Translational breast cancer research : a journal focusing on translational research in breast cancer最新文献

Background: The redox status of nicotinamide adenine dinucleotide (NAD; including oxidized form NAD⁺ and reduced form NADH) plays key roles in both health and disease and has been actively studied to develop cancer biomarkers and therapeutic strategies. With the optical redox imaging (ORI) technique, we have been investigating the relationship of NADH redox status, reactive oxygen species (ROS), and invasiveness in breast cancer cell cultures, and have associated higher invasiveness with more oxidized NADH redox state. However, the cell cultures may have phenotypic drift and metabolic change with increased passage numbers.

Methods: We investigated the passage-dependence of NADH redox status and ROS levels in two triple-negative breast cancer (TNBC) cell cultures: the more invasive/metastatic MDA-MB-231 and the less invasive/metastatic HCC1806 cell lines. We measured the NADH redox status, redox plasticity, and cytoplasmic and mitochondrial ROS levels under the basal condition and metabolic perturbations of the mitochondrial electron transport chain. We evaluated the dependence of redox and ROS profiles on the cell passage number by comparing the early (<20 passages) with the late (>60 passages) passage cells.

Results: (I) NADH redox and ROS baselines are stable and independent of cell passage number, but can vary with passage number under metabolic perturbations depending on specific perturbation and cell line; (II) NADH redox status and intracellular ROS levels can change discordantly in cancer cells; (III) under both basal and metabolically perturbed conditions, the more invasive cell line has a more oxidized NADH redox status with a higher basal cytoplasmic ROS level than the less invasive line, regardless of passage number.

Conclusions: The general correlation between redox, ROS, and invasiveness in studied TNBC cells is not very sensitive to passage number. These results indicate that NADH redox and basal ROS status in TNBC likely reflect the intrinsic progressive nature of TNBC cells.

Human epidermal growth factor receptor 2 (HER2)-low breast cancer is a newly identified targetable subset of breast tumors, and its clinical characteristics and treatment strategies are controversial. The emergence of novel anti-HER2 antibody-drug conjugate (ADC) has brought promising approaches for HER2-low breast cancer treatment. Several clinical trials have validated the efficacy and safety of trastuzumab deruxtecan (T-Dxd) in HER2-low breast cancer at different treatment settings. The treatment timing, candidate identification, long-term management, and overcoming drug resistance are crucial questions to improve breast cancer patient survival. Here we present a clinical case of hormone receptor-positive (HR⁺) HER2-low breast cancer patient who experienced neoadjuvant chemotherapy, surgery, adjuvant, and first-line endocrine therapy with limited effectiveness. After the treatment failure of CDK4/6 inhibitors, the utilization of T-Dxd brought a long-term disease response and tolerable low toxicities. In this round table discussion, we summarized opinions and recommendations from breast cancer surgeons and oncologists on treatment strategies for this patient. The discussion mainly focused on the precise diagnosis of HER2-low breast cancer, treatment design at different disease status, regimens selection according to drug response, strategies consideration for overcoming drug resistance and the management of adverse events in long-term survival. These opinions would provide critical insights to improve HER2-low breast cancer treatment and offer valuable suggestions for clinical practice.

The phosphatidylinositol-3-kinase (PI3K) signaling plays a key role in various cellular functions and is frequently activated in cancer, making it an attractive therapeutic target. The PI3K signaling pathway influencing glucose metabolism, lipid synthesis, nucleotide production, and protein synthesis, all of which contribute to cancer cell proliferation and survival. It enhances glucose uptake through the activation of glucose transporters and glycolysis, while also promoting lipid synthesis via downstream factors like mTORC1. This pathway boosts nucleotide synthesis by regulating transcription factors like MYC, activating key enzymes for purine and pyrimidine production. Additionally, due to its essential role in cancer cell growth, the PI3K pathway is a key target for anticancer therapies. However, treatment using PI3K inhibitors alone has limitations, including drug resistance and significant side effects such as hyperglycemia, fatigue, and liver dysfunction. Clinical trials have led to the development of isoform-specific PI3K inhibitors to reduce toxicity. Combining PI3K inhibitors with other treatments, such as hormone therapy or surgery, may improve efficacy and minimize side effects. Further research is needed to fully understand the mechanisms of PI3K inhibitors and improve individualized treatment approaches. In this review, we introduce the characteristic of three classes of PI3Ks, discuss the regulation of cancer metabolism including the control of glucose uptake, glycolysis, de novo lipid synthesis, nucleotide synthesis and protein synthesis, and review the current statuses of different PI3K inhibitors therapy.

