Breast cancer is the most common cancer and the leading cause of cancer‐related death among women worldwide. Advances in molecular biology, high‐throughput sequencing, and integrative‐omics have deepened the understanding of its heterogeneity by clarifying mechanisms linked to genetic susceptibility, epigenetic regulation, oncogenic signaling, and immune evasion. Although those developments have driven progress in targeted therapy and screening, concerns on drug resistance, toxicity, global inequities, and suboptimal risk stratification continue to limit outcomes. This review systematically summarizes current advances across four interconnected areas of breast cancer research and management, including molecular pathogenesis, targeted therapy, screening, and prevention. It describes key biological processes that shape tumor heterogeneity and examines targeted therapies, including endocrine agents, HER2‐directed drugs, CDK4/6 and PI3K/AKT/mTOR inhibitors, antibody–drug conjugates, and immunotherapies, together with mechanisms of resistance and emerging treatment targets. It also evaluates evolving approaches in risk stratification and screening, highlighting progress in digital breast tomosynthesis, magnetic resonance imaging, contrast‐enhanced mammography, and artificial intelligence‐assisted interpretation. By integrating cutting‐edge molecular insights with clinical advances, this review further highlights the expanding opportunities for personalized therapy and precision prevention. It outlines future directions linking multiomics and artificial intelligence to more equitable and effective breast cancer management.

MUTYH plays an essential role in preventing oxidation-caused DNA damage. Pathogenic germline variations in MUTYH damage its function, causing intestinal polyposis and colorectal cancer. Determination of the evolutionary origin of the variation is essential to understanding the etiological relationship between MUTYH variation and cancer development. In this study, we analyzed the origins of pathogenic germline variants in human MUTYH. Using a phylogenic approach, we searched MUTYH pathogenic variants in modern humans in the MUTYH of 99 vertebrates across eight clades. We did not find pathogenic variants shared between modern humans and the non-human vertebrates following the evolutionary tree, ruling out the possibility of cross-species conservation as the origin of human pathogenic variants in MUTYH. We then searched the variants in the MUTYH of 5031 ancient humans and extinct Neanderthals and Denisovans. We identified 24 pathogenic variants in 42 ancient humans dated between 30,570 and 480 years before present (BP), and three pathogenic variants in Neanderthals dated between 65,000 and 38,310 years BP. Data from our study revealed that human MUTYH pathogenic variants mostly arose in recent human history and partially originated from Neanderthals.

Objective: Ovarian cancer is a deadly gynecologic malignancy with a poor prognosis. It is essential to evaluate the early detection and screening programs of ovarian cancer via timely assessment of long-time survival, particularly in China where those data are incredibly limited. Here, we aimed to provide timely and accurately assessment of long-term survival estimate of ovarian cancer patients from eastern China. Methods: Data of 770 ovarian cancer patients diagnosed between 2004–2018 were obtained from four cancer registries in Taizhou, eastern China, were included. We used period analysis to calculate five-year relative survival (RS) of aforementioned ovarian cancer patients for overall and the stratification by age at diagnosis and region. Results: Our findings demonstrated that the overall five-year RS for ovarian cancer patients in Taizhou between 2014 and 2018 was 69.2%, while urban areas were higher compared to rural areas (77.6% vs. 64.9%). We also observed a significant age gradient with the five-year RS decreasing from 79.6% for age group < 55 years to 66.9% for age group > 74 years. Furthermore, we identified a clear upward trend of five-year RS over the study period, both overall and stratified by region and age at diagnosis. Conclusion: This is the first study in China using period analysis to provide the most up-to-date five-year RS for ovarian cancer patients from Taizhou, eastern China, which reaches 69.2% during 2014–2018. Our results provide valuable information for timely assessment of early detection and screening programs for ovarian cancer in eastern China.

DNA damage repair (DDR) genes play critical roles in maintaining genome stability. However, they are prone to genetic variation, of which pathogenic variation (PV) is a predisposing factor for high risk of cancer development in modern humans. Knowing the origin of DDR PV is critical for understanding the genetic basis and developing strategies against cancer risk for modern humans. So far, there is no consensus on the original sources of DDR PV in modern humans. We performed phylogenic analysis, and the results ruled out non-human species as the original source for the PV in modern humans through evolutionary conservation. We performed anthropological analyses by tracing the PV from modern humans in over 5000 ancient humans spanning the past 40,000 years. We observed a widespread distribution of DDR PV shared between modern and ancient humans. The shared DDR PV was predominantly found in modern non-Africans within the past 10,000 years rather than in modern Africans, highlighting that the arising time should be post the latest Out-of-Africa human migration. We also observed the rich distribution of Portuguese BRCA founder PV in Brazilian, highlighting that human admixture facilitated DDR PV transmission globally between ethnic human populations. The shorter arising time of DDR PV was further supported by the haplotyping results of DDR founder PV in multiple DDR genes and the predominant heterozygotic nature of DDR PV. Our comprehensive investigation reveals that DDR PV was mainly originated from the recent evolutionary history of modern humans, and highlights that the high cancer risk caused by DDR PV in modern humans is a by-product of the human evolution process.