Racial and survival disparities in inflammatory breast cancer (IBC) and non-IBC: a population-based study focused on Native Hawaiians and other Pacific Islanders.

Background: It is well known that race is an independent predictor of breast cancer mortality and advanced stage at diagnosis. Inflammatory breast cancer (IBC) is the most aggressive type of breast cancer and has distinct clinical and biological features. Previous studies have shown that Blacks have a higher incidence of IBC than Whites. However, the proportion of IBC and the role of race on prognosis in Native Hawaiian and other Pacific Islander (NH/PI) populations with breast cancer are poorly understood. In this study, we aimed to examine the proportion of IBC to non-IBC in NH/PIs and to identify the clinicopathological, biological, and socioeconomic factors associated with the overall survival of NH/PIs compared to other races. Methods: Utilizing a comprehensive cancer registry from the largest hospital in Hawaii, newly diagnosed primary invasive breast cancer patients diagnosed between 2000 and 2018 were identified. Univariate and multivariate Cox proportional hazards models were used to test the association between race and clinical outcomes. Variables with P-values <0.05 in the univariate analysis and race (variable of interest) were included in a multivariate analysis. Results: The cohort included 3691 patients, 60 of whom had IBC. NH/PI race had the highest proportion of IBC compared to other races (3.44%) but was not found to be an independent poor prognostic factor in IBC (HR 1.17 [95%CI 0.26-5.22]). Conversely, NH/PI race was associated with worse survival outcomes in patients with non-IBC (HR 1.65 [95%CI, 1.14-2.39]) along with other factors such as lack of insurance, underinsured status, triple-negative breast cancer (TNBC) subtype, age, and advanced clinical stage. Conclusions: The findings of this study highlight that NH/PIs had higher rates of IBC and inferior survival in non-IBC compared to other races but not in IBC. It is essential to disaggregate NH/PI race from Asians in future population-based research studies. Further research is needed to understand the factors contributing to higher rates of IBC and poor survival outcomes in NH/PIs with non-IBC as well as targeted interventions to improve breast cancer outcomes in this population to ultimately help improve survival rates and reduce health inequities in NH/PIs with breast cancer.

Self-Tuning of Signal Detection Level for Energy Detection-Based Carrier Sense in Low-Power Wide-Area Networks.

Carrier sense allows end devices to improve the communication quality through autonomous decentralization by consuming power. In particular, energy detection-based carrier sense can improve communication quality compared with peak detection-based carrier sense. To improve the trade-off between communication quality and energy consumption in low-power wide-area networks (LPWANs), this study proposes a self-tuning method for the signal detection level of an energy detection-based carrier sense, that is, the carrier sense level in sub-GHz band LPWANs. In the proposed method, the carrier sense level of each end device is determined based on the reception success probability of the acknowledgment packet, such that they become low carrier sense levels for an end device with low probability and high carrier sense levels for an end device with high probability. The proposed method enables autonomous decentralized derivation of the carrier sense level using only existing protocols. Numerical examples show that the proposed method can improve the performance of end devices with a high path loss to a gateway.

Phase 2 study of neoadjuvant enzalutamide and paclitaxel for luminal androgen receptor-enriched TNBC: Trial results and insights into "ARness".

Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m2 weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC. Eligibility criteria included a percentage of cells expressing nuclear AR by immunohistochemistry (iAR) of at least 10% and a reduction in sonographic volume of less than 70% after four cycles of doxorubicin and cyclophosphamide. Twenty-four patients were enrolled. Ten achieved a pathologic complete response or residual cancer burden-I. ZT was safe, with no unexpected side effects. An iAR of at least 70% had a positive predictive value of 0.92 and a negative predictive value of 0.97 in predicting LAR-enriched TNBC according to RNA-based assays. Our data support future trials of AR blockade in early-stage LAR-enriched TNBC.

An Environment-Aware Adaptive Data-Gathering Method for Packet-Level Index Modulation in LPWA.

