MammaPrint predicts chemotherapy benefit in HR+HER2- early breast cancer: FLEX Registry real-world data.

Background: Gene expression assays help personalize adjuvant chemotherapy decisions for hormone receptor-positive, HER2-negative (HR+HER2-) early breast cancer (EBC). The 70-gene risk of distant-recurrence signature, MammaPrint, demonstrated clinical utility in guiding chemotherapy de-escalation in genomically low risk patients in the MINDACT trial. This study evaluates MammaPrint as a continuous predictor of chemotherapy benefit in HR+HER2- EBC using real-world data (RWD) from the FLEX Registry.

US expert Delphi consensus on the prevention and management of stomatitis in patients treated with datopotamab deruxtecan.

Background: Datopotamab deruxtecan (Dato-DXd) is an investigational antibody-drug conjugate that has shown promising results in phase III clinical trials of lung and breast cancers. Stomatitis is a common adverse event associated with Dato-DXd in these trials, and there are currently no formalized guidelines for its prevention and management. An expert consensus was needed to establish these guidelines.

Limitations in the Application of Clinicopathologic Factors Alone in Predicting Radiation Benefit for Women With Low-Risk Ductal Carcinoma In Situ After Breast Conserving Surgery: The Impact of a 7-Gene Biosignature Based on 10-Year Ipsilateral Breast Recurrence Rates.

Purpose: Clinicopathologic (CP) factors are used to estimate 10-year ipsilateral breast recurrence (IBR) risk and inform shared decision making regarding postoperative radiation therapy (RT) for ductal carcinoma in situ (DCIS) patients. This study assesses the clinical value of the 7-gene biosignature (DCISionRT) compared to traditional CP definitions for predicting IBR rates and RT benefit.

Methods And Materials: DCIS patients (n = 926) treated with breast conserving surgery (BCS) ± RT were categorized as CP low-risk or high-risk based on established CP factors, study criteria, and nomograms.

Q-TWiST Analysis to Assess Benefit-Risk of Sacituzumab Govitecan in Previously Treated Patients With Metastatic Triple-Negative Breast Cancer.

Purpose: In ASCENT, sacituzumab govitecan (SG) showed significantly longer overall survival and progression-free survival than chemotherapy of physician's choice with similar rates of treatment-emergent adverse events (TEAEs) in previously treated patients with metastatic triple-negative breast cancer (mTNBC). We assessed the benefit-risk of SG versus chemotherapy by integrating patient preferences (health utilities) with clinical benefits in this analysis.

Methods: Quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment (Q-TWiST) methodology was used to compare treatments where survival was partitioned into three health states using the intention-to-treat ASCENT population: (1) toxicity (grade ≥3 TEAE after random assignment and before disease progression), (2) TWiST (progression-free period without grade ≥3 TEAE), and (3) relapse (disease progression until death or end of follow-up, whichever came first).

MammaTrace - a cell-free DNA methylation plasma only assay for minimal residual disease detection in breast cancer patients.

Introduction: Metastatic breast cancer (MBC) remains an incurable disease with a 5-year overall survival rate below 25%. Metastases often emerge from subclinical, disseminated tumor cells that persist despite systemic therapy of primary disease - referred to as minimal residual disease (MRD). Detecting MRD is critical for identifying patients at high risk of recurrence and enabling timely intervention.

Long-Term Safety and Efficacy of the Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Injection in Patients With HER2-Positive Early Breast Cancer in PHranceSCa, a Randomized, Open-Label Phase II Study.

Background: We assessed long-term safety, efficacy, and health-related quality of life during the continuation phase after 3 years' follow-up in PHranceSCa (NCT03674112).

Patients And Methods: This was a randomized, open-label, international, multicenter, crossover, Phase II study in adjuvant HER2-positive early breast cancer. One hundred fifty nine patients received 3 cycles of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC), then 3 of intravenous pertuzumab and trastuzumab (P + H IV), or vice versa.

Real-World Evidence Acceptability and Use in Breast Cancer Treatment Decision-Making in the United States: Call-to-Action from a Multidisciplinary Think Tank.

