Multiphonon-coupling yellow laser in Yb:La2CaB10O19 crystal.

Yellow lasers at 590 nm have many extensive applications in our daily life, but extremely difficult to attain by traditional solid-state laser technology, owing to the absence of highly-efficient transition channels at this spectral range. In this work, we proposed a cooperative lasing mechanism to obtain the yellow light emission, with multiphonon-assisted electronic transitions and phase-matched frequency-doubling. Based on the predictable configurational coordinate model, we can calculate the multiphonon-assisted emission step-by-step. Using Yb3+-doped La2CaB10O19 crystal as an example, it is capable of producing yellow laser at 581-590 nm, with a maximum output power of 4.83 W and a high slope efficiency of 31.6%. To the best of our knowledge, it represents the highest power of solid-state yellow laser realized in one single crystal pumped by a laser diode. This power scaling can be assigned to the amplified phonon-assisted emission beyond the fluorescence spectrum, and optimized crystal angle for phase-matching condition. Such a compact, low-cost, and high-power laser device, provides an alternative candidate for the spectral "yellow-gap" where no practical solid-state laser exists at present.

Risk of interstitial lung disease with the use of programmed cell death 1 (PD-1) inhibitor compared with programmed cell death ligand 1 (PD-L1) inhibitor in patients with breast cancer: A systematic review and meta-analysis.

Background: Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have become integral elements within the current landscape of breast cancer treatment modalities; however, they are associated with interstitial lung disease (ILD), which is rare but potentially fatal. Notably, only a few studies have compared the difference in ILD incidence between PD-1 and PD-L1 inhibitors. Therefore, this study aimed to assess the discrepancies regarding ILD risk between the two immune checkpoint inhibitors. We also reported three cases of ILD after PD-1 inhibitor treatment. Methods: We comprehensively searched PubMed, EMBASE, and the Cochrane Library to identify clinical trials that investigated PD-1/PD-L1 inhibitor treatment for patients with breast cancer. Pooled overall estimates of incidence and risk ratio (RR) were calculated with a 95% confidence interval (CI), and a mirror group analysis was performed using eligible studies. Results: This meta-analysis included 29 studies with 4639 patients who received PD-1/PD-L1 inhibitor treatment. A higher ILD incidence was observed among 2508 patients treated with PD-1 inhibitors than among 2131 patients treated with PD-L1 inhibitors (0.05 vs. 0.02). The mirror group analysis further revealed a higher ILD event risk in patients treated with PD-1 inhibitors than in those treated with PD-L1 inhibitors (RR = 2.34, 95% CI, 1.13-4.82, P = 0.02). Conclusion: Our findings suggest a greater risk of ILD with PD-1 inhibitors than with PD-L1 inhibitors. These findings are instrumental for clinicians in treatment deliberations, and the adoption of more structured diagnostic approaches and management protocols is necessary to mitigate the risk of ILD.

Application of TiLOOP bra in implant-based breast reconstruction is associated with decreased complication risk compared with other meshes: A systematic review and meta-analysis.

BACKGROUND: TiLOOP bra has been used for over 15 years, however, evidence regarding its safety in implant-based breast reconstruction (IBBR) for patients with breast cancer after mastectomy is still limited. We performed this meta-analysis to evaluate its risks and benefits in IBBR comparing with other meshes. METHODS: Electronic databases were searched to identify relevant studies comparing postoperative complications between TiLOOP bra and other reconstruction techniques in IBBR with or without meshes. We also compared patient satisfaction in physical well-being between two groups. Risk ratios (RRs) and mean differences with 95% confidence interval (CI) were calculated. RESULTS: Seven studies representing 1203 cases were analyzed. Compared with other meshes, the use of TiLOOP bra significantly reduced the risk of infection (RR = 0.53, 95% CI, 0.32-0.86), seroma (RR = 0.21, 95% CI, 0.07-0.61), red breast syndrome (RR = 0.10, 95% CI, 0.02-0.45), and capsular contracture (RR = 0.20, 95% CI, 0.05-0.75). Patient satisfaction in physical well-being was comparable between two groups. CONCLUSIONS: TiLOOP bra in IBBR has a favored safety profile over other meshes, which significantly reduced postoperative complication risk and did not affect patient satisfaction. Although prospective well-designed controlled studies are still warranted, TiLOOP bra is safe and reliable at present.

