Outcomes in stage IIA versus stage IIB/III in the PALLAS trial [ABCSG-42/AFT-05/PrE0109/BIG-14-13]).

Background: The PALLAS trial investigated the addition of palbociclib to standard adjuvant endocrine therapy to reduce breast cancer recurrence. This pre-specified analysis was conducted to determine whether adjuvant palbociclib benefited patients diagnosed with lower risk stage IIA disease compared to those with higher stage disease.

Methods: PALLAS was an international, multicenter, randomized, open-label, phase III trial, representing a public-private partnership between Pfizer, the Austrian Breast Cancer Study Group, and the U.

HER2DX in HER2-positive inflammatory breast cancer: correlative insights and comparative analysis with noninflammatory breast cancers.

Background: The HER2DX assay predicts long-term prognosis and pathologic complete response (pCR) in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant systemic therapy but has not been evaluated in inflammatory breast cancer (IBC).

Patients And Methods: HER2DX was analyzed in baseline biopsy tissues from 23 patients with stage III HER2-positive IBC on a phase II trial (NCT01796197) treated with neoadjuvant trastuzumab, pertuzumab, and paclitaxel (THP). To assess the assay's predictive accuracy for pCR in IBC, clinical-pathological features and outcomes from this IBC cohort were compared with 156 patients with stage III HER2-positive non-IBC from four different cohorts.

Utility of ursodiol prophylaxis against sinusoidal obstruction syndrome (SOS)/ veno-occlusive disease (VOD) in acute leukemia patients receiving gemtuzumab-ozogamicin (GO) or inotuzumab-ozogamicin (InO).

Purpose: Sinusoidal obstructive syndrome (SOS)/veno-occlusive disease (VOD) is a serious complication in hematopoietic stem-cell transplant (HSCT) patients. Gemtuzumab-ozogamicin (GO) and InO are known to cause SOS/VOD in leukemic and transplant populations. Due to limited data on ursodiol prophylaxis in non-HSCT patients, we aimed to assess hepatotoxicity, SOS/VOD incidences, time to hepatotoxicity, and confirmed SOS/VOD in adults receiving GO or InO ± ursodiol.

Avoiding positivity at a cost: Evidence of reward devaluation in the novel valence selection task.

Reward devaluation theory (RDT) posits that some depressed individuals may not only be biased toward negative material but also actively avoid positive material (i.e., devaluing reward).

Adjuvant Dose-Dense Chemotherapy in Hormone Receptor-Positive Breast Cancer.

Purpose: In light of evolving evidence that some patients with node-positive estrogen receptor-positive (ER+) disease may receive less benefit from chemotherapy, this study reports 12-year outcomes of the C9741 trial overall, and by the sensitivity to endocrine therapy (SET2,3) test index, a biomarker measuring endocrine transcriptional activity, to identify patients most likely to benefit from dose-dense chemotherapy.

Methods: In all, 1,973 patients were randomly assigned to dose-dense versus conventional chemotherapy. Hazard ratios (HRs) for prognosis and for predictive interaction with chemotherapy schedule were estimated from Cox models of long-term disease-free survival (DFS) and overall survival (OS).

Active Monitoring With or Without Endocrine Therapy for Low-Risk Ductal Carcinoma In Situ: The COMET Randomized Clinical Trial.

Importance: Active monitoring for low-risk ductal carcinoma in situ (DCIS) of the breast has been proposed as an alternative to guideline-concordant care, but the safety of this approach is unknown.

Objective: To compare rates of invasive cancer in patients with low-risk DCIS receiving active monitoring vs guideline-concordant care.

Design, Setting, And Participants: Prospective, randomized noninferiority trial enrolling 995 women aged 40 years or older with a new diagnosis of hormone receptor-positive grade 1 or grade 2 DCIS without invasive cancer at 100 US Alliance Cancer Cooperative Group clinical trial sites from 2017 to 2023.

