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Keywords = HR+/HER2− advanced or metastatic breast cancer

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14 pages, 1279 KiB  
Article
Real-World Toxicity and Effectiveness Study of Abemaciclib in Greek Patients with Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: A Multi-Institutional Study
by Elena Fountzilas, Eleni Aravantinou-Fatorou, Katerina Dadouli, Panagiota Economopoulou, Dimitrios Tryfonopoulos, Anastasia Vernadou, Eleftherios Vorrias, Anastasios Vagionas, Adamantia Nikolaidi, Sofia Karageorgopoulou, Anna Koumarianou, Ioannis Boukovinas, Davide Mauri, Stefania Kokkali, Athina Christopoulou, Nikolaos Tsoukalas, Avraam Assi, Nikolaos Spathas, Paris Kosmidis, Angelos Koutras, George Fountzilas and Amanda Psyrriadd Show full author list remove Hide full author list
Cancers 2025, 17(15), 2543; https://doi.org/10.3390/cancers17152543 - 31 Jul 2025
Viewed by 129
Abstract
Background/Objectives: This study aimed to assess real-world toxicity and efficacy data of patients with early and advanced breast cancer (BC) who received treatment with abemaciclib. Methods: This was a prospective/retrospective multi-institutional collection of clinicopathological, toxicity, and outcome data from patients with early or [...] Read more.
Background/Objectives: This study aimed to assess real-world toxicity and efficacy data of patients with early and advanced breast cancer (BC) who received treatment with abemaciclib. Methods: This was a prospective/retrospective multi-institutional collection of clinicopathological, toxicity, and outcome data from patients with early or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative BC who received treatment with abemaciclib in combination with endocrine therapy in departments of oncology in Greece. Treatment combinations of abemaciclib with any endocrine therapy were accepted. The primary end point was toxicity rate in all patients of the study. Results: From June/2021 to May/2024, 245 women received abemaciclib/endocrine combination therapy; the median age was 57 years. Of these, 169 (69%) received abemaciclib as adjuvant therapy for early-stage disease, while 76 (31%) were treated for advanced BC. At the time of the data cutoff, 133 (84.7%) patients remained in the 2-year treatment period. The most common adverse event (AE) was diarrhea (51%), primarily Grade ≤ 2. Dose modifications due to AEs were required in 19.2% of cases, while treatment discontinuation occurred in 5.1%. There was no difference in dose modification/discontinuation rates between older patients (>65 years) and the remaining patients. For early-stage BC patients, the 2-year DFS and OS rates were 90.8% and 100%, respectively. In patients with advanced cancer (70, 30.8%), 1-year PFS and OS rates were 78% and 96.3%, respectively. Conclusions: This study confirms the safety and effectiveness of abemaciclib in alignment with registrational trials offering valuable insights into toxicity management and clinical outcomes in routine practice without identifying new safety concerns. Clinical Trial Registration: ClinicalTrials.gov NCT04985058. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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12 pages, 535 KiB  
Review
The Role of Immunotherapy and Immune Modulators in Hormone-Positive Breast Cancer: Implications for Localized and Metastatic Disease
by Justin O’Farrell, Caroline Lapp, Heidi Kuznia and Muhammad Z. Afzal
J. Clin. Med. 2025, 14(12), 4322; https://doi.org/10.3390/jcm14124322 - 17 Jun 2025
Viewed by 647
Abstract
Background: Hormone receptor-positive (HR+) breast cancer, which accounts for approximately 70% of all breast cancer cases, is primarily treated with endocrine therapies as monotherapy or in combination with other targeted therapies and traditional cytotoxic therapy. While these therapies have significantly improved survival [...] Read more.
