How Breast Cancer Arises Breakthrough

2023

Researchers from Harvard Medical School have uncovered a novel mechanism behind certain types of breast cancer, offering a new perspective on the disease's development. The study, detailed in the journal Nature, identifies genomic reshuffling, involving the rearrangement of chromosomes, as the trigger for breast cancer in cases that defy the classical model of its development. The research challenges the prevailing belief that the hormone estrogen merely fuels breast cancer growth and reveals that estrogen can directly cause genomic rearrangements, shedding light on previously unexplained cases.

In essence, the study suggests that approximately one-third of breast cancer cases may originate from this newly identified mechanism. While estrogen's role in breast cancer has traditionally been viewed as stimulating the proliferation of breast tissue and contributing to cancer-causing mutations, the research demonstrates that estrogen can also induce genomic rearrangements directly.

The team, led by Professor Peter Park, delved into the genomic data of 780 breast cancer cases. They anticipated the classical chromosomal disarray in most samples but were surprised to find a distinctive pattern in one-third of the tumors. Instead of the anticipated misshapen single chromosome, two chromosomes had fused near "hot spots" where cancer genes are located. This pattern indicated a new mechanism by which a "disfigured" chromosome is generated, subsequently contributing to certain breast cancer cases.

Zooming in on the cancer-gene activation hot spots, researchers noted their proximity to estrogen-binding areas on DNA. This observation prompted further experiments with breast cancer cells, exposing them to estrogen and using CRISPR gene editing to make DNA cuts. The repair process resulted in the same genomic rearrangement observed in the genomic analyses.

These findings suggest a new role for estrogen in breast cancer genesis, indicating that estrogen-suppressing drugs, like tamoxifen, may work more directly by preventing estrogen from initiating cancer-causing genomic rearrangements. The study's insights could lead to improved breast cancer testing, enabling the detection of specific genomic rearrangements associated with disease recurrence.

In conclusion, this research challenges conventional understandings of breast cancer development, highlighting the importance of DNA sequencing and data analysis in deepening our understanding of cancer biology. The study's implications may extend beyond breast cancer, emphasizing the broader value of such investigative approaches in comprehending the complexities of cancer development.

This work received funding from various sources, including the Ludwig Center at Harvard, Cancer Grand Challenges, Cancer Research UK, the Mark Foundation for Cancer Research, and the National Institutes of Health.