LEACS: a learnable and efficient active contour model with space-frequency pooling for medical image segmentation.

Diseases can be diagnosed and monitored by extracting regions of interest (ROIs) from medical images. However, accurate and efficient delineation and segmentation of ROIs in medical images remain challenging due to unrefined boundaries, inhomogeneous intensity and limited image acquisition. To overcome these problems, we propose an end-to-end learnable and efficient active contour segmentation model, which integrates a global convex segmentation (GCS) module into a light-weighted encoder-decoder convolutional segmentation network with a multiscale attention module (ED-MSA). The GCS automatically obtains the initialization and corresponding parameters of the curve deformation according to the prediction map generated by the ED-MSA, while provides the refined object boundary prediction for ED-MSA optimization. To provide precise and reliable initial contour for the GCS, we design the space-frequency pooling operation layers in the encoder stage of ED-MSA, which can effectively reduce the number of iterations of the GCS. Beside, we construct ED-MSA using the depth-wise separable convolutional residual module to mitigate the overfitting of the model. The effectiveness of our method is validated on four challenging medical image datasets. Code is here:https://github.com/Yang-fashion/ED-MSA_GCS.

Improvement on Magnetocaloric Effect through Structural Evolution in Gadolinium Borate Halides Ba2Gd(BO3)2X (X = F, Cl).

A new Gd3+-containing borate Ba2Gd(BO3)2F has been successfully grown via the high-temperature solution method using BaF2-NaF-B2O3 flux. Ba2Gd(BO3)2F crystallizing in the orthorhombic space group Pnma is with lattice parameters a = 7.571(4) Å, b = 10.424(5) Å, c = 8.581(4) Å, α = ß = γ = 90°, and Z = 2. Its three-dimensional framework was constructed from interesting pinwheel-like [Gd(BO3)F]∞ layers bridged by sharing [BO3]3-, which is different from the [Gd(BO3)]∞ layer in the model structure Ba2Gd(BO3)2Cl. The magnetic measurements indicated that Ba2Gd(BO3)2F has a larger magnetocaloric effect with -ΔSm,max = 27.82 J·kg-1·K-1at 2 K and 9 T than that of Ba2Gd(BO3)2Cl under the same conditions. Moreover, thermal stability, infrared spectrum (IR), and ultraviolet-visible-near-infrared diffuse reflectance spectrum were carried out to characterize the title compounds. The first-principles computations also looked into the electronic band structures, densities of states, and refractive indices.

Phonon engineering in Yb:La2CaB10O19 crystal for extended lasing beyond the fluorescence spectrum.

Since the first invention of the laser in 1960, direct lasing outside the fluorescence spectrum is deemed impossible owing to the "zero-gain" cross-section. However, when electron-phonon coupling meets laser oscillation, an energy modulation by the quantized phonon can tailor the electronic transitions, thus directly creating some unprecedented lasers with extended wavelengths by phonon engineering. Here, we demonstrate a broadband lasing (1000-1280 nm) in a Yb-doped La2CaB10O19 (Yb:LCB) crystal, far beyond its spontaneous fluorescence spectrum. Numerical calculations and in situ Raman verify that such a substantial laser emission is devoted to the multiphonon coupling to lattice vibrations of a dangling "quasi-free-oxygen" site, with the increasing phonon numbers step-by-step (n = 1-6). This new structural motif provides more alternative candidates with strong-coupling laser materials. Moreover, the quantitative relations between phonon density distribution and laser wavelength extension are discussed. These results give rise to the search for on-demand lasers in the darkness and pave a reliable guideline to study those intriguing electron-phonon-photon coupled systems for integrated photonic applications.