Background: Hormone receptor-positive (HR+) breast cancer, which accounts for approximately 70% of all breast cancer cases, is primarily treated with endocrine therapies as monotherapy or in combination with other targeted therapies and traditional cytotoxic therapy. While these therapies have significantly improved survival outcomes, resistance often develops, especially in metastatic disease where treatment options are limited. Immunotherapy, particularly immune checkpoint inhibitors, has emerged as a promising adjunct to traditional therapies in triple negative breast cancer. However, its role in HR+ breast cancer is not well established yet and is under active investigation. In addition, a deeper understanding of the tumor microenvironment (TME) and its role in immune evasion has spurred interest in immune modulators as additional potential therapeutic strategies for HR+ breast cancers. Objective: This review aims to synthesize the current evidence on the role of immunotherapy in HR+ breast cancer, with a focus on its clinical application in both localized and metastatic disease. It also explores the impact of immune modulators within the TME, highlighting their potential to improve the efficacy of immunotherapy in this subtype of breast cancer. Methods: A thorough review of recent clinical trials, preclinical studies, and meta-analyses was conducted. Studies published from 2015 to 2024 were included to provide the most up-to-date perspectives. Key Findings: While immune checkpoint inhibitors like pembrolizumab and atezolizumab have shown promising results in combination with chemotherapy for triple negative breast cancer, their efficacy in HR+ breast cancer has generally been modest. However, recent studies indicate that such therapies may help overcome endocrine resistance in metastatic disease. Furthermore, immune modulators, including cytokines and myeloid-derived suppressor cell inhibitors, are being investigated for their ability to reshape the TME, potentially enhancing the immune response and improving treatment outcomes. Despite these advances, challenges remain in identifying predictive biomarkers and managing immune-related adverse events. Conclusions: Immunotherapy holds potential for improving outcomes in HR+ breast cancer, particularly in metastatic settings where treatment options are limited. The integration of immune modulators to enhance therapeutic efficacy in HR+ breast cancer, along with ongoing research into biomarkers, promises to refine patient selection and improve clinical outcomes. Full article
(This article belongs to the Section Oncology)
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10 pages, 419 KiB  
Article
Trastuzumab Deruxtecan in Previously Treated HER2-Low Metastatic Breast Cancer: Real-World Multicentric Study in the Portuguese Population
by Luísa Soares Miranda, Maria João Sousa, Miguel Martins Braga, Marisa Couto, Isabel Vieira Fernandes, Francisca Abreu, Inês Eiriz, Catarina Lopes Fernandes, Alice Fonseca Marques, Maria Teresa Marques, Raquel Romão, Fernando Gonçalves, Joana Simões and António Araújo
Cancers 2025, 17(12), 1911; https://doi.org/10.3390/cancers17121911 - 9 Jun 2025
Viewed by 1126
Abstract
Background/Objectives: Breast cancer is the most common malignant neoplasm in women and the leading cause of cancer-related death. Approximately 50% of HER2-negative breast cancers exhibit low expression of this protein (HER2-low). Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate targeting the HER2 [...] Read more.
Background/Objectives: Breast cancer is the most common malignant neoplasm in women and the leading cause of cancer-related death. Approximately 50% of HER2-negative breast cancers exhibit low expression of this protein (HER2-low). Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate targeting the HER2 receptor which has shown benefit in patients with HER2-low metastatic breast cancer in the DESTINY-Breast04 study. However, few data are available on its efficacy in real-world practice. Methods: We conducted a retrospective multicenter national study (eight centers) including patients with advanced HER2-low breast cancer (immunohistochemistry 1+ or 2+/ in situ hybridization negative) who started T-DXd treatment between January 2022 and March 2024. Patients had received at least one previous line of treatment. The primary endpoint was real-world progression-free survival (rwPFS) in patients with metastatic HER2-low breast cancer treated with T-DXd. The secondary endpoints were real-world overall survival (OS) and objective response rate (ORR). Results: The study included 35 patients (34 female and 1 male patient), with a median age of 54 years at the start of T-DXd. All patients had an ECOG-PS 0–1, and 26 patients (74%) had hormone receptor (HR)-positive disease. The median number of prior lines of treatment was 4 [1–7], and 23 patients (65.8%) had metastases in three or more sites. With a median follow-up of 7.8 months, rwPFS was 6 months (95% CI, 2.3–9.7), and OS was 15 months (95% CI, 4.7–25.3). In HR-positive patients, the median rwPFS was 6 months (95% CI, 1.2–10.7), compared to 4 months (95% CI, 2.1–5.9) in HR-negative patients. The overall ORR was 52.9%. Adverse events of grade 3 or higher were neutropenia (2.9%) and fatigue (2.9%). Conclusions: This study provides real-world data on T-DXd in the treatment of advanced HER2-low breast cancer. It is noteworthy that the population was heavily pre-treated and had a higher proportion of HR-negative patients, which may explain the lower efficacy compared to the DESTINY-Breast04 study. Full article
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25 pages, 3297 KiB  
Article
TreC_Metha: A Digital Application to Enhance Patient Agency, Therapy Compliance and Quality of Life in Metastatic Breast Cancer Patients
by Antonella Ferro, Maria Chiara Pavesi, Lucia Pederiva and Claudio Eccher
Curr. Oncol. 2025, 32(6), 299; https://doi.org/10.3390/curroncol32060299 - 23 May 2025
Viewed by 641
Abstract
The prognosis for Hormonal Receptor positive-HER2-negative (HR+ HER2-negative) metastatic breast cancer (mBC) has significantly improved by advances in hormone therapies, targeted drugs, and antibody–drug conjugates (ADCs). Nevertheless, maintaining quality of life (QoL), managing symptoms, and reducing treatment-related toxicity remain essential. Background: eHealth solutions [...] Read more.
