Clinicopathological differences and survival benefit in ER+/PR+/HER2+ vs ER+/PR-/HER2+ breast cancer subtypes.

INTRODUCTION: Breast cancer subtypes based on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression have significant implications for prognosis. HER2-positive tumors historically demonstrated poorer survival, but anti-HER2 targeted therapy improved outcomes. However, hormone receptor (HR)-positive patients may experience reduced benefit due to HER2-HR signaling crosstalk. METHODS: Data from two databases, the Shanghai Jiao Tong University Breast Cancer Data Base (SJTUBCDB) and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, were analyzed. Propensity score adjustments were used to balance patient characteristics between ER+/PR+/HER2+ and ER+/PR-/HER2+ subtypes. Kaplan-Meier survival curves estimated disease-free survival (DFS), breast cancer-specific survival (BCSS), overall survival (OS) for these subtypes in the SJTUBCDB, while subgroup analyses using multivariable models were performed based on menstruation, pN stage, HER2-targeted therapy, and endocrinotherapy. RESULTS: The ER+/PR+/HER2+ group showed significantly better DFS and BCSS than the ER+/PR-/HER2+ group, particularly in postmenopausal and pN0 stage patients. Survival outcomes were similar after anti-HER2 therapy or endocrine aromatase inhibitor (AI) therapy in both groups. However, among patients receiving selective estrogen receptor modulator (SERM) treatment, those in the ER+/PR-/HER2+ group had a significantly worse prognosis compared to ER+/PR+/HER2+ patients. CONCLUSIONS: HER2-positive breast cancers with different HR statuses exhibit distinct clinicopathological features and survival outcomes. Patients in the ER+/PR+/HER2+ group generally experience better survival, particularly in postmenopausal and pN0 stage patients. Treatment strategies should consider HR status and specific modalities for better personalized management.

Survival outcomes of low-risk papillary thyroid carcinoma at different risk levels: a corollary for active surveillance.

Background: This study aims to compare the outcomes of active surveillance (AS) in low-risk papillary thyroid carcinoma (PTC) patients with different tumor sizes and lymph node metastasis status, in order to establish appropriate management strategies. By analyzing these results, this study provides valuable insights for the effective management of such patients, addressing the issues and challenges associated with AS in practical clinical practice. Methods: The study utilized the SEER database supported by the National Cancer Institute of the United States, extracting data of PTC diagnosed between 2000 and 2015. Statistical analyses were conducted using inverse probability weighting (IPTW) and propensity score matching (PSM), including Kaplan-Meier survival curves and Cox regression models, to evaluate the impact of different tumor sizes and lymph node metastasis status on thyroid cancer-specific survival (TCSS). Results: A total of 57,000 PTC patients were included, with most covariates having standardized mean differences below 10% after IPTW and PSM adjustments. The TCSS of PTC with a diameter smaller than 13mm is significantly better than that of tumors with a diameter larger than 13mm, regardless of the presence of lymph node metastasis. Among PTC cases with a diameter smaller than 13mm, the TCSS of patients is similar, regardless of the presence of lymph node metastasis. However, in PTC cases with a diameter larger than 13mm, the presence of lateral neck lymph node metastasis (N1b stage) significantly impacts the TCSS, although the absolute impact on TCSS rate is minimal. Conclusion: The treatment strategy of AS is safe for patients with T1a stage papillary thyroid microcarcinoma (PTMC). However, for patients with T1b stage, if the tumor diameter exceeds 13mm or there is lymph node metastasis in the lateral neck region, the TCSS will be significantly affected. Nevertheless, the absolute impact on survival is relatively small.

Survival Benefit of Adjuvant Chemotherapy in Node-Positive Breast Cancer With a 21-Gene Recurrence Score of 14 to 25: A Real-World Study Based on the Inverse Probability of Treatment Weighting Method.