Low-power wide-area (LPWA) is a communication technology for the IoT that allows low power consumption and long-range communication. Additionally, packet-level index modulation (PLIM) can transmit additional information using multiple frequency channels and time slots. However, in a competitive radio access environment, where multiple sensors autonomously determine packet transmission, packet collisions occur when transmitting the same information. The packet collisions cause a reduction in the throughput. A method has been proposed to design a mapping table that shows the correspondence between indexes and information using a packet collision minimization criterion. However, the effectiveness of this method depends on how the probability of the occurrence of the information to be transmitted is modeled. We propose an environment-aware adaptive data-gathering method that identifies the location of factors affecting sensor information and constructs a model for the probability of the occurrence of sensor information. The packet collision rate of the environment-aware adaptive data-gathering method was clarified through computer simulations and actual experiments on a 429 MHz LPWA. We confirm that the proposed scheme improves the packet collision rate by 15% in the computer simulation and 30% in the experimental evaluation, respectively.

Non-invasive blood glucose estimation method based on the phase delay between oxy- and deoxyhemoglobin using visible and near-infrared spectroscopy.

Significance: Many researchers have attempted to estimate blood glucose levels (BGLs) noninvasively using near-infrared (NIR) spectroscopy. However, the optical absorption change induced by blood glucose is weak in the NIR region and often masked by interference from other components such as water and hemoglobin. Aim: Instead of using direct optical absorption by glucose, this study proposes an index calculated from oxy- and deoxyhemoglobin signals that shows a good correlation with BGLs while using conventional visible and NIR spectroscopy. Approach: The metabolic index, which is based on tissue oxygen consumption, was derived through analytical methods and further verified and reproduced in a series of glucose challenge experiments. Blood glucose estimation units were prototyped by utilizing commercially available smart devices. Results: Our experimental results showed that the phase delay between the oxy- and deoxyhemoglobin signals in near-infrared spectroscopy correlates with BGL measured by a conventional continuous glucose monitor. The proposed method was also confirmed to work well with visible spectroscopy systems based on smartphone cameras. The proposed method also demonstrated excellent repeatability in results from a total of 19 oral challenge tests. Conclusions: This study demonstrated the feasibility of non-invasive glucose monitoring using existing photoplethysmography sensors for pulse oximeters and smartwatches. Evaluating the proposed method in diabetic or unhealthy individuals may serve to further increase its practicality.

Dual-inhibition of NAMPT and PAK4 induces anti-tumor effects in 3D-spheroids model of platinum-resistant ovarian cancer.

Ovarian cancer follows a characteristic progression pattern, forming multiple tumor masses enriched with cancer stem cells (CSCs) within the abdomen. Most patients develop resistance to standard platinum-based drugs, necessitating better treatment approaches. Targeting CSCs by inhibiting NAD+ synthesis has been previously explored. Nicotinamide phosphoribosyltransferase (NAMPT), which is the rate limiting enzyme in the salvage pathway for NAD+ synthesis is an attractive drug target in this pathway. KPT-9274 is an innovative drug targeting both NAMPT and p21 activated kinase 4 (PAK4). However, its effectiveness against ovarian cancer has not been validated. Here, we show the efficacy and mechanisms of KPT-9274 in treating 3D-cultured spheroids that are resistant to platinum-based drugs. In these spheroids, KPT-9274 not only inhibited NAD+ production in NAMPT-dependent cell lines, but also suppressed NADPH and ATP production, indicating reduced mitochondrial function. It also downregulated of inflammation and DNA repair-related genes. Moreover, the compound reduced PAK4 activity by altering its mostly cytoplasmic localization, leading to NAD+-dependent decreases in phosphorylation of S6 Ribosomal protein, AKT, and ß-Catenin in the cytoplasm. These findings suggest that KPT-9274 could be a promising treatment for ovarian cancer patients who are resistant to platinum drugs, emphasizing the need for precision medicine to identify the specific NAD+ producing pathway that a tumor relies upon before treatment.

Reassessing Estrogen Receptor Expression Thresholds for Breast Cancer Prognosis in HER2-negative Patients Using Shape Restricted Modeling.

