E.M. Ciruelos’s research while affiliated with SOLTI – Academic Research Group in Breast Cancer and other places

... and 62.3% (95% CI: 50.1-74.5) in the overall patient group and in patients with stable and active brain metastases, respectively [17]. None of these clinical trials reported on how many patients with brainstem metastasis were enrolled, but such patients were not specifically excluded from the trials [15][16][17]. ...

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Excellent response to trastuzumab deruxutecan of a large medullary metastasis from HER2-positive breast cancer: A case report

... HER2DX facilitates treatment decision-making in stage I-III HER2-positive breast cancer by integrating genomic profiling with a clinical factor-based model. 23 However, regarding HER2-positive MIBC, there is still a lack of studies exploring the efficacy of anti-HER2 therapy. ...

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The characteristics of HER2-positive microinvasive breast cancer and the necessity of systemic adjuvant therapy in these patients: a multicenter real-world study

... In addition, with improvements in systemic therapy efficacy and the rapid development of imaging techniques, the incidence of BCBM has increased in recent years (15,16). Systemic therapy has led to significant survival benefit in HER2-positive BCBMs, but due to the blood-brain barrier (BBB), which partially excludes macromolecules from the CNS compartment, it serves the main role in the control of the extracranial disease. ...

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Anti‑HER2‑targeted therapies for the treatment of advanced HER2‑positive breast cancer with brain metastases (Review)

... The ILD/pneumonitis occurred in 16% of patients in the BM cohort and 12.9% in the non-BM cohort, with some cases coinciding with opportunistic infections. T-DXd showed substantial intracranial and overall activity with no new safety flags, which supports its use in HER2-positive metastatic BC, including BM patients [22,24]. ...

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Advances in oncology after the 2024 European Society for Medical Oncology (ESMO) congress

... Clinically, HER2-positive tumors identified as HER2DX ERBB2-low across several studies in both early-stage and advanced HER2-positive disease seem to respond less effectively to anti-HER2-based therapy compared to HER2DX ERBB2-medium/high tumors. 12,13,19,20 ...

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HER2DX genomic test in early-stage HER2-positive breast cancer

... Various therapeutic approaches, including SERDs, SERCAs, PROTACs, CERANs, and other targeted drugs [10][11][12][13], have been explored to inhibit the metastatic potential of mutant ERα variants. Promisingly, clinical trials have demonstrated the e cacy of some of these agents, such as elacestrant [6] and camizestrant [5,7], in combating receptor mutations, leading to the approval of elacestrant for clinical use [2,6]. ...

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The natural L370F ERα Variant Confers Endocrine Resistance and Sensitivity to ATRA in Metastatic Breast Cancer Cells

... To date, no biomarker has been validated for predicting prognosis or treatment efficacy in advanced HER2+ breast cancer. However, in early-stage HER2+ breast cancer, the 27-gene HER2DX genomic assay, which provides a pathological complete response (pCR) likelihood score and a risk score, has demonstrated both prognostic and predictive value [12][13][14][15][16][17][18][19] . In addition, HER2DX provides the ERBB2 mRNA score, offering a continuous assessment of ERBB2 mRNA levels associated with HER2 protein expression, reported on a scale from 1 to 99 15 . ...

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HER2DX ERBB2 mRNA score in first-line advanced HER2-positive breast cancer treated with chemotherapy, trastuzumab, and pertuzumab

... Fourth, and of particular relevance for survival-related endpoints, the IMpassion031 trial was unblinded after pCR assessment and patients not experiencing a pCR were allowed standard systemic adjuvant chemotherapy at the investigator's discretion. This reflects the current standard of care in the postneoadjuvant setting based on the OS benefit from postoperative capecitabine in patients with residual disease after neoadjuvant chemotherapy 14 16 , which showed no improvement in the primary endpoint (EFS) with the addition of atezolizumab to a non-anthracycline-containing neoadjuvant regimen (without adjuvant atezolizumab continuation) 17 . They also contrast with the recently reported randomized phase 3 NSABP B-59/GBG 96-GeparDouze trial that did not show a significant improvement in EFS (primary endpoint) with atezolizumab given in combination with platinum-based neoadjuvant therapy and continued as adjuvant therapy 18 . ...

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Peri-operative atezolizumab in early-stage triple-negative breast cancer: final results and ctDNA analyses from the randomized phase 3 IMpassion031 trial

... The observation that imlunestrant achieved significant tumor and brain exposure in preclinical models indicated broad and extensive biodistribution, which may overcome the limitations of other SERDs. This was corroborated by clinical evidence in the EMBER-2 preoperative window of opportunity phase I study (NCT04647487), in which imlunestrant tumor exposures were significantly greater than plasma exposures, and consistent target engagement and pharmacodynamic biomarker modulation was demonstrated across all evaluated dose levels in patients with ER + , HER2 � early breast cancer (27). ...

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Imlunestrant Is an Oral, Brain-Penetrant Selective Estrogen Receptor Degrader with Potent Antitumor Activity in ESR1 Wild-Type and Mutant Breast Cancer

... Stem cell plasticity represents one of the major therapeutic challenges for differentiation therapies. Poorly differentiated tumors (portraying a mesenchymal phenotype) are better suited to tolerate chemotherapy, while well-differentiated tumors are more sensitive to treatment [203,204]. Plasticity can also dictate the changes between distinct CSC states such as ones with varying specialization for invasion and metastasis [205]. Cancer cell plasticity has been linked to the epithelial-mesenchymal transition program, which describes a constant shift through the spectrum of phenotypic states, capable of driving local invasion, generate cancer stem cells and facilitate metastasis by the dissemination of circulating tumor cells [206]. ...

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Prolonged Low-Dose Administration of FDA-Approved Drugs for Non-Cancer Conditions: A Review of Potential Targets in Cancer Cells