Breast Cancer Tumor Origins and Immune System Insights
Breast cancer has long been believed to be caused by random mutations or bad luck. However, a recent study conducted by Stanford Medicine challenges this notion. The study, led by Christina Curtis, Ph.D., and postdoctoral scholar Kathleen Houlahan, examined thousands of breast cancer tumors and found that fetal DNA patterns can actually predict the type and severity of cancer decades later.
This groundbreaking discovery suggests that hereditary factors play a significant role in the development of cancer. It appears that our parents’ germline DNA can affect how the immune system detects and eliminates cancer-causing mutations or allows them to proliferate. In other words, genes and immunity are key players in the fight against cancer.
The study also sheds light on the origins of breast cancer and tumor development. It was previously proposed in 2015 that some tumors are born malignant and metastatic, and these findings confirm that theory. What is particularly interesting is how early this process occurs, highlighting the importance of early detection and intervention.
Understanding the causes of breast cancer has been an evolving journey for researchers. While certain gene mutations, such as BRCA1, BRCA2, and TP53, have been linked to increased cancer risk, finding other germline changes associated with future cancers has proven to be challenging.
Most cancer-related mutations are somatic, meaning they occur during DNA replication in the body’s cells. However, by comparing tumor DNA to blood or tissue germline genomes, scientists can identify cancer-causing mutations. This knowledge can help predict and treat breast cancer by providing insights into both the immune system and cancer cells.
In 2012, Curtis conducted a study that used machine learning to analyze somatic mutations in hundreds of breast cancers. This analysis led to the identification of 11 subtypes with different prognoses and recurrence rates. Four of these subtypes were found to have a higher likelihood of recurrence 10 to 20 years after diagnosis, enabling clinicians to make informed treatment decisions and discuss long-term prognoses with patients.
The team also explored how inherited DNA shapes tumor evolution and immune responses. They focused on HLA mutants, which are T lymphocytes that monitor abnormal cells. Oncogenes, which are normal genes that defy cell control, were also studied. Interestingly, Curtis initially identified breast cancer subgroups by studying oncogene amplifications.
The researchers discovered that breast tumors at various stages had different impacts on subtype based on inherited oncogene sequences. Tumors with a high germline epitope load and an HLA type that prominently displayed that epitope were less likely to develop breast cancer subtypes that amplified that oncogene. This finding was quite surprising but sheds light on the complex interactions between tumors and immune cells.
The study also revealed that immune escape mechanisms can develop in cancers, leading to aggressive and poor-prognosis breast cancer. By understanding these mechanisms, researchers hope to develop therapeutic timings and methods that can effectively target immunologically “cold” tumors.
Moving forward, Curtis and her team plan to further stratify the 11 breast cancer subtypes using the germline genome. This will not only aid in optimizing treatment and prognosis but also enable the development of cancer immunotherapies and risk assessment for healthy individuals based on blood samples.
Curtis emphasizes that this study takes a new perspective on tumor origins and evolution, considering the interplay between inherited factors, acquired mutations, and the tumor-immune system co-evolution. The findings have the potential to revolutionize our understanding of cancer variations and pave the way for more targeted and effective treatments.
In conclusion, this study has provided valuable insights into the complex relationship between genes, immunity, and breast cancer. By unraveling the mysteries surrounding tumor origins and immune responses, researchers are one step closer to improving diagnosis, treatment, and prevention strategies for this devastating disease.