"Understanding the Inherited Risk of Breast Cancer"

"How a Common PCSK9 Gene Variant Could Fuel Breast Cancer Spread and a Potential Antibody Solution"  

A widely inherited version of the PCSK9 gene, known for its role in cholesterol regulation, may also drive breast cancer cells to spread to other parts of the body (a process called metastasis). Excitingly, a lab-developed antibody already approved for managing cholesterol could hold promise in halting this cancer progression.

A gene involved in setting cholesterol levels may also determine whether breast cancer spreads to other parts of the body.

A variant of the PCSK9 gene drives the spread of breast cancer, but a lab-made antibody already approved to treat high cholesterol may help stop the exodus, researchers report December 9 in Cell.

"For years, scientists have been on a detective hunt, meticulously examining normal tissues and breast cancers that had spread to other parts of the body. Their goal? To uncover the genetic 'smoking guns' the mutations within the cancer cells themselves  that trigger this dangerous migration. But despite their best efforts, these detectives have come up empty-handed."

"Enter Wenbin Mei, a brilliant cancer biologist working in the lab of Dr. Sohail Tavazoie at Rockefeller University. Mei took a different approach. He wondered if the culprit might not be hidden within the cancer cells themselves, but rather inherited from our parents. Could subtle variations in our genes, passed down through generations, be secretly granting cancer

In a major breakthrough, Mei and his team discovered a strong link between a specific version of the PCSK9 gene and the deadly spread of breast cancer. This isn't about mutations that arise within the cancer itself, but rather inherited variations passed down from our parents. In a large Swedish study, individuals who inherited two copies of this 'spread associated' variant faced a stark reality: a 22% chance of their breast cancer spreading within 15 years of diagnosis. This grim statistic stands in stark contrast to those who inherited one or no copies of the variant, who faced a much lower risk of spread – only 2%.

"To further solidify these findings, the researchers meticulously re-examined the results of three other independent studies. This comprehensive analysis revealed a sobering truth: breast cancer patients who inherited two copies of this concerning variant had a significantly lower survival rate compared to those who did not. This discovery underscores the critical role that inherited genetic factors can play in determining the aggressive behavior of breast cancer."

A significant portion of the global population carries this specific version of the PCSK9 gene. In fact, around 70% of people of European or African descent inherit two copies. This variant is even more prevalent in certain populations, with nearly all Asians, particularly those of East Asian descent, and a large proportion of South Americans also carrying two copies."

"The PCSK9 gene was initially identified for its role in elevating cholesterol levels. This led researchers to investigate whether cholesterol-lowering medications like statins could also curb the spread of cancer. However, experiments in mice yielded unexpected results. Despite effectively lowering cholesterol, statins failed to prevent the cancer from spreading. This intriguing observation strongly suggests that the PCSK9 variant exerts its influence on cancer metastasis through mechanisms beyond its impact on cholesterol levels."

Long-form style for a blog:

Imagine your body has a set of brakes designed to keep cancer cells from spreading. New research reveals that a specific version of the PCSK9 gene, often linked to higher cholesterol, can interfere with these vital brakes.

Think of it like this: the problematic PCSK9 gene produces a protein that acts like a saboteur, removing the brakes that normally restrain two key genes involved in cancer metastasis. This essentially gives cancer cells the freedom to spread throughout the body, increasing the risk of the disease becoming more aggressive and harder to treat.

The good news is that scientists have discovered a potential countermeasure. An antibody drug, already approved to lower cholesterol, can effectively neutralize this saboteur protein. By blocking its actions, this antibody can help limit the spread of breast cancer in individuals with this specific genetic variation.

While this groundbreaking discovery doesn't offer a cure, it represents a significant step forward in the fight against aggressive breast cancer. Researchers believe that earlier intervention, potentially even before the development of cancer, could yield even more promising results for individuals who carry this specific genetic variation.