Breast cancer: hereditary risk and embryo screening

Most families who worry about hereditary breast cancer are thinking about one thing: BRCA. That's understandable. BRCA is the name that shows up in genetic testing ads, in conversations at the oncologist's office, and in the news. But BRCA mutations account for roughly 3% of all breast cancer cases. The other 97% involve a completely different kind of genetic risk, one most families have never heard of.

About 1 in 8 women will develop breast cancer in their lifetime, and genetics plays a real role in who gets it. But the genetics are more complicated than a single mutation. Understanding that distinction changes what you can actually do about it.

The 3% everyone knows about

BRCA1 and BRCA2 are single-gene mutations with very high penetrance. If you carry a BRCA1 mutation, your cumulative risk of developing breast cancer by age 80 is approximately 72%. For BRCA2 carriers, it's about 69%. Those are large numbers, and they explain why BRCA testing changed how we approach cancer prevention.

For families who know they carry a BRCA variant, preimplantation genetic testing for monogenic disorders (PGT-M) has been available since around 2009. The process is straightforward: during an IVF cycle, embryos are biopsied and tested for the specific pathogenic variant. Parents can then transfer an embryo that doesn't carry the mutation. It's been accepted clinical practice for more than 15 years.

But BRCA is rare. The general population carrier frequency is roughly 1 in 300 to 1 in 400. So while these mutations carry enormous individual risk, they explain only a small fraction of breast cancer overall. If you don't carry a BRCA mutation, that doesn't mean genetics isn't involved in your family's breast cancer story. It almost certainly is.

Twin studies have given us a clear picture of just how much genetics matters. The Nordic Twin Study of Cancer, one of the largest ever conducted, found that breast cancer heritability is approximately 31%. That means nearly a third of the variation in who gets breast cancer and who doesn't comes down to genetic differences. Not lifestyle, not environment, not luck. Genetics.

So if BRCA accounts for 3% and genetics overall explains 31% of the risk, where's the rest coming from?

The 97% most people miss

The answer is polygenic risk. Unlike BRCA, which involves a single high-impact mutation, polygenic risk comes from hundreds of common genetic variants that each contribute a small amount to overall breast cancer risk. Individually, each variant barely moves the needle. Together, they add up.

This isn't a theoretical concept. Polygenic risk scores for breast cancer have been validated in large studies and are now being integrated into clinical screening programs to help decide when women should start mammography and how often they should be screened.

But here's where it gets genuinely surprising. Polygenic risk doesn't just operate independently from monogenic risk. It modifies it.

A 2020 study in Nature Communications by Mars and colleagues looked at women who carry pathogenic variants in genes like PALB2 and CHEK2 (both associated with elevated breast cancer risk, similar to BRCA). They found that a PALB2 carrier's lifetime breast cancer risk isn't fixed. It ranges from 49% to 84%, depending on where that woman falls on the polygenic risk spectrum. For CHEK2 carriers, the range is even more dramatic: 9% to 59%.

Think about what that means. Two women can carry the exact same rare mutation. One faces roughly a coin flip of developing breast cancer. The other