Publications by authors named "Gabriel Hortobagyi"
Background: The phase III RxPONDER trial has impacted treatment for node-positive(1-3), hormone receptor-positive, HER2-negative breast cancer with 21-gene recurrence score (RS) ≤ 25. We investigated how these findings apply to different racial and ethnic groups within the trial.
Methods: The trial randomized women to endocrine therapy (ET) or to chemotherapy plus ET.
Article Synopsis
- - The RSClinN+ tool was developed to better predict recurrence risk and the benefits of chemotherapy specifically for patients with HR+/HER2-negative, lymph node-positive breast cancer, by incorporating both the Oncotype DX score and other clinical factors like tumor size and age.
- - Analysis of data from over 5,000 patients revealed that RSClinN+ offered significantly improved prognostic accuracy compared to using the Oncotype DX score alone or clinicopathological models, especially for premenopausal and postmenopausal women.
- - Validation of RSClinN+ showed that it effectively estimates prognosis and potential chemotherapy benefits, making it a valuable personalized tool for clinicians in managing breast cancer treatment decisions.
Article Synopsis
- The study investigates the effectiveness of the anti-EGFR monoclonal antibody panitumumab combined with carboplatin and paclitaxel for treating chemotherapy-resistant triple-negative breast cancer (TNBC) patients.
- It included 43 patients who had not sufficiently responded to prior doxorubicin and cyclophosphamide treatment, achieving a combined pathological complete response/residual cancer burden class I rate of 30.2%.
- The results indicate that panitumumab shows promise as part of neoadjuvant therapy for TNBC, warranting further evaluation in larger clinical trials.
Importance: Over the past 2 decades, systemic therapy for early-stage breast cancer has gradually moved from the adjuvant to the neoadjuvant setting. Administration of systemic therapy before surgery leads to potential improvements in surgical outcomes and allows for the assessment of the pathologic response to treatment. For patients with residual disease (RD), 3 adjuvant strategies have been shown to improve outcomes: (1) adjuvant trastuzumab emtansine for ERBB2-positive disease, (2) adjuvant capecitabine for triple-negative disease, and (3) adjuvant olaparib for patients with germline BRCA variants.
View Article and Find Full Text PDFPhase III Randomized, Placebo-Controlled Trial of Endocrine Therapy ± 1 Year of Everolimus in Patients With High-Risk, Hormone Receptor-Positive, Early-Stage Breast Cancer.
J Clin Oncol
September 2024
Article Synopsis
- The study investigated the effects of everolimus, an mTOR inhibitor, when used alongside endocrine therapy (ET) in high-risk, hormone receptor-positive metastatic breast cancer after chemotherapy, aiming to improve survival rates.
- In a phase III trial with 1,939 patients, results showed that adding everolimus to ET did not significantly enhance invasive disease-free survival (IDFS) or overall survival (OS) rates compared to a placebo, with hazard ratios indicating no substantial benefit.
- Subgroup analysis highlighted that premenopausal patients saw improved IDFS and OS with everolimus, whereas postmenopausal patients did not show significant differences, and treatment completion rates were lower in the everolimus group.
Article Synopsis
- - The study examined the relationship between pre-treatment blood levels of amino acids and the occurrence and severity of chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer patients treated with paclitaxel.
- - While histidine levels were found not to be linked to the incidence of CIPN, some associations were noted between higher concentrations of glutamate, phenylalanine, tyrosine, and valine with increased CIPN severity, although these were not significant after further adjustments.
- - Overall, the findings suggest that amino acid concentrations are not strong predictors of CIPN severity, indicating a need for future research to explore other potential biomarkers.
Background: Ribociclib has been shown to have a significant overall survival benefit in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Whether this benefit in advanced breast cancer extends to early breast cancer is unclear.
Methods: In this international, open-label, randomized, phase 3 trial, we randomly assigned patients with HR-positive, HER2-negative early breast cancer in a 1:1 ratio to receive ribociclib (at a dose of 400 mg per day for 3 weeks, followed by 1 week off, for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI; letrozole at a dose of 2.
Hyperglycemia and rash are expected but challenging adverse events of phosphatidylinositol-3-kinase inhibition (such as with alpelisib). Two modified Delphi panels were conducted to provide consensus recommendations for managing hyperglycemia and rash in patients taking alpelisib. Experts rated the appropriateness of interventions on a 1-to-9 scale; median scores and dispersion were used to classify the levels of agreement.
View Article and Find Full Text PDFPurpose: Triple-negative breast cancer (TNBC) is a heterogeneous disease. We previously showed that homologous recombination deficiency (HRD) and the DNA damage immune response (DDIR) signature are prognostic in TNBC. We hypothesized that these biomarkers reflect related but not completely interdependent biological processes, that their combined use would be prognostic, and that simultaneous assessment of the immunologic microenvironment and susceptibility to DNA damaging therapies might be able to identify subgroups with distinct therapeutic vulnerabilities.
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- This study examines the link between vitamin D insufficiency and the risk of chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer patients receiving paclitaxel.
- Out of 1,191 patients analyzed, those with vitamin D insufficiency showed a higher incidence of severe CIPN compared to those with sufficient levels, suggesting a significant association.
- Additionally, mouse experiments demonstrated that a vitamin D-deficient diet increased sensitivity to mechanical pain and enhanced the effects of paclitaxel, supporting the idea that vitamin D levels may influence CIPN risk.