Concomitant PIK3CA and TP53 Mutations in Breast Cancer: An Analysis of Clinicopathologic and Mutational Features, Neoadjuvant Therapeutic Response, and Prognosis.

PURPOSE: PIK3CA and TP53 are the most prevalently mutated genes in breast cancer (BC). Previous studies have indicated an association between concomitant PIK3CA/TP53 mutations and shorter disease-free survival. As its clinical utility remains largely unknown, we aimed to analyze the prognostic and predictive roles of this co-mutation. METHODS: We retrospectively analyzed patients who were diagnosed with BC at Guangdong Provincial People's Hospital (GDPH) who underwent next-generation sequencing. The correlation of concomitant PIK3CA/TP53 mutations with clinicopathological and mutational characteristics, and neoadjuvant systemic therapy (NST) responses was analyzed. The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was used to verify associations between concurrent mutations and survival outcomes. RESULTS: In the GDPH cohort, concomitant PIK3CA/TP53 mutations were associated with more aggressive phenotypes, including human epidermal growth factor receptor 2 positive status, hormone receptor negative status, high Ki-67 expression, high histological grade, advanced TNM stage, and additional genetic alterations. Co-mutations also portended a worse response to NST, especially taxane-containing regimens, when compared with the TP53 mutant alone (odds ratio, 3.767; 95% confidence interval, 1.205-13.087; p = 0.028). A significant association was observed between concomitant PIK3CA/TP53 mutations and poor survival outcomes in the METABRIC cohort. CONCLUSION: Concomitant PIK3CA/TP53 mutations not only suggested unfavorable features and poor prognosis in BC but also conferred less benefit to NST than TP53 mutations alone.

Sr14.06Gd14.63(BO3)24: A Gadolinium-Rich Borate with Magnetic Refrigeration Performance.

A single crystal of Sr14.06Gd14.63(BO3)24 has been successfully grown through a high-temperature solution technique with K2O-KF-B2O3 as the flux. It crystallizes in the Pnma space group with parameters a = 22.3153(5) Å, b = 15.9087(4) Å, c = 8.7507(2) Å, and Z = 2. Sr14.06Gd14.63(BO3)24 has a three-dimensional (3D) framework built from [GdO] chains, in which the isolate [BO3]3- groups and Sr2+ ions fill in the space of the 3D framework. The magnetic measurements revealed that the title compound exhibits a large magnetocaloric effect with the magnetic entropy change of -ΔSm = 42.2 J kg-1 K-1 at 2 K for 7 T, which is higher than that of the commercial material, Gd3Ga5O12 (GGG), with -ΔSm of 38.4 J kg-1 K-1 under the same conditions. Moreover, the infrared spectrum (IR), UV-vis-NIR diffuse reflectance spectrum, and thermal stability were investigated.

5.32 W ultraviolet laser generation at 266†nm using sum-frequency method with CsB3O5 crystal.

Ultraviolet (UV) beam generation at 266 nm using the sum-frequency (SFG) method with CsB3O5 (CBO) crystals was first suggested in 1997 [Opt. Lett.22, 1840 (1997).10.1364/OL.22.001840]; however, there has been no further research in the past 25 years. Herein, by sum-frequency mixing in CBO crystals, we obtained a high conversion efficiency picosecond (ps) and a high-power nanosecond (ns) 266 nm UV beam output. First, a ps laser device with simultaneously radiated wavelengths of 1064 and 355 nm and repetition frequency of 10 Hz was used as the fundamental laser source, and the conversion efficiency from 1064 + 355 nm to 266 nm reached 20.35%. We then used a 1064 nm ns laser with a high output power and repetition frequency of 10 kHz as the pump source. We accurately modified the optimal phase matching direction of the CBO crystal, and the achieved output power at 266 nm reached 5.32 W.

Genomic alteration profile and PD-L1 expression among different breast cancer subtypes in Chinese population and their correlations.

