Real-World Evidence on Prescribing Patterns and Clinical Outcomes of Metastatic Breast Cancer Patients Treated with PARP Inhibitors: The Mayo Clinic Experience.

Purpose: This study evaluates real-world outcomes, toxicities, and prescribing patterns of PARP inhibitors (PARPis) for the treatment of metastatic breast cancer (MBC).

Patients And Methods: Electronic health records of 62 MBC patients treated with olaparib (n = 48) or talazoparib (n = 14) at Mayo Clinic System between 2017 and 2022 were analyzed. Time-to-treatment-failure (TTF) was assessed utilizing the Kaplan-Meier method.

Resistance Management for Cancer: Lessons from Farmers.

One of the main reasons we have not been able to cure cancers is that treatments select for drug-resistant cells. Pest managers face similar challenges with pesticides selecting for pesticide-resistant insects, resulting in similar mechanisms of resistance. Pest managers have developed 10 principles that could be translated to controlling cancers: (i) prevent onset, (ii) monitor continuously, (iii) identify thresholds below which there will be no intervention, (iv) change interventions in response to burden, (v) preferentially select nonchemical control methods, (vi) use target-specific drugs, (vii) use the lowest effective dose, (viii) reduce cross-resistance, (ix) evaluate success based on long-term management, and (x) forecast growth and response.

QTc prolongation across CDK4/6 inhibitors: a systematic review and meta-analysis of randomized controlled trials.

Background: Cyclin-dependent kinases (CDK) 4/6 inhibitors have significantly improved outcomes for patients with ER+/HER2- breast cancer. Nevertheless, they differ from each other in terms of chemical, biological, and pharmacological features, as well as toxicity profiles. We aim to determine whether QTc prolongation is caused by CDK4/6i in general or if it is associated with ribociclib only.

Prospective Study of Supplemental Screening With Contrast-Enhanced Mammography in Women With Elevated Risk of Breast Cancer: Results of the Prevalence Round.

Purpose: Contrast-enhanced mammography (CEM) and magnetic resonance imaging (MRI) have shown similar diagnostic performance in detection of breast cancer. Limited CEM data are available for high-risk breast cancer screening. The purpose of the study was to prospectively investigate the efficacy of supplemental screening CEM in elevated risk patients.

Factors influencing U.S. women's interest and preferences for breast cancer risk communication: a cross-sectional study from a large tertiary care breast imaging center.

Background: Breast imaging clinics in the United States (U.S.) are increasingly implementing breast cancer risk assessment (BCRA) to align with evolving guideline recommendations but with limited uptake of risk-reduction care.

Neoadjuvant talazoparib in patients with germline BRCA1/2 mutation-positive, early-stage triple-negative breast cancer: exploration of tumor BRCA mutational status.

Background: Talazoparib monotherapy in patients with germline BRCA-mutated, early-stage triple-negative breast cancer (TNBC) showed activity in the neoadjuvant setting in the phase II NEOTALA study (NCT03499353). These biomarker analyses further assessed the mutational landscape of the patients enrolled in the NEOTALA study.

Methods: Baseline tumor tissue from the NEOTALA study was tested retrospectively using FoundationOneCDx.

Testing Adaptive Therapy Protocols Using Gemcitabine and Capecitabine in a Preclinical Model of Endocrine-Resistant Breast Cancer.

Adaptive therapy, an ecologically inspired approach to cancer treatment, aims to overcome resistance and reduce toxicity by leveraging competitive interactions between drug-sensitive and drug-resistant subclones, prioritizing patient survival and quality of life instead of killing the maximum number of cancer cells. In preparation for a clinical trial, we used endocrine-resistant MCF7 breast cancer to stimulate second-line therapy and tested adaptive therapy using capecitabine, gemcitabine, or their combination in a mouse xenograft model. Dose modulation adaptive therapy with capecitabine alone increased survival time relative to MTD but not statistically significantly (HR = 0.

Metastatic ER+ Breast Cancer: Mechanisms of Resistance and Future Therapeutic Approaches.

Endocrine therapy is the main treatment for hormone receptor-positive (HR+) breast cancer. However, advanced tumors develop resistance to endocrine therapy, rendering it ineffective as the disease progresses. There are several molecular mechanisms of primary and secondary endocrine resistance.

Testing Adaptive Therapy Protocols using Gemcitabine and Capecitabine on a Mouse Model of Endocrine-Resistant Breast Cancer.

Highly effective cancer therapies often face limitations due to acquired resistance and toxicity. Adaptive therapy, an ecologically inspired approach, seeks to control therapeutic resistance and minimize toxicity by leveraging competitive interactions between drug-sensitive and drug-resistant subclones, prioritizing patient survival and quality of life over maximum cell kill. In preparation for a clinical trial in breast cancer, we used large populations of MCF7 cells to rapidly generate endocrine-resistance breast cancer cell line.

Neoadjuvant Talazoparib in Patients With Germline BRCA1/2 Mutation-Positive, Early-Stage Triple-Negative Breast Cancer: Results of a Phase II Study.

Background: The undetermined efficacy of the current standard-of-care neoadjuvant treatment, anthracycline/platinum-based chemotherapy, in patients with early-stage triple-negative breast cancer (TNBC) and germline BRCA mutations emphasizes the need for biomarker-targeted treatment, such as poly(ADP-ribose) polymerase inhibitors, in this setting. This phase II, single-arm, open-label study evaluated the efficacy and safety of neoadjuvant talazoparib in patients with germline BRCA1/2-mutated early-stage TNBC.