Complementing randomized controlled trials, real-world evidence (RWE) from observational analyses can extend clinical insights in oncology. While healthcare stakeholders have published rigorous RWE frameworks and resources, a multidisciplinary think tank was established to further advance acceptance and use of RWE in treatment decision-making, with the focus on breast cancer (while recognizing relevance in oncology more broadly). Members discussed perceptions of RWE from a clinical perspective, across domains of data, methodology, and mindset, and "calls-to-action" for stakeholders.

Phase 2 trial of imprime and pembrolizumab immunotherapy in metastatic triple negative breast cancer patients who have progressed beyond first line chemotherapy.

The Phase 2 IMPRIME 1 study evaluated the combination of the pathogen-associated molecular pattern (PAMP) Imprime with the immune checkpoint inhibitor (ICI) pembrolizumab as second or later line of treatment (2 L+) for patients with metastatic triple-negative breast cancer (mTNBC). Eligible patients with mTNBC received weekly Imprime (4 mg/kg) intravenously in combination with pembrolizumab (200 mg every 3 weeks). Primary endpoints were overall response rate (ORR) and safety.

TROPION-Breast05: a randomized phase III study of Dato-DXd with or without durvalumab versus chemotherapy plus pembrolizumab in patients with PD-L1-high locally recurrent inoperable or metastatic triple-negative breast cancer.

Background: Standard of care (SoC) for patients with advanced triple-negative breast cancer (TNBC) whose tumors express PD-L1 (combined positive score ⩾ 10) is chemotherapy plus anti-PD-(L)1 inhibitors; however, prognosis and survival for most patients is poor. Datopotamab deruxtecan (Dato-DXd), a novel antibody-drug conjugate comprising a humanized anti-TROP2 IgG1 monoclonal antibody conjugated to a potent topoisomerase I inhibitor payload via a plasma-stable, cleavable, tetrapeptide-based linker, has shown preliminary activity as mono or combination therapy in advanced/metastatic TNBC.

Objectives: TROPION-Breast05 is an ongoing randomized, open-label, multicenter phase III study.

Correlation analysis of invasive disease-free survival and overall survival in a real-world population of patients with HR+/HER2- early breast cancer.

Background: Overall survival (OS) is the gold standard for assessing clinical benefit in oncology but requires extended follow-up to detect sufficient events. Invasive disease-free survival (iDFS) requires shorter follow-up times and is considered an objective and clinically meaningful end point in early breast cancer (EBC) trials. The authors assessed iDFS as a surrogate end point for OS in adjuvant HR+/HER2- EBC using real-world patient-level data.

Real-world risk of recurrence and treatment outcomes with adjuvant endocrine therapy in patients with stage II-III HR+/HER2- early breast cancer.

Background: Despite adjuvant endocrine therapy (ET), recurrence is still a concern for patients with HR+/HER2- early breast cancer (EBC). We assessed recurrence risk in real-world patients with stage II/III HR+/HER2- EBC treated with adjuvant ET.

Methods: A retrospective analysis was conducted using the ConcertAI Patient360 database (January 1995 to April 2021) of patients with stage II/III HR+/HER2- EBC ≥18 years who underwent surgery and received adjuvant ET.

Neoadjuvant Chemotherapy for T3 Tumors in the Era of Precision Medicine-Biology Is Still King.

Clinical T3 (cT3) breast cancer (BC) presents a challenge for achieving cosmetically acceptable breast conservation, and neoadjuvant chemotherapy (NAC) is commonly used for cytoreduction in these high-risk cancers. MammaPrint risk-of-recurrence and BluePrint molecular subtyping genomic signatures have demonstrated high accuracy in predicting chemotherapy benefits. Here, we examined the utility of MammaPrint/BluePrint for predicting pathological Complete Response (pCR) rates to NAC among 404 patients diagnosed with cT3 early-stage BC.

Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

Imlunestrant with or without Abemaciclib in Advanced Breast Cancer.

Background: Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations in the gene encoding ERα ().

Methods: In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy, administered alone or with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib.

Current Clinical Utility of Circulating Tumor DNA Testing in Breast Cancer: A Practical Approach.