Anhedonia in flux: Understanding the associations of emotion regulation and anxiety with anhedonia dynamics in a sample with major depressive disorder.

Negative rumination and emotion regulation difficulties have been consistently linked with depression. Despite anhedonia-the lack of interest in pleasurable experiences-being a cardinal symptom of depression, emotion regulation of positive emotions, including dampening, are considered far less in the literature. Given that anhedonia may manifest through blunted responses to previously positive or enjoyable experiences, it is vital to understand how different positive emotion regulation strategies impact anhedonia symptom severity and how it can vary or change over time.

Patient-reported outcomes, and perceptions and knowledge about recurrence in women with hormone receptor-positive breast cancer.

Purpose: Over half of hormone receptor-positive (HR+) breast cancer recurrences occur >5 years from diagnosis, however, little is known about well-being or breast cancer risk perceptions and knowledge in long-term HR+ breast cancer survivors.

Methods: From 1/2021 to 1/2022, we surveyed patients with a history of stage II/III, HR+ breast cancer, ≥5 years from diagnosis, without recurrence about concerns and perceptions related to their diagnosis and recurrence risk, physical and emotional health, knowledge, and risk reduction. Logistic regression identified factors associated with overestimation of 5-10 year distant recurrence risk.

Virtual stressors with real impact: what virtual reality-based biobehavioral research can teach us about typical and atypical stress responsivity.

Stress contributes to transdiagnostic morbidity and mortality across a wide range of physical and mental health problems. VR tasks have been validated as stressors with robust effect sizes for VR-based stressors to evoke stress across the most common autonomic and adrenocortical stress biomarkers. However, meta-analytic validation of VR stressors have resulted in inconsistent logic: why should something that isn't real evoke a very real suite of stress responses? This review posits that conceptually addressing this question requires differentiating a cause, "stressor", from effects, "stress".

Lower-intensity CPX-351 plus venetoclax induction for adults with newly diagnosed AML unfit for intensive chemotherapy.

Preclinical data suggest a rationale for combining CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine, with venetoclax, a B-cell lymphoma-2 inhibitor. This phase 1b study evaluated lower-intensity CPX-351 combined with venetoclax in adults with acute myeloid leukemia (AML) considered unfit/ineligible for intensive chemotherapy. In a dose-exploration phase using a 3+3 design, patients received stepwise dosing of CPX-351 IV on days 1 and 3 plus venetoclax 400 mg orally on days 2 to 21 per cycle to determine the recommended phase 2 dose (RP2D) for this combination.

AML in the Elderly - When less may be more.

Purpose Of Review: We herein assess the distinct biological and clinical features of AML in older patients. We emphasize the importance of pre-treatment assessment to individualize care but note the changing treatment paradigm from intensive towards non-intensive therapy.

Recent Finding: Geriatric assessments and genetic data provide predictive information that guides treatment.

Adaptation of the socioecological model to address disparities in engagement of Black men in prostate cancer genetic testing.

Background: Black men consistently have higher rates of prostate cancer (PCA)- related mortality. Advances in PCA treatment, screening, and hereditary cancer assessment center around germline testing (GT). Of concern is the significant under-engagement of Black males in PCA GT, limiting the benefit of precision therapy and tailored cancer screening despite longstanding awareness of these disparities.

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.

A Phase II Study of Atezolizumab, Pertuzumab, and High-Dose Trastuzumab for Central Nervous System Metastases in Patients with HER2-Positive Breast Cancer.

Purpose: Patients with HER2-positive breast cancer brain metastases have few effective systemic therapy options. In a prior study, pertuzumab with high-dose trastuzumab demonstrated a high clinical benefit rate (CBR) in the central nervous system (CNS) in patients with brain metastases. The current trial evaluated whether the addition of atezolizumab to this regimen would produce further improvements in CNS response.

Analysis of HER2 expression changes from breast primary to brain metastases and the impact of HER2-low expression on overall survival.