Breast ultrasound utilizes various scanning techniques to acquire optimal images for diagnostic evaluation. During interventional procedures, such as ultrasound-guided biopsies or preoperative localizations, knowledgeable and purposeful scanning adjustments are critical for successfully identifying the targeted mass or biopsy marker or clip. While most ultrasound scanning parameters are similar across different vendors, detailed descriptions specifically addressing the scanning parameters-often referred to as "knobology"- for breast ultrasound is at best limited in the literature. This review highlights ten key operator-controlled adjustments (including transducer selection, beam focusing, power, depth, gain and time gain compensation, harmonic imaging, spatial compounding, dynamic range, beam steering, and color Doppler) that significantly influence image quality in breast ultrasound. Each adjustment is accompanied by an "In practice" section providing examples and practical tips on implementation. The last topic discusses color Doppler which is generally used in breast ultrasound for evaluating the vascularity of a finding. Color Doppler, or more specifically, color Doppler twinkling, can be leveraged as a technique to detect certain breast biopsy markers that are challenging to detect by conventional B-mode ultrasound. While the cause of color Doppler twinkling is still under active investigation, twinkling is a clinically well-known, compelling ultrasound feature typically described with kidney stones. A step-by-step guide on how to use color Doppler twinkling to detect these markers is provided.

Background and objective: The novel antibody-drug conjugate (ADC) analogues are emerging in the field of human epidermal growth factor receptor 2 (HER2) low and ultralow breast cancer, and accurate screening of patients with HER2 low expression poses a serious challenge to both pathological testing processes and diagnostic assessment. The purpose is to provide some suggestions on how to correctly understand HER2 low and ultralow breast cancer.

Methods: This paper explores the clinicopathological features, immunohistochemical staining and its heterogeneity of HER2 low and ultralow expression breast cancer through literature search.

Key content and findings: This article mainly elaborates on four aspects: the differences in clinical pathological characteristics and prognosis between HER2 immunohistochemistry (IHC) low expression and ultralow expression, which are suitable for screening new detection methods for HER2 ultralow expression and HER2 unstained expression, the heterogeneity of HER2 low expression and ultralow expression, and the factors affecting the pre detection process of HER2 low expression and ultralow expression.

Conclusions: For the precise pathological diagnosis of HER2 ultralow expression and low expression, further standardization of the definition of HER2 low expression is needed to ensure consistency and accuracy in clinical practice. At the same time, it is recommended to reevaluate the HER2 status in the event of disease recurrence or metastasis, even if the previous test result is HER2-0. On the other hand, it is recommended to further improve and optimize detection techniques and methods, reduce false negatives and false positives, and enhance the sensitivity and specificity of detection.

Background and objective: The composition of gut microbiota plays an important role in predicting and influencing outcomes of cancer treated with immunotherapy. Our objective is to summarize the role of gut microbiota and immunotherapy in breast cancer.

Methods: A systematic search from inception until July 2024 of key search terms including immunity, breast neoplasm, gastrointestinal microbiome/microbiota, fecal microbiota transplantation, pro- and prebiotics, antibiotics and immunotherapy using EMBASE, MEDLINE and CENTRAL was conducted. The results were screened by two reviewers independently and synthesized and presented descriptively.