The prognosis for Hormonal Receptor positive-HER2-negative (HR+ HER2-negative) metastatic breast cancer (mBC) has significantly improved by advances in hormone therapies, targeted drugs, and antibody–drug conjugates (ADCs). Nevertheless, maintaining quality of life (QoL), managing symptoms, and reducing treatment-related toxicity remain essential. Background: eHealth solutions offer new opportunities to enhance patient engagement and well-being through digital tools. This paper aims to delineate the fundamental functionalities and objectives of TreC_Metha, a technologically advanced instrument to provide effective support during all care process of patients diagnosed with HR+HER2-negative mBC able to proactively change its configuration depending on the treatment line or on the intra-line treatment phase the patient undergoes, as set by the healthcare team. Methods: The TreC_Metha platform was developed through a structured, evidence-based four-phase process aimed at scalability, usability, and clinical relevance. The development began with a formal analysis of the metastatic breast cancer (mBC) care pathway using BPMN modeling to map phases, activities, and stakeholders, highlighting differences from early-stage breast cancer. This analysis informed the identification of key points where digital support could enhance care. Patient needs were assessed through a web-based questionnaire (N = 20) and two focus groups (N = 11), enabling a participatory design approach. Based on these insights, the platform’s functional and non-functional requirements were defined, leading to the design and implementation of a patient-facing mobile app and a clinical dashboard tailored to mBC-specific needs. Results: Preliminary findings from the web survey focus groups revealed significant gaps in communication and information delivery during the mBC care journey, contributing to patient anxiety and reduced confidence. Participants expressed a preference for digital and printed resources to improve understanding and facilitate interactions with healthcare providers. These insights informed the development of the TreC_Metha platform. The clinical dashboard enables real-time monitoring and decision-making, while the mobile app supports bidirectional communication, therapy adherence, and patient-reported data collection. A system prototype is currently under refinement and will undergo usability testing with a small cohort of users. Following this phase, the pilot study will evaluate the platform’s impact on QoL, aiming for a ≥10% improvement in outcome measures and contributing to a more patient-centered care model in the mBC setting. Conclusions: TreC_Metha represents an innovative tool that may enable involvement and active participation in the mBC care process for both a multidisciplinary care team of professionals and the patient, and that can be easily adapted to other cancer types and chronic diseases. Full article
(This article belongs to the Section Breast Cancer)
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13 pages, 1231 KiB  
Protocol
Real-World, National Study of Palbociclib in HR+/HER2− Metastatic Breast Cancer: A 2.5-Year Follow-Up PALBO01/2021
by Cristina Marinela Oprean, Larisa Maria Badau, Ramona Petrita, Mircea Dragos Median and Alis Dema
Diagnostics 2025, 15(9), 1173; https://doi.org/10.3390/diagnostics15091173 - 5 May 2025
Cited by 1 | Viewed by 1051
Abstract
Background: Palbociclib, when combined with endocrine therapy, represents a valuable treatment option for patients diagnosed with hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative advanced breast cancer (BC) or metastatic breast cancer (MBC). Approved in Europe following phase II/III trials, [...] Read more.
Background: Palbociclib, when combined with endocrine therapy, represents a valuable treatment option for patients diagnosed with hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative advanced breast cancer (BC) or metastatic breast cancer (MBC). Approved in Europe following phase II/III trials, it became the first CDK4/6 inhibitor used alongside hormone therapy. Available real-world data demonstrate the strong performance of Palbociclib in unselected, heavily pretreated patient groups. Our retrospective, observational, multicenter study, conducted in six Romanian institutions during a follow-up period of 2.5 years, aimed to assess Palbociclib’s safety and effectiveness in clinical practice. Objectives: The primary endpoints included response rate such as overall response rate (ORR), duration of response (DOR), disease control rate (DCR) and best clinical response (BCR), progression free survival (PFS) and overall survival (OS). The secondary objectives focused on treatment duration with aromatase inhibitors (AI) or fulvestrant and subsequent therapies after disease progression. Grade 3/4 adverse events were individually recorded. Exploratory analysis evaluated the potential predictive biomarkers such as Ki67, lower levels of HER2 expression (HER2-low), and histological or luminal subtype. Methods: Approximately 650 patients were planned for inclusion. PFS and OS were analyzed via the Kaplan–Meier method, with median times, 1- and 2-year estimates, and 95% confidence intervals reported. Conclusions: This study supports the integration of clinical trial evidence into real-world settings, enhancing patient selection and treatment personalization. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Prognosis of Breast Cancer)
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23 pages, 9992 KiB  
Article
The Influence of AQP5 on the Response to Hydrogen Peroxide in Breast Cancer Cell Lines
by Ivan Lučić, Monika Mlinarić, Ana Čipak Gašparović and Lidija Milković
Int. J. Mol. Sci. 2025, 26(7), 3243; https://doi.org/10.3390/ijms26073243 - 31 Mar 2025
Viewed by 934
Abstract
Breast cancer is a heterogeneous disease with varying responses to therapies. While targeted treatments have advanced, conventional therapies inducing oxidative stress remain widely used. H2O2 has emerged as a therapeutic candidate due to its role in signaling and cell-function regulation. [...] Read more.