Circulating tumor DNA (ctDNA) refers to DNA fragments released from cancer cells into the bloodstream. Clinical utility of ctDNA in breast cancer has been explored in both metastatic breast cancer (MBC) and early-stage breast cancer (EBC) settings. In MBC, ctDNA can detect therapeutically targetable genomic alterations and has shown great potential in predicting treatment response or resistance.

Trastuzumab Duocarmazine in Pretreated Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Breast Cancer: An Open-Label, Randomized, Phase III Trial (TULIP).

Purpose: Human epidermal growth factor receptor 2 (HER2)-targeted therapy is standard of care for HER2-positive (HER2+) breast cancer, but most patients develop progressive disease with persistent HER2 expression. No definitive treatment guidance currently exists beyond second line. Trastuzumab duocarmazine (T-Duo) is a third-generation, HER2-targeted antibody-drug conjugate that demonstrated efficacy and acceptable safety in phase I studies of heavily pretreated patients with HER2+/HER2-low breast cancer.

Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer.

Background: In patients with early-stage triple-negative breast cancer, the phase 3 KEYNOTE-522 trial showed significant improvements in pathological complete response and event-free survival with the addition of pembrolizumab to platinum-containing chemotherapy. Here we report the final results for overall survival.

Methods: We randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide.

Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer.

Background: Outcomes in patients with hormone receptor-positive metastatic breast cancer worsen after one or more lines of endocrine-based therapy. Trastuzumab deruxtecan has shown efficacy in patients with metastatic breast cancer with low expression of human epidermal growth factor receptor 2 (HER2) after previous chemotherapy.

Methods: We conducted a phase 3, multicenter, open-label trial involving patients with hormone receptor-positive metastatic breast cancer with low HER2 expression (a score of 1+ or 2+ on immunohistochemical [IHC] analysis and negative results on in situ hybridization) or ultralow HER2 expression (IHC 0 with membrane staining) who had received one or more lines of endocrine-based therapy and no previous chemotherapy for metastatic breast cancer.

Ipatasertib plus Paclitaxel for Patients with PIK3CA/AKT1/PTEN-Altered Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer in the IPATunity130 Phase III Trial.

Purpose: In the randomized phase II LOTUS trial, combining ipatasertib with first-line paclitaxel for triple-negative breast cancer (TNBC) improved progression-free survival (PFS), particularly in patients with PIK3CA/AKT1/PTEN-altered tumors. We aimed to validate these findings in a biomarker-selected TNBC population.

Patients And Methods: In Cohort A of the randomized double-blind placebo-controlled phase III IPATunity130 trial, taxane-eligible patients with PIK3CA/AKT1/PTEN-altered measurable advanced TNBC and no prior chemotherapy for advanced disease were randomized 2:1 to ipatasertib (400 mg, days 1-21) or placebo, both plus paclitaxel (80 mg/m2, days 1, 8, and 15), every 28 days until disease progression or unacceptable toxicity.

Randomized Phase III Study of Amcenestrant Plus Palbociclib Versus Letrozole Plus Palbociclib in Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Primary Results From AMEERA-5.

Purpose: AMEERA-5 investigated amcenestrant (oral selective estrogen receptor [ER] degrader) plus palbociclib versus letrozole plus palbociclib as first-line treatment for ER-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced/metastatic breast cancer (aBC).

Materials And Methods: In AMEERA-5 (ClinicalTrials.gov identifier: NCT04478266), a double-blind, double-dummy, international phase III trial, adult pre-/post-menopausal women and men without previous systemic therapy for ER+/HER2- aBC were randomly assigned 1:1 to amcenestrant 200 mg once daily + standard palbociclib dosage (125 mg once daily, 21 days on/7 days off) or letrozole 2.

A clinical systematic literature review of treatments among patients with advanced and/or metastatic human epidermal growth factor receptor 2 positive breast cancer.

This systematic literature review aims to summarize the efficacy/effectiveness of treatments, including eribulin (ERI)-based and anti-human epidermal growth factor receptor 2 (HER2) treatments in advanced/metastatic HER2+ breast cancer. Three databases from 2016 to September 2021 were searched for clinical trials and observational studies in patients receiving first-line (1L) standard of care (SOC), second-line (2L) SOC or third-line or subsequent lines (3L+). 2692 citations were screened, and 38 studies were included.