Neoadjuvant endocrine therapy for strongly hormone receptor-positive and HER2-negative early breast cancer: results of a prospective multi-center study.

PURPOSE: For estrogen receptor (ER)-positive breast cancer, neoadjuvant endocrine therapy (NET) has been shown to be as effective as neoadjuvant chemotherapy (NACT). We evaluated the prognostic significance of Preoperative Endocrine Prognostic Index (PEPI). METHODS: We conducted a prospective, multi-center, non-randomized, controlled trial that enrolled postmenopausal early-stage strongly ER-positive (≥ 50%) and HER2-negative breast cancer patients. All patients were given 4-month NET before surgery. The primary objective was to investigate the 5-year recurrence-free survival (RFS) in patients who had PEPI 0-1 or pathological complete response (pCR) without chemotherapy. Patients who had PEPI 0-1 or pCR were recommended to receive adjuvant endocrine therapy only and patients had PEPI ≥ 2 may receive adjuvant chemotherapy at the discretion of the treating physician. RESULTS: A total of 410 patients were included and 352 patients constituted the per-protocol population. Overall, 9 patients (2.5%) had pCR (ypT0/is ypN0), 128 patients (36.4%) had PEPI = 0, and 56 patients (15.9%) had PEPI = 1. After a median follow-up of 60 months (4-104 months), patients who had PEPI 0-1 or pCR showed an improved 5-year RFS [99.5% (95% CI 98.5-99.9%) for PEPI 0-1 or pCR group vs. 93.7% (95% CI 89.6-97.8%) for PEPI ≥ 2 group, P = 0.028]. No survival difference was detected between patients received adjuvant chemotherapy vs. no chemotherapy among PEPI ≥ 2 cases. CONCLUSION: PEPI 0-1 or pCR may be used to define a group of ER-positive and HER2-negative postmenopausal early breast cancer patients with low relapse risk for whom adjuvant chemotherapy can be safely withheld. Studies on the identification and alternative treatment options for endocrine-resistant tumors are warranted. CLINICAL TRIAL REGISTRATION: NCT01613560.

Effectiveness and safety of pegylated liposomal doxorubicin versus epirubicin as neoadjuvant or adjuvant chemotherapy for breast cancer: a real-world study.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is an improved formulation of doxorubicin with comparable effectiveness but significantly lower cardiotoxicity than conventional anthracycline. This study aimed to evaluate the real-world effectiveness and safety of PLD versus epirubicin as neoadjuvant or adjuvant treatment for breast cancer. METHODS: Clinical data of invasive breast cancer patients who received neoadjuvant or adjuvant chemotherapy with PLD or epirubicin were retrospectively collected. Propensity score matching (PSM) was performed to reduce the risk of selection bias. The molecular typing of these patients included Luminal A, Luminal B, HER2-positive, and basal-like/triple-negative. The primary outcome was pathological complete response (pCR) rate for neoadjuvant chemotherapy and 3-year disease-free survival (DFS) rate for adjuvant chemotherapy. Noninferiority was suggested if the lower limit of the 95% CI for the 3-year DFS rate difference was greater than - 10%. The secondary outcome was adverse reactions. RESULTS: A total of 1213 patients were included (neoadjuvant, n = 274; adjuvant, n = 939). pCR (ypT0/Tis ypN0) rates of patients who received neoadjuvant chemotherapy were 11.6% for the PLD group and 7.0% for the epirubicin group, but the difference was not statistically significant (P = 0.4578). The 3-year DFS rate of patients who received adjuvant chemotherapy was 94.9% [95%CI, 91.1-98.6%] for the PLD group and 95.4% [95%CI, 93.0-97.9%] for the epirubicin group (P = 0.5684). Rate difference between the two groups and its 95% CI was - 0.55 [- 5.02, 3.92]. The lower limit of the 95% CI was - 5.0% > - 10.0%, suggesting that PLD is not be inferior to epirubicin in adjuvant chemotherapy for breast cancer. The incidences of myelosuppression, decreased appetite, alopecia, gastrointestinal reactions, and cardiotoxicity were lower in the PLD group than in the epirubicin group, while the incidence of nausea was higher in the PLD group. CONCLUSIONS: In the neoadjuvant and adjuvant treatment of breast cancer, effectiveness is similar but toxicities are different between the PLD-containing regimen and epirubicin-containing regimen. Therefore, further study is warranted to explore PLD-based neoadjuvant and adjuvant chemotherapy for breast cancer.

