Breast Cancer最新文献

Breast cancer (BC) is widely recognized as a prevalent contributor to cancer mortality and ranks as the second most prevalent form of cancer among women across the globe. Hence, the development of innovative therapeutic strategies is imperative to effectively manage BC. The B- and T-lymphocyte attenuator (BTLA)-Herpesvirus entry mediator (HVEM) complex has garnered significant scientific interest as a crucial regulator in various immune contexts. The interaction between BTLA-HVEM ligand on the surface of T cells results in reduced cellular activation, cytokine synthesis, and proliferation. The BTLA-HVEM complex has been investigated in various cancers, yet its specific mechanisms in BC remain indeterminate. In this study, we aim to examine the function of BTLA-HVEM and provide a comprehensive overview of the existing evidence in relation to BC. The obstruction or augmentation of these pathways may potentially enhance the efficacy of BC treatment.

Background: The combination of immune checkpoint inhibitors and anti-angiogenic agents has been proposed as a promising strategy to improve the outcome of advanced triple-negative breast cancer (TNBC). However, further investigation is warranted to elucidate the specific mechanisms underlying the effects of combination therapy and its potential as neoadjuvant therapy for early-stage TNBC.

Methods: In this study, we constructed humanized mouse models by engrafting the human immune system into severely immunodeficient mice and subsequently implanting TNBC cells into the model. The mice were treated with neoadjuvant combination therapy (bevacizumab combined with nivolumab), followed by in vivo imaging system to assess tumor recurrence and metastasis after surgery. The immune microenvironment of tumors was analyzed to investigate the potential mechanisms. Furthermore, we verified the impact of extending the interval before surgery or administering adjuvant therapy after neoadjuvant therapy on the prognosis of mice.

Results: Neoadjuvant combination therapy significantly inhibited tumor growth, prevented recurrence and metastasis by normalizing tumor vessels and inducing robust CD8⁺ T cell infiltration and activation in primary tumors (p < 0.001). In vivo experiments demonstrated that prolonging the interval before surgery or administering adjuvant therapy after neoadjuvant therapy did not enhance its efficacy.

Conclusion: The preclinical study has demonstrated the therapeutic efficacy and mechanism of neoadjuvant combination therapy (nivolumab plus bevacizumab) in treating early TNBC.

Background: Patients with breast cancer (BC) at advanced stages have poor outcomes because of high rate of recurrence and metastasis. Biomarkers for predicting prognosis remain to be explored. This study aimed to evaluate the relationships between circulating tumor cells (CTCs) and outcomes of BC patients.

Patients and methods: A total of 50 female were enrolled in this study. Their diagnoses were determined by clinical characteristics, image data, and clinical pathology. CTC subtypes and TOP2A gene expression on CTCs were detected by CanPatrol™ technology and triple color in situ RNA hybridization (RNA-ISH), which divided into epithelial CTCs (eCTCs), mesenchymal CTCs (MCTCs), and hybrid CTCs (HCTCs) based on their surface markers. Hormone receptor, including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, was measured by immunohistochemistry (IHC) method before treatment. The risk factors for predicting recurrence and metastasis were calculated by COX risk regression model. The progression-free survival (PFS) of patients was determined using Kaplan-Meier survival curve.

Results: The patients with a large tumor size (≥ 3 cm) and advanced tumor node metastasis (TNM) stages had high total CTCs (TCTCs) (P < 0.05). These patients also had high TOP2A expression level. COX risk regression analysis indicated that TOP2A expression levels in TCTCs, ER + , HER-2 + , and TNM stages were critical risk factors for recurrence and metastasis of patients (P < 0.05). The PFS of patients with ≥ 5 TCTCs, ≥ 3 HCTCs, and positive TOP2A expression in ≥ 3 TCTCs was significantly longer than that in patient with < 5 TCTCs, < 3 HCTCs, and TOP2A expression in < 3 TCTCs (P < 0.05). In contrast, the PFS of patients with positive hormone receptors (ER + , PR + , HER-2 +) also was dramatically lived longer than that in patients with negative hormone receptor expression.

Conclusions: High TCTC, HCTCs, and positive TOP2A gene expression on CTCs were critical biomarkers for predicting outcomes of BC patients. Positive hormone receptor expression in BC patients has significant favor PFS.

BACKGROUND: Characteristics of taxane-induced peripheral neuropathy (PN) could be different between paclitaxel and nab-paclitaxel. The purpose of this prospective observational multicenter cohort study was to compare tri-weekly nab-paclitaxel to weekly standard paclitaxel regarding the severity, onset and recovery of sensory and motor PN in patients with breast cancer.

Methods: Patients with histologically confirmed breast cancer who were scheduled to receive standard weekly paclitaxel (80 mg/m²) or tri-weekly nab-paclitaxel (260 mg/m²) at institutions in our multicenter group were eligible for this study. Sensory and motor PN were evaluated every 3 weeks until PN improved for up to one year using patient-reported outcome.

