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

Background: Human epidermal growth factor receptor 2 (HER2) is an important driver gene and prognostic indicator of breast cancer and also a key predictor of HER2-targeted therapies. Both the low expression and the positive expression of the HER2 protein are clinically significant for disease treatment and prognosis.

Methods: (I) Establishment of expert group: the expert group consists of experts from departments such as medical oncology, breast surgery, and pathology; (II) literature search: mainly conducted in English databases (such as PubMed, Embase, and Cochrane Library) with a search cutoff date of June 1, 2025; (III) assessment of evidence quality and recommendation strength: evidence quality and recommendation opinions are graded based on the evidence category and recommendation level of the Chinese Society of Clinical Oncology (CSCO) guidelines.

Results: The emerging anti-HER2 drugs have greatly changed the diagnosis and treatment modalities of breast cancer and dramatically improved the prognosis of patients with HER2 expression in breast cancer. To optimize the treatment, an update of expert consensus on breast cancer with HER2 expression was made to adjust the different recommendation levels from early stage to metastatic stage. In this consensus, we also talk about the importance of clinical research, real-world evidence, biosimilars and so on.

Conclusions: The overarching goal of this consensus is to deliver individualized treatment strategies that not only prolong survival but also enhance quality of life, ensuring HER2-positive breast cancer patients receive the most advanced, patient-centered care available.

Background: There are limited clinical data to compare the efficacy of trastuzumab deruxtecan (T-DXd) between the immunohistochemistry (IHC) 1+ and 2+ subgroups of human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer (MBC). This study investigated the outcomes of T-DXd across distinct IHC statuses in HER2-low MBC.

Methods: Patients with HER2-low MBC treated with T-DXd from June 2022 to December 2023 at The Fifth Medical Centre of Chinese PLA General Hospital were enrolled. The IHC status of patients was defined by the higher IHC score between the primary and metastatic lesions. The primary study endpoint was progression-free survival (PFS), and the secondary endpoint was safety.

Results: Among the 70 patients, the IHC 1+ group comprised 37 patients, and the IHC 2+ group included 33 patients. Thirty-three (47.1%) patients had received ≥3 lines of chemotherapy before T-DXd treatment. The median initial T-DXd dose was 4.6 mg/kg [interquartile range (IQR): 3.7-5.3 mg/kg] every 3 weeks. A statistically significant difference in PFS was found between the IHC 1+ and 2+ groups in both univariate and multivariate analyses (median PFS: 3 vs. 5 months; adjusted hazard ratio: 0.51, 95% confidence interval: 0.28-0.95, P=0.03). The multivariate analysis also indicated that intensive prior chemotherapy and insufficient initial T-DXd doses might negatively impact the efficacy of T-DXd. The safety analysis showed similar profiles between the IHC 1+ and 2+ groups.

Conclusions: In real-world treatment scenarios, HER2-low MBC patients with higher IHC scores are more likely to benefit from T-DXd, regardless of whether the scores are detected from primary or metastatic lesions.

Breast cancer is the most commonly diagnosed cancer in women globally and remains the leading cause of cancer-related death among women. De novo metastatic breast cancer accounts for 5-10% of annual diagnoses, and approximately 30% of women with early-stage disease will eventually experience metastatic recurrence. Median survival varies by tumor subtype: 64-68 months for hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative cancers, 57-60 months for HER2-positive cancers, and around 13 months for triple-negative cancers. While current treatments-including chemotherapy, antibody-drug conjugates, endocrine therapy, HER2-targeted therapies, and immunotherapy-have significantly improved outcomes, resistance and disease progression remain ongoing challenges. Advances in next-generation sequencing (NGS) have enabled the identification of molecular alterations amenable to targeted therapy, underscoring the need for continued research into novel therapeutic targets. As more targeted agents become available and others are in development, staying informed about emerging targetable molecular alterations is increasingly essential. This review aims to summarize current data on targetable molecular alterations in metastatic breast cancer, focusing on available therapeutic options, key clinical trials, and practical insights for oncologists to support informed decision-making.

Background: Despite the benefits of breastfeeding to both infant and mother, many mothers find breastfeeding difficult secondary to many complications such as pain, breast engorgement, mastitis, and clogged milk ducts. The latter is typically treated conservatively with techniques such as gentle massage, breast pumping, and compresses. When conservative therapies are unsuccessful, more invasive options are considered to ensure the continuation of breastfeeding.