Fabrication of Weak C-Axis Preferred AlN Thin Film for Temperature Measurement.

A weak C-axis preferred AlN thin film with a lot of defects was fabricated for temperature measurement. It was found that the (002) diffraction peak of the thin film increased monotonously with the increase in annealing temperature and annealing time. This phenomenon is ascribed to the evolution of defects in the lattice of the AlN film. Therefore, the relationship between defects and annealing can be expressed by the offset of (002) diffraction peak, which can be used for temperature measurement. Furthermore, a temperature interpretation algorithm Equation based on the lattice parameter (2θ), annealing temperature and annealing time was established, and a temperature interpretation software was built with MATLAB. Visual temperature interpretation is realized by the software, and the relative error is less than 7%. This study is of great significance for promoting the accurate temperature measurement on the surface of high temperature component.

Multi-center investigation of breast reconstruction after mastectomy from Chinese Society of Breast Surgery: A survey based on 31 tertiary hospitals (CSBrS-004).

OBJECTIVE: Multi-center data on the current status and trends of breast reconstruction after mastectomy in China are lacking. Herein, we conducted a cross-sectional survey to investigate the current clinical practice pattern of postmastectomy breast reconstruction among Chinese female patients with breast cancer. METHODS: A standardized questionnaire used to collect information on breast reconstruction among females diagnosed with breast cancer was distributed by 31 members of the Chinese Society of Breast Surgery between January 1, 2018 and December 31, 2018. Information was collected on tumor characteristics, treatment, mesh application, nipple-areola complex (NAC) preservation, postoperative complications, bilateral reconstruction, patient satisfaction and local recurrence. The overall rate of breast reconstruction was assessed, and the characteristics were compared across patient groups with different reconstruction approaches. RESULTS: A total of 1,554 patients underwent breast reconstruction after total mastectomy, with a reconstruction rate of 9.6%. Among them, 1,190 were implant-based, and 262 underwent autologous reconstructions, while 102 cases underwent a combination of both. Patients who underwent implant-based reconstruction were younger than those who received autologous reconstruction (40.1±4.6 vs. 45.0±5.9, P=0.004). Compared to patients with autologous reconstruction, mesh application (25.5% vs. 6.5%), NAC preservation (51.8% vs. 40.5%) and reconstruction failure (1.8% vs. 0) were more frequently reported among those with implant-based reconstruction. There was no significant difference in general satisfaction across three reconstruction approaches, though patients with autologous reconstruction reported the highest aesthetic satisfaction among the three groups (P=0.044). CONCLUSIONS: Implant-based breast reconstruction remains the dominant choice among patients, while autologous reconstruction was associated with higher aesthetic satisfaction. Our multi-center investigation based on the findings of the tertiary hospitals of Chinese Society of Breast Surgery may guide a future series of clinical studies on breast reconstruction in China.

miR-511 inhibits proliferation and metastasis of breast cancer cells by targeting FGF4.

BACKGROUND: The present study aimed to explore the functions and molecular mechanisms of miR-511 in breast cancer. METHODS: A quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect miR-511 levels in breast cancer tissues; a chi-squared test was used to analyze the relationship between miR-511 expression level and pathological parameters of breast cancer patients; the proliferation of breast cancer cell lines MDA-MB-231 and MCF-7 was determined by the cell counting kit-8 (CCK-8) assay; migration was determined by scratch wound healing assay and transwell assay; TargetScan was used to predict the binding site between the 3'-untranslated region (3'-UTR) of fibroblast growth factor 4 (FGF4) and miR-511; and qRT-PCR, western blot and a luciferase reporter gene assay were conducted to further validate the targeting relationship between miR-511 and FGF4. RESULTS: The expression level of miR-511 was lower in breast cancer tissues than that in adjacent normal tissues. Low expression of miR-511 was associated with larger tumor size, lymph node metastasis and short survival time. In vitro experiments showed that miR-511 modulated the proliferation and metastasis of breast cancer cells. It was also confirmed that miR-511 directly targeted 3'-UTR of FGF4 and reduced its expression, and FGF4 overexpression reversed the effect of miR-511 on the malignant phenotypes of breast cancer cells. CONCLUSIONS: The results obtained in the present study demonstrate that miR-511 inhibits breast cancer proliferation and metastasis by down-regulating FGF4 expression, which may be helpful in the development of new treatment strategies for breast cancer.

