Rationale and trial design of NATALEE: a Phase III trial of adjuvant ribociclib + endocrine therapy versus endocrine therapy alone in patients with HR+/HER2− early breast cancer

Therapeutic Advances in Medical Oncology, Journal Year: 2023, Volume and Issue: 15

Published: Jan. 1, 2023

Background: Ribociclib has demonstrated a statistically significant overall survival benefit in pre- and postmenopausal patients with hormone receptor positive/human epidermal growth factor 2 negative (HR+/HER2−) advanced breast cancer. New Adjuvant Trial [LEE011] (NATALEE) is trial evaluating the efficacy safety of adjuvant ribociclib plus endocrine therapy (ET) versus ET alone HR+/HER2− early nonmetastatic cancer (EBC). Methods/design: NATALEE multicenter, randomized, open-label, Phase III EBC. Eligible include women, regardless menopausal status, men aged ⩾18 years. Select stage IIA, IIB, or disease (per anatomic classification AJCC Cancer Staging Manual, 8th edition) an initial diagnosis ⩽18 months prior to randomization are eligible. Patients receiving standard (neo)adjuvant eligible if treatment was initiated ⩽12 before randomization. undergo 1:1 400 mg/day (3 weeks on/1 week off) +ET (letrozole 2.5 anastrozole 1 [investigator’s discretion] goserelin [men premenopausal women]) alone. duration 36 months; ⩾60 months. The primary end point invasive disease-free survival. Discussion: 36-month extended compared that other cyclin-dependent kinases 4 6 (CDK4/6) inhibitor trials intended maximize due longer CDK4/6 inhibition. Compared 600-mg/day dose used cancer, reduced may improve tolerability while maintaining efficacy. includes broadest population EBC any currently treatment. registration: ClinicalTrials.gov identifier: NCT03701334 ( https://clinicaltrials.gov/ct2/show/NCT03701334 )

Language: Английский

---

Five-year relative survival by stage of breast and colon cancers in northern Italy

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Oct. 31, 2022

The aim of this study is to present the 5-year relative survival by stage breast and colorectal cancer patients in a northern Italian province. For period 2013-2015, cases were selected from Reggio Emilia Cancer Registry. Breast divided into 3 age groups: <45, 45-74 (the target screening population) 74+. Colorectal cancers classified <50, 50-69 population), over 69 years. Carcinomas situ unknown both excluded analyses. five-year was estimated using Pohar Perme method. During examined, 1,450 992 registered. Analyzing detail with for entire 2013-2015 period, we noted that 50.4% I, 33.6% II, 10.8% III 3.8% IV. only 1.3% (19 cases). data showed 24.5% 26.1% 23.4% III, 24.6% IV, 1.4% unknown. 100%, 89.7%, 71.4%, 29.1% stages respectively colon 96.7%, 83.4%, 70.8% 16.2%, respectively.The presence screening, associated effective treatments, account high rate early-stage cancers.

Language: Английский

---

Features and applications of Ehrlich tumor model in cancer studies: a literature review

Translational Breast Cancer Research, Journal Year: 2023, Volume and Issue: 4, P. 22 - 22

Published: July 1, 2023

Background and Objective: Breast cancer is the most prevalent worldwide, responsible for a large number of deaths, especially among women.Therapeutic options breast include surgery, radiotherapy, chemotherapy, hormone therapy, immunotherapy, but further studies pathogenesis this disease new treatments are still needed.In vitro in vivo models important research tools.Murine Ehrlich tumors one these models, hormone-positive cancer.The present narrative review discusses characteristics tumor model, laboratory manipulations cells (ECs), applications pharmacological, pathological, translational studies.Methods: This was based on scientific articles, books, theses tumors.We searched PubMed, SciELO, Google Scholar, Google, Clarivate databases.Key Content Findings: Hormone-positive ECs produce solid carcinoma (SEC) ascitic (AEC), with different features applications.The presence SEC or AEC induces systemic immunological alterations that similar to humans, what makes model applicable field.Conclusions: relevant tool improving our understanding investigating microenvironment, side effects therapies, treatment options.Despite some limitations, such as absence an invasive phenotype metastasis, both preclinical cancer.