Purpose: To assess the dynamic link between continuous estrogen receptor (ER) expression and long-term clinical outcomes in non-metastatic breast cancer and to identify the ideal cutoff value for ER expression to optimize endocrine therapy use. Methods: The study included 3055 female patients with stage II or III HER2-negative breast cancer. The primary outcomes were time to recurrence or death (TTR) and overall survival (OS). We used a novel shape-restricted Cox model to determine the desirable ER expression cutoff to predict breast cancer prognoses. Our novel model allows ER as a continuous variable, utilizing a flexible monotone-shaped Cox regression to assess its association with survival outcomes holistically. Results: The shape-restricted Cox model identified 10% ER as the preferred cutoff to predict TTR. The finding was confirmed by the log-rank test and standard Cox model that patients with ER ≥ 10% had TTR benefit over ER < 10% (log-rank p < 0.001). No OS or TTR benefit of adjuvant endocrine therapy was observed in patients with 1% ≤ ER < 10% (HR 0.877, 95% CI 0.481-1.600, p = 0.668 for TTR and HR 0.698, 95% CI 0.337-1.446, p = 0.333 for OS). Conclusions: Using the shape-restricted Cox model, this study suggests a potential preferred threshold of 10% for predicting TTR. The findings could assist physicians in effectively weighing the benefits and risks of adjuvant endocrine therapy for patients with ER < 10% disease, particularly in cases involving severe adverse events. Further prospective studies are warranted to validate the recommended cutoff value.

Three Level Recognition Based on the Average of the Phase Differences in Physical Wireless Parameter Conversion Sensor Networks and Its Effect to Localization with RSSI.

In recent years, there have been increased demands for aggregating sensor information from several sensors owing to the spread of the Internet of Things (IoT). However, packet communication, which is a conventional multiple-access technology, is hindered by packet collisions owing to simultaneous access by sensors and waiting time to avoid packet collisions; this increases the aggregation time. The physical wireless parameter conversion sensor network (PhyC-SN) method, which transmits sensor information corresponding to the carrier wave frequency, facilitates the bulk collection of sensor information, thereby reducing the communication time and achieving a high aggregation success rate. However, when more than one sensor transmits the same frequency simultaneously, the estimation accuracy of the number of accessed sensors deteriorates significantly because of multipath fading. Thus, this study focuses on the phase fluctuation of the received signal caused by the frequency offset inherent to the sensor terminals. Consequently, a new feature for detecting collisions is proposed, which is a case in which two or more sensors transmit simultaneously. Furthermore, a method to identify the existence of 0, 1, 2, or more sensors is established. In addition, we demonstrate the effectiveness of PhyC-SNs in estimating the location of radio transmission sources by utilizing three patterns of 0, 1, and 2 or more transmitting sensors.

Estimation Based on Chirp Modulation for Desired and Interference Power and Channel Occupancy Ratio in LoRa.

In terms of low power consumption and long-range communication-low-power wide-area networks (LPWAN) are suitable for wireless sensor networks. Long-range (LoRa) wireless communication is one of the standards of LPWAN. LoRa shares common frequency spectrum bands with both multiple transmitters, which are the sensors in the LoRa system (and those in the other system). Therefore, co-channel interference (CCI) degrades the packet delivery rate. To avoid CCI, the CCI power and the occurrence probability of CCI in the target channel are estimated, then the sensor decides whether to use the channel and where the occurrence probability of CCI is defined as the channel occupancy ratio (COR). If a large signal power is obtained at the receiver, the received signal can be demodulated because of the capture effect. The desired signal power must also be estimated for the capture effect. In this study, we propose an estimation scheme based on chirp modulation of LoRa under spectrum sharing among other systems. The proposed scheme estimates the desired signal power, CCI power, and COR. From the computer simulation results, we clarify the advantages of the proposed scheme in terms of estimation accuracy and packet delivery rate.

Treatment with Granulocyte-colony Stimulating Factor (G-CSF) is not associated with Increased Risk of Brain Metastasis in Patients with De Novo Stage IV Breast Cancer.

Background: Survival outcome after developing brain metastasis is poor and there is an unmet need to identify factors that can promote brain metastasis. Granulocyte-colony stimulating factor (G-CSF) is given to support neutrophil recovery after myelosuppressive chemotherapy to some patients. However, there is emerging evidence that neutrophils can promote metastasis, including through the formation of neutrophil extracellular traps (NETs), scaffolds of chromatin with enzymes expelled from neutrophils to the extracellular space. In animal models, G-CSFs can induce NETs to promote liver and lung metastasis. The primary objective of this study was to test the association between G-CSF use and the later incidence of brain metastasis. Methods: Patients with de novo Stage IV breast cancer, without known brain metastasis at the time of initial diagnosis, were identified from electronic medical records covering the period from 1/1/2013 to 12/31/2020 at Northwell Health. Univariate and multivariate logistic regression models were used to test the association between variables of interest, including G-CSF use, and brain metastasis. Results: A total of 78 patients were included in the final analysis. Among those 78 patients, 24 patients (30.8%) had received G-CSF along with chemotherapy at least once. In logistic regression models, G-CSF use was not a significant factor to predict brain metastasis (OR 1.89 [95%CI 1.89-5.33]; P=0.23). Interestingly, in multivariate logistic models, pulmonary embolism (PE)/deep venous thrombosis (DVT) was a significant predictive factor of brain metastasis (OR 6.74 [95%CI 1.82-25.01]; P=0.004) (38.5% vs 21.5%). Conclusions: The use of G-CSF was not associated with increased risk of brain metastasis in patients with de novo Stage IV breast cancer. Interestingly, PE/DVT, which can be associated with elevated NETs, was associated with brain metastasis. Further studies are warranted to determine whether DVT/PE with or without elevated NETs levels in the blood, is predictive of developing brain metastasis in patients with de novo Stage IV breast cancer.