Flexible nanofiber sensor for low-concentration hydrogen detection.

A palladium nanoparticle-decorated three-dimensional polyacrylonitrile nanofiber network (Pd-PAN) is prepared as a hydrogen sensor by a chemical bath method. A simple low-temperature annealing treatment is adopted to stabilize the active materials and eliminate the zero-drift of the sensor. The prepared Pd-PAN device exhibits stable performance for hydrogen detection with high sensitivity, especially in a low-concentration hydrogen environment. A minimum detectable limitation of 2 ppm is achieved. In addition, an excellent repeatability is confirmed by continuous measurement under 1% hydrogen. Although the response amplitude decreases with the increased temperature from 30 °C to 70 °C, the fast and stable sensitivity demonstrate the excellent environmental adaptivity and device stability. Notably, due to the accelerated diffusion speed under higher testing temperature, the response time and recovery time are shortened. Moreover, the difference of response as low as 0.01% under bending states at 70 °C strongly confirms the robust mechanical flexibility and superior device performance. The systematic measurements demonstrate the promising application of Pd-PAN sensors for low-concentration hydrogen detection.

Association of PTPN1 polymorphisms with breast cancer risk: A case-control study in Chinese females.

BACKGROUND: Breast cancer (BC) risk, development, and prognosis were closely related to obesity, diabetes mellitus, and metabolic syndrome. Protein tyrosine phosphatase, non-receptor type 1 (PTPN1) located on chromosome 20q13, could negatively regulate insulin and leptin signaling. In this study, we determined the association of PTPN1 polymorphisms with BC risk. METHODS: We analyzed the distribution of 11 selected PTPN1 single nucleotide polymorphisms in Chinese female patients with BC (n = 953) and healthy controls (n = 963) based on a multicenter case-control study. The association of PTPN1 genotypes and haplotypes frequencies with BC risk were determined by logistic regression analysis. Analyses were further stratified by body mass index (BMI), waist-hip rate (WHR), diabetes mellitus history, and fasting plasma glucose level. The eQTL (expression Quantitative Trait Loci) analysis for PTPN1 was conducted by GTEx database. RESULTS: There were significant differences between BC cases and control groups in menopausal status, number of births, and BMI. Four single nucleotide polymorphisms (SNPs; rs3215684, rs3787345, rs718049, and rs718050) decreased overall BC risk, and other seven SNPs showed no significant association with BC risk. In multivariate analysis, BMI and rs3215684 DT + DD genotype were identified as independent risk factors for BC, and mutated genotypes of rs3215684 were correlated with increased PTPN1 expression. There are no haplotypes showed different frequencies between cases and controls. In the stratified analysis, rs2206656 showed a significant association with decreased BC risk in the subgroup of BMI ≤ 24 kg/m 2 , while rs3215684 and rs718049 showed lower BC risk in the subgroup of WHR > 0.85. Seven SNPs showed lower BC risk in the subgroup with diabetes mellitus history and/or fasting plasma glucose level ≥ 7 mM, while rs754118 decreased BC risk in the subgroup of fasting plasma glucose level < 7 mM. CONCLUSION: Our findings suggest that PTPN1 SNPs associated with BC susceptibility in Chinese females, which also suggested a novel mechanism between obesity, diabetes mellitus, and BC risk.

Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer.

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.

Flexible and Highly Sensitive Hydrogen Sensor Based on Organic Nanofibers Decorated by Pd Nanoparticles.

A highly sensitive and flexible hydrogen sensor based on organic nanofibers decorated by Pd nanoparticles (NPs) was designed and fabricated for low-concentration hydrogen detection. Pd NPs were deposited on organic nanofiber materials by DC magnetron sputtering. The temperature dependence of the sensitivity at 25 ppm H2 was characterized and discussed, and the maximum response of the sensor increased linearly with increasing measurement temperature. Performances of the hydrogen sensor were investigated with hydrogen concentration ranging from 5 ppm to 50 ppm. This sensor exhibits high sensitivity, with the response up to 6.55% for H2 as low as 5 ppm, and the output response of the hydrogen sensor increased linearly with the square root of hydrogen concentration. A cycling test between pure nitrogen and 25 ppm hydrogen concentration was performed, and the hydrogen sensor exhibited excellent consistency.

Low Concentration Response Hydrogen Sensors Based on Wheatstone Bridge.