Results: Between February 2011 and April 2013, 115 patients were enrolled, including 57 and 58 in the paclitaxel and nab-paclitaxel groups, respectively. The incidence of moderate or severe sensory PN was not significantly different between the two groups (p = 0.40). The incidence of moderate or higher motor PN was more frequent in the nab-paclitaxel group than in the paclitaxel group (p = 0.048). The median period for demonstrating PN were shorter in the nab-paclitaxel group than in the paclitaxel group (sensory, p = 0.003; motor, p = 0.001). The recovery of motor PN was slower in the nab-paclitaxel group than in the paclitaxel group (p = 0.035), while the recovery period of sensory PN was not statistically different.

Conclusion: Nab-paclitaxel induced sensory PN sooner than paclitaxel, and no difference was observed in the severity and recovery duration between the two agents. Motor PN was more severe, started sooner, and improved over a longer period in the nab-paclitaxel-treated patients than in the paclitaxel-treated patients.

The Japanese Breast Cancer Society Clinical Practice Guidelines are published as timely guidance on clinical issues in breast cancer treatment in Japan. In the recent edition of these guidelines, we addressed a new clinical question 34 (CQ 34, systemic treatment part) "Is trastuzumab deruxtecan recommended for patients with unresectable or metastatic HER2-low breast cancer?" and a new future research question 7 (FRQ 7, pathological diagnosis part) "How is HER2-low breast cancer diagnosed for the indication of trastuzumab deruxtecan?". These questions address use of trastuzumab deruxtecan in patients with unresectable or metastatic HER2-low breast cancer who have previously received chemotherapy for metastatic disease. The strengths of evidence and recommendation were determined through a quantitative and qualitative systematic review using multiple outcomes, including efficacy and safety. We conclude that trastuzumab deruxtecan is recommended for this patient population (strength of recommendation: 1; strength of evidence: moderate; CQ34) and that HER2-low expression for the indication of trastuzumab deruxtecan should be diagnosed using companion diagnostics based on appropriate criteria (FRQ7).

Purpose: Oncotype DX® is a frequently used multigene assay for hormone receptor-positive breast cancers. However, limited evidence is available regarding its application in Japan owing to the lack of insurance coverage. Therefore, we conducted this large-scale, retrospective study by collecting data from nine Japanese institutes and assessed postoperative treatment choice and prognosis by using Oncotype DX®.

Methods: Six hundred thirty-two patients who underwent breast surgery and whose recurrence score (RS) data were available were included. They were divided into RS 0-25 and RS ≥ 26 groups. The groups were compared in terms of clinicopathological factors, treatment options, and prognosis.

Results: After the median follow-up period of 10.1 years, the disease-free survival (DFS) rates were significantly better in the RS 0-25 group (p = 0.02). Per the recurrent event type, there was no significant intergroup difference in locoregional recurrence (p = 0.139). However, a trend toward better distant DFS was observed in the RS 0-25 group (p = 0.08). Overall survival was also significantly better in this group (p = 0.027). Considering chemotherapy use, DFS worsened among chemotherapy-treated patients with an RS of 0-25 and those with an RS ≥ 26 who did not receive chemotherapy (p < 0.001). Seven (1.35%) chemotherapy-treated patients with an RS of 0-25 showed disease recurrence.

Conclusions: This study presents the largest database-derived prognostic data in Japanese patients, utilizing the Oncotype DX® treatment selection. Further studies are needed to determine the impact on treatment choice, considering the clinical risk, and the need for additional postoperative treatment.

Background

Human epidermal growth factor receptor 2 (HER2)-low status has recently gained attention because of the potential therapeutic benefits of antibody–drug conjugates (ADCs) in breast cancer patients. We aimed to investigate the concordance of HER2 status between core needle biopsy (CNB) and subsequent surgical resection specimens focusing on the HER2-low status.

Methods

This retrospective study was conducted in 1,387 patients with invasive breast cancer whose HER2 status was evaluated in both CNB and surgical resection specimens. The discordance rates between CNB and surgical resection specimens and the clinicopathological features associated with HER2 status discordance were analyzed.

Results

The overall concordance rates of HER2 status between CNB and surgical resection specimens were 99.0% (κ = 0.925) for two-group classification (negative vs. positive) and 78.5% (κ = 0.587) for three-group classification (zero vs. low vs. positive). The largest discordance occurred in CNB-HER2-zero cases with 42.8% of them reclassified as HER2-low in surgical resection. HER2 discordance was associated with lower histologic grade, tumor multiplicity, and luminal A subtype. In multivariate analysis, tumor multiplicity and estrogen receptor (ER) positivity were independent predictive factors for HER2-zero to low conversion.

Conclusions

Incorporation of HER2-low category in HER2 status interpretation reduces the concordance rate between CNB and surgical resection specimens. Tumor multiplicity and ER positivity are predictive factors for conversion from HER2-zero to HER2-low status. Therefore, HER2 status should be re-evaluated in resection specimens when considering ADCs in tumors exhibiting multiplicity and ER positivity.