Aeroacoustic characteristics of owl-inspired blade designs in a mixed flow fan: effects of leading- and trailing-edge serrations.

There is an increasing need in industry for noise reduction in fans. Inspired by owls' silent flight, we propose four owl-inspired blade designs for a mixed-flow fan to examine whether leading-edge (LE) and/or trailing-edge (TE) serrations can resolve the tradeoff between sound suppression and aerodynamic performance. We investigate the blades' aeroacoustic characteristics through various experimental methods and large-eddy simulation (LES)-based numerical analyses. Experimental results suggest that 'slotted', simply-fabricated LE serrations can achieve a lowering of the noise level while sustaining the aerodynamic performance of the fan, whereas TE serrations fail. In addition, the inclination angle can improve LE serration performance in aeroacoustic and aerodynamic performance with a reduction in the specific noise level by around 1.4 dB. LES results and noise spectral analysis indicate that the LE serrations can suppress flow separation, reducing the broadband noise at low-to-middle frequencies (40-4k Hz). This passive-flow-control mechanism, likely due to local higher incidence angles associated with LE serrations, is capable of alleviating the intensive pressure gradient while suppressing wall-pressure fluctuations over the LE region, hence weakening the Kelvin-Helmholtz instability. The tonal noise also shows a marked reduction at the highest peak frequency associated with fan-vane interaction. Moreover, we find that the high-frequency noise by-product radiates mainly from the LE serrations andsurroundings, due to the small eddies broken up when the vortical flows pass through the LE serrations. Our results demonstrate that the biomimetic design of the LE serrations can facilitate the break-up of LE vortices passively and effectively without negatively impacting aerodynamic performance, which can be utilized as an effective device to improve the aeroacoustic performance of fan blades.

A 95-gene signature stratifies recurrence risk of invasive disease in ER-positive, HER2-negative, node-negative breast cancer with intermediate 21-gene signature recurrence scores.

PURPOSE: A subset of patients with intermediate 21-gene signature assay recurrence score may benefit from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk. METHODS: Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11-25 who underwent definitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included. RNA was extracted from archived formalin-fixed, paraffin-embedded samples, and 95-gene signature was calculated. RESULTS: 206 patients had RS of 11-25 (95GC-L, N = 163; 95GC-H, N = 43). In Cox proportional hazards model, 95GC-H was significantly associated with shorter time to recurrence than was 95GC-L (HR 5.94; 95%CI 1.81-19.53; P = 0.005). The correlation between 95-gene signature and 21-gene signature assay scores was not strong (correlation coefficient r = 0.27), which might suggest that 95-gene signature reflects biological characteristics differing from what 21-gene signature shows. CONCLUSIONS: The 95-gene signature stratifies patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS of 11-25 into high and low groups that are associated with recurrence risk of invasive disease. Further retrospective analysis in the prospectively accrued TAILORx population is warranted to confirm that 95-gene signature can identify patients who would benefit from adjuvant chemoendocrine therapy.

Theoretical study on proton diffusivity in Y-doped BaZrO3 with realistic dopant configurations.

