Gene Variants Predict Future Breast Cancer Types

Researchers at Stanford Medicine have made a new discovery, identifying genetic markers that can predict the type of breast cancer a person might develop, providing a deeper understanding of tumor evolution.

Inherited Genes and Breast Cancer

The study, led by Dr. Christina Curtis, reveals that genes inherited at birth play a crucial role in determining the type and severity of breast cancer. This finding challenges the longstanding belief that most cancers result from random mutations accumulated over a person's lifetime. Instead, it underscores the significance of inherited genes, or the germline genome, in influencing whether potential cancer cells are detected and eliminated by the immune system or evade detection and develop into cancer.

Key Findings

Published in Science on May 31, the study was led by postdoctoral scholar Dr. Kathleen Houlahan. The research demonstrates that some tumors are "born to be bad," with their malignant potential determined early. This discovery suggests that numerous additional gene variants—beyond the well-known BRCA1, BRCA2, and TP53 genes—interact with the immune system to influence cancer development.

Germline and Somatic Genomes

Inherited genes, known as the germline genome, can include mutations that increase cancer risk. Most cancer-associated genes, however, are part of the somatic genome, where mutations accumulate as cells divide and die over time. Previous studies have shown a link between BRCA1 mutations and triple-negative breast cancer, indicating that inherited genes affect the type of breast cancer that develops.

Immune System and Tumor Growth

The study delves into the role of the immune system in tumor development. Healthy cells display fragments of their proteins on their surfaces, which are monitored by immune cells called T cells. T cells destroy cells with abnormal proteins, such as those from cancer. The researchers found that inherited genes with highly noticeable protein fragments are less likely to develop into cancer because they are more readily detected by the immune system.

However, tumors with a high "epitope burden"—large amounts of recognizable protein fragments—that manage to evade the immune system tend to be more aggressive and have worse outcomes. This "tug of war" between tumor cells and the immune system highlights the complex interplay in cancer development.

Future Applications

Dr. Curtis envisions using this genetic information to better classify breast cancer subtypes, guide treatment decisions, and improve patient outcomes. The findings could also aid in the development of personalized cancer immunotherapies and enable clinicians to predict cancer risk from simple blood tests.

The study was funded by the National Institutes of Health, the Canadian Institutes of Health Research, and the Chan Zuckerberg Biohub. Dr. Curtis and her team continue to explore the role of these genetic factors in other types of cancer, promising to shed new light on cancer origins and progression.