The NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget's disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The panel convenes annually to update recommendations based on a review of recently published clinical trials. This selection from the NCCN Guidelines for Breast Cancer focuses on the recommendations for the management of recurrent or stage IV (M1) metastatic breast cancer. It summarizes the treatment strategies stratified by tumor biology, including hormone receptor status and HER2 expression, as well as clinical factors such as prior therapy and disease-free interval. Throughout all treatment lines, supportive care, quality of life preservation, toxicity minimization, and clinical trial participation are emphasized as integral components of patient care.

The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are a group of heterogenous hematologic malignancies characterized by the proliferation of blood cells and consist of myelofibrosis, polycythemia vera, and essential thrombocythemia. The NCCN Guidelines for MPN were developed as a result of meetings convened by a multidisciplinary panel with expertise in MPN, with the aim of providing recommendations for the comprehensive care of adults with these diseases. The panel of experts convenes at least once a year to discuss requested changes to the Guidelines and to evaluate emerging data. These Guideline Insights focus on some of the recent updates for myelofibrosis.

HER2-positive breast cancer accounts for approximately 15%-20% of breast cancers and was historically associated with poor outcomes. The introduction of HER2-targeted therapies has significantly improved prognosis, particularly in the treatment of early-stage disease. Neoadjuvant HER2-directed therapy combined with chemotherapy is the standard of care for patients with stage II and III HER2-positive breast cancer, enabling pathologic complete response-guided treatment personalization. This review summarizes current evidence guiding the neoadjuvant management of early-stage HER2-positive breast cancer. We discuss pivotal trials establishing dual HER2 blockade with trastuzumab and pertuzumab, strategies to optimize and de-escalate chemotherapy backbones, and emerging data supporting chemotherapy-sparing approaches in selected patients. Recent studies evaluating taxane-only regimens, carboplatin omission, antibody-drug conjugates, and immunotherapy-based combinations are reviewed with attention to efficacy, toxicity, and clinical applicability. We further examine validated and emerging biomarkers of response, including molecular subtyping, genomic assays, tumor immune features, circulating tumor DNA, and functional imaging, all of which may enable risk-adapted treatment strategies. Finally, we review mechanisms of resistance to HER2-targeted therapies, as well as novel therapeutic approaches under investigation to overcome treatment resistance. This review provides a contemporary, evidence-based framework for individualized neoadjuvant treatment of early-stage HER2-positive breast cancer.