The PdNi film hydrogen sensors with Wheatstone bridge structure were designed and fabricated with the micro-electro-mechanical system (MEMS) technology. The integrated sensors consisted of four PdNi alloy film resistors. The internal two were shielded with silicon nitride film and used as reference resistors, while the others were used for hydrogen sensing. The PdNi alloy films and SiN films were deposited by magnetron sputtering. The morphology and microstructure of the PdNi films were characterized with X-ray diffraction (XRD). For efficient data acquisition, the output signal was converted from resistance to voltage. Hydrogen (H2) sensing properties of PdNi film hydrogen sensors with Wheatstone bridge structure were investigated under different temperatures (30 °C, 50 °C and 70 °C) and H2 concentrations (from 10 ppm to 0.4%). The hydrogen sensor demonstrated distinct response at different hydrogen concentrations and high repeatability in cycle testing under 0.4% H2 concentration. Towards 10 ppm hydrogen, the PdNi film hydrogen sensor had evident and collectable output voltage of 600 µV.

Comparison of surgical complication between immediate implant and autologous breast reconstruction after mastectomy: A multicenter study of 426 cases.

BACKGROUND AND OBJECTIVES: There is a lack of multicenter immediate breast reconstruction data comparing the surgical complication of implant and autologous breast reconstruction, especially in China. In this study, we used the data from eight centers to study the complications and their risk factors in this population. METHODS: Sociodemographic and clinicopathological data were obtained and compared for patients who received immediate implant and autologous breast reconstruction after breast cancer surgery in the eight hospitals between 2012 and 2016. Logistic regression analysis was used to identify risk factors associated with the complication of breast reconstruction. RESULTS: Immediate autologous reconstruction (IAR) was associated with significantly higher rates of overall complications (P = 0.036), fat liquefaction (P < 0.001), and reconstructive failure (P = 0.019), but lower rates of wound complications (P = 0.01) compared with the immediate implant reconstruction (IIR) at the median follow-up time of 13.6 months. With the logistic regression analysis, older patient (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.15-4.28; P = 0.017), and obesity (OR, 2.17; 95% CI, 1.08-4.37; P = 0.030) were significant predictors of increased complications. CONCLUSION: Our multicenter results demonstrated that the rates of overall complications and reconstruction failure were higher after IAR than IIR. These findings can be used to better help surgeons and their patients with objective and reliable information to assist in selecting the modality of reconstruction.

Distinct Effects of Body Mass Index and Waist/Hip Ratio on Risk of Breast Cancer by Joint Estrogen and Progestogen Receptor Status: Results from a Case-Control Study in Northern and Eastern China and Implications for Chemoprevention.

BACKGROUND: Obesity is a consideration in the pharmacologic intervention for estrogen receptor (ER) positive (ER+) breast cancer risk. Body mass index (BMI) and waist/hip ratio (WHR) have demonstrated different effects on breast cancer risk in relation to estrogen receptor (ER) status, but the results have been inconsistent. Furthermore, the situation in Chinese women remains unclear. MATERIALS AND METHODS: We conducted a case-control study including 1,439 breast cancer cases in Northern and Eastern China. Both ER and progesterone receptor (PR) statuses were available for 1,316 cases. Associations between body size-related factors and breast cancer risk defined by receptor status were assessed by multiple polytomous unconditional logistic regression analysis. RESULTS: Body mass index and WHR were positively associated with overall breast cancer risk. Body mass index was positively associated with both ER+/PR positive (PR+) and ER negative (ER-)/PR negative(PR-) subtype risks, although only significantly for ER+/PR+ subtype. Waist-hip ratio was only positively correlated with ER-/PR- subtype risk, although independent of BMI. Body mass index was positively associated with risk of ER+/PR+ and ER-/PR- subtypes in premenopausal women, whereas WHR was inversely correlated with ER+/PR- and positively with ER-/PR- subtype risks. Among postmenopausal women, WHR >0.85 was associated with increased risk of ER-/PR- subtype. CONCLUSION: Both general and central obesity contribute to breast cancer risk, with different effects on specific subtypes. General obesity, indicated by BMI, is more strongly associated with ER+/PR+ subtype, especially among premenopausal women, whereas central obesity, indicated by WHR, is more specific for ER-/PR- subtype, independent of menopausal status. These results suggest that different chemoprevention strategies may be appropriate in selected individuals. IMPLICATIONS FOR PRACTICE: The results of this study suggest that general and central obesity may play different roles in different breast cancer subtypes, supporting the hypothesis that obesity affects breast carcinogenesis via complex molecular interconnections, beyond the impact of estrogens. The results also imply that different chemoprevention strategies may be appropriate for selected individuals, highlighting the need to be particularly aware of women with a high waist/hip ratio but normal body mass index. Given the lack of any proven pharmacologic intervention for estrogen receptor negative breast cancer, stricter weight-control measures may be advised in these individuals.

