Predictive power of tertiary lymphoid structure signature for neoadjuvant chemotherapy response and immunotherapy benefit in HER2-negative breast cancer

Dear Editor,Pembrolizumab,an immune checkpoint inhibitor(ICI),was recently approved for early-stage triple-negative breast cancer(eTNBC),and promising results have been reported in advanced hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR+/HER2-)and HER2+BCs[1].Given the costs and potential toxicity,markers predictive of ICI benefits are needed.Currently,neither programmed death-ligand 1(PD-L1)expression nor other tested markers(i.e.,tumor mutational burden,microsatellite instability)effectively predict ICI benefit[2].Tertiary lymphoid structures(TLS)are secondary lymphoid organ-like aggregates that reside in the tumor microenvironment and are associated with clinical response to ICIs in metastatic melanoma,renal cell carcinoma.

The Monarch Etrial:improving the clinical outcome in HR^(+)/HER2^(−)early breast cancer:recent results and next steps

Breast cancer(BC)is the most frequent cancer in women worldwide,and hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR^(+)/HER2^(−))is the most frequent BC subtype.The adjuvant systemic treatment of HR^(+)/HER2^(−)early-stage BC(eBC),based on prognostic factors[1],sometimes includes chemotherapy,and in most cases,it includes endocrine therapy(ET).In the past decade,advancements in ET,such as successive approvals of tamoxifen and aromatase inhibitors and the extension of ET duration to 10 years in high-risk patients.

A 10-miRNA risk score-based prediction model for pathological complete response to neoadjuvant chemotherapy in hormone receptor-positive breast cancer

Patients with hormone receptor(HR)-positive tumors breast cancer usually experience a relatively low pathological complete response(p CR)to neoadjuvant chemotherapy(NAC).Here,we derived a 10-micro RNA risk score(10-mi RNA RS)-based model with better performance in the prediction of p CR and validated its relation with the disease-free survival(DFS)in 755 HRpositive breast cancer patients(273,265,and 217 in the training,internal,and external validation sets,respectively).This model,presented as a nomogram,included four parameters:the 10-mi RNA RS found in our previous study,progesterone receptor(PR),human epidermal growth factor receptor 2(HER2)status,and volume transfer constant(K).Favorable calibration and discrimination of 10-mi RNA RS-based model with areas under the curve(AUC)of 0.865,0.811,and 0.804 were shown in the training,internal,and external validation sets,respectively.Patients who have higher nomogram score(>92.2)with NAC treatment would have longer DFS(hazard ratio=0.57;95%CI:0.39–0.83;P=0.004).In summary,our data showed the 10-mi RNA RS-based model could precisely identify more patients who can attain p CR to NAC,which may help clinicians formulate the personalized initial treatment strategy and consequently achieves better clinical prognosis for patients with HRpositive breast cancer.

Low cholesterol biosynthesis favors epithelial-to-mesenchymal transition maintenance and influences tumor molecular subtyping and disease-free survival in colon cancer patients

Dear Editor,To metastasize,epithelial cancer cells undergo an epithelial-to-mesenchymal transition(EMT)during migration,whereupon they activate a mesenchymal-toepithelial transition(MET)when colonizing the new niche[1].Targeting EMT or MET inducers might thus impair the metastatic process[2,3].However,the identification of genes involved in epithelium-mesenchyme switches(EMS)is difficult in complex samples such as human tumors.To overcome this problem,we used spheroids of a colorectal cancer(CRC)cell line,HT29,to mimic EMS in a controlled environment.