After decades of research, improving the efficacy of adjuvant endocrine therapy (ET) for early-stage breast cancer becomes increasingly difficult. Beyond technological breakthroughs and the availability of new classes of drugs, further improvement of adjuvant ET will require applying a rigorous research approach in poorly investigated areas. We critically discuss some key principles that should inform future research to improve ET efficacy, including identifying specific subgroups of patients who can benefit from escalating or de-escalating approaches, optimizing available and new treatment strategies for different clinical contexts, and dissecting the direct and indirect biological effects of therapeutic interventions.
View Article and Find Full Text PDFBackground: Chemotherapy-induced peripheral neuropathy (CIPN) is a treatment-limiting and debilitating neurotoxicity of many commonly used anti-cancer agents, including paclitaxel. The objective of this study was to confirm the previously found inverse association between pre-treatment blood concentrations of histidine and CIPN occurrence and examine relationships of other amino acids with CIPN severity.
Methods: Pre-treatment levels of 20 amino acid concentrations were measured via a targeted mass spectrometry assay in banked serum from the SWOG S0221 (NCT00070564) trial of patients with early-stage breast cancer receiving paclitaxel.
This study tested associations of genotype-predicted activity of CYP3A4, other pharmacogenes, (rs11648166) and (rs28845026) with systemic concentrations of the endocrine therapies anastrozole and fulvestrant in SWOG S0226 trial participants. Participants in the anastrozole-only arm with low CYP3A4 activity (i.e.
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- * An analysis of data from 4,217 ILC patients showed that 45% had co-existing LCIS, and those with ILC + LCIS had better survival rates compared to those with pure ILC, highlighting significant differences in tumor characteristics and treatment received.
- * The results indicated that absence of LCIS in ILC patients was linked to poorer outcomes, suggesting LCIS presence may serve as a favorable prognostic marker, warranting further investigation.
The secretory enzyme human ribonuclease 1 (RNase1) is involved in innate immunity and anti-inflammation, achieving host defense and anti-cancer effects; however, whether RNase1 contributes to adaptive immune response in the tumor microenvironment (TME) remains unclear. Here, we established a syngeneic immunocompetent mouse model in breast cancer and demonstrated that ectopic RNase1 expression significantly inhibited tumor progression. Overall changes in immunological profiles in the mouse tumors were analyzed by mass cytometry and showed that the RNase1-expressing tumor cells significantly induced CD4 Th1 and Th17 cells and natural killer cells and reduced granulocytic myeloid-derived suppressor cells, supporting that RNase1 favors an antitumor TME.
View Article and Find Full Text PDFImportance: Little is known about regional nodal irradiation (RNI) practice patterns or rates of locoregional recurrence (LRR) with and without RNI in patients with limited nodal disease and favorable biology treated with modern surgical and systemic therapy, including approaches that de-escalate those latter treatments.
Objective: To investigate how often patients with low-recurrence score breast cancer with 1 to 3 nodes involved receive RNI, incidence and predictors of LRR, and associations between locoregional therapy and disease-free survival.
Design, Setting, And Participants: In this secondary analysis of the SWOG S1007 trial, patients with hormone receptor-positive, ERBB2-negative breast cancer, and a Oncotype DX 21-gene Breast Recurrence Score assay result of no more than 25, were randomized to endocrine therapy alone vs chemotherapy then endocrine therapy.
Article Synopsis
- Triple-negative breast cancer (TNBC) is associated with high relapse and metastasis rates due to the presence of cancer stem-like cells (CSCs) that promote tumor growth, with MELK being a key protein involved in maintaining these cells.
- The study revealed that high levels of MELK expression correlate with worse overall survival and increased risk of metastasis in breast cancer patients.
- Experimenting with MELK knockdown and inhibitor treatments showed reduced invasiveness and metastasis in TNBC cells, highlighting MELK as a significant driver of tumor aggressiveness and the metastatic process.
Article Synopsis
- Ribociclib has been shown to improve overall survival for patients with HR+/HER2- advanced breast cancer, and the NATALEE trial aims to evaluate its safety and effectiveness when combined with endocrine therapy for early nonmetastatic cases.* -
- This Phase III trial involves a randomized, multicenter design, enrolling men and women with specific stages of breast cancer, and compares ribociclib with endocrine therapy alone, focusing on invasive disease-free survival as the main outcome.* -
- The trial extends ribociclib treatment to 36 months to enhance effectiveness and uses a lower dosage to improve tolerability, including a diverse patient population for more comprehensive results on adjuvant therapy.*
We assessed the predictive value of an image analysis-based tumor-infiltrating lymphocytes (TILs) score for pathologic complete response (pCR) and event-free survival in breast cancer (BC). About 113 pretreatment samples were analyzed from patients with stage IIB-IIIC HER-2-negative BC randomized to neoadjuvant chemotherapy ± bevacizumab. TILs quantification was performed on full sections using QuPath open-source software with a convolutional neural network cell classifier (CNN11).
View Article and Find Full Text PDFImportance: The American Institute for Cancer Research and American Cancer Society regularly publish modifiable lifestyle recommendations for cancer prevention. Whether these recommendations have an impact on high-risk breast cancer survival remains unknown.
Objective: To investigate whether adherence to cancer prevention recommendations before, during, and 1 and 2 years after breast cancer treatment was associated with disease recurrence or mortality.
Purpose: Triple-negative breast cancer (TNBC) is defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. In this study, we compared response to neoadjuvant chemotherapy and survival between patients with TNBC and non-TNBC.
Patients And Methods: Analysis of a prospectively collected clinical database was performed.
Article Synopsis
- Researchers created a new way to understand how serious metastatic breast cancer (MBC) is when it's first diagnosed, which helps predict patient survival better.
- They looked at data from a lot of patients and grouped them based on certain health information to see how long they survived after diagnosis.
- The new staging system is divided into four groups based on survival rates, and it has been tested and proven to be effective with other patient data sets.