Integrated Temperature and Hydrogen Sensors with MEMS Technology.

In this work, a PdNi thin film hydrogen gas sensor with integrated Pt thin film temperature sensor was designed and fabricated using the micro-electro-mechanical system (MEMS) process. The integrated sensors consist of two resistors: the former, based on Pt film, is used as a temperature sensor, while the latter had the function of hydrogen sensing and is based on PdNi alloy film. The temperature coefficient of resistance (TCR) in both devices was measured and the output response of the PdNi film hydrogen sensor was calibrated based on the temperature acquired by the Pt temperature sensor. The SiN layer was deposited on top of Pt film to inhibit the hydrogen diffusion and reduce consequent disturbance on temperature measurement. The TCR of the PdNi film and the Pt film was about 0.00122/K and 0.00217/K, respectively. The performances of the PdNi film hydrogen sensor were investigated with hydrogen concentrations from 0.3% to 3% on different temperatures from 294.7 to 302.2 K. With the measured temperature of the Pt resistor and the TCR of the PdNi film, the impact of the temperature on the performances of the PdNi film hydrogen sensor was reduced. The output response, response time and recovery time of the PdNi film hydrogen sensors under the hydrogen concentration of 0.5%, 1.0%, 1.5% and 2.0% were measured at 313 K. The output response of the PdNi thin film hydrogen sensors increased with increasing hydrogen concentration while the response time and recovery time decreased. A cycling test between pure nitrogen and 3% hydrogen concentration was performed at 313 K and PdNi thin film hydrogen sensor demonstrated great repeatability in the cycling test.

[Utilisation of electrical impedance tomography and/or ultrasound and mammography in breast disease diagnosis: a controlled study].

Objective: To investigate the diagnostic accuracy of electrical impedance tomography (EIT) for benign and malignant breast diseases incomparison to conventional ultrasonography and mammography. Methods: A total of 121 patients with 126 breast lesions who underwent mammography ultrasonography and EIT were enrolled in the study. All of these lessions were were confirmed by pathological biopsy. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of EIT, ultrasonography and mammography were calculated with histology as the gold standard. Results: The accuracy of EIT, ultrasonography and mammography were 75.4%, 81.7% and 76.1% respectively. The sensitivity was 76.8%, 94.6% and 74.4% respectively. The specificity was 74.3%, 71.4% and 77.6% respectively. The accuracy, sensitivity and specificity of EIT combined with ultrasound in diagnosis of breast lesions were 91.3%, 98.2% and 85.7%, respectively. The accuracy(χ(2)=4.896, P=0.027) and specificity(χ(2)=4.242, P=0.039) ere significantly higher on EIT compared to ultrasound.The accuracy, sensitivity and specificity of EIT combined with mammography were 95.5%, 97.4% and 93.9%, respectively, which were significantly higher than those of mammography (χ(2)=13.474, P<0.001; χ(2)=8.573, P=0.003; χ(2)=5.333, P=0.021). Conclusion: When together with ultrasound or mammography, electrical impedance tomography (EIT) could be a valuable complementary examination in the diagnosis of breast diseases. Furthermore, EIT could provide very useful additional information for metabolic assessment of mammary glands, which may be used for early screening of breast diseases.

Health-related quality of life of postmenopausal Chinese women with hormone receptor-positive early breast cancer during treatment with adjuvant aromatase inhibitors: a prospective, multicenter, non-interventional study.