Breast cancer is a heterogeneous disease with varying responses to therapies. While targeted treatments have advanced, conventional therapies inducing oxidative stress remain widely used. H2O2 has emerged as a therapeutic candidate due to its role in signaling and cell-function regulation. Its transport is tightly regulated through peroxiporins such as AQP5, expression of which is linked to poor prognosis and metastatic spread, and its role in therapy resistance remains underexplored. This study examined AQP5’s role in the acute oxidative stress response. We overexpressed AQP5 in breast cancer cell lines with low basal levels—HR+ (MCF7), HER2+ (SkBr-3), and TNBC (SUM 159)—and exposed them to H2O2 for 24 h. We assessed cell viability, intracellular ROS, changes in AQP3 and AQP5, and key antioxidative and cancer-related pathways (NRF2, PI3K/AKT, FOXOs). AQP5 overexpression elicited a cell-type-specific response. H2O2 treatment reduced viability in SkBr-3-AQP5 and MCF7-AQP5 cells, increased ROS levels in MCF7-AQP5, and decreased ROS in SUM 159-AQP5. It also increased AQP3 in MCF7-AQP5 and differentially affected NRF2, FOXOs, and PI3K/AKT signaling, notably activating NRF2/AKR1B10 axis in MCF7-AQP5 and decreasing FOXO1 in SUM 159-AQP5. These findings highlight the need for further research into AQP5’s role in the oxidative stress response in breast cancer cells. Full article
(This article belongs to the Special Issue New Players in the Research of Oxidative Stress and Cancer)
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15 pages, 1086 KiB  
Article
Oncologic Outcomes of Breast-Conserving Surgery in a Colombian Cancer Center: An Observational, Analytical, Retrospective Cohort Study
by Sandra E. Díaz-Casas, Flavio J. Rosero-Díazdel Castillo, Sara Mendoza-Díaz, Andersson Sáenz-Ladino, Ricardo Sánchez-Pedraza, Sonia P. Silva-Cárdenas, Andrea Zuluaga-Liberato, Ximena Briceño-Morales, Luis Guzmán-AbiSaab, Óscar Gamboa-Garay, Javier Ángel-Aristizábal, Iván Mariño-Lozano, Raúl Suárez-Rodríguez, Mauricio García-Mora, Carlos Duarte-Torres and Marcela Núñez-Lemus
Cancers 2025, 17(7), 1131; https://doi.org/10.3390/cancers17071131 - 28 Mar 2025
Viewed by 613
Abstract
Background: Breast-conserving surgery (BCS) is one of the major surgical advances in breast cancer treatment. This study evaluated the oncological outcomes of BCS in patients with non-metastatic breast cancer at a referral cancer center in a medium-resource country between 2013 and 2019. Methods: [...] Read more.
Background: Breast-conserving surgery (BCS) is one of the major surgical advances in breast cancer treatment. This study evaluated the oncological outcomes of BCS in patients with non-metastatic breast cancer at a referral cancer center in a medium-resource country between 2013 and 2019. Methods: An observational, analytical, retrospective cohort study was conducted on patients with stage I–IIIC breast cancer treated at the Instituto Nacional de Cancerología (Bogotá, Colombia) from September 2013 to March 2019. Demographic data, tumor characteristics, treatment types, and survival outcomes were retrospectively collected. Results: A total of 409 patients were included. In 64.1% of cases, BCS was performed as the initial treatment and in 35.9%, after neoadjuvant chemotherapy (NACT). With a median follow-up of 85.2 months, tumor recurrence was documented in 9.04% of patients, local recurrence in 2.9%, regional in 2.2%, and distant in 5.6%. The identified risk factors for mortality were a locally advanced clinical stage (HR 5.13; p = 0.01), triple-negative subtype (HR 8.02; p < 0.01), and nodal involvement of more than four lymph nodes in the surgical specimen (HR 4.00; p < 0.01). Conclusions: Breast-conserving surgery is an oncologically safe procedure for patients with early and locally advanced breast cancer who respond to NACT. The time to recurrence and overall survival are determined by the clinical stage, axillary tumor burden, and biological subtype of the disease. Full article
(This article belongs to the Section Cancer Therapy)
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15 pages, 1758 KiB  
Article
The Extent to Which Artificial Intelligence Can Help Fulfill Metastatic Breast Cancer Patient Healthcare Needs: A Mixed-Methods Study
by Yvonne W. Leung, Jeremiah So, Avneet Sidhu, Veenaajaa Asokan, Mathew Gancarz, Vishrut Bharatkumar Gajjar, Ankita Patel, Janice M. Li, Denis Kwok, Michelle B. Nadler, Danielle Cuthbert, Philippe L. Benard, Vikaash Kumar, Terry Cheng, Janet Papadakos, Tina Papadakos, Tran Truong, Mike Lovas and Jiahui Wong
Curr. Oncol. 2025, 32(3), 145; https://doi.org/10.3390/curroncol32030145 - 2 Mar 2025
Cited by 1 | Viewed by 2062
Abstract
The Artificial Intelligence Patient Librarian (AIPL) was designed to meet the psychosocial and supportive care needs of Metastatic Breast Cancer (MBC) patients with HR+/HER2− subtypes. AIPL provides conversational patient education, answers user questions, and offers tailored online resource recommendations. This study, conducted in [...] Read more.