We theoretically revisit the proton diffusivity in yttrium-doped barium zirconate (Y-doped BaZrO3) with realistic dopant configurations under processing conditions. In a recent study employing the replica exchange Monte Carlo method, the equilibrium Y configurations at typical sintering temperatures were shown to deviate from the random configuration assumed in earlier theoretical studies. In the present study, we took this observation into account and evaluated the effect of the Y configuration on the proton diffusivity. Using the master equation approach based on local diffusion barriers calculated from first principles, the proton diffusivities under realistic Y configurations were estimated to be higher than those in the random configuration. This is explained by the fact that realistic Y configurations have fewer trap sites with deep potential wells compared to the random configuration due to the isolation trend of Y dopants. In addition, the effects of proton-proton interaction and the abundance of preferential conduction pathways are discussed; it is found that both are relatively minor factors compared to the trap site effect in determining the dependence of the proton diffusivity on the Y configurations.

Energy Constrained Optimization for Spreading Factor Allocation in LoRaWAN.

This paper discusses a spreading factor allocation for Long Range Wide Area Network (LoRaWAN). Because Long Range (LoRa) is based on chirp spread spectrum that each spreading factor is approximately orthogonal to each other, the performance of LoRaWAN can be enhanced by allocating the spreading factor appropriately to end devices (EDs). Several spreading factor allocation techniques have been reported. Techniques shown in existing studies can improve some characteristics (e.g. throughput or packet reception probability (PRP)); however, there are a few studies that have focused on the energy consumption of the EDs. The LoRa communication offers a low power communication and this enables the improvement of the performance in exchange for the energy consumption. This paper presents a performance improvement technique via spreading factor allocations for LoRaWAN. We define the optimization problem for the spreading factor allocation to maximize the PRP under a constraint for the average energy consumption of all the EDs. It enables for the performance improvement under the constraint of the average energy consumption of all the EDs by solving the problem. This study further develops a method to solve the defined problem based on a distributed genetic algorithm, which is metaheuristics method. Although the techniques shown in the existing studies give the average energy consumption as a result of the performance improvement by the spreading factor allocation, the presented technique can enhance the LoRaWAN performance by allocating the spreading factor to EDs under the constraint for the average energy consumption of all the EDs. Numerical examples validate the effectiveness of the presented technique. The PRP performance of the presented technique is superior to that of the techniques shown in the existing studies despite that the average energy consumption of all the EDs of the presented technique is less than that of the techniques shown in the existing studies.

The efficacy of first-line chemotherapy in endocrine-resistant hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer.

PURPOSE: Combinations of endocrine therapy (ET) and targeted therapy (CDK4/6 or mTOR inhibitors) are standard of care for HR+/HER2- metastatic breast cancer (MBC). When ET is not effective, chemotherapy is commonly used. However, clinical outcomes of chemotherapy in the endocrine-resistant setting are limited. The purpose of this study was to identify predictive factors and the compare efficacies of chemotherapy agents in endocrine-resistant MBC. METHODS: We conducted a retrospective study of patients with HR+/HER2- MBC who received chemotherapy after progression on ET with or without targeted therapy at MD Anderson Cancer Center from 1999 to 2017. We collected baseline clinicopathological and all treatment data. Primary endpoint was time to treatment failure (TTF) of first-line chemotherapy for MBC. RESULTS: For the 1258 patients analyzed, mean age was 55.3 years (range 21-91). Previous treatment with targeted therapy was recorded for 390 patients (31%): 264 with CDK4/6 inhibitor, 205 with mTOR inhibitor, and 79 treated with both. The most frequent chemotherapy agents were capecitabine (48.9%) and taxanes (28.6%). After adjustment for all factors in a multivariate model, previous treatment with a CDK4/6 inhibitor had the strongest negative effect on TTF regardless of ET duration (hazard ratio [HR] 1.84; 95%CI 1.49-2.27; p < 0.001). Conversely, capecitabine had significantly longer median TTF than taxanes regardless of whether patients had prior exposure to taxanes in primary setting (6.1 vs 4.9 months; HR 0.64; 95%CI 0.55-0.75; p < 0.001). CONCLUSIONS: Previous exposure to CDK4/6 inhibitor had a negative predictive effect for the efficacy of chemotherapy. Capecitabine had the best efficacy against endocrine-resistant breast cancer.

EpCAM-independent isolation of circulating tumor cells with epithelial-to-mesenchymal transition and cancer stem cell phenotypes using ApoStream® in patients with breast cancer treated with primary systemic therapy.