BACKGROUND: Estimating quality of life (QoL) in patients with breast cancer is of importance in assessing treatment outcomes. Adjuvant endocrine therapy is widely used for hormone receptor-positive (HR+) early-stage breast cancer (EBC), and evidence suggests that aromatase inhibitors (AIs) may improve QoL for these patients. This study evaluated QoL in postmenopausal Chinese patients with HR+ EBC taking AIs. METHODS: This was a prospective, multicenter, and observational study that had no intent to intervene in the current treatment of recruited patients. Eligible patients were recruited within 7 days of beginning adjuvant treatment with AIs. The Functional Assessment of Cancer Therapy-Breast (FACT-B) scale was used to evaluate the patients' QoL. Data were collected at baseline and at 6, 12, 18, and 24 months. RESULTS: From June 2010 to October 2013, a total of 494 patients with HR+ EBC were recruited from 21 centers. There was a 7.51-point increase in the patients' mean FACT-B trial outcome index (TOI), from 90.69 at baseline to 98.72 at 24 months (P < .0001). The mean TOI scores at baseline, 6, 12, and 18 months were 90.69, 94.36, 97.71, and 96.75, respectively (P < .0001, for all). The mean (FACT-B) emotional well-being subscale scores at baseline, 6, 12, 18, and 24 months were 16.32, 16.55, 17.34 (P < .0001), 17.47 (P < .0001), and 17.85 (P < .0001), respectively, and social well-being scores were 18.61, 19.14 (P < .04), 19.35 (P < .008), 18.32, and 18.40, respectively. In the mixed model, baseline TOI, clinical visits, prior chemotherapies, age group, and axillary lymph-node dissection presented statistically significant effects on the change of FACT-B TOI and FACT-B SWB, whereas only baseline TOI, clinical visits, and prior chemotherapies presented statistically significant effects on the change of FACT-B EWB. FACT-B TOI, being the most pertinent and precise indicator of patient-reported QoL, demonstrated significant changes reflecting clinical benefit of adjuvant AIs endocrine therapy in the QoL of HR + EBC patients. CONCLUSIONS: The study demonstrated significant improvements in the long-term QoL of postmenopausal Chinese patients with HR+ EBC at 6, 12, 18, and 24 months after starting treatment with AIs. The current study indicates improved long-term QoL with AI adjuvant treatment, which will aid clinicians in optimizing treatment to yield effective healthcare outcomes. TRIAL REGISTRATION: Clinicaltrials.gov NCT01144572.

[A multicenter, randomized, controlled, phase â ¢ clinical study of PEG-rhG-CSF for preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer].

OBJECTIVE: To explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application. METHODS: According to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle. RESULTS: The duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 µg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 µg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 µg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 µg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 µg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 µg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 µg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 µg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581). CONCLUSIONS: In patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 µg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 µg/kg/d, a single 100 µg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

[Role of magnetic resonance imaging for response evaluation and predictive value of tumor biomarkers in the neoadjuvant chemotherapy for breast cancer:a multi-center prospective study].

OBJECTIVE: To explore the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in monitoring therapy responses and analyze the predictive value of tumor biomarkers in neoadjuvant chemotherapy for breast cancer. METHODS: From August 2010 to August 2013, the patients diagnosed as primary invasive breast cancer were admitted into this multi-center study. All of them received 6 cycles of neoadjuvant chemotherapy and DCE-MRI during the procedure and underwent surgery. The associations between clinical therapy response and pathologic response as well as predictive factors were analyzed. RESULTS: As for evaluating neoadjuvant treatment response, DCE-MRI had statistically significant correlations with histopathology. PR negativity, HER-2 over-expression and high Ki-67 index were statistically correlated with pathologic complete response (pCR) (P < 0.05). CONCLUSION: DCE-MRI is a reliable method of assessing the response of neoadjuvant therapy for breast cancer. And the immunohistochemistry status of PR, HER-2 and Ki-67 were related with pCR.

Integrating molecular pathway with genome-wide association data for causality identification in breast cancer.

