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The global phase 3 DESTINY‐Breast03 study (ClinicalTrials.gov; NCT03529110) showed statistically significant and clinically meaningful improvements in progression‐free survival (PFS) and overall survival (OS) with trastuzumab deruxtecan (T‐DXd) over trastuzumab emtansine (T‐DM1) in patients with human epidermal growth factor receptor 2 (HER2)‐positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. Here, we report a subgroup analysis of Asian patients enrolled in DESTINY‐Breast03. In total, 309 patients (149 in the T‐DXd arm and 160 in the T‐DM1 arm) from Asian countries and regions were randomized. At data cutoff (July 25, 2022), the median duration of follow‐up in the Asian subpopulation was 29.0 months with T‐DXd and 26.0 months with T‐DM1. The PFS (determined by blinded independent central review) hazard ratio was 0.30 (95% confidence interval 0.22–0.41) favoring T‐DXd over T‐DM1 (median PFS 25.1 vs. 5.4 months). Median OS was not reached in the T‐DXd arm and was 37.7 months in the T‐DM1 arm. The median treatment duration was 15.4 months with T‐DXd and 5.5 months with T‐DM1. The incidence of grade ≥3 drug‐related treatment‐emergent adverse events was similar between both treatment arms (49.0% vs. 46.5%) and was consistent with the overall DESTINY‐Breast03 population. Adjudicated drug‐related interstitial lung disease or pneumonitis occurred in 12.9% of patients treated with T‐DXd and 2.5% treated with T‐DM1, with a higher incidence in Japanese patients; none of these were grade ≥4 events. These efficacy and safety data reinforce the favorable benefit–risk profile of T‐DXd in HER2‐positive mBC, including in the Asian subgroup. [ABSTRACT FROM AUTHOR]

The discovery of early diagnosis and prognostic markers for breast cancer can significantly improve survival and reduce mortality. LSM1 is known to be involved in the general process of mRNA degradation in complexes containing LSm subunits, but the molecular and biological functions in breast cancer remain unclear. Here, the expression of LSM1 mRNA in breast cancer was estimated using The Cancer Genome Atlas (TCGA), Oncomine, TIMER and bc‐GenExMiner databases. We found that functional LSM1 inactivation caused by mutations and profound deletions predicted poor prognosis in breast cancer (BRCA) patients. LSM1 was highly expressed in both BRCA tissues and cells compared to normal breast tissues/cells. High LSM1 expression is associated with poorer overall survival and disease‐free survival. The association between LSM1 and immune infiltration of breast cancer was assessed by TIMER and CIBERSORT algorithms. LSM1 showed a strong correlation with various immune marker sets. Most importantly, pharmacogenetic analysis of BRCA cell lines revealed that LSM1 inactivation was associated with increased sensitivity to refametinib and trametinib. However, both drugs could mimic the effects of LSM1 inhibition and their drug sensitivity was associated with MEK molecules. Therefore, we investigated the clinical application of LSM1 to provide a basis for sensitive diagnosis, prognosis and targeted treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Most genome‐wide association studies (GWASs) identify genetic variants for breast cancer occurrence. In contrast, few are for recurrence and mortality. We conducted a GWAS on breast cancer survival after diagnosis in estrogen receptor‐positive patients, including 953 Taiwanese patients with 159 events. Through Cox proportional hazard models estimation, we identified 24 risk SNPs with p < 1 × 10−5. Based on imputation and integrated analysis, one SNP, rs1024176 (located in 1q24.2, p = 2.43 × 10−5) was found to be a functional variant associated with breast cancer survival and XCL1 gene expression. A series of experimental approaches, including cell‐based analyses and CRISPR/Cas9 genome‐editing system, were then used and identified the transcription factor MYBL2 was able to discriminately bind to the A allele of rs1024176, the protective variant for breast cancer survival, which promoted XCL1 expression, but not to the G allele of rs1024176. The chemokine XCL1 attracts type 1 dendritic cells (DC1s) to the tumor microenvironment. In breast cancer tissues, we applied a two‐step Mendelian randomization analysis, using expression quantitative trait loci as instrumental variables, to confirm higher XCL1 expression was correlated with higher DC1 signatures and