Key content and findings: Thirteen studies (5 clinical, 8 pre-clinical) met the eligibility criteria and were published from 2020-2024. Clinical studies showed that the composition and diversity of gut microbiota was associated with patient response to immunotherapy. In pre-clinical studies, dysbiotic states induced by obesity, antibiotics, and diet were associated with immunosuppression and influenced response to programmed cell death-ligand 1 (PD-L1) inhibitors. Microbiota-modulating treatments such as probiotics showed the ability to enhance response to immunotherapy, indicating their potential use as adjunct therapies in breast cancer treatment.

Conclusions: The composition of gut microbiota could help predict the chance of response to immunotherapy, and modulating gut microbiota has the potential to enhance the efficacy of chemo-immunotherapy in breast cancer. However, the available data relating to breast cancer are limited. Larger prospective studies are required to further elucidate their role as a biomarker and treatment.

Background and objective: Breast cancer was the second frequently diagnosed cancer in 2022 among all cancers. Besides classical chemotherapy and radiation, immunotherapy and targeted therapy are both identical treatment options for patients with advanced breast cancer. Immunotherapy is a therapeutic approach to control and eliminate tumors by restarting and maintaining the tumor-immunity cycle and restoring the body's normal anti-tumor immune response. Immunotherapy alone or in combination with other therapies has been shown to be clinically beneficial in a variety of solid tumors with a manageable safety profile. However, immunotherapy alone cannot fully satisfy the therapeutic needs for patients with breast cancer. Therefore, there is an urgent need for immunotherapy to be combined with other therapeutic approaches to increase treatment efficacy.

Methods: We systematically searched PubMed database for relevant studies published over the past 5 years. Articles were screened for eligibility and key data extracted.

Key content and findings: We assess the current breast cancer treatment landscape, summarizing efficacy and safety of recent immunotherapy, chemotherapy combined with immunotherapy, immunotherapy combined with anti-angiogenic therapy. In the treatment of breast cancer, aiming to promote further research and applications of this novel treatment regimen in patients with breast cancer. Since anti-angiogenic therapy can reprogramme the tumor immune microenvironment, immunotherapy in combination with anti-angiogenic therapy might have a synergistic effect, igniting a new hope for immunotherapy for breast cancer patients. The review's conclusions offer insightful information on the state of breast cancer treatment today. In the end, improving clinical practice and pertinent research for immunotherapy combination therapy will contribute to bettering patient outcomes, raising quality of life, and creating more potent treatments.

Conclusions: This review emphasizes the potential of immunotherapy combinations, especially with anti-angiogenic therapeutic regimens, as a viable strategy for the treatment of breast cancer through a thorough study of the literature. To improve treatment approaches, lessen side effects for patients, and find trustworthy biomarkers to forecast response to immunotherapy combo medicines, further research is necessary.

Background: Comprehensive treatment of breast cancer includes surgery, radiotherapy, chemotherapy, endocrine therapy, targeted therapy and immunotherapy, and the means are extremely rich. In recent years, the antibody-drug conjugates (ADCs) have become one of the significant treatment drugs for patients with human epidermal growth factor receptor 2 (HER2)-positive. ADCs provides new treatment options, and it improves outcomes and quality of life for patients with HER2-positive advanced breast cancer. However, we need to pay special attention to the adverse events (AEs) caused by ADCs, such as gastrointestinal reactions, bone marrow suppression, and interstitial lung disease (ILD), etc. At present, clinicians are in the initial stage of understanding the AEs caused by ADCs, and there is no expert consensus for the treatment on the AEs caused by ADC. For example, ILD caused by ADCs.

Case description: Here, we reported one case with HER2-positive advanced breast cancer. The patient was treated with ADCs of ARX-788 for third-line treatment, she had ILD. After treatment of ILD, the patient was treated with ADCs of trastuzumab-DM1 (T-DM1) for fourth-line treatment and she had ILD again. After suspension of such drugs, the patient's condition was stable without significant progress over 1 year.

Conclusions: For such patients, how to diagnose and treat them appropriately has become a new challenge for oncologists. Whether other anti-HER2 ADCs can be tried in the later lines is still being cautious. Whether there is a certain relationship between the side effects and efficacy of ADCs, there is no evidence-based data.