Breast Cancer Research and Treatment最新文献

Background: Human epidermal growth factor receptor 2 (HER2)-negative operable breast cancer (BC) patients with germline BRCA1/2 pathogenic variants may benefit from adjuvant olaparib treatment. However, data about how many patients were eligible for olaparib treatment in operable BC patients with BRCA1/2 variants after neoadjuvant chemotherapy (NACT) is lacking.

Methods: A total of 341 operable BC with germline BRCA1/2 pathogenic variants who received NACT at our institute between October 2003 and May 2015 were included. Pathological complete response (pCR) and survival were estimated.

Results: Of the 341 BRCA1/2 carriers (BRCA1: 139; BRCA2: 202), 295 (88.1%) cases exhibited HER2-negative BC in the entire cohort. The most common subtype was triple-negative (TN) BC (62.0%) for BRCA1 carriers and hormone receptor (HR)-positive/HER2-negative BC (68.2%) for BRCA2 carriers, respectively. The pCR rate were 39.6% for BRCA1 carriers and 28.2% for BRCA2 carries. The pCR rate in TNBC, HR-positive/HER2-negative BC, and HER2-positive BC were 45.0%, 22.3%, and 45.0% in the entire cohort, respectively. Of these HR-positive/HER2-negative BC patients, 16.0% had non-pCR and exhibited CPS+EG≥3. Overall, 31.9% of the HER2-negative BC cohort were potential candidates for adjuvant olaparib, with 44.0% for BRCA1 carriers and 22.9% for BRCA2 carriers. Furthermore, patients with non-pCR exhibited a worse survival regardless of TNBC and HR-positive/HER2-negative BC disease, especially for HR-positive/HER2-negative BC with CPS+EG≥3.

Conclusion: Approximately one-third of HER2-negative BC patients with BRCA1/2 pathogenic variants are potential candidates for adjuvant olaparib treatment after NACT, with a higher proportion for BRCA1 carriers compared to BRCA2 carriers.

Background: Transfer RNA (tRNA) fragments (tRFs) are a group of small non-coding RNAs with biological functions. The involvement of tRNAs in cancer has also been recognized, but most studies focused on nuclear tRFs, very few on mitochondrial tRFs.

Methods: We analyzed the TCGA microRNAseq data to identify differentially expressed mitochondrial tRFs (mt-tRFs) in breast tumors and evaluated their associations with the disease outcome. Cox proportional hazards regression was used to determine the associations between mt-tRFs and patient survival while adjusting for clinicopathological variables. Quantitative RT-PCR was developed to measure a specific tRF expression in a validation study.

Results: Our analysis of 1,060 tumor samples from TCGA revealed that mt-tRF-Tyr-GTA-001 (tRF-21-X3OJI8EWB or t00018104) expression, a tRF from mitochondrial tRNA with tyrosine anticodon GTA (mt-tRNA-Tyr-GTA), was significantly lower in breast tumors than the adjacent tissues (p< 0.0001). Patients with low expression had significantly higher risk of death (HR = 1.69, p = 0.0018) regardless of their age at diagnosis, disease stage, tumor grade, and hormone receptor status. This survival association was replicated in an independent study where mt-tRF-Tyr-GTA-001 expression was measured with qRT-PCR. Further analysis suggested that the mt-tRF expression was correlated with ribonuclease ANG and RNase 4 known to cleave tRNAs and upregulated under hypoxia. IPA interrogation of the mt-tRF-Tyr-GTA-001 expression signature indicated the inhibitory effects of mt-tRF-Tyr-GTA-001 on malignant transformation, tumor growth, and cell invasion. In silico analysis showed that the binding targets of mt-tRF-Tyr-GTA-001 included several oncogenic transcription factors (E2Fs, CCNE1, FOXM1). We also found the mt-tRF correlated with the abundances of M0 macrophages and resting mast cells, two of the immune cells known for innate immunity.