The Artificial Intelligence Patient Librarian (AIPL) was designed to meet the psychosocial and supportive care needs of Metastatic Breast Cancer (MBC) patients with HR+/HER2− subtypes. AIPL provides conversational patient education, answers user questions, and offers tailored online resource recommendations. This study, conducted in three phases, assessed AIPL’s impact on patients’ ability to manage their advanced disease. In Phase 1, educational content was adapted for chatbot delivery, and over 100 credible online resources were annotated using a Convolutional Neural Network (CNN) to drive recommendations. Phase 2 involved 42 participants who completed pre- and post-surveys after using AIPL for two weeks. The surveys measured patient activation using the Patient Activation Measure (PAM) tool and evaluated user experience with the System Usability Scale (SUS). Phase 3 included focus groups to explore user experiences in depth. Of the 42 participants, 36 completed the study, with 10 participating in focus groups. Most participants were aged 40–64. PAM scores showed no significant differences between pre-survey (mean = 59.33, SD = 5.19) and post-survey (mean = 59.22, SD = 6.16), while SUS scores indicated good usability. Thematic analysis revealed four key themes: AIPL offers basic wellness and health guidance, provides limited support for managing relationships, offers limited condition-specific medical information, and is unable to offer hope to patients. Despite showing no impact on the PAM, possibly due to high baseline activation, AIPL demonstrated good usability and met basic information needs, particularly for newly diagnosed MBC patients. Future iterations will incorporate a large language model (LLM) to provide more comprehensive and personalized assistance. Full article
(This article belongs to the Section Breast Cancer)
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8 pages, 728 KiB  
Communication
Real-World Experience with CDK4/6 Inhibitors in the First-Line Palliative Setting for HR+/HER2− Advanced Breast Cancer
by Ram Patel, John Mathews, Caroline Hamm, Swati Kulkarni, Rasna Gupta, Tarquin Opperman, John Dean Chiong and Abdullah Nasser
Curr. Oncol. 2025, 32(1), 52; https://doi.org/10.3390/curroncol32010052 - 20 Jan 2025
Cited by 1 | Viewed by 2117
Abstract
Introduction: CDK4/6 inhibitors in combination with aromatase inhibitors (AIs) are the standard first-line treatment for hormone receptor-positive (HR+), HER2-negative (HER2−) metastatic breast cancer. Landmark trials have demonstrated a comparable progression-free survival (PFS) across CDK4/6 inhibitors, but the overall survival (OS) outcomes have varied. [...] Read more.
Introduction: CDK4/6 inhibitors in combination with aromatase inhibitors (AIs) are the standard first-line treatment for hormone receptor-positive (HR+), HER2-negative (HER2−) metastatic breast cancer. Landmark trials have demonstrated a comparable progression-free survival (PFS) across CDK4/6 inhibitors, but the overall survival (OS) outcomes have varied. This study aimed to evaluate the real-world PFS and OS for palbociclib and ribociclib when combined with AIs in patients with HR+/HER2− advanced breast cancer. Materials and Methods: This was a retrospective chart review of adult patients with HR+/HER2− metastatic breast cancer treated at a single academic center between 1 January 2015 and 1 December 2022. The baseline demographics, clinical characteristics, and treatment details were extracted. A Kaplan–Meier analysis was used to estimate the PFS and OS, and differences between the treatment groups were assessed using the log-rank test. Cox proportional hazards models were constructed to adjust for confounding factors. Results: Seventy-five patients were included in the final analysis. The cohort was predominantly female (98.7%) and postmenopausal (77.3%), with 52.0% having de novo stage IV disease. Palbociclib was prescribed to 74.7% of the patients, and ribociclib to 25.3%. The patients receiving ribociclib were significantly younger (57.6 vs. 67.5 years, p = 0.013) and more likely to be premenopausal (42.1% vs. 5.4%, p < 0.001). The real-world median PFS and OS for palbociclib were 20.3 months (95% CI: 14.8–46) and 37.2 months (95% CI: 20.3–not reached [NR]), respectively. For ribociclib, the median PFS and OS were not reached. The Cox proportional hazards models adjusting for age and menopausal status found no significant differences between ribociclib and palbociclib for the PFS (HR = 0.92, p = 0.86) or OS (HR = 0.95, p = 0.92). Conclusion: In this real-world analysis, palbociclib demonstrated a median PFS consistent with the results from landmark trials, although the observed OS was shorter. The ribociclib-treated patients had a numerically longer PFS and OS compared with those treated with palbociclib, but the differences were not statistically significant. The discontinuation rates were similar between the two groups. Full article
(This article belongs to the Special Issue Advances in Personalized Therapy for Breast Cancer)
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18 pages, 1134 KiB  
Article
Evaluating the Effectiveness of Cyclin-Dependent Kinase 4/6 Inhibitors in Early- and Very Early-Onset Metastatic Breast Cancer: A Multicenter Study
by Akif Doğan, Nurullah İlhan, Goncagül Akdağ, Sedat Yıldırım, Mustafa Seyyar, Zeynep Yüksel Yaşar, Hande Nur Erölmez, Heves Sürmeli, Buğra Öztosun, Özlem Nuray Sever, Hatice Odabaş, Mahmut Emre Yıldırım, Devrim Çabuk, Nedim Turan and Mahmut Gümüş
Medicina 2025, 61(1), 154; https://doi.org/10.3390/medicina61010154 - 17 Jan 2025
Viewed by 1320
Abstract
Background and Objectives: Early-onset breast cancer (EOBC), particularly in patients under 40, presents with distinct biological characteristics and worse survival outcomes compared to late-onset cases. Despite intensive treatments, EOBC patients, especially those with hormone receptor-positive, HER2-negative (HR+/HER2-) subtypes, show poorer prognosis. CDK4/6 inhibitors, combined [...] Read more.