BACKGROUD: There were limitations existing in programmed cell-death ligand 1 (PD-L1) as predictive biomarkers for breast cancer (BC), hence exploring the correlation between PD-L1 levels and other biomarkers in BC may become a very useful therapeutic clinical tool. METHODS: A total of 301 Chinese patients with different BC subtypes including 47 HR+/HER2+, 185 HR+/HER2-, 38 HR-/HER2+, and 31 triple-negative breast cancer (TNBC) were enrolled in our study. Next-generation sequencing based Yuansu450 gene panel was used for genomic alteration identification and PD-L1 expression was tested using immunohistochemistry. RESULTS: The most prevalent BC-related mutations were TP53 mutations, followed by mutations in PIK3CA, ERBB2, CDK12, and GATA3 in our Chinese cohort. We found that mutations DDR2 and MYCL were only mutated in HR-/HER2+ subtype, whereas H3-3A and NRAS mutations were only occurred in HR-/HER2- subtype. The percentage of patients with PD-L1-positive expression was higher in patients with HR-/HER2- mainly due to the percentage of PD-L1-high level. Mutational frequencies of TP53, MYC, FAT4, PBRM1, PREX2 were observed to have significant differences among patients with different BC subtypes based on PD-L1 levels. Moreover, a positive correlation was observed between TMB and PD-L1 level in HR+/HER2- subtype, and showed that the proportion of patients with high PD-L1 expression was higher than that of patients with low PD-L1 expression in the HR+/HER2- and HR+/HER2+ cohorts with high Ki67 expression. CONCLUSIONS: The genomic alterations based on PD-L1 and other biomarkers of different cohorts may provide more possibilities for the treatment of BC with different subtypes.

Preparation and Application of a Magnetic Oxidized Micro/Mesoporous Carbon with Efficient Adsorption for Cu(II) and Pb(II).

Water pollution is a worldwide problem that requires urgent attention and prevention and exceeding use of heavy-metal ions is one of the most harmful factors, which poses a serious threat to human health and the ecological environment. In this work, a magnetic oxidized micro/mesoporous carbon (MOMMC) was prepared for the easy separation of Cu(II) and Pb(II) from water. The dual-template method was used to prepare micro/mesoporous carbon using sucrose as the carbon source, silica nanoparticles formed by tetraethyl orthosilicate as the microporous templates, and triblock copolymer F127 as the mesoporous template. MOMMC was obtained by oxidation using potassium persulfate and then magnetized through in situ synthesis of Fe3O4 nanoparticles. FTIR, TG-DSC, XRD, TEM, SEM, nitrogen adsorption-desorption isotherms, zeta potential, and VSM were used to confirm the synthetic process, structure, and basic properties of MOMMC. The high-saturation magnetization (59.6 emu·g-1) of MOMMC indicated its easy and fast separation from water by an external magnetic field. Kinetics studies showed that the adsorption of Cu(II) and Pb(II) on MOMMC fit the pseudo-second-order model well. Isotherm studies showed that the adsorption behavior of Cu(II) was better described by the Langmuir model, and the adsorption behavior of Pb(II) was better described by both Langmuir and Redlich-Peterson models. MOMMC obtained efficient adsorption for Cu(II) and Pb(II) with the large adsorption capacity of 877.19 and 943.40 mg·g-1 according to the Langmuir adsorption isotherm equation, and a better selectivity for Pb(II) was observed in competitive adsorption. MOMMC still possessed a large adsorption capacity for Cu(II) and Pb(II) after three adsorption-desorption cycles. These findings show that MOMMC represents an excellent adsorption material for the efficient removal of heavy-metal ions.

Distinct clinicopathological characteristics, genomic alteration and prognosis in breast cancer with concurrent TP53 mutation and MYC amplification.