INTRODUCTION: The role of recurrence score in predicting the benefits of adjuvant chemotherapy for lymph-node-positive breast cancer remains uncertain. We studied chemotherapy usage in patients with 1 to 3 positive lymph nodes and a recurrence score (RS) of 25 or lower to assess changes in clinical practice based on the RxPONDER trial. METHODS: A retrospective study using the SEER database identified female patients diagnosed with ER-positive, HER2-negative breast cancer, 1 to 3 positive lymph nodes, and an RS of 25 or lower between 2010 and 2015. Patients were divided into nonchemotherapy and chemotherapy groups, with propensity score weighting to balance clinicopathologic factors. RESULTS: Among 7965 patients, 5774 (72.5%) were in the nonchemotherapy group, while 2191 (27.5%) were in the chemotherapy group. Median follow-up was 39 months. Breast cancer accounted for 67 deaths, while 128 deaths were due to other causes. The weighted 5-year overall survival (OS) rates were 95.7% for the nonchemotherapy group and 97.2% for the chemotherapy group. For high-risk patients, the weighted 5-year OS rates were 95.2% and 97.0% for the nonchemotherapy and chemotherapy groups, respectively, with a significant absolute difference of 1.8% (P = .014). Multivariate analysis showed a significant difference in weighted hazard ratios for OS between the nonchemotherapy and chemotherapy groups in high-risk patients (hazard ratio: 0.64; 95% CI: 0.48-0.86). However, there were no significant differences in weighted hazard ratios for lower-risk patients, and similar results were observed for breast cancer-specific survival (BCSS). CONCLUSION: Patients with ER-positive, HER2-negative breast cancer and 1 to 3 positive lymph nodes, assessed by a 21-gene RS of 0 to 25, exhibited heterogeneous prognosis. Adjuvant chemotherapy provided a significant survival benefit, especially for patients with RS of 14 to 25, particularly those with invasive ductal carcinoma (IDC) and 2 to 3 positive lymph nodes.

New Strategy for High-Performance Integrated Catalysts for Cracking Hydrocarbon Fuels.

In this study, we described the synthesis, characterization, and application of hyperbranched polymer-encapsulated metal nanoparticles (HEMNs) as integrated catalysts for the supercritical cracking of hydrocarbon fuels. The metal precursor was extracted into the organic phase using a hydrocarbon-soluble hyperbranched poly(amidoamine) (CPAMAM) and then reduced in situ by NaBH4 to produce HEMNs with virtually a single-size distribution. The monitoring of the preparation process by UV-vis demonstrated the feasibility of this encapsulation approach, and the successful synthesis of three different types of HEMNs, metal (Pd, Pt, Au)@CPAMAM, reflected the universality of this method. Compared with the existing catalyst octadecylamine-stabilized Pd nanoparticle, Pd@18N, HEMNs were superior in every aspect. The new encapsulation method allowed metal NPs to have a smaller particle size beneficial to their overall specific surface area and a higher proportion of active surface atoms for a better catalytic activity. Moreover, the space-limiting effect of the polymer allowed the three HEMNs to be highly dispersed in decalin and exhibited admirable stability under storage tests for up to 12 months and high-temperature stability tests at 180 °C. During the supercritical cracking of decalin, Pd@CPAMAM possessed a much better catalytic performance than Pd@18N and CPAMAM (which can also be used as a macroinitiator). To obtain the same heat sink of 3.02 MJ/kg, the temperature could be lowered from 725 to 701, 693, and 699 °C for Pd, Pt, and Au HEMNs, respectively. Pt HEMN turned out to be the best due to its excellent catalytic dehydrogenation/cracking performance, with the conversion of decalin increasing from 22.3 to 50.7% and the heat sink rising from 2.18 to 2.62 MJ/kg with the existence of 50 ppm Pt@CPAMAM, at 675 °C. The significant enhancements were ascribed to the synergistic catalysis through the remarkable abilities of nanometals to catalyze dehydrogenation/cracking of fuel, the supercritical stabilization effects from CPAMAM, and the initiation effects of the hyperbranched polymer CPAMAM.

Genistein inhibits the S-phase kinase-associated protein 2 expression in breast cancer cells.

Breast cancer is one of the most lethal cancers affecting women worldwide and was estimated to account for ~30% of all new cancer diagnoses in women. Although available evidence has proved the tumor suppressor role of genistein in cancer, the underling mechanisms have remained to be fully elucidated. S-phase kinase-associated protein 2 (Skp2) has been revealed to critically enhance the pathogenesis of multiple human cancers. The present study determined whether genistein exerts its anti-tumor function by suppressing Skp2 in breast cancer cells. Genistein significantly inhibited the proliferation, invasion and migration of breast cancer cells. Furthermore, genistein treatment also induced marked apoptosis and a typical cell cycle arrest in G2/M phase. Mechanistically, genistein treatment was identified to cause a significant downregulation of Skp2. Two crucial tumor suppressors, p21 and p27, were upregulated in genistein-treated breast cancer cells. The present results revealed that genistein exerted its tumor suppressor effect at least partially via inhibition of Skp2 and promotion of its downstream targets p21 and p27. Therefore, inactivation of Skp2 by genistein may be a promising approach for breast cancer treatment.