Language: Английский

---

Prognostic value of adjuvant chemotherapy for hormone receptor-negative T1a and T1bN0M0 breast cancer patients

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 17, 2025

The benefit of adjuvant chemotherapy (CT) for hormone receptor-negative T1a and T1bN0M0 breast cancer remains uncertain. Our study was to explore prognostic value identify candidates CT these patients. data patients were extracted from the Surveillance, Epidemiology, End Results (SEER) database 2010 2015. All divided into two groups according history namely group no (No CT) group. Univariate multivariate Cox regression analysis utilized factors linked with specific survival (CSS) overall (OS) Kaplan-Meier method employed determine CT. A total 3889 included. After propensity score-matching, 1217 assigned No respectively. Based on OS, older age, single, T1b stage, triple-negative tumor absence identified as risk related OS. Besides, multivariable CSS showed significant association between grade III+IV, CSS. results curves revealed that could bring OS more than improve one factor. supports implementation individualized strategies Adjuvant recommended potential beneficial after undertaking a risk-benefit discussion.

Language: Английский

---

Clinician’s guide: expert insights on the use of CDK4/6 inhibitors in patients with early breast cancer

Therapeutic Advances in Medical Oncology, Journal Year: 2025, Volume and Issue: 17

Published: Jan. 1, 2025

The introduction of the cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors abemaciclib ribociclib to adjuvant setting marks a significant advancement in treatment hormone-receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer (HR+, HER2− EBC). Despite strides detection treatment, many patients continue face risk disease recurrence, highlighting need for more effective therapies. These CDK4/6 inhibitors, combined with endocrine therapy, have shown promising efficacy reducing recurrence rates while maintaining manageable safety profile, as evidenced by monarchE NATALEE trials. This paper explores integration into clinical practice, focusing on disease-free survival outcomes. Key considerations selecting between are discussed, including patient profiles, duration, individual preferences. In addition, we discuss managing adverse events prevent premature discontinuation, strategies that include dose holds, reductions, proactive symptom management, education. also highlights enhance medication adherence involvement multidisciplinary care teams support delivery. As research continues evolve, additional follow-ups trials future will further refine selection sequencing, ultimately improving outcomes enhancing quality life HR+, EBC.

Language: Английский

---

The diagnostic value of a breast cancer diagnosis model based on serum MiRNAs and serum tumor markers

World Journal of Surgical Oncology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 29, 2025

Abstract Background Breast cancer (BCa) is the leading cause of cancer-related death among women worldwide. MicroRNAs (miRNAs) are promising tools for diagnosis and prognosis. This study investigated role serum miRNAs tumor markers (TMs) in BCa. Methods Differentially expressed were screened from samples BCa patients healthy individuals via high-throughput sequencing. The expression hsa-miR-1911-3p, hsa-miR-4694-5p, hsa-miR-548ao-5p, hsa-miR-4804-3p 169 116 controls was detected qRT-PCR. Serum tumor-associated antigens by chemiluminescence. Logistic regression subsequently used to develop miRNA panel I, TM II, (miRNA + TM) III models. Receiver operating characteristic (ROC) curve, precision-recall (PR) curve decision analyses (DCA) performed assess accuracy three models diagnosis. Additionally, relationships between clinical characteristics with assessed. Results Four (hsa-miR-1911-3p, hsa-miR-4804-3p) newly associated I based on hsa-miR-548ao-5p showed greater diagnostic effectiveness than II antigen 125 (CA125) 153 (CA153), AUC values 0.816 0.777, respectively. had higher an value 0.870. miR-548ao-5p miR-4804-3p closely related features, such as human epidermal growth factor receptor 2 (HER2), estrogen (ER), progesterone (PR), HER2-enriched subtype, stage III/IV, lymph node-transplanted breast cancer. Conclusion MiR-548ao-5p miR-4804-3 could serve potential biomarkers

Language: Английский

---

Screening History, Stage at Diagnosis, and Mortality in Screen-Detected Breast Cancer

JAMA Network Open, Journal Year: 2025, Volume and Issue: 8(4), P. e255322 - e255322

Published: April 15, 2025

Importance Screening mammography promotes early detection of breast cancer and is associated with reduced mortality. history prior to diagnosis may impact stage at mortality but has not been comprehensively examined within a diverse US cohort. Objective To determine whether having screening earlier lower cancer–specific Design, Setting, Participants This cohort study used linked Surveillance, Epidemiology, End Results–Medicare data women aged least 70 years, diagnosed estrogen receptor–positive or human epidermal growth factor receptor 2–negative from 2010 2017, enrolled in fee-for-service Medicare Parts A B 5 years through 1 year after diagnosis. Data were analyzed March September 18, 2024. Exposure Presence more mammograms during the mammogram Main Outcomes Measures interest diagnosis, dichotomized into very (T1N0) vs later (T2+ N1+) Results Among 13 028 included women, most had (10 094 [77.5%]) between 79 (9034 [69.4%]) dual-eligible for Medicaid (11 475 [88.1%]). Additionally, 3812 (29.3%) later-stage disease time In multivariable analyses, was 54% odds (adjusted ratio, 0.46; 95% CI, 0.42-0.50) 36% hazard death 0.63; 0.52-0.76) compared no screenin. adjusted Cox proportional hazards model, 3 4 screenings 37% 0.44-0.89). Conclusions Relevance this older screen-detected cancer, These findings support potential routine improve outcomes. As all observational studies, limited by effects other differences nonscreening groups.