BACKGROUND: Both TP53 mutation and MYC amplification indicate poor outcomes in breast cancer (BC), but the clinical values of concurrent TP53 and MYC alterations have not been well-characterized. METHODS: A total of 494 BC patients diagnosed at Guangdong Provincial People's Hospital (GDPH) were retrospectively analyzed. Genomic alterations were determined using next-generation sequencing. Survival analysis was applied to assess the effects of genetic alterations on relapse-free survival. The prognosis was verified based on 1405 patients from METABRIC cohort. Additionally, we used logistic regression to identify the factors associated with pathological complete response (pCR) after neoadjuvant chemotherapy. RESULTS: In GDPH cohort, patients with TP53/MYC co-alteration exhibited higher grade and stage, more positive HER2 status and higher Ki67 levels, but less luminal A subtypes. They also had more mutations in genes involved in ERBB and TGF-ß signaling pathways, as well as exclusive FANCG/CDKN2B/QKI copy number amplifications and SUFU/HIST3H3/ERCC4/JUN/BCR mutations. Concurrent TP53 and MYC alterations independently increased hazards of relapse (HR, 5.425; 95% CI: 2.019-14.579; p < 0.001). They maintained independent significance for relapse-free (HR, 1.310; 95% CI: 1.012-1.697; p = 0.041) and overall survival (HR, 1.373; 95% CI: 1.093-1.725; p = 0.006) in METABRIC cohort. Among the 81 patients receiving chemotherapy, TP53 mutation (OR, 5.750; 95% CI: 1.553-25.776; p = 0.013) and earlier stage (OR, 0.275; 95% CI 0.088-0.788; p = 0.020) were associated with pCR, while the co-alteration did not serve as an independent predictor (p = 0.199). CONCLUSIONS: TP53/MYC co-alteration was associated with distinct clinicopathological and genomic features. They also conferred unfavorable prognosis in BC patients, and did not improve pCR after neoadjuvant chemotherapy.

Expression and prognosis analysis of mitochondrial ribosomal protein family in breast cancer.

Breast cancer (BC) is characterized by high morbidity. Mitochondrial ribosomal protein (MRP) family participates in mitochondrial energy metabolism, underlying BC progression. This study aims to analyze the expression and prognosis effect of the MRP genes in BC patients. GEPIA2, UALCAN, cBioPortal, and MethSurv were used to demonstrate the differential expression, genomic alteration profiles, and DNA methylation of the MRP gene family in BC. Functional enrichment analysis and protein-protein interaction network construction were performed to understand the biological function. Based on 1056 TCGA samples with the transcriptional level of MRPs, Kaplan-Meier curves, Cox, and LASSO regression were applied to explore their prognostic effects. 12 MRPs were upregulated in BC, which were associated with gene amplification and DNA methylation. MRP genetic alteration occurred in 42% of BC patients, and amplification was the most frequent variation. Functioning in its entirety, the MRP family was involved in mitochondrial translational termination, elongation, translation, and poly(A) RNA binding. High expression of MRPL1, MRPL13, MRPS6, MRPS18C, and MRPS35, as well as low levels of MRPL16, and MRPL40 significantly indicated poor prognosis in BC patients. Thus, a novel MRP-based prognostic nomogram was established and verified with favorable discrimination and calibration. We not only provided a thorough expression and prognosis analysis of the MRP family in BC patients but also constructed an MRP-based prognostic nomogram. It was suggested that MRPs acted as biomarkers in individualized risk prediction and may serve as potential therapeutic targets in BC patients.

Using an Improved Residual Network to Identify PIK3CA Mutation Status in Breast Cancer on Ultrasound Image.

