CA: A Cancer Journal for Clinicians最新文献

The hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer subtype accounts for most early and metastatic breast cancer (MBC) cases. HR-positive/HER2-negative MBC is characterized by a relatively prolonged, although variable, disease course and substantial intertumoral and intratumoral heterogeneity. Although endocrine-based therapies remain the cornerstone of treatment, nearly all patients eventually develop resistance, which is increasingly addressed with biologically targeted agents and newer-generation cytotoxic drugs. This review summarizes the current understanding of HR-positive/HER2-negative MBC biology, highlighting mechanisms of intrinsic and acquired resistance, including driver genomic alterations that, along with clinical factors, help guide therapeutic choices and sequencing. The authors specify and discuss how genomic and transcriptomic profiling inform treatment selection and how side effects and overall patient experience are considered in decision making. Advances in targeted therapies, such as CDK4/6 (cyclin-dependent kinase 4/6), PI3K (phosphatidylinositol 3-kinase), and AKT (protein kinase B) inhibitors, and next-generation estrogen receptor degraders are reviewed along with the expanding role of antibody–drug conjugates and biomarker-guided tumor-agnostic biologic therapies. The authors also explore evolving biologic concepts, including the impact of the tumor microenvironment on resistance and disease progression, and consider the distinct clinical behavior of invasive lobular carcinoma and current approaches. Emerging data from contemporary clinical trials promise to refine clinical and biomarker-driven algorithms and improve outcomes for patients with HR-positive/HER2-negative MBC. Ongoing multi-omic research and adaptive clinical strategies will be essential to further the application of precision oncology in this most common subtype of MBC. Importantly, patient-reported outcomes, shared decision making, and real-world evidence are increasingly useful in formulating comprehensive care plans, guidelines, and policy. The modern treatment landscape features a personalized approach that integrates clinical features, biomarkers, and patient preferences across the disease continuum.

Since 2021, the American Cancer Society has published its biennial report on the status of cancer disparities in the United States. In this 2025 report, the authors provide updated data on disparities in cancer occurrence and outcomes by sex, race, ethnicity, socioeconomic status (SES [educational attainment as a proxy]), and geographic location (including urbanicity of county of residence and congressional district), along with contributors to these disparities, including major cancer risk factors, screening, and select social determinants of health (SDOH) and health-related social needs. The authors found substantial disparities across the cancer continuum, including risk factors, incidence, stage at diagnosis, receipt of care, survival, and mortality for many cancers and in evaluated SDOH by race and ethnicity, educational attainment, and geographic location. During 2019 through 2023, Black and American Indian/Alaska Native populations had the highest cancer mortality rates, both overall and for the leading causes of cancer death. Cancer mortality rates were also consistently higher among adults with lower SES. However, differences in cancer mortality were substantially larger by education than by race, indicating that SES plays a major role in driving racial disparities in cancer mortality. Overall cancer mortality rates were higher in Black adults than in White adults with the same education level by 7%–28% among males and by 2%–43% among females. Within each race, however, overall cancer mortality rates were higher in adults with ≤12 years of education than in those with ≥16 years of education by 143%–192% among males and by 71%–140% among females. Mortality from all cancers combined was 21% higher in nonmetropolitan than in large metropolitan counties, with the greatest differences for lung (45%) and cervical (36%) cancers and the smallest for prostate, female breast, and pancreatic cancers (7%–8%). By congressional district, the highest cancer mortality rates both overall and for lung, colorectal, and breast cancers were largely found in the South and East North-Central division of the Midwest; however, for prostate cancer, there was no distinct geographic pattern. Sociodemographic groups that had higher cancer mortality generally had higher exposure to risk factors, lower health insurance coverage, and limited access to cancer prevention, early detection, and treatment compared with groups that had lower cancer mortality, largely reflecting fundamental disparities in SDOH. Mitigating cancer disparities in the United States requires intersectoral stakeholder engagement, targeted funding, effective policies at the federal, state, and local levels, and broad implementation of evidence-based interventions, such as expanding health insurance coverage, including through strengthening Marketplaces and protecting and expanding access to Medicaid.