively reduce the background and increase the sensitivity of the biosensor.The calibration curve of ATP was obtained in the range of 0.025-0.900 nmol/L with the detection limit of 13 pmol/L (S/N=3).Also,the biosensor exhibited a good specificity.Besides,the sensor was constructed easily and possessed excellent regeneration ability.The proposed biosensor was applied in detection of real sample such as mice blood.Therefore,the proposed ATP-sensing biosensor could be expected to be applied in clinical,pharmaceutical and environmental detection.

BACKGROUNDRegulatory T-cells (Treg) play key roles in suppressing cell-mediated immunity in cancer patients. Little is known about perioperative Treg fluctuations in nonsmall cell lung cancer (NSCLC). Video-assisted thoracoscopic (VATS) lobectomy, as a minimal invasive procedure for treating NSCLC, may have relatively less impact on the patient's immune system. This study aimed to observe perioperative dynamics of circulating Treg and natural killer (NK) cell levels in NSCLC patients who underwent major lobectomy by VATS or thoracotomy.

METHODSTotally, 98 consecutive patients with stage I NSCLC were recruited and assigned into VATS or thoracotomy groups. Peripheral blood samples were taken on 1-day prior to operation, postoperative days (PODs) 1, 3, 7, 30, and 90. Circulating Treg and NK cell counts were assayed by flow cytometry, defined as CD4 + CD25 + CD127 low cells in CD4 + lymphocytes and CD56 + 16 + CD3- cells within CD45 + leukocytes respectively. With SPSS software version 21.0 (SPSS Inc., USA), differences between VATS and thoracotomy groups were determined by one-way analysis of variance (ANOVA), and differences between preoperative baseline and PODs in each group were evaluated by one-way ANOVA Dunnett t-test.

RESULTSIn both groups, postoperative Treg percentages were lower than preoperative status. No statistical difference was found between VATS and thoracotomy groups on PODs 1, 3, 7, and 30. On POD 90, Treg percentage in VATS group was significantly lower than in thoracotomy group (5.26 ± 2.75 vs. 6.99 ± 3.60, P = 0.012). However, a higher level of NK was found on all PODs except on POD 90 in VATS group, comparing to thoracotomy group.

CONCLUSIONSLower Treg level on POD 90 and higher NK levels on PODs 1, 3, 7, 30 in VATS group might imply better preserved cell-mediated immune function in NSCLC patients, than those in thoracotomy group.

Aged ; Carcinoma, Non-Small-Cell Lung ; immunology ; surgery ; Female ; Flow Cytometry ; Humans ; Killer Cells, Natural ; immunology ; Male ; Middle Aged ; Postoperative Period ; T-Lymphocytes, Regulatory ; immunology ; Thoracic Surgery, Video-Assisted ; methods ; Thoracotomy ; methods

Anthracycline-Taxane chemotherapy is widely used in neoadjuvant treatment for breast cancers. However, there is limited data reported in patients with triple negative breast cancer (TNBC). Here, we evaluated the pathologic responses and survival of neoadjuvant epirubicin and taxanes chemotherapy in patients with locally advanced TNBC to provide some useful information for clinical practice. A total of 43 patients with locally advanced TNBC were enrolled in this study. Patients were administered with epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2) or docetaxel 75 mg/m(2) every 3 weeks for at least 2 cycles. The primary endpoint was pathologic complete response (pCR), which was defined as no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node, while relapse-free survival (RFS) and overall survival (OS) were secondary endpoints. Thirty-nine (90.7%) patients were at clinical stages IIB-IIIC. Thirty-seven (86%) completed 4-6 cycles of preoperative chemotherapy, and objective response rate (ORR) was 81.4% (35/43). Forty-two patients underwent radical surgery subsequently. The pCR rate was 14.3% (6/42). The most common adverse events in neoadjuvant chemotherapy were nausea/vomiting (88.4%, 38/43) and neutropenia (88.4%). After a median follow-up period of 34.0 months, 3-year RFS and OS rate was 53.6% and 80.1%, respectively. All events of recurrence and death occurred in non-pCR patients, in whom the 3-year RFS and OS rates were 44.3% and 76.6%, respectively. This study suggest that neoadjuvant chemotherapy with epirubicin plus taxanes has a relatively low pCR rate and high early recurrence risk in locally advanced TNBC, which indicates the necessity for more efficacious treatment. Further study is needed to validate these results.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Chemoradiotherapy, Adjuvant ; methods ; Disease-Free Survival ; Epirubicin ; administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; methods ; Neoplasm Recurrence, Local ; pathology ; prevention & control ; Neoplasm, Residual ; pathology ; prevention & control ; Paclitaxel ; administration & dosage ; Taxoids ; administration & dosage ; Treatment Failure ; Treatment Outcome ; Triple Negative Breast Neoplasms ; drug therapy ; pathology

OBJECTIVETo evaluate the clinical characteristics and prognosis of adrenal metastasis from breast cancer, and to explore methods to improve prognosis.