Background: The detection of phosphatidylinositol-3 kinase catalytic alpha (PIK3CA) gene mutations in breast cancer is a key step to design personalizing an optimal treatment strategy. Traditional genetic testing methods are invasive and time-consuming. It is urgent to find a non-invasive method to estimate the PIK3CA mutation status. Ultrasound (US), one of the most common methods for breast cancer screening, has the advantages of being non-invasive, fast imaging, and inexpensive. In this study, we propose to develop a deep convolutional neural network (DCNN) to identify PIK3CA mutations in breast cancer based on US images. Materials and Methods: We retrospectively collected 312 patients with pathologically confirmed breast cancer who underwent genetic testing. All US images (n=800) of breast cancer patients were collected and divided into the training set (n=600) and test set (n=200). A DCNN-Improved Residual Network (ImResNet) was designed to identify the PIK3CA mutations. We also compared the ImResNet model with the original ResNet50 model, classical machine learning models, and other deep learning models. Results: The proposed ImResNet model has the ability to identify PIK3CA mutations in breast cancer based on US images. Notably, our ImResNet model outperforms the original ResNet50, DenseNet201, Xception, MobileNetv2, and two machine learning models (SVM and KNN), with an average area under the curve (AUC) of 0.775. Moreover, the overall accuracy, average precision, recall rate, and F1-score of the ImResNet model achieved 74.50%, 74.17%, 73.35%, and 73.76%, respectively. All of these measures were significantly higher than other models. Conclusion: The ImResNet model gives an encouraging performance in predicting PIK3CA mutations based on breast US images, providing a new method for noninvasive gene prediction. In addition, this model could provide the basis for clinical adjustments and precision treatment.

Enhanced Electron-Phonon Coupling Effect in Rare-Earth Borate Crystals Containing a "Quasi-Free-Oxygen" Motif.

Revealing the interaction between electrons and phonons, e.g., electron-phonon coupling or decoupling, is a great challenge for physics and functional material communities. For rare-earth single crystals, the electron-phonon coupling and fluorescence behaviors strongly depend on the crystal structure and constituent motifs. Here, we proposed a universal "quasi-free O" as an effective structural motif to enhance phonon-assisted electronic transitions and photoluminescence. Using Gd3+ ion as a probe, we studied Gd:La2CaB10O19 (Gd:LCB) and GdMgB5O10 (GdMB) crystals composed of double B-O layers and dangling "quasi-free O", respectively, which enable strengthened phonon-involved luminescence. Especially, a GdMB crystal features an infinite [O-Gd-O-Gd-O] chain (O represents quasi-free oxygen), thus greatly promoting the energy transfer and electron-phonon coupling effect. As a result, its Huang-Rhys S factor is two times larger than that of a Gd:LCB crystal under room temperature. These results put forward "quasi-free O" to improve the electron-phonon coupling intensity and allow LCB and GdMB crystals to serve as potential hosts for phonon-terminated vibronic lasers.

Characteristics of MYC Amplification and Their Association with Clinicopathological and Molecular Factors in Patients with Breast Cancer.

MYC amplification is detected in ∼15% of breast tumors and is associated with poor prognosis by mediating acquired resistance to anticancer therapies. This study aimed to determine the prevalence of MYC amplifications in Chinese women with breast cancer (BRCA) and investigate the correlation between MYC amplification and clinicopathological and molecular characteristics and its clinical implications. We analyzed MYC alterations in tissue specimens from 410 women diagnosed with BRCA in our hospital from June 1, 2017 to September 27, 2018. We compared our results with publicly available data from The Cancer Genome Atlas (TCGA) BRCA cohort (n = 1079). MYC amplification was identified in 12.4% (51/410) of our cohort, with mean copy number (CN) of 4.42 (range: 2.84-11.27). In TCGA cohort, MYC amplification was identified in 21.2% (229/1079) and was associated with age, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 (HER2) status, and molecular subtype, whereas in our cohort, MYC amplification was associated with smaller tumor size (T1-2, p = 0.023) and higher Ki-67 levels (≥20%; p = 0.031). Analysis of molecular profiles revealed that MYC-amplified breast tumors had significantly more concurrent CN variations compared with MYC nonamplified BRCA in both Guangdong Provincial People's Hospital (GDPH) and TCGA cohorts (p < 0.001). Pathway mapping analysis demonstrated that MYC-amplified tumors had more mutations involved in 15 different but interrelated pathways critical in DNA repair, cell cycle, and cell proliferation. Patients in TCGA cohort with MYC-amplified hormone receptor (HR)-positive/HER2-positive BRCA (p = 0.038) and MYC nonamplified triple-negative BRCA (p = 0.027) had significantly shorter overall survival. In conclusion, this study contributes to a better understanding that MYC-amplified breast tumors had distinct clinicopathological and molecular features compared with MYC nonamplified breast tumors. Further research with a larger sample size is necessary to further elucidate the clinical and survival implications of MYC amplifications.