Language: Английский

---

The burden and long-term trends of breast cancer by different menopausal status in China

Journal of the National Cancer Center, Journal Year: 2024, Volume and Issue: 4(4), P. 326 - 334

Published: July 2, 2024

The burden of breast cancer in women different menopausal status has not been assessed China previously. We aim to evaluate and project the China.

Language: Английский

---

PSAT1 Promotes Metastasis via p-AKT/SP1/ITGA2 Axis in Estrogen Receptor-Negative Breast Cancer Cell

Biomolecules, Journal Year: 2024, Volume and Issue: 14(8), P. 990 - 990

Published: Aug. 12, 2024

Background: Accumulating evidence indicates that PSAT1 not only reprogrammed metabolic function but also exhibits “moonlighting” functions in promoting tumor malignancy. However, the underlying molecular mechanisms of ER-negative breast cancer cell migration need further investigation. Methods: Briefly, and ITGA2 expression cells tissues was detected using qRT-PCR, immunofluorescence staining western blot assay. The effect verified both vitro vivo. RNA-seq analysis explored a series differently expressed genes. regulation between SP1 investigated by ChIP analysis. Results: We reported highly ER-breast positively correlated with metastasis. Moreover, genes, including ITGA2, overexpressed cells. Mechanistically, facilitated metastasis via p-AKT/SP1/ITGA2 axis. elucidated promoted entry into nucleus through upregulation p-AKT confirmed is target SP1. In addition, enhanced remarkably reversed depletion or inhibitor treatment. Conclusion: This study clarified mechanism metastasis, which may provide mechanistic clues for attenuating

Language: Английский

---

Real-World Observational Study of Incidence and Outcomes in an HR+/HER2– Early Breast Cancer Population with High-Risk of Recurrence in Finland

Oncology and Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Real-world data on patients with early breast cancer (EBC) high-risk features remains limited. This population-based study determined the incidence, outcomes and characteristics of hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative EBC treated in everyday clinical care two Finnish hospital districts which represent approximately 40% (2.5 million) total population (5.5 million). Adult female BC (ICD-10 C50*) diagnosed between January 2012–June 2019 were indexed at first diagnosis followed until December or death. was defined as having no records metastasis within 90 days index. High-risk status ≥ 4 positive axillary lymph nodes (ALNs) 1–3 ALNs either grade 3 tumor size 5 cm. Outcomes included invasive disease-free survival (IDFS), distant relapse-free (DRFS) overall (OS) assessed using Kaplan-Meier methods Cox regression models. Among 8678 HR+/HER2– EBC, risk classification feasible 8081 (93.1%) individuals. Of these, 1407 (17.4%) remaining 6674 (82.6%) low-risk patients. The average annual incidence 2012–2018 21.8/100,000 women. Five-year (IDFS) recurrence-free showed higher recurrence for group: IDFS 79.7% (95% CI 77.0–82.2) vs 89.3% (88.3–90.2) group; DRFS 82.4% (79.7–84.7) 92.9% (92.1–93.7) low-risk. group 89.5% (87.3–91.4) 95.4% (94.7–96.0) group. that account 17% newly Finland. profile associated increased recurrence, relapse death compared to poorer emphasizes a clear unmet need improving identification treatment these most common type is cancer, means cells have HR but not HER2 their surface. Some HR-positive, HER2-negative stage may experience despite use standard adjuvant (i.e., post-surgical) treatment. It known high-grade (high aggressivity cells), high number affected armpit large are cancer-related A recent trial, called monarchE, utilized combination criteria define patient benefit from abemaciclib, cyclin-dependent kinase (CDK) 4/6 inhibitor, endocrine therapy. However, there limited occurrence rate this real world. specific monarchE routine These Moreover, had 3.8-fold experiencing beyond nearby who did features, they displayed reduced survival. consistently poor among emphasize an identifying improved treatments

Language: Английский

---