Case description: A 34-year-old lactating female presented with a 3-month history of worsening left breast and nipple pain radiating to the left upper outer quadrant, not relieved with conservative therapies. The physical exam revealed a small indentation and a small palpable nodule of the left nipple. There was no associated erythema or redness. Targeted ultrasound and subareolar magnification views revealed findings most consistent with a probably benign inspissated clogged milk duct. Given the patient's history, inability to express milk from the left breast, and plan to lactate for another year, ultrasound-guided aspiration was desired. Post-aspiration images demonstrated complete resolution of the nipple mass. Pathology revealed blood and proteinaceous material, in keeping with the diagnosis of inspissated clogged milk duct. Following the procedure, the patient's symptoms resolved completely.

Conclusions: We present a case of irretractable milk duct plug treated with ultrasound-guided direct aspiration of the plug with complete resolution and minimal side effects to the patient.

For hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (BC), the combinations of endocrine therapy (ET) and cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are considered the standard first-line treatment. However, the unfortunate reality is that most patients will eventually develop drug resistance, necessitating the exploration of effective treatment strategies. Multiple treatment options exist, including phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) inhibitors, histone deacetylase (HDAC) inhibitors, oral selective estrogen receptor degraders (SERDs), and antibody-drug conjugates (ADCs), yet no optimal treatment sequence has been established. The activation of the PI3K/AKT/phosphatase and tensin homolog (PTEN) signaling pathway is significantly associated with resistance to ET and CDK4/6i in patients with HR+/HER2- BC, highlighting the need for targeted interventions. In light of this, antitumor therapies targeting key molecules within this pathway have become a hot spot in current BC research. With the rapid development of precision diagnosis and treatment of BC, the importance of detecting mutant genes in the PI3K/AKT/PTEN signaling pathway is increasingly coming to the fore, especially concerning test timing, sample selection, and detection methods. This article aims to discuss in depth the treatment landscape of HR+/HER2- advanced BC, the development of PI3K/AKT/PTEN signaling pathway inhibitors, and underscore the importance of mutation detection in promoting the precision diagnosis and treatment of HR+/HER2- BC. Understanding these aspects is critical to developing more effective personalized treatment strategies that can overcome CDK4/6i resistance and improve outcomes for patients with this challenging disease.

Antibody-drug conjugates (ADCs) have become the standard of care for metastatic advanced breast cancers, regardless of tumour subtype. Optimal positioning and treatment sequences are being studied, and many new therapies and combinations are also under development. Research into the application of ADC to early breast cancer is spreading. More than 10 clinical trials are being conducted regarding escalation and de-escalation of systemic treatment. In addition, in the sequence of neoadjuvant and adjuvant therapy, multiple key issues are investigated, such as effective sequences of treatments among ADC, cytotoxic chemotherapy, immunotherapy, and anti-human epidermal growth factor receptor 2 antibody therapy to improve treatment response, prognosis and quality of life (QOL). The postoperative activity of ADC with topoisomerase inhibitors for residual diseases is also being studied in post-neoadjuvant therapy settings. At the same time, many studies have focused on the appropriate timing of surgical therapy and response-guided approach. On the other hand, ADCs can cause serious side effects, although these are infrequent. Therefore, careful management is necessary during both pre-operative and post-operative adjuvant therapy. It is also crucial to focus on developing prognostic and predictive biomarkers to assess efficacy, alongside monitoring markers through translational research and image analysis. This review summarizes the development trends in both neoadjuvant and adjuvant settings, as well as recent data on ADCs for primary breast cancer, while addressing unresolved clinical questions. It discusses the escalation and optimization of treatment for primary breast cancer using ADCs, along with the relevant challenges and perspectives.

Background: Triple-negative breast cancer (TNBC) is a distinct form of breast cancer that poses a significant threat to patients due to its high invasiveness, high recurrence and metastasis rates, and its lack of clear and definitive therapeutic targets. Cysteine-rich intestinal protein 2 (CRIP2, GeneID 1397) plays a role in many diseases, including cancer. However, its effect on proliferation and invasion of TNBC and its mechanism are not yet fully elucidated. The study aims to investigate the role and mechanism of CRIP2 (GeneID 1397) in the development and progression of TNBC and preliminary exploration of the relationship between CRIP2 and MAP2K4.

Methods: Bioinformatics tools, GEPIA and UALCAN, were used to analyze CRIP2 expression in breast cancer tissues and normal breast tissues from The Cancer Genome Atlas (TCGA) database. Western blot (WB) was utilized to detect the expression differences of CRIP2 in normal breast epithelial cells and breast cancer cells. The effects of CRIP2 on breast cancer cell proliferation were examined using Cell Counting Kit-8 (CCK-8) and EdU assays. The impact of CRIP2 on breast cancer cell migration and invasion was assessed through Transwell assays. The influence of CRIP2 on NF-κB pathway marker proteins p65 and phosphorylated p65 was evaluated by WB. Potential interacting proteins of CRIP2 were predicted using the Biogrid database.