Distinct clinical and somatic mutational features of breast tumors with high-, low-, or non-expressing human epidermal growth factor receptor 2 status.

BACKGROUND: HER2-low breast cancers were reported to have distinct clinicopathological characteristics from HER2-zero; however, the difference in their genetic features remains unclear. This study investigated the clinical and molecular features of breast tumors according to HER2 status. METHODS: We analyzed the clinicopathological and genomic data of 523 Chinese women with breast cancer. Genomic data was generated by targeted next-generation sequencing (NGS) of breast tumor samples using a commercial 520 gene panel. The cohort was stratified according to HER2 status as HER2-zero (n = 90), HER2-low (n = 231), and HER2-positive (n = 202) according to their immunohistochemistry and fluorescence in situ hybridization results. RESULTS: HER2-low breast tumors were enriched with hormone receptor-positive tumors, and who had lower Ki67 expression levels. Genes were differentially mutated across HER2 subgroups. HER2-low tumors had significantly more mutations involved in PI3K-Akt signaling than HER2-positive (p < 0.001) and HER2-zero breast tumors (p < 0.01). HER2-zero tumors had more mutations in checkpoint factors (p < 0.01), Fanconi anemia (p < 0.05), and p53 signaling and cell cycle pathway (p < 0.05) compared to HER2-low breast tumors. Compared with HER2-zero tumors, HER2-low tumors had significantly lower pathological complete response rates after neoadjuvant therapy (15.9% vs. 37.5%, p = 0.042) and proportion of relapsed/progressed patients across follow-up time points (p = 0.031), but had comparable disease-free survival (p = 0.271). CONCLUSION: Our results demonstrate the distinct clinical and molecular features and clinical outcomes of HER2-low breast tumors.

Clinicopathologic and Genomic Features in Triple-Negative Breast Cancer Between Special and No-Special Morphologic Pattern.

Background: Triple-negative breast cancer (TNBC) is refractory and heterogeneous, comprising various entities with divergent phenotype, biology, and clinical presentation. As an aggressive subtype, Chinese TNBC patients with special morphologic patterns (STs) were restricted to its incidence of 10-15% in total TNBC population. Methods: We recruited 89 patients with TNBC at Guangdong Provincial People's Hospital (GDPH) from October 2014 to May 2021, comprising 72 cases of invasive ductal carcinoma of no-special type (NSTs) and 17 cases of STs. The clinical data of these patients was collected and statistically analyzed. Formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matched blood samples were collected for targeted next-generation sequencing (NGS) with cancer-related, 520- or 33-gene assay. Immunohistochemical analysis of FFPE tissue sections was performed using anti-programmed cell death-ligand 1(PD-L1) and anti-androgen receptor antibodies. Results: Cases with NSTs presented with higher histologic grade and Ki-67 index rate than ST patients (NSTs to STs: grade I/II/III 1.4%, 16.7%,81.9% vs 0%, 29.4%, 58.8%; p<0.05; Ki-67 ≥30%: 83.3% vs. 58.8%, p<0.05), while androgen receptor (AR) and PD-L1 positive (combined positive score≥10) rates were lower than of STs cases (AR: 11.1% vs. 47.1%; PD-L1: 9.6% vs. 33.3%, p<0.05). The most commonly altered genes were TP53 (88.7%), PIK3CA (26.8%), MYC (18.3%) in NSTs, and TP53 (68.8%), PIK3CA (50%), JAK3 (18.8%), KMT2C (18.8%) in STs respectively. Compared with NSTs, PIK3CA and TP53 mutation frequency showed difference in STs (47.1% vs 19.4%, p=0.039; 64.7% vs 87.5%, p=0.035). Conclusions: In TNBC patients with STs, decrease in histologic grade and ki-67 index, as well as increase in PD-L1 and AR expression were observed when compared to those with NSTs, suggesting that TNBC patients with STs may better benefit from immune checkpoint inhibitors and/or AR inhibitors. Additionally, lower TP53 and higher PIK3CA mutation rates were also found in STs patients, providing genetic evidence for deciphering at least partly potential mechanism of action.