Conclusions: In summary, our study suggests that mt-tRF-Tyr-GTA-001, a mitochondrial tRF, may suppress breast cancer progression through its involvement in regulation of cell phenotype and tumor immunity.

Purpose: National Comprehensive Cancer Network (NCCN) guidelines for inflammatory breast cancer (IBC) recommend trimodal therapy: neoadjuvant chemotherapy, modified radical mastectomy (MRM), and adjuvant radiation therapy. Historically, a minority received NCCN-guideline-concordant trimodal therapy (GCT). We explored factors associated with non-concordance, types of non-concordance, and the association of GCT with survival.

Methods: The National Cancer Database (NCDB) was analyzed for patients with non-metastatic IBC who underwent surgery from 2006 to 2019. Multivariate logistic regression identified factors associated with GCT. Cox proportional hazard models assessed the impact of GCT, and components of non-concordance, on mortality.

Results: Of 13,733 patients, 47.6% received GCT. Of non-GCT patients, 39.7% had mixed non-concordance, 25.5% exclusive chemotherapy non-concordance, 24.0% exclusive radiation non-concordance, and 10.8% exclusive surgical non-concordance. A higher burden of comorbidities, node-negative disease, and positive human epidermal growth factor receptor 2 (HER2) and hormone receptor status were associated with reduced odds of receiving GCT. GCT was associated with reduced 3-(hazard ratio [HR] = 0.83, 95% CI 0.73-0.95) and 5-year (HR = 0.83, 95% CI 0.76-0.91) mortality. Chemotherapy non-concordance and mixed non-concordance were associated with higher three-(HR = 1.28, 95% CI 1.07-1.53; HR = 1.20, 95% CI 1.01-1.43 respectively) and 5-year (HR = 1.42, 95% CI 1.26-1.60; HR = 1.17, 95% CI 1.03-1.33) mortality. Radiation non-concordance was associated with increased hazard of 1-year mortality (HR = 3.03, 95% CI 1.75-5.23). Exclusive surgical non-concordance was not associated with survival; however, simple mastectomy portended a higher hazard of 5-year mortality (HR = 1.26, 95% CI 1.08-1.46).

Conclusion: Despite improved survival, a minority of patients received GCT. Omitting neoadjuvant chemotherapy or adjuvant radiation was associated with reduced survival, whereas surgical non-concordance in patients with concordant chemoradiation did not impact survival. Simple mastectomy was associated with reduced survival, supporting the rationale for axillary lymphadenectomy.

Purpose: Breast cancer ranks as the most prevalent cancer type impacting women globally, both in terms of incidence and mortality rates, making it a major health concern for females. There's an urgent requirement to delve into new cancer treatment methods to improve patient survival rates.

Methods: Immunotherapy has gained recognition as a promising area of research in the treatment of breast cancer, with targeted immune checkpoint therapies demonstrating the potential to yield sustained clinical responses and improve overall survival rates. Presently, the predominant immune checkpoints identified on breast cancer cells include CD47, CD24, PD-L1, MHC-I, and STC-1, among others. Nevertheless, the specific roles of these various immune checkpoints in breast carcinogenesis, metastasis, and immune evasion have yet to be comprehensively elucidated. We conducted a comprehensive review of the existing literature pertaining to breast cancer and immune checkpoint inhibitors, providing a summary of findings and an outlook on future research directions.

Results: This article reviews the advancements in research concerning each immune checkpoint in breast cancer and their contributions to immune evasion, while also synthesizing immunotherapy strategies informed by these mechanisms. Furthermore, it anticipates future research priorities, thereby providing a theoretical foundation to guide immunotherapy as a potential interventional approach for breast cancer treatment.

Conclusion: Knowledge of immune checkpoints will drive the creation of novel cancer therapies, and future breast cancer research will increasingly emphasize personalized treatments tailored to patients' specific tumor characteristics.

Background: This study aimed to determine whether clinical treatment score post-5 years (CTS5) could predict the clinical benefits of extended endocrine therapy (ExET) in young and old patients.