Background and Objectives: Early-onset breast cancer (EOBC), particularly in patients under 40, presents with distinct biological characteristics and worse survival outcomes compared to late-onset cases. Despite intensive treatments, EOBC patients, especially those with hormone receptor-positive, HER2-negative (HR+/HER2-) subtypes, show poorer prognosis. CDK4/6 inhibitors, combined with endocrine therapy (ET) have become the standard for HR+/HER2- metastatic breast cancer, yet younger patients are underrepresented in clinical trials. This study aims to evaluate the efficacy of ribociclib and palbociclib with ET in HR+/HER2- metastatic breast cancer, addressing the critical gap in understanding treatment outcomes in younger patient populations. Materials and Methods: This multicenter, retrospective study evaluated the efficacy and safety of cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors, ribociclib, and palbociclib, in combination with endocrine therapy in patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer. Results: A total of 198 patients treated between 2019 and 2023 were analyzed for progression-free survival, overall survival, and prognostic factors. Very early-onset breast cancer, which is diagnosed before the age of 35, was identified as an independent prognostic factor for poor progression-free survival. Additional factors associated with poorer outcomes included liver metastasis, progesterone receptor negativity, high tumor grade, and the concurrent use of fulvestrant with CDK4/6 inhibitors. Both ribociclib and palbociclib demonstrated similar efficacy, and dose reductions due to treatment-related adverse events did not compromise therapeutic outcomes. Conclusions: This study is the first to focus specifically on the treatment of early-onset breast cancer with CDK4/6 inhibitors, providing critical insights into the unique challenges faced by this patient population. The findings underscore the urgent need for personalized treatment strategies, routine genetic testing, and dedicated clinical trials designed to address the specific needs of these high-risk subgroups. By advancing our understanding of the clinical and molecular landscape of early-onset breast cancer and very early-onset breast cancer, this study lays the groundwork for improving outcomes in these underserved patients through tailored therapeutic approaches. Full article
(This article belongs to the Section Oncology)
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16 pages, 2534 KiB  
Article
Molecular Profiling of Endocrine Resistance in HR+/HER2-Metastatic Breast Cancer: Insights from Extracellular Vesicles-Derived DNA and ctDNA in Liquid Biopsies
by Ana Martínez-Rodríguez, Jesús Fuentes-Antrás, Víctor Lorca, Alfonso López de Sá, Pedro Pérez-Segura, Fernando Moreno, Jose Angel García-Sáenz and Vanesa García-Barberán
Int. J. Mol. Sci. 2024, 25(23), 13045; https://doi.org/10.3390/ijms252313045 - 4 Dec 2024
Cited by 4 | Viewed by 1930
Abstract
Standard treatments in hormone receptor-positive (HR+)/HER2-metastatic breast cancer (mBC) typically involve endocrine therapy (ET) combined with CDK4/6 inhibitors, yet resistance to ET remains a persistent challenge in advanced cases. A deeper knowledge of the use of liquid biopsy is crucial for the implementation [...] Read more.