METHODSThirty-four breast cancer patients with adrenal metastasis were diagnosed and treated in our hospital from Jan. 1999 to Dec. 2010. SPSS 17.0 was used for survival analysis.

RESULTSDuring the Jan. 1999 to Dec. 2010 period, 13 595 patients with breast cancer were treated in our hospital. Among them, 34 cases had adrenal metastasis from breast cancer, with an incidence of 0.25%. The median time to progression (TTP) and overall survival of the 34 patients was 6.2 months (95%CI 3.1-9.3 months) and 21.4 months (95%CI 0-44.0 months), respectively. Eleven patients (34.4%) achieved partial response among 32 patients who received chemotherapy, and 10 (31.2%) achieved stable disease. Patients who achieved best response of PR or SD were superior in TTP and OS than patients with disease progression after chemotherapy (TTP: 18.1 months vs. 2.3 months, P < 0.001; OS: 35.2 months vs. 10.3 months, P = 0.003). Patients who received 1st or 2nd line chemotherapy were superior in TTP than patients who received over 2nd line chemotherapy (TTP: 15.7 months vs. 4.2 months, P = 0.005).

CONCLUSIONSThe incidence of adrenal metastasis from breast cancer is low. Chemotherapy-based systemic therapy should be recommended to improve the prognosis for these patients.

Adrenal Gland Neoplasms ; drug therapy ; secondary ; surgery ; Adrenalectomy ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Carcinoma, Ductal, Breast ; drug therapy ; pathology ; surgery ; Disease Progression ; Female ; Humans ; Middle Aged ; Remission Induction ; Retrospective Studies ; Survival Rate

OBJECTIVETo evaluate the efficacy, safety and survival of combination of carboplatin plus paclitaxel as neoadjuvant chemotherapy (NACT) for patients with locally advanced triple-negative breast cancer (TNBC), and explore an optimal regimen for TNBC.

METHODSPatients with core needle biopsy confirmed pathological diagnosis of IIA ∼ IIIC invasive breast cancer, negative for estrogen and progesterone receptors and HER2 by immunohistochemistry, and with indication for NACT were eligible in this study. The biopsy tumor tissues were tested for CK5/6, CK14, EGFR and Ki67. The patients received paclitaxel 175 mg/m(2) on day 1, carboplatin at an area under the curve 5 mg×min/ml on day 2 of every 21 days. The clinical response was evaluated every 2 cycles according to Standard RECIST 1.0 criteria and surgery was done after four to six cycles. Pathological complete remission (pCR) was defined if absence of invasive tumor in the breast and axillary lymph nodes samples or residual carcinoma in situ only.

RESULTSOverall, thirty-one patients were enrolled from January 2008 to November 2010. The median age was 51 years and 83.9% of the patients were diagnosed as stage IIB to IIIC diseases. 30 Patients completed chemotherapy as planed while one patient changed regimen due to paclitaxel allergy. Twenty-eight patients could be evaluated for clinical efficacy, of which CR, PR, SD, PD were achieved in 4, 20, 3 and 1 women, respectively. The objective response rate was 85.7%. The expression rate of CK5/6, CK14 and EGFR were 88.9% (24/27), 59.3% (16/27) and 63% (17/27), respectively. Among 27 patients who received modified radical mastectomy or breast-conserving surgery, 11 patients obtained pCR, with a pCR rate of 40.7% (95%CI 22.2% - 59.3%). Five of six CK5/6- and CK14-positive patients achieved pCR. All the 31 patients could be evaluated for toxicity according to the NCI-CTC v3.0 criteria. The major toxicities were neutropenia (93.5%), vomiting (45.2%) and ALT/AST increase (32.3%), and grade 3-4 toxicities accounted for 74.2%, 3.2%, 0, respectively. Until December 2011, at a median follow-up of 28.9 months (range 5 - 47.9), eight patients developed recurrence including 5 patients died. Among 11 patients with pCR, one suffered from lung metastasis at 45 months after diagnosis and survived with tumor until now. The other ten were alive and disease free. The 3-year DFS and OS were 62% and 74.7%, respectively.

