Adjuvant Pertuzumab and Trastuzumab in Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in the APHINITY Trial: Third Interim Overall Survival Analysis With Efficacy Update.

JCO The APHINITY trial (ClinicalTrials.gov identifier: NCT01358877) previously demonstrated that pertuzumab added to adjuvant trastuzumab and chemotherapy improved invasive disease-free survival (iDFS) for patients with early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC). Here, we report the preplanned third interim analysis of overall survival (OS) and a descriptive updated iDFS analysis with 8.

Long-term behavioral symptom clusters among survivors of early-stage breast cancer: Development and validation of a predictive model.

Background: Fatigue, cognitive impairment, anxiety, depression, and sleep disturbance are cancer-related behavioral symptoms that may persist years after early-stage breast cancer, affecting quality of life. We aimed to generate a predictive model of long-term cancer-related behavioral symptoms clusters among breast cancer survivors 4 years after diagnosis.

Methods: Patients with early-stage breast cancer were included from the CANcer TOxicity trial (ClinicalTrials.

[Adherence to endocrine therapy: A major issue in breast cancer management].

Endocrine therapy plays a crucial role in the treatment of women with hormone receptor-positive breast cancer. However, non-adherence remains a frequent issue known to negatively impact survival. Based on a comprehensive literature review, this article explores the terminologies employed to describe adherence and methods used for its assessment, the adherence data reported with adjuvant endocrine therapy with targeted therapies, the determinants of adherence or non-adherence, and finally, tested solutions to address it.

Impact of coadministration of proton-pump inhibitors and palbociclib in hormone receptor-positive/HER2-negative advanced breast cancer.

Background: The capsule formulation of CDK4/6 inhibitor palbociclib has reduced solubility at gastric pH > 4.5 and may have decreased activity when used with proton-pump inhibitors (PPI). Herein, we report the effect of PPI on palbociclib capsule activity and safety in the PARSIFAL study.

Identification of non-adherence to adjuvant letrozole using a population pharmacokinetics approach in hormone receptor-positive breast cancer patients.

Background: Letrozole, an aromatase inhibitor metabolised via CYP2A6 and CYP3A4/5 enzymes, is used as adjuvant therapy for women with hormone receptor (HR)-positive early breast cancer. The objective of this study was to quantify the impact of CYP2A6 genotype on letrozole pharmacokinetics (PK), to identify non-adherent patients using a population approach and explore the possibility of a relationship between non-adherence and early relapse.

Methods: Breast cancer patients enrolled in the prospective PHACS study (ClinicalTrials.

Health-related quality of life with sacituzumab govitecan in HR+/HER2- metastatic breast cancer in the phase III TROPiCS-02 trial.

Background: The TROPiCS-02 study (NCT03901339) demonstrated that sacituzumab govitecan (SG) has superior clinical outcomes over treatment of physician's choice (TPC) chemotherapy in patients with hormone receptor-positive, human epidermal growth factor 2 receptor-negative (HR+/HER2-) metastatic breast cancer (mBC). Here, we present health-related quality of life (HRQoL) patient-reported outcome (PRO) findings from this study.

Patients And Methods: Eligible adults with HR+/HER2- mBC who previously received a taxane, endocrine-based therapy, a CDK4/6 inhibitor, and 2-4 lines of chemotherapy were randomized 1:1 to receive SG or TPC until progression or unacceptable toxicity.

Association between endocrine adjuvant therapy intake timing and disease-free survival in patients with high-risk early breast cancer: results of a sub-study of the UCBG- UNIRAD trial.

Background: Circadian rhythms regulate cellular physiology and could influence the efficacy of endocrine therapy (ET) in breast cancer (BC). We prospectively tested this hypothesis within the UNIRAD adjuvant phase III trial (NCT01805271).

Methods: 1278 patients with high-risk hormonal receptor positive (HR+)/HER2 negative (HER2-) primary BC were randomly assigned to adjuvant ET with placebo or everolimus.

3-year invasive disease-free survival with chemotherapy de-escalation using an F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): a randomised, open-label, phase 2 trial.

Background: PHERGain was designed to assess the feasibility, safety, and efficacy of a chemotherapy-free treatment based on a dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab and pertuzumab in patients with HER2-positive early breast cancer (EBC). It used an fluorine-fluorodeoxyglucose-PET-based, pathological complete response (pCR)-adapted strategy.

Methods: PHERGain was a randomised, open-label, phase 2 trial that took place in 45 hospitals in seven European countries.

Optimal [F]FDG PET/CT Cutoff for Pathologic Complete Response in HER2-Positive Early Breast Cancer Patients Treated with Neoadjuvant Trastuzumab and Pertuzumab in the PHERGain Trial.

The PHERGain trial investigated the potential of metabolic imaging to identify candidates for chemotherapy deescalation in human epidermal growth factor receptor 2 (HER2)-positive, invasive, operable breast cancer with at least 1 breast lesion evaluable by [F]FDG PET/CT. [F]FDG PET/CT responders were defined as patients with an SUV reduction (ΔSUV) of at least 40% in all of their target lesions after 2 cycles of trastuzumab and pertuzumab (HP) (with or without endocrine therapy). In total, 227 of 285 patients (80%) included in the HP arm showed a predefined metabolic response and received a total of 8 cycles of HP (with or without endocrine therapy).

Nonlinear Mixed-Effects Model of Z-Endoxifen Concentrations in Tamoxifen-Treated Patients from the CEPAM Cohort.