Standard treatments in hormone receptor-positive (HR+)/HER2-metastatic breast cancer (mBC) typically involve endocrine therapy (ET) combined with CDK4/6 inhibitors, yet resistance to ET remains a persistent challenge in advanced cases. A deeper knowledge of the use of liquid biopsy is crucial for the implementation of precision medicine in mBC with real-time treatment guidance. Our study assesses the prognostic value of PIK3CA and ESR1 mutations in DNA derived from extracellular vesicles (EV-DNA) in longitudinal plasma from 59 HR+/HER2-mBC patients previously exposed to aromatase inhibitors, with a comparative analysis against circulating tumor DNA (ctDNA). Mutations were evaluated by digital PCR. PIK3CA and ESR1 mutations were found in 22 and 25% of patients. Baseline ESR1 mutations in EV-DNA were associated with shorter progression-free survival (PFS) across the cohort, with the Y537S mutation showing a particularly strong impact on the outcome of fulvestrant-treated patients. In contrast, PIK3CA mutations in EV-DNA did not significantly correlate with PFS, whereas in ctDNA, they were linked to poor outcomes. Altogether, this study positions EV-DNA as a valuable biomarker alongside ctDNA, enriching the understanding of different analytes in liquid biopsy and supporting strategies for HR+/HER2-mBC in precision oncology. Full article
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9 pages, 763 KiB  
Communication
Molecular Analysis of PIK3CA in Metastatic Hormone Receptor-Positive Breast Cancer in Chile: Clinical and Pathological Insights
by Carla Araya, Bárbara Mino, Patricio Le Cerf, Fancy Gaete, Ricardo Armisen and Daniel E. Carvajal-Hausdorf
Int. J. Mol. Sci. 2024, 25(22), 12246; https://doi.org/10.3390/ijms252212246 - 14 Nov 2024
Viewed by 1714
Abstract
Breast cancer is the most common cancer among women and a leading cause of cancer-related deaths. PIK3CA gene mutations, which are often present in advanced HR+ breast cancer, can be targeted by alpelisib. However, data on PIK3CA mutations in Chile are limited. Here, [...] Read more.
Breast cancer is the most common cancer among women and a leading cause of cancer-related deaths. PIK3CA gene mutations, which are often present in advanced HR+ breast cancer, can be targeted by alpelisib. However, data on PIK3CA mutations in Chile are limited. Here, we aim to assess the mutational status of PIK3CA in metastatic breast cancer tissues from Chilean patients and describe their clinicopathological characteristics and survival outcomes. We analyzed 102 formalin-fixed, paraffin-embedded metastatic breast cancer samples from 96 patients diagnosed at three Chilean hospitals between 2007 and 2023. PIK3CA mutations were identified using targeted sequencing, and clinicopathological data were collected. We evaluated associations between mutational status, clinicopathological features, and survival. The median age at diagnosis was 56 years. The most common metastatic sites were liver (29.4%), bone (17.6%), and lung/pleura (16.7%). Most patients were HR+ HER2− (83.3%), with 57.3% showing HER2-low status. PIK3CA mutations were present in 40.6% of patients, mainly in exons 7, 9, and 20. No significant associations were found between PIK3CA mutations and clinicopathological characteristics or survival. Our study reveals a high frequency of PIK3CA mutations in HR+ metastatic breast cancer, consistent with global data. The majority of mutations are targetable with alpelisib. The proportion of HER2-low status patients suggests potential benefits from novel HER2-targeted therapies. These findings highlight the need for routine molecular diagnostics in Chile to improve personalized treatment and address economic and access challenges. Full article
(This article belongs to the Section Molecular Oncology)
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19 pages, 4429 KiB  
Review
Double-Faced Immunological Effects of CDK4/6 Inhibitors on Cancer Treatment: Challenges and Perspectives
by Yongqin Liu, Yiying Deng, Chang Yang and Hua Naranmandura
Bioengineering 2024, 11(11), 1084; https://doi.org/10.3390/bioengineering11111084 - 29 Oct 2024
Cited by 1 | Viewed by 2984
Abstract
Cyclin-dependent kinases (CDKs) are generally involved in the progression of cell cycle and cell division in normal cells, while abnormal activations of CDKs are deemed to be a driving force for accelerating cell proliferation and tumorigenesis. Therefore, CDKs have become ideal therapeutic targets [...] Read more.
Cyclin-dependent kinases (CDKs) are generally involved in the progression of cell cycle and cell division in normal cells, while abnormal activations of CDKs are deemed to be a driving force for accelerating cell proliferation and tumorigenesis. Therefore, CDKs have become ideal therapeutic targets for cancer treatment. The U.S FDA has approved three CDK4/6 inhibitors (CDK4/6is) for the treatment of patients with hormone receptor-positive (HR+) or human epidermal growth factor receptor 2-negative (HER2) advanced or metastatic breast cancer, and these drugs showed impressive results in clinics. Besides cell-cycle arrest, there is growing evidence that CDK4/6is exert paradoxical roles on cancer treatment by altering the immune system. Indeed, clinical data showed that CDK4/6is could change the immune system to exert antitumor effects, while these changes also caused tumor resistance to CDK4/6i. However, the molecular mechanism for the regulation of the immune system by CDK4/6is is unclear. In this review, we comprehensively discuss the paradoxical immunological effects of CDK4/6is in cancer treatment, elucidating their anticancer mechanisms through immunomodulatory activity and induction of acquired drug resistance by dysregulating the immune microenvironment. More importantly, we suggest a few strategies including combining CDK4/6is with immunotherapy to overcome drug resistance. Full article
(This article belongs to the Section Biomedical Engineering and Biomaterials)
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Graphical abstract

8 pages, 932 KiB  
Communication
A Novel AKT1, ERBB2, ESR1, KRAS, PIK3CA, and TP53 NGS Assay: A Non-Invasive Tool to Monitor Resistance Mechanisms to Hormonal Therapy and CDK4/6 Inhibitors
by Alessandra Virga, Caterina Gianni, Michela Palleschi, Davide Angeli, Filippo Merloni, Roberta Maltoni, Paola Ulivi, Giovanni Martinelli, Ugo De Giorgi and Sara Bravaccini
Biomedicines 2024, 12(10), 2183; https://doi.org/10.3390/biomedicines12102183 - 26 Sep 2024
Cited by 4 | Viewed by 2170
Abstract
Background: Patients with hormone receptor-positive (HR+)/HER2- metastatic breast cancer (mBC) generally receive hormonal therapy (HT) combined with CDK4/6 inhibitors (CDK4/6i). Despite this treatment, resistance mechanisms to CDK4/6i emerge and the majority of these patients experience disease progression (PD). This highlight the necessity [...] Read more.