Background: There are limited data regarding HER2-low expression dynamics between matched primary tumors and brain metastases (BrMs) in breast cancer. HER2-low expression has emerged as a new therapeutic biomarker for highly active antibody-drug conjugates with emerging intracranial activity.

Methods: Patients with metastatic breast cancer and BrMs seen at an NCI-designated center between 2003 and 2023 were identified.

Assessing relinquishment of positivity as a central symptom bridging anxiety and depression.

Anxiety and depression are often comorbid and chronic disorders. Previous research indicates that positivity relinquishment is a moderator of anxiety and depression, such that only anxious individuals who endorsed relinquishing positivity were also depressed. We sought to extend those findings by conducting three network analyses with self-report measures of anxiety, depression, activity avoidance, and perceived positivity of avoided activities (N = 104).

Barriers to and facilitators of improving physical activity and nutrition behaviors during chemotherapy for breast cancer: a sequential mixed methods study.

Purpose: Use qualitative and quantitative methods to explore factors influencing the adoption of guideline-based physical activity (PA) and dietary recommendations among participants enrolled in a lifestyle intervention during and after chemotherapy for breast cancer.

Methods: Among women with stage I-III breast cancer who participated in the intervention arm of the Lifestyle, Exercise, and Nutrition early after diagnosis (LEANer) trial, we used stratified, purposeful sampling to interview women who met both, one, or neither intervention goal after the 1-year intervention: (1) 150 min/week moderate-to-vigorous intensity exercise via a self-reported PA questionnaire and (2) improved self-reported diet quality measured by the Healthy Eating Index-2015. Semi-structured interviews were audio-recorded, transcribed verbatim, and analyzed using thematic content analysis.

Hypofractionated vs Conventionally Fractionated Postmastectomy Radiation After Implant-Based Reconstruction: A Randomized Clinical Trial.

Importance: Postmastectomy radiation therapy (PMRT) improves local-regional disease control and patient survival. Hypofractionation (HF) regimens have comparable efficacy and complication rates with improved quality of life compared with conventional fractionation (CF) schedules. However, the use of HF after mastectomy in patients undergoing breast reconstruction has not been prospectively examined.

Subunit-specific analysis of cohesin-mutant myeloid malignancies reveals distinct ontogeny and outcomes.

Mutations in the cohesin complex components (STAG2, RAD21, SMC1A, SMC3, and PDS5B) are recurrent genetic drivers in myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML). Whether the different cohesin subunit mutations share clinical characteristics and prognostic significance is not known. We analyzed 790 cohesin-mutant patients from the Dana-Farber Cancer Institute (DFCI) and the Munich Leukemia Laboratory (MLL), 390 of which had available outcome data, and identified subunit-specific clinical, prognostic, and genetic characteristics suggestive of distinct ontogenies.

Neratinib and ado-trastuzumab emtansine for pretreated and untreated human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases: Translational Breast Cancer Research Consortium trial 022.

Background: Treatment options for human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases (BCBMs) remain limited. We previously reported central nervous system (CNS) activity for neratinib and neratinib-capecitabine. Preclinical data suggest that neratinib may overcome resistance to ado-trastuzumab emtansine (T-DM1) when given in combination.

CRISPR-based rapid molecular diagnostic tests for fusion-driven leukemias.

Fusion oncogenes can be cancer-defining molecular alterations that are essential for diagnosis and therapy selection.1,2 Rapid and accessible molecular diagnostics for fusion-driven leukemias such as acute promyelocytic leukemia (APL), Philadelphia chromosome-positive acute lymphoblastic leukemia, and chronic myeloid leukemia (CML) are unavailable, creating a barrier to timely diagnosis and effective targeted therapy in many health care settings, including community hospitals and low-resource environments. We developed CRISPR-based RNA-fusion transcript detection assays using SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) for the diagnosis of fusion-driven leukemias.