Results: (I) UALCAN and GEPIA databases revealed that CRIP2 expression is higher in breast cancer tissues compared to normal breast tissues. (II) CCLE database cell expression profiles and WB showed that CRIP2 expression in TNBC cells is lower than in other breast cancer subtypes. (III) CCK-8, EdU, and Transwell assays confirmed that upregulating CRIP2 inhibits the proliferation, migration, and invasion capacities of MDA-MB-231 cells. (IV) WB indicated that upregulating CRIP2 can inhibit the expression of phosphorylated p65 protein. (V) Upregulation of CRIP2 can reverse the proliferation, migration, and invasion capacities of breast cancer cells overexpressing MAP2K4.

Conclusions: Up-regulation of CRIP2 inhibits the proliferation, migration and invasive capacity of MDA-MB-231 cells, up-regulation of CRIP2 inhibits P65 phosphorylation, over-expression of MAP2K4 down-regulates CRIP2 expression, and up-regulation of CRIP2 reverses the ability of MAP2K4 over-expression to promote the malignant phenotype of breast cancer.

Approximately 60% of human epidermal growth factor receptor 2-negative (HER2-) breast cancers (BCs) are HER2-low [immunohistochemistry (IHC) 1+ or 2+/in situ hybridization (ISH)-]. The proportion of BC patients with hormone receptor-positive (HR+)/HER2- are more likely to metastasize to bone. The phase 3 Destiny-Breast04 study led to the approval of the antibody drug conjugate trastuzumab deruxtecan (T-DXd) in HER2-low patients, even HR+, after lines of endocrine therapy and one line of chemotherapy. Recently, the Destiny-Breast06 study showed a progression-free survival advantage of T-DXd also in first-line. T-DXd has an immunological effect as it can produce antibody-dependent cellular cytotoxicity-like effects by recruiting dendritic cells and CD8+ T cells. This immunological effect can be enhanced using immune checkpoint inhibitors but also the anti-RANK-ligand (RANKL) antibody denosumab, which can be used for the prevention of skeletal-related events (SREs). RANK modulates HER2-driven carcinogenesis because both RANK and HER2 activate nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Thus, increased RANK signaling may contribute to the development of resistance to anti-HER2 therapy through NF-κB activation. It remains to be seen whether patients with HER2-positive or HER2-low BC that express RANK may benefit from concomitant HER2 and RANK inhibition therapy. Except for the Destiny-Breast06 study, which included only 3% of enrolled patients with exclusive bone metastases, we have no clinical data on the efficacy of T-DXd in bone metastases and on the concomitant use of T-DXd and denosumab, although the biological rationale for the increased efficacy of the combination is strong.

Background and objective: Adjuvant partial breast irradiation (PBI) is a well-established treatment for appropriately selected women with early-stage breast cancer. Preoperative PBI is a newer approach with some advantages compared to post-operative PBI, including potential for decreased toxicity, tumor response assessment, treatment stratification, and prognostication. Here, we summarize emerging data from prospective studies demonstrating safety and efficacy of preoperative PBI and explore techniques for assessing tumor response. We further review ongoing studies and discuss the intriguing possibility of utilizing this technique to adopt a non-operative approach for select patients with early-stage breast cancer.

Methods: We conducted a comprehensive literature search utilizing PubMed and ClinicalTrials.gov prior to August 01, 2024 to identify prospective studies in English documenting outcomes for women treated with a neoadjuvant partial breast approach. We utilized keywords of "partial breast radiation", "breast cancer radiation", "breast cancer radiotherapy", "partial breast radiotherapy for breast cancer".

Key content and findings: A growing number of prospective studies demonstrate that preoperative PBI may be a safe and effective alternative to postoperative PBI for appropriately selected patients with early-stage breast cancer. A subset of women treated with preoperative PBI achieve a pathologic complete response (pCR) following treatment. However, careful preoperative evaluation is critical to select patients suitable for a partial breast approach to avoid overtreatment.

Conclusions: Preoperative PBI is a promising alternative to traditional postoperative radiotherapy for appropriately selected women with early-stage breast cancer. Further prospective studies are necessary to further refine understanding of the optimal selection criteria and clinical outcomes for patients treated with this approach.