favorable disease progression, through the causal effect of rs1024176‐A allele. Our study supports the genetic effect on preventing breast cancer survival through XCL1‐induced DC1 recruitment in tumor microenvironment. What's new? Although many prognostic predictors have been identified, the factors that determine patient differences in breast cancer progression and survival are not fully understood. This study addresses the important role of cancer immune control in promoting human breast cancer survival. Using genetic, cell‐based, and multi‐omic analyses, the authors find that one of the most significant SNP, rs1024176 at 1q24.2 could be a functional variant regulating XCL1 gene expression and thus recruiting type 1 dendritic cells to the breast tumor microenvironment. These findings reveal a pathway to prevent breast cancer progression through XCL1‐induced type 1 dendritic cells recruitment in the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Aims: Invasive breast cancer patients with human epidermal growth factor receptor 2 (HER2) immunohistochemical (IHC) scores of 3+ or 2+ with reflex in‐situ hybridisation (ISH) positivity are suitable for anti‐HER2 therapies. The aim of this study is to investigate whether the prognoses between IHC 3+ patients and IHC 2+/ISH+ patients are different. Methods and results: We analysed the clinicopathological information of 886 consecutive cases of HER2‐positive early breast cancer. The influences of the patients' age, cancer stage, hormone receptor status and anti‐HER2 treatment were adjusted using a multivariate Cox regression model. Both HER2 copy numbers and HER2 ISH ratios of the IHC 3+ group were significantly higher than those of the IHC 2+/ISH+ group. The outcomes of IHC 3+ patients were significantly better than those of IHC 2+/ISH+ patients in the univariate and multivariate analyses. HER2 copy numbers of ≥8 represented the best prognostic value, and it was chosen to be the cut‐off value. The reflex ISH for IHC 2+ patients with high HER2 copy numbers (≥8) predicted a better overall survival than that for those with low HER2 copy numbers. Conclusion: HER2 IHC scores and HER2 copy numbers can provide prognostic information for patients with HER2‐positive invasive breast cancer. Both IHC 3+ and IHC 2+ patients with high HER2 copy numbers had a better prognosis. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 59-year-old woman has come for health checkup. Topics include mammography showed grouped pleomorphic microcalcifications within the right nipple-areolar complex (NAC); and breast sonography revealed multiple tiny echogenic foci suggestive of calcifications in the right NAC.

Recurrent triple-negative breast cancer ( TNBC) needs new therapeutic targets. Src homology region 2 domain-containing phosphatase-1 ( SHP-1) can act as a tumor suppressor by dephosphorylating oncogenic kinases. One major target of SHP-1 is STAT3, which is highly activated in TNBC. In this study, we tested a sorafenib analogue SC-60, which lacks angiokinase inhibition activity, but acts as a SHP-1 agonist, in TNBC cells. SC-60 inhibited proliferation and induced apoptosis by dephosphorylating STAT3 in both a dose- and time-dependent manner in TNBC cells ( MDA- MB-231, MDA- MB-468, and HCC1937). By contrast, ectopic expression of STAT3 rescued the anticancer effect induced by SC-60. SC-60 also increased the SHP-1 activity, but this effect was inhibited when the N- SH2 domain ( DN1) was deleted or with SHP-1 point mutation (D61A), implying that SHP-1 is the major target of SC-60 in TNBC. The use of SC-60 in combination with docetaxel synergized the anticancer effect induced by SC-60 through the SHP-1/ STAT3 pathway in TNBC cells. Importantly, SC-60 also displayed a significant antitumor effect in an MDA- MB-468 xenograft model by modulating the SHP-1/ STAT3 axis, indicating the anticancer potential of SC-60 in TNBC treatment. Targeting SHP-1/p- STAT3 and the potential combination of SHP-1 agonist with chemotherapeutic docetaxel is a feasible therapeutic strategy for TNBC. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. Patients diagnosed with GBM have a poor prognosis, and it has been reported that tumor malignancy and GBM recurrence are promoted by STAT3 signaling. As resveratrol (RV), a polyphenol in grapes, is reported to be a potent and non-toxic cancer-preventive compound, the aim of this study was to investigate the therapeutic effect and molecular mechanisms of RV on GBM-derived radioresistant tumor initiating cells (TIC). Firstly, our results showed that primary GBM-CD133+ TIC presented high tumorigenic and radiochemoresistant properties as well as increased protein levels of phosphorylated STAT3. We consistently observed that treatment with shRNA-STAT3 (sh-STAT3) or AG490, a STAT3 inhibitor, significantly inhibited the cancer stem-like cell properties and radioresistance of GBM-CD133+ in vitro and in vivo. Furthermore, treatment of GBM-CD133+ with 100 µM RV induced apoptosis and enhanced radiosensitivity by suppressing STAT3 signaling. Microarray results suggested that RV or AG490 inhibited the stemness gene signatures of GBM-CD133+ and facilitated the differentiation of GBM-CD133+ into GBM-CD133− or astrocytoma cells. Finally, xenotransplant experiments indicated that RV or sh-STAT3 therapy could significantly improve the survival rate and synergistically enhance the radiosensitivity of radiation-treated GBM-TIC. In summary, RV can reduce in vivo tumorigenicity and enhance the sensitivity of GBM-TIC to radiotherapies through the STAT3 pathway. J. Cell. Physiol. 227: 976-993, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND: The objective of this international field study was to test the reliability, validity, and responsiveness of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BM22 module to assess health-related quality of life (HRQOL) in patients with bone metastases. METHODS: Patients undergoing a variety of bone metastases-specific treatments were accrued. The QLQ-BM22 was administered with the QLQ-C30 at baseline and at 1 follow-up time point internationally. A debriefing questionnaire was administered to determine patient acceptability and understanding. RESULTS: Large-scale field testing of the QLQ-BM22 in addition to the QLQ-C30 took place in 7 countries: Brazil, Canada, Cyprus, Egypt, France, India, and Taiwan. A total of 400 patients participated. Multitrait scaling analyses confirmed 4 scales in the 22-item module. The scales were able to discriminate between clinically distinct patient groups, such as between those with a poor and those with a better performance status. The QLQ-BM22 was well received in all 7 countries, and the majority of patients did not recommend any significant changes from the module in its current form. CONCLUSIONS: The final QLQ-BM22 module contains 22 items and 4 scales assessing Painful Sites, Painful Characteristics, Functional Interference, and Psychosocial Aspects. Results confirmed the validity, reliability, cross-cultural applicability, and sensitivity of the 22-item EORTC QLQ-BM22. It is therefore recommended that the QLQ-BM22 be used in addition to the QLQ-C30 in clinical trials to assess HRQOL in patients with bone metastases. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

The expression of Rab proteins has been associated with cancer. However, few data are available on Rab5A expression in human breast cancer or its impact on disease progression. First, we examined the functional role of Rab5A in breast cancer cells. The expression of Rab5A in MDA-MB-231 cells can be stimulated by epidermal growth factor in a dose-dependent manner. The epidermal growth factor-induced increase of Rab5A expression correlated well with enhanced migration in wound healing migration assays in these cells. Furthermore, we evaluated the expression of Rab5A in breast cancer specimens using immunohistochemical staining, then analyzed the relationship between the expression of Rab5A and clinicopathological parameters. The increased expression of Rab5A protein in 123 breast cancer samples was associated with higher histological grade ( P = 0.004), more lymphovascular invasion ( P = 0.027), more axillary lymph node (LN) metastasis ( P = 0.008), and a higher number of axillary LN metastases ( P = 0.043). Among 218 axillary LNs of more than 10 breast cancer patients with node metastases, 167 metastatic LNs were found to have increased Rab5A expression. Rab5A is associated with axillary LN metastasis in breast cancer patients. ( Cancer Sci 2011; 102: 2172-2178) [ABSTRACT FROM AUTHOR]

The article discusses the case study concerning a 71-year-old female who had undergone mammoplasty surgery with silicon injection. It notes that she had also undergone breast surgery for removal of implants. It mentions that mammography shows dense soft tissue mass in left breast with compression of the glandular tissue.