Background: Patients with hormone receptor-positive (HR+)/HER2- metastatic breast cancer (mBC) generally receive hormonal therapy (HT) combined with CDK4/6 inhibitors (CDK4/6i). Despite this treatment, resistance mechanisms to CDK4/6i emerge and the majority of these patients experience disease progression (PD). This highlight the necessity to uncover the resistance mechanism to CDK4/6i through the identification of specific biomarkers. The primary objective is to assess the accuracy and feasibility of a novel multi-gene target panel NGS assay on circulating tumor DNA (ctDNA) to detect molecular alterations of AKT1, ERBB2, ESR1, KRAS, PIK3CA, and TP53 genes in women with BC undergoing HT plus CDK4/6i treatment. Secondarily, the study aims to explore the relationship between genomic profiling and clinical outcomes. Materials and Methods: Plasma samples were collected from 16 patients diagnosed with advanced/locally advanced HR+/HER2- BC at 2 time points: T0 (baseline) and at T1 (3 months after CDK4/6i treatment). Starting from 2 mL of plasma, ctDNA was isolated and libraries were set up using the Plasma-SeqSensei (PQS)® Breast Cancer IVD Kit, sequenced on Nextseq 550 and analyzed using the Plasma-SeqSensei™ IVD Software®. Results: Among the five patients who presented PD, three had PIK3CA mutations and, of these, two showed a higher mutant allele frequency (MAF) at T1. In three patients with stable disease and in eight patients with partial response, the MAF of the detected alterations decreased dramatically or disappeared during CDK4/6i treatment. Conclusions: Based on our findings, the liquid biopsy analysis using the PQS panel seems to be both feasible and accurate, demonstrating a strong sensitivity in detecting mutations. This exploratory analysis of the clinical outcome associated to the mutational status of patients highlights the potential of molecular analysis on liquid biopsy for disease monitoring, although further validation with a larger patient cohort is necessary to confirm these preliminary observations. Full article
(This article belongs to the Special Issue Breast Cancer: New Diagnostic and Therapeutic Approaches)
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15 pages, 593 KiB  
Review
Canadian Expert Recommendations on Safety Overview and Toxicity Management Strategies for Sacituzumab Govitecan Based on Use in Metastatic Triple-Negative Breast Cancer
by Mita Manna, Michelle Brabant, Rowen Greene, Michael Dean Chamberlain, Aalok Kumar, Nimira Alimohamed and Christine Brezden-Masley
Curr. Oncol. 2024, 31(9), 5694-5708; https://doi.org/10.3390/curroncol31090422 - 21 Sep 2024
Cited by 2 | Viewed by 4053
Abstract
Sacituzumab Govitecan (SG) is an antibody-drug conjugate (ADC) comprised of an anti-Trop-2 IgG1 molecule conjugated to SN-38, the active metabolite of irinotecan, via a pH-sensitive hydrolysable linker. As a result of recent Canadian funding for SG in advanced hormone receptor (HR)-positive breast cancer [...] Read more.
Sacituzumab Govitecan (SG) is an antibody-drug conjugate (ADC) comprised of an anti-Trop-2 IgG1 molecule conjugated to SN-38, the active metabolite of irinotecan, via a pH-sensitive hydrolysable linker. As a result of recent Canadian funding for SG in advanced hormone receptor (HR)-positive breast cancer and triple-negative breast cancer (TNBC), experience with using SG and managing adverse events (AEs) has grown. This review presents a summary of evidence and adverse event recommendations derived from Canadian experience, with SG use in metastatic TNBC for extrapolation and guidance in all indicated settings. SG is dosed at 10 mg/kg on day 1 and day 8 of a 21-day cycle. Compared to treatment of physicians’ choice (TPC) the phase III ASCENT and TROPiCS-02 studies demonstrated favorable survival data in unresectable locally advanced or metastatic TNBC and HR-positive HER2 negative metastatic breast cancer, respectively. The most common AEs were neutropenia, diarrhea, nausea, fatigue, alopecia, and anemia. This review outlines AE management recommendations for SG based on clinical trial protocols and Canadian guidelines, incorporating treatment delay, dose reductions, and the use of prophylactic and supportive medications. Full article
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