Heterogenous and Low Expression of HER2 in Breast Cancer Overcome by DS-8201a in a Heavily Treated Patient: Case Report and Review of the Literature.

Breast cancer is highly heterogenous with temporal and spatial heterogeneity making it necessary for rebiopsy. DS-8201a, a new potential therapy for human epidermal growth factor receptor 2 (HER2) low expression breast cancer, had been proved that it could overcome heterogenous HER2 expression in a preclinical setting. In January 2014, a 23-year-old woman was presented with a lump in the right breast with bone metastasis, diagnosed as infiltrating ductal carcinoma, estrogen receptor (ER)+, progesterone receptor (PR)+, HER2 immunohistochemistry (IHC) 2+, and fluorescence in situ hybridization negative. The patient received a series of therapies including surgery, radiotherapy, endocrine therapy, target therapy, and chemotherapy. The longest progression-free survival was 17 months after surgery. Biopsy of liver metastasis in February 2020 showed triple negative (HER2-, ER-, PR-), which was quite different from the initial diagnosis in 2014, so retesting was performed and the results showed ER-, PR+ by 10%, HER2 IHC score of 1+, indicating heterogeneity of HER2 expression. In May 2020, DS-8201a treatment was initiated and continued for 10 cycles until November 2020. Remarkable relief in symptoms was observed after the first dose. A reduction in the metastatic lesion size (liver and brain) and improved liver function was observed during the therapy. This case indicated the heterogeneity of breast cancer, and impressive efficacy of DS-8201a in a heavily treated patient with HER2-low and HER2 heterogeneity.

YTHDF1 amplification is correlated with worse outcome and lower immune cell infiltrations in breast cancer.

OBJECTIVE: N6-methyladenosine (m6A) is a common RNA modification on eukaryotic mRNA and some of the m6A regulatory proteins play a crucial role in breast cancer. However, the copy number variations for m6A regulatory proteins and their role in clinicopathological characteristics and survival in breast cancer remain unclear. METHODS: In this study, we screened the m6A related genes alterations in breast cancer by analyzing the Molecular Taxonomy of Breast Cancer International Consortium and The Cancer Genome Atlas database, and further analyzed the clinical prognostic value of YTHDF1 amplification. RESULTS: The YTH domain family (YTHDF3 and YTHDF1) amplification exhibited higher alteration rates among 10 m6A regulatory genes. YTHDF1 and YTHDF3 amplification resulted in higher mRNA expression (P< 0.0001). Protein expression of YTHDF1 and YTHDF3 were higher in breast cancer (P< 0.0001). YTHDF1 amplification presented a high correlation with worse clinicopathological characteristics and overall survival in patients with breast cancer. Cox regression analysis showed that YTHDF1 amplification was an independent risk factor for 10-year overall survival in breast cancer (Hazard ratio: 1.663; 95% confidence interval: 1.298-2.131; P< 0.001). Gene set enrichment analysis revealed that the downstream target of YTHDF1 may be related to MYC signaling regulation and T cell differentiation. Moreover, YTHDF1 amplification and high expression resulted in lower immune cell infiltration. YTHDF1 knockdown retrained proliferation, migration and invasion in breast cancer cells in vitro. CONCLUSIONS: We found significant worse clinical characteristics and lower immune infiltrates in patients with YTHDF1 amplification. The findings indicate that YTHDF1 amplification may be a potential target for the treatment of breast cancer.