CONCLUSIONSAs a neoadjuvant treatment for triple-negative breast cancer, carboplatin plus paclitaxel regimen achieves notable higher objective response rate and pCR rate compared with the anthracycline plus paclitaxel regimen reported in the literature, and is well tolerable. It is an optimized regimen for TNBC.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Biopsy, Large-Core Needle ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Carboplatin ; administration & dosage ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; secondary ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neutropenia ; chemically induced ; Paclitaxel ; administration & dosage ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Remission Induction ; Survival Rate ; Young Adult

OBJECTIVEEndobronchial metastases (EBM) secondary to extrapulmonary solid malignant tumors are rare but may occur. The most common extrathoracic malignancies associated with EBM are colorectal, renal and breast cancer. This study aimed to evaluate the clinicopathological aspects of EBM from breast cancer and the prognosis of the patients.

METHODSClinicopathological data of 11 cases diagnosed as EBM from breast cancer treated in our hospital from 2003 to 2010 were re-evaluated. Their symptoms, recurrence interval, radiological features, histopathological properties, and prognosis were assessed.

RESULTSEleven cases were diagnosed by bronchoscopic bronchial biopsy. The median interval from diagnosis of breast cancer was 57 months (range: 11 - 189 mo). All patients had other proven metastases when the EBM was diagnosed. The most frequently observed symptoms were cough (8 cases). Interestingly, two patients were asymptomatic. Hilar mass (5 cases) was a common radiological finding. No disaccordance between the hormone receptor status in the primary and metastatic lesions in these patients was found. The median survival after EBM diagnosis was 21 months (range: 6 - 36) with four patients still alive and one of these four patients was surviving more than 7 years.

CONCLUSIONSOn average, EBM is diagnosed about 5 years after the diagnosis of breast cancer, which is a relatively long lead time, but the median survival time is short, as 21 months in our group. The treatment plan must be individualized, because in some cases, long-term survival can be expected.

Adult ; Antineoplastic Agents ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Bronchial Neoplasms ; drug therapy ; secondary ; Carcinoma, Ductal, Breast ; drug therapy ; pathology ; radiotherapy ; secondary ; surgery ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Mastectomy, Modified Radical ; Middle Aged ; Nitriles ; therapeutic use ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Analysis ; Triazoles ; therapeutic use

OBJECTIVEThe aim of this study was to evaluate the effect of anastrozole, a new generation aromatase inhibitor, on the lipid metabolism in postmenopausal Chinese women with early breast cancer, and observe the adverse reactions as well.

METHODSPostmenopausal women with early breast cancer patients took anastrozole 1 mg per day. The lipid profiles of total cholesterol, triglyceride, low density lipoprotein, and high density lipoprotein were assessed before taking the drug, 3 months, 6 months after taking medication, and later once a year, until the end of medication or follow-up. Patients taking lipid-lowering drugs were excluded. The adverse reactions during the process of taking medication was followed-up by telephone.

RESULTSTwo hundred and eighty-five postmenopausal breast cancer patients took part in the trial from Jan. 2003 to Jun. 2009. All patients had completed primary surgery and demonstrated a postmenopausal status. ER or PR positivity was confirmed by histopathology. Taking the medication from a minimum of one year to a maximum of 5 years, with a median time of 3.61 years. During the medication time, anastrozole significantly increased the levels of low density lipoprotein-cholesterol after 6 months of treatment, continuing to 5 years, from (3.08 ± 0.90) mmol/L to (3.59 ± 0.59) mmol/L, with a maximal increase of 18.2% higher than that before medication. Anastrozole significantly increased the levels of total cholesterol and high density lipoprotein-cholesterol after 1 years of treatment. Anastrozole significantly reduced the levels of triglycerides after 1 years of treatment. Anastrozole showed no significant effect on serum lipids in the patients with pre-existing hyperlipidemia. A more significant effect on blood lipids was observed in patients aged ≥ 60-years than that in patients less than 60 years of age. The rate of other adverse events were similar to that reported in foreign patients.

CONCLUSIONSFor the postmenopausal patients with breast cancer, taking anastrozole may lead to an abnormal lipid metabolism. Anastrozole significantly increases the levels of low density lipoprotein-cholesterol, total cholesterol and high density lipoprotein-cholesterol, and significantly reduces the level of triglycerides. The rate of other adverse events were similar to that reported in foreign patients. it is suggested that the blood lipid levels should be regularly assessed in patients with long-term anastrozole treatment. The rate of other adverse events similar to that reported with foreign patients, and patients tolerate this treatment well.

Age Factors ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal ; therapeutic use ; Aromatase Inhibitors ; therapeutic use ; Breast Neoplasms ; blood ; complications ; drug therapy ; surgery ; Chemotherapy, Adjuvant ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Female ; Follow-Up Studies ; Humans ; Hyperlipidemias ; blood ; complications ; Lipid Metabolism ; drug effects ; Lipids ; blood ; Middle Aged ; Neoplasm Staging ; Nitriles ; therapeutic use ; Postmenopause ; Triazoles ; therapeutic use ; Triglycerides ; blood