BACKGROUND: Tumor cells with a mesenchymal phenotype and/or cancer stem-like cells (CSCs) are known to contribute to metastasis and drug resistance. Circulating tumor cells (CTCs) undergoing epithelial-mesenchymal transition (EMT) and CTCs reflecting a dedifferentiated CSC phenotype may not be detected using only an anti-EpCAM antibody to capture them. We used an antibody-independent CTC enrichment platform, ApoStream®, which does not rely on any antibody, including anti-EpCAM, to capture EMT- and CSC-CTCs in breast cancer patients who received neoadjuvant chemotherapy and correlated them to pathological complete response (pCR). METHODS: Blood samples from newly diagnosed breast cancer patients were prospectively collected before neoadjuvant chemotherapy (T0), after chemotherapy but before surgery (T1), and after surgery (T2) and processed using ApoStream. CTCs detected were stained with additional markers to define 3 CTC subsets with the following phenotypes: epithelial CTCs (CK+, EpCAM+ or E-cadherin+), EMT-CTCs (ß-catenin+ or vimentin+), and CSC-CTCs (CD44+ and CD24low). RESULTS: We enrolled 55 patients, 47 of which had data for analysis. EMT-CTCs were detected in 57%, 62%, and 72% and CSC-CTCs in 9%, 22%, and 19% at the T0, T1, and T2 time points, respectively. Counts of epithelial (P = 0.225) and EMT (P = 0.522) phenotypes of CTCs at T0 did not significantly predict pCR. Moreover, no correlation between CTC count change and pCR was demonstrated. CONCLUSIONS: ApoStream was successful in detecting EMT-CTCs among patients after neoadjuvant chemotherapy. However, EMT-/CSC-CTC counts did not correlate with pCR. Due to the small sample size and heterogeneity of this patient population, further study in a larger cohort of molecularly homogeneous patients is warranted.

Prognostic Value of HER2 to CEP17 Ratio on Fluorescence In Situ Hybridization Ratio in Patients with Nonmetastatic HER2-Positive Inflammatory and Noninflammatory Breast Cancer Treated with Neoadjuvant Chemotherapy with or without Trastuzumab.

BACKGROUND: We previously reported that in patients with HER2-positive (HER2+) locally advanced breast cancer treated with neoadjuvant trastuzumab-containing regimens, high HER2 to centromere enumerator probe 17 ratio on fluorescence in situ hybridization (HER2 FISH ratio) was an independent predictor of high pathologic complete response (pCR) rate, which translated into improved recurrence-free survival (RFS). We sought to determine whether high HER2 FISH ratio is a predictor of pCR and prognosis in patients with HER2+ nonmetastatic inflammatory breast cancer (IBC) and non-IBC treated with neoadjuvant chemotherapy with or without trastuzumab. MATERIALS AND METHODS: This study included all patients with histologically proven stage III, HER2+ primary IBC, and non-IBC treated with neoadjuvant chemotherapy with or without trastuzumab and definitive surgery during 1999-2012. Univariate and multivariate logistic regression models were applied to assess the effect of covariates on pCR. Kaplan-Meier estimates with log-rank test were employed for survival analysis. Univariate and multivariate Cox proportional hazards models were used to assess the effect of covariates on RFS and overall survival (OS). RESULTS: The study included 555 patients with stage III, HER+ breast cancer, 181 patients with IBC, and 374 with non-IBC. In the IBC cohort, HER2 FISH ratio was not significantly associated with pCR, RFS, or OS. In the non-IBC cohort, higher HER2 FISH ratio was significantly associated with higher pCR rate and longer OS. CONCLUSION: HER2 FISH ratio showed prognostic value among patients with HER2+ non-IBC but not HER2+ IBC treated with neoadjuvant chemotherapy. This disparity may be due to the underlying aggressive nature of IBC. IMPLICATIONS FOR PRACTICE: The findings of this study indicate that the HER2 to fluorescence in situ hybridization ratio as a continuous variable has promise as a predictor of pathologic complete response to neoadjuvant chemotherapy in patients with HER2-positive (HER2+) noninflammatory breast cancer (non-IBC) regardless of the results on HER2 immunohistochemical testing. In the future, some patients with HER2+ non-IBC and a high HER2 FISH ratio might even be offered personalized treatment options, such as nonsurgical treatment.

Phase II study of Radium-223 dichloride combined with hormonal therapy for hormone receptor-positive, bone-dominant metastatic breast cancer.