Methods: We reviewed 2495 hormone receptor-positive breast cancer patients treated between 2001 and 2012 who were free from recurrence or death during the 5 years post-surgery in South Korea. The cohort was analyzed separately based on age (≤ 50 years and > 50 years). Multivariable analysis was conducted, and a cutoff of CTS5 < 3.13 was defined as the low group and CTS5 ≥ 3.13 as the intermediate/high (int/high) group.

Results: The median follow-up duration was 115 months. Regardless of young and old age at diagnosis, the low group displayed considerably enhanced disease-free survival. Multivariate analysis revealed that the low group emerged as an independent and favorable prognostic factor for disease-free survival after adjusting for ExET use and prognostic parameters. Patients in the low group demonstrated a trend toward improved overall survival compared to those in the int/high group, reaching marginal statistical significance. ExET use demonstrated a significant correlation with improved disease-free survival, particularly in patients aged ≤ 50 years.

Conclusions: ExET should be considered in premenopausal and postmenopausal breast cancer patients with high CTS5 levels.

Purpose: To evaluate the role of Postoperative Radiotherapy (PORT) in HER2-positive metastatic breast cancer (MBC) in the context of targeted therapy and clarify the subgroups that may benefit from PORT.

Methods: Clinical data of female patients with HER2-positive MBC from the surveillance, epidemiology, and end results (SEER) database for the years 2016-2020 were collected according to established inclusion and exclusion criteria. The impact of PORT on patient survival was assessed, and subgroup analyses were performed to identify populations with potential benefits from PORT.

Results: A total of 541 patients from the SEER database were included in the analysis. The 3-year overall survival (OS) of the PORT group was significantly higher than that of the non-PORT group. (86.7% vs. 80.2%, P = 0.011). Multivariate analysis revealed that race and PORT were independent prognostic factors. Black patients and those who received PORT had longer overall survival (OS) (P < 0.05). Subgroup analysis suggested that PORT further improved OS in patients with mastectomy, advanced TN stage, high tumor grade, positive hormone receptor status, and multiple metastatic organs (P < 0.05).

Conclusion: PORT further improves the survival of HER2-positive MBC. Subgroup analysis suggests that patients with locally advanced stage (T3-4, N2-3), Grade III, HR-positive status, bone-and-visceral metastasis, and those who have undergone mastectomy benefit significantly.

Purpose: Recent studies have shown that the truncated isoform of the neurokinin-1 receptor (NK-1R) and its ligand, substance P (SP), are overexpressed in tumor cells playing a crucial role in chemoresistance, leading to proliferation, angiogenesis, and metastasis. Hence, this study aims to assess if the polymorphisms of the NK-1R-encoding gene influence the truncated NK-1R level, chemoresistance, and pathological complete response (pCR) achievement in breast cancer patients.

Methods: The real-time PCR-HRMA was performed to genotype TACR1 eighteen tag SNPs in 153 neoadjuvant chemotherapy-receiving breast cancer patients. Univariate analysis was performed to assess the association of baseline and tumor characteristics with pCR achievement. The association of each variant and pCR achievement was assessed by executing logistic regression while adjusting for covariates and correcting for multiple tests using permutation.

Results: The probability of pCR to neoadjuvant chemotherapy is higher for patients with tumor grade-III as well as stage-I. Assuming the additive, dominant, or recessive models, rs17010664, rs6715729, and rs3771869 were significantly associated with pCR achievement.

Conclusion: Positioned close to the truncation-occurring region, belonging to an exon-splicing enhancer motif, the rs17010664 C allele seems to play a crucial role in enhancing the TACR1 last exon splicing leading to increased truncated NK-1R production, chemoresistance, and decreased pCR achievement. Accordingly, The SP/truncated NK-1R axis blockade by NK-1R antagonists seems to be a therapeutic approach to overcoming chemoresistance and achieving pCR in the rs17010664 risk-allele-bearing patients. Hence, conducting further studies to determine the required dose of NK-1R antagonists, repurposed as an antitumor agent, is favored.