Patients And Methods: Patients with germline BRCA1/2-mutated early-stage TNBC received talazoparib 1 mg once daily for 24 weeks (0.

Comparison of PARPi efficacy according to homologous recombination deficiency biomarkers in patients with ovarian cancer: a systematic review and meta-analysis.

Background: Mutations in the BRCA1/2 (BRCA) genes are associated with response to poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi). In addition, there are different homologous recombination deficiency (HRD) biomarkers available in clinical practice [e.g.

Outcomes of the "BRCA Quality Improvement Dissemination Program": An initiative to improve patient receipt of cancer genetics services at five health systems.

Objective: A quality improvement initiative (QII) was conducted with five community-based health systems' oncology care centers (sites A-E). The QII aimed to increase referrals, genetic counseling (GC), and germline genetic testing (GT) for patients with ovarian cancer (OC) and triple-negative breast cancer (TNBC).

Methods: QII activities occurred at sites over several years, all concluding by December 2020.

PARP Inhibitors for Breast Cancer: Germline and Beyond.

Poly-adenosine diphosphate ribose polymerase (PARP) inhibitors (PARPi) are approved for carriers with HER2-negative breast cancer in the adjuvant setting with a high risk of recurrence as well as the metastatic setting. However, the indications for PARPi are broader for patients with other cancer types (e.g.

Determinants of Response to Talazoparib in Patients with HER2-Negative, Germline BRCA1/2-Mutated Breast Cancer.

Purpose: PARP inhibitors (PARPi) have demonstrated efficacy in tumors with germline breast cancer susceptibility genes (gBRCA) 1 and 2 mutations, but further factors influencing response to PARPi are poorly understood.

Experimental Design: Breast cancer tumor tissue from patients with gBRCA1/2 mutations from the phase III EMBRACA trial of the PARPi talazoparib versus chemotherapy was sequenced using FoundationOne CDx.

Results: In the evaluable intent-to-treat population, 96.

Personalized Breast Cancer Risk Assessment: Incorporation of Genetic and High-Risk Factorson Breast Cancer Risk and Management.

Breast cancer remains the second most diagnosed cancer in women worldwide and the number one cause of cancer in women in the United States. It is unfortunately the primary cause of cancerrelated deaths among women, with 14% of all cancer deaths attributed to it. Over the past decade, screening methods have matured, and imaging modalities are continuously improving.

A Breast Radiology Department-operated, Proactive Same-day Program Identifies Pathogenic Breast Cancer Mutations in Unaffected Women.

Rationale And Objectives: Pathogenic mutations in some genes elevate women's breast cancer risk, necessitating risk-reduction strategies. Unfortunately, women are underscreened for cancer risk, and when identified as potentially high risk, women seldom pursue genetic counseling or testing. To improve cancer risk management, this project determined the feasibility of radiology-operated, proactive, same-day risk assessment and genetic testing programs to diagnose high-risk women undergoing breast imaging.

Relations of Mindfulness and Illness Acceptance With Psychosocial Functioning in Patients With Metastatic Breast Cancer and Caregivers.

Objectives: To examine relationships in mindfulness and illness acceptance and psychosocial functioning in patients with metastatic breast cancer and their family caregivers.

Sample & Setting: 33 dyads from an academic cancer center in the United States.

Methods & Variables: Participants completed questionnaires on mindfulness, illness acceptance, relationship quality, anxiety, and depressive symptoms.

Outcomes in Clinically Relevant Patient Subgroups From the EMBRACA Study: Talazoparib vs Physician's Choice Standard-of-Care Chemotherapy.

Background: Talazoparib is a poly(adenosine diphosphate-ribose) polymerase inhibitor that causes death in cells with breast cancer susceptibility gene 1 or 2 () mutations.

Methods: EMBRACA (NCT01945775) was a randomized phase III study comparing efficacy, safety, and patient-reported outcomes (PROs) of talazoparib (1 mg) with physician's choice of chemotherapy (PCT: capecitabine, eribulin, gemcitabine, vinorelbine) in locally advanced or metastatic breast cancer with a germline (g) mutation. Prespecified patient subgroups were analyzed for progression-free survival, objective response, clinical benefit, duration of response, and safety.

Talazoparib in Patients with a Germline BRCA-Mutated Advanced Breast Cancer: Detailed Safety Analyses from the Phase III EMBRACA Trial.

Background: In the EMBRACA phase III study (NCT01945775), talazoparib was associated with a significantly prolonged progression-free survival (PFS) compared with physician's choice of chemotherapy (PCT) in germline BRCA1/2-mutated HER2-negative advanced breast cancer (ABC). Herein, the safety profile of talazoparib is explored in detail.

Materials And Methods: Overall, 412 patients received ≥1 dose of talazoparib (n = 286) or PCT (n = 126).

Precise and Programmable Detection of Mutations Using Ultraspecific Riboregulators.

The ability to identify single-nucleotide mutations is critical for probing cell biology and for precise detection of disease. However, the small differences in hybridization energy provided by single-base changes makes identification of these mutations challenging in living cells and complex reaction environments. Here, we report a class of de novo-designed prokaryotic riboregulators that provide ultraspecific RNA detection capabilities in vivo and in cell-free transcription-translation reactions.

Immunotherapy for the Treatment of Breast Cancer: Emerging New Data.

Breast cancer is the most common type of cancer affecting women in the United States. Triple-negative breast cancer remains the most aggressive molecular subtype secondary to a lack of therapeutic targets. The search for a target has led us to investigate immunotherapeutic agents.