BACKGROUND: Radium-223 dichloride (Ra-223) is a targeted alpha therapy that induces localized cytotoxicity in bone metastases. We evaluated the efficacy and safety of Ra-223 plus hormonal therapy in hormone receptor-positive (HR+), bone-dominant metastatic breast cancer. METHODS: In this single-center phase II study, 36 patients received Ra-223 (55 kBq/kg intravenously every 4 weeks) up to 6 cycles with endocrine therapy. The primary objective was to determine the clinical disease control rate at 9 months. Secondary objectives were to determine (a) tumor response rate at 6 months, (b) progression-free survival (PFS) durations, and (c) safety. RESULTS: The median number of prior systemic treatments for metastatic disease was 1 (range, 0-4). The disease control rate at 9 months was 49%. The tumor response rate at 6 months was 54% (complete response, 21%; partial, 32%). The median PFS was 7.4 months (95% CI, 4.8-not reached [NR]). The median bone-PFS was 16 months (95% CI, 7.3-NR). There were no grade 3/4 adverse events. CONCLUSIONS: Ra-223 with hormonal therapy showed possible efficacy in HR+ bone-dominant breast cancer metastasis, and adverse events were tolerable. We plan to further investigate the clinical application of Ra-223 in these patients. (NCT02366130).

Prediction of Bone Metastasis in Inflammatory Breast Cancer Using a Markov Chain Model.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare yet aggressive variant of breast cancer with a high recurrence rate. We hypothesized that patterns of metastasis differ between IBC and non-IBC. We focused on the patterns of bone metastasis throughout disease progression to determine statistical differences that can lead to clinically relevant outcomes. Our primary outcome of this study is to quantify and describe this difference with a view to applying the findings to clinically relevant outcomes for patients. SUBJECTS, MATERIALS, AND METHODS: We retrospectively collected data of patients with nonmetastatic IBC (n = 299) and non-IBC (n = 3,436). Probabilities of future site-specific metastases were calculated. Spread patterns were visualized to quantify the most probable metastatic pathways of progression and to categorize spread pattern based on their propensity to subsequent dissemination of cancer. RESULTS: In patients with IBC, the probabilities of developing bone metastasis after chest wall, lung, or liver metastasis as the first site of progression were high: 28%, 21%, and 21%, respectively. For patients with non-IBC, the probability of developing bone metastasis was fairly consistent regardless of initial metastasis site. CONCLUSION: Metastatic patterns of spread differ between patients with IBC and non-IBC. Selection of patients with IBC with known liver, chest wall, and/or lung metastasis would create a population in whom to investigate effective methods for preventing future bone metastasis. IMPLICATIONS FOR PRACTICE: This study demonstrated that the patterns of metastasis leading to and following bone metastasis differ significantly between patients with inflammatory breast cancer (IBC) and those with non-IBC. Patients with IBC had a progression pattern that tended toward the development of bone metastasis if they had previously developed metastases in the liver, chest wall, and lung, rather than in other sites. Selection of patients with IBC with known liver, chest wall, and/or lung metastasis would create a population in whom to investigate effective methods for preventing future bone metastasis.

ID Insertion and Data Tracking with Frequency Offset for Physical Wireless Parameter Conversion Sensor Networks.

As the applications of the internet of things are becoming widely diversified, wireless sensor networks require real-time data reception, accommodation of access from several sensors, and low power consumption. In physical wireless parameter conversion sensor networks (PhyC-SN), all the sensors use frequency shift keying as the modulation scheme and then access the channel to the fusion center, simultaneously. As a result, the fusion center can recognize the statistical tendency of all the sensing results at a time from the frequency spectrum of the received signal. However, the information source, i.e., the sensor, cannot be specified from the received signal because no ID-indicating sensor is inserted to the signal. The data-tracking technique for tracing the time continuity of the sensing results is available for decomposing the sequence of the sensing results per sensor but the error tracking, which is a wrong recognition between the sensing results and the sensor, occurs owing to the similarity of the sensing results. This paper proposes the sensing result separation technique using a fractional carrier frequency offset (CFO) for PhyC-SN. In the proposed scheme, the particular fractional CFO is assigned to each user and it is useful for the ID specifying sensor. The fractional CFO causes inter-carrier interference (ICI). The ICI cancellation of the narrowband wireless communications is proposed. The two types of data-tracking techniques are proposed and are selectively used by the fusion center. Since the proposed data-tracking technique is multi-dimensional, high accuracy of data tracking is achieved even under the similar tendency of the sensing results. Based on computer simulation, we elucidate the advantage of the proposed sensing results separation.