Tamoxifen is widely used in patients with hormone receptor-positive breast cancer. The polymorphic enzyme CYP2D6 is primarily responsible for metabolic activation of tamoxifen, resulting in substantial interindividual variability of plasma concentrations of its most important metabolite, Z-endoxifen. The Z-endoxifen concentration thresholds below which tamoxifen treatment is less efficacious have been proposed but not validated, and prospective trials of individualized tamoxifen treatment to achieve Z-endoxifen concentration thresholds are considered infeasible.

p4EBP1 staining predicts outcome in ER-positive endocrine-resistant metastatic breast cancer patients treated with everolimus and exemestane.

Background: To identify patients most likely to respond to everolimus, a mammalian target of rapamycin (mTOR) inhibitor, a prospective biomarker study was conducted in hormone receptor-positive endocrine-resistant metastatic breast cancer patients treated with exemestane-everolimus therapy.

Methods: Metastatic tumor biopsies were processed for immunohistochemical staining (p4EBP1, PTEN, pAKT, LKB1, and pS6K). ESR1, PIK3CA and AKT1 gene mutations were detected by NGS.

Chemotherapy-Related Amenorrhea and Quality of Life Among Premenopausal Women With Breast Cancer.

Importance: Younger survivors of breast cancer frequently report more treatment-related symptoms, mostly related to the menopausal transition.

Objective: To assess factors associated with chemotherapy-related amenorrhea (CRA) and to evaluate its association with long-term quality of life (QOL).

Design, Setting, And Participants: The prospective, longitudinal Cancer Toxicities Study, a multicenter French cohort study, includes women with a diagnosis of stage I to III breast cancer and collects data approximately yearly after diagnosis.

Paclitaxel plus Eftilagimod Alpha, a Soluble LAG-3 Protein, in Metastatic, HR+ Breast Cancer: Results from AIPAC, a Randomized, Placebo Controlled Phase IIb Trial.

Purpose: Eftilagimod alpha (efti), a soluble lymphocyte activation gene (LAG-3) protein and MHC class II agonist, enhances innate and adaptive immunity. Active Immunotherapy PAClitaxel (AIPAC) evaluated safety and efficacy of efti plus paclitaxel in patients with predominantly endocrine-resistant, hormone receptor-positive, HER2-negative metastatic breast cancer (ET-resistant HR+ HER2- MBC).

Patients And Methods: Women with HR+ HER2- MBC were randomized 1:1 to weekly intravenous paclitaxel (80 mg/m2) and subcutaneous efti (30 mg) or placebo every 2 weeks for six 4-week cycles, then monthly subcutaneous efti (30 mg) or placebo maintenance.

Overall Survival With Circulating Tumor Cell Count-Driven Choice of Therapy in Advanced Breast Cancer: A Randomized Trial.

.In patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer, the STIC CTC trial established that, for choosing between endocrine therapy (ET) or chemotherapy, the use of circulating tumor cell (CTC) count is noninferior to the investigator's choice in terms of progression-free survival. Here, we report overall survival (OS) results, a secondary end point.

Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial.

Background: Sacituzumab govitecan demonstrated significant progression-free survival benefit over chemotherapy in the phase 3 TROPiCS-02 trial in patients with pretreated, endocrine-resistant hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ and HER2-) metastatic breast cancer with limited treatment options. Here, we report the protocol-specified final analysis of overall survival and endpoints by trophoblast cell-surface antigen 2 (Trop-2) expression and other variables.

Methods: In this randomised, open-label, multicentre, phase 3 trial, which took place in 91 centres across North America (the USA and Canada) and Europe (Belgium, France, Germany, Italy, the Netherlands, Spain, and the UK), patients were randomly assigned (1:1) to receive sacituzumab govitecan or chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine).

Pertuzumab Plus Trastuzumab With or Without Chemotherapy Followed by Emtansine in ERBB2-Positive Metastatic Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial.

Importance: In ERBB2 (formerly HER2)-positive metastatic breast cancer (MBC), combining trastuzumab and pertuzumab with taxane-based chemotherapy is the first line of standard care. Given that trastuzumab plus pertuzumab was proven effective in ERBB2-positive MBC, even without chemotherapy, whether the optimal first-line strategy could be trastuzumab plus pertuzumab alone instead of with chemotherapy is unresolved.

Objective: To assess overall survival (OS) at 2 years and progression-free survival (PFS) for patients randomly assigned to receive first-line pertuzumab plus trastuzumab alone or with chemotherapy followed by trastuzumab and emtansine at progression; PFS of second-line trastuzumab and emtansine treatment following trastuzumab plus pertuzumab; and OS and PFS in the ERBB2-enriched and ERBB2-nonenriched subtypes.

Pattern and risk factors of isolated local relapse among women with hormone receptor-positive and HER2-negative breast cancer and lymph node involvement: 10-year follow-up analysis of the PACS 01 and PACS 04 trials.

Purpose: We aimed to determine the pattern of isolated local recurrences (ILR) in women with stage II-III hormone receptor-positive and human epidermal growth factor receptor 2 breast cancer (HR + /HER2-BC) after 10-year follow-up.

Methods: UNICANCER-PACS 01 and PACS 04 trials included 5,008 women with T1-T3 and N1-N3 to evaluate the efficacy of different anthracycline ± taxanes-containing regimens after modified mastectomy or lumpectomy plus axillary lymph node dissection. We analyzed the data from 2,932 women with HR + /HER2- BC to evaluate the cumulative incidence of ILR and describe the factors associated with ILR.