Treatment-associated survival outcomes in real-world patients with de novo metastatic triple-negative breast cancer: Age as a significant treatment effect-modifier.

PURPOSE: Evidence for optimizing the first-line chemotherapy for patients with metastatic triple-negative breast cancer (mTNBC) is lacking. This study assessed the utilization patterns of chemotherapy and associated survival outcomes in de novo mTNBC patients. METHODS: Taiwan's cancer registry was utilized to extract study patients with newly-diagnosed breast cancer during 2011-2015 and confirmed metastatic triple-negative status. The patients' medical records (e.g., diseases, treatments) and death status were obtained from the National Health Insurance Research Database. Utilization of first-line chemotherapy regimens was analyzed and associated survival outcomes were assessed using Cox models. RESULTS: 93.60% of the mTNBC patients (n = 297) received chemotherapy, where combination regimens (75.54%) were more common than single-agent regimens (24.46%) in the first-line setting. A non-statistically lower all-cause death associated with combination versus single-agent chemotherapy (hazard ratio: 0.830 [0.589, 1.168]) was observed. Age was identified as a significant effect-modifier in treatment-associated survival outcomes (p = 0.008); younger patients (aged < 40 and 40-59 years) versus older patients (aged ≥ 60 years) had a lower all-cause mortality when receiving combination versus single-agent chemotherapy. A lower all-cause mortality associated with taxane- versus non-taxane-based therapy was revealed among those on single-agent chemotherapy (hazard ratio: 0.557 [0.311, 0.999]). CONCLUSION: Generally, single-agent and combination chemotherapies yielded comparable survival outcomes as the first-line treatment for de novo mTNBC. Younger patients may benefit more from combination regimens, in terms of better survival outcomes. Single-agent chemotherapy may be preferable as the first-line choice for elderly patients who are vulnerable to the toxicity of multiple chemotherapy agents.

A Polymer with "Locked" Degradability: Superior Backbone Stability and Accessible Degradability Enabled by Mechanophore Installation.

Though numerous applications require degradable polymers, there are surprisingly few polymer systems that combine superior stability and controllable degradability. Particularly, the degradability of a conventional degradable polymer is typically enabled by cleavable groups on the backbone, which can be attacked by stimuli in ambient conditions, causing undesirable material deterioration. Here we report a general strategy to overcome this issue: "locking" the degradability during handling and use of the polymers and "unlocking" it when degradation is needed. This strategy is demonstrated with a cyclobutane-fused lactone (CBL) polymer. The cyclobutane keeps polymer backbone intact under conditions that hydrolyze the lactone and allows the ester group to be recovered when undesirable hydrolysis occurs. When backbone degradation is needed, the degradability can be unlocked by mechanochemical activation that converts the polyCBL into a linear polyester. The rare combination of two intrinsically conflicting properties, i.e., backbone stability and accessible degradability, can make this polymer a potential option for new sustainable materials.

Evaluating Trans-Benzocyclobutene-Fused Cyclooctene as a Monomer for Chemically Recyclable Polymer.

Chemically recyclable polymers offer a promising solution to address the issues associated with the unsustainable use of plastics by converting the traditional linear plastic economy into a circular one. Central to developing chemically recyclable polymers is to identify the appropriate monomers that enable practical conditions for polymerization and depolymerization and ensure useful stability and material properties. Our group has recently demonstrated that trans-cyclobutane-fused cyclooctene (tCBCO) meets the abovementioned requirements and is a promising candidate for developing chemically recyclable polymers. Herein, encouraged by the success with tCBCO, we investigate the thermodynamics of polymerization of a relevant system, trans-benzocyclobutene-fused-cyclooctene, which can be viewed as tCBCO with an additional benzene ring. The study shows that introducing an additional benzene ring favors polymerization and disfavors depolymerization, and the effect is predominantly entropic. The benzo-effect can be leveraged to fine-tune the thermodynamics of polymerization and depolymerization to facilitate the chemical recycling of polymers.

Real-life analysis of neoadjuvant-therapy-associated benefits for pathological complete response and survival in early breast cancer patients - role of trastuzumab in HER2+ BC and platinum in TNBC.

Background: Neoadjuvant therapy, which aims to achieve a pathological complete response (pCR) for better overall survival (OS) has several advantages for patients with early breast cancer (eBC) and subtypes of HER2-positive (HER2+) and triple-negative breast cancer (TNBC). However, there has been no large-scale real-world investigation on the clinical outcomes associated with trastuzumab-based and platinum-based neoadjuvant treatments for patients with HER2+ and TNBC, respectively. Material and methods: Taiwan Cancer Registry and National Health Insurance Research Database were utilized in this study. Patients diagnosed with clinically lymph-node-positive (LN+) HER2+ or TNBC were identified for analysis. Logistic regression and Cox proportional hazard models were employed to estimate the adjusted odds ratios (aOR) of achieving pCR and adjusted hazard ratios (aHR) of overall survival associated with treatment agents, respectively. Results: A total of 1,178 HER2+ eBC and 354 early TNBC patients were identified, respectively. Neoadjuvant trastuzumab significantly increased the pCR rates by 3.87-fold among HER2+ patients. Trastuzumab-associated survival benefit was found in HER2+ patients who achieved pCR (aHR [95% CI]: 0.30 [0.11-0.84]) but not in those without pCR (1.13 [0.77-1.67]). Among the TNBC patients, platinum was associated with a 1.6-fold increased pCR rate; however, it did not improve OS regardless of pCR status. Conclusions: Trastuzumab improved pCR and OS for patients with HER2+ subtype. Using platinum agents for TNBC patients increased pCR rates but was not linked to better survival. Optimal neoadjuvant anti-HER2 therapy for patients with HER2+ eBC and the introduction of novel therapy for patients with TNBC should be considered.

Olefin metathesis-based chemically recyclable polymers enabled by fused-ring monomers.

A promising solution to address the challenges in plastics sustainability is to replace current polymers with chemically recyclable ones that can depolymerize into their constituent monomers to enable the circular use of materials. Despite some progress, few depolymerizable polymers exhibit the desirable thermal stability and strong mechanical properties of traditional polymers. Here we report a series of chemically recyclable polymers that show excellent thermal stability (decomposition temperature >370 °C) and tunable mechanical properties. The polymers are formed through ring-opening metathesis polymerization of cyclooctene with a trans-cyclobutane installed at the 5 and 6 positions. The additional ring converts the non-depolymerizable polycyclooctene into a depolymerizable polymer by reducing the ring strain energy in the monomer (from 8.2 kcal mol-1 in unsubstituted cyclooctene to 4.9 kcal mol-1 in the fused ring). The fused-ring monomer enables a broad scope of functionalities to be incorporated, providing access to chemically recyclable elastomers and plastics that show promise as next-generation sustainable materials.