OBJECTIVE: The study purpose was to explore the causal association between pyruvate metabolism and breast cancer (BC), as well as the molecular role of key metabolic genes, by using bioinformatics and Mendelian randomization (MR) analysis. METHODS: We retrieved and examined diverse datasets from the GEO database to ascertain differentially acting genes (DAGs) in BC via differential expression analysis. Following this, we performed functional and pathway enrichment analyses to ascertain noteworthy molecular functions and metabolic pathways in BC. Employing MR analysis, we established a causal association between pyruvate metabolism and the susceptibility to BC. Additionally, utilizing the DGIdb database, we identified potential targeted medications that act on genes implicated in the pyruvate metabolic pathway and formulated a competing endogenous RNA (ceRNA) regulatory network in BC. RESULTS: We collected the datasets GSE54002, GSE70947, and GSE22820, and identified a total of 1127 DEGs between the BC and NC groups. GO and KEGG enrichment analysis showed that the molecular functions of these DEGs mainly included mitotic nuclear division, extracellular matrix, signaling receptor activator activity, etc. Metabolic pathways were mainly concentrated in PI3K-Akt signaling pathway, Cytokine-cytokine receptor binding and Pyruvate, Tyrosine, Propanoate and Phenylalanine metabolism, etc. In addition, MR analysis demonstrated a causal relationship between pyruvate metabolism and BC risk. Finally, we constructed a regulatory network between pathway genes (ADH1B, ACSS2, ACACB, ADH1A, ALDH2, and ADH1C) and targeted drugs, as well as a ceRNA (lncRNA-miRNA-mRNA) regulatory network for BC, further revealing their interactions. CONCLUSIONS: Our research revealed a causal association between pyruvate metabolism and BC risk, found that ADH1B, ACSS2, ACACB, ADH1A, ALDH2, and ADH1C takes place an important part in the development of BC in the molecular mechanisms related to pyruvate metabolism, and identified some potential targeted small molecule drugs.

Integrative analysis of homologous recombination repair patterns unveils prognostic signatures and immunotherapeutic insights in breast cancer.

Globally, breast cancer (BC) is the leading cause of female death and morbidity. Homologous recombination repair (HRR) is critical in BC. However, the prognostic role and immunotherapy response of HRR in BC remains to be clarified. Firstly, we identified HRR types in BC samples from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset (GSE42568) based on 65 HRR genes (HRRGs). A differentially expressed gene (DEG) list for different HRR types was generated. Then, the influences of gene sets composed of these DEGs on biological pathways and BC prognosis were explored. Next, we identified gene clusters based on gene sets composed of DEGs. Genes associated with prognosis for DEGs were identified using univariate Cox regression. Finally, the HRR score was constructed based on genes associated with prognosis. We analyzed how HRR score correlates with tumor mutation burden (TMB), immune cell infiltration (ICI), and immunotherapy response. Three HRR clusters were discovered. HRR subtype A demonstrated decreased infiltration and a high number of immunosuppressive cells with a poor prognosis. DEGs among various HRR types were predominantly enriched in cell cycle and genomic stability-related pathways. The prognostic model based on sixteen DEGs accurately predicted BC prognosis. The HRRGs were differentially expressed in three DEG clusters. TMB, ICI, and immunotherapy responses differed significantly between the high and low HRR groups (HSG, LSG). The HSG was distinguished by a high degree of ICI and low TMB. LSG had a better response to anti-PD-1 or anti-PD-1 and anti-CTLA4 combination therapy. This work revealed that HRR patterns would contribute to predicting prognosis and immunotherapy response in BC, which may benefit patients.

A nomogram for predicting pathologic node negativity after neoadjuvant chemotherapy in breast cancer patients: a nationwide, multicenter retrospective cohort study (CSBrS-012).

Purpose: This study aimed to investigate the factors associated with pathologic node-negativity (ypN0) in patients who received neoadjuvant chemotherapy (NAC) to develop and validate an accurate prediction nomogram. Methods: The CSBrS-012 study (2010-2020) included female patients with primary breast cancer treated with NAC followed by breast and axillary surgery in 20 hospitals across China. In the present study, 7,711 eligible patients were included, comprising 6,428 patients in the primary cohort from 15 hospitals and 1,283 patients in the external validation cohort from five hospitals. The hospitals were randomly assigned. The primary cohort was randomized at a 3:1 ratio and divided into a training set and an internal validation set. Univariate and multivariate logistic regression analyses were performed on the training set, after which a nomogram was constructed and validated both internally and externally. Results: In total, 3,560 patients (46.2%) achieved ypN0, and 1,558 patients (20.3%) achieved pathologic complete response in the breast (bpCR). A nomogram was constructed based on the clinical nodal stage before NAC (cN), ER, PR, HER2, Ki67, NAC treatment cycle, and bpCR, which were independently associated with ypN0. The area under the receiver operating characteristic curve (AUC) for the training set was 0.80. The internal and external validation demonstrated good discrimination, with AUCs of 0.79 and 0.76, respectively. Conclusion: We present a real-world study based on nationwide large-sample data that can be used to effectively screen for ypN0 to provide better advice for the management of residual axillary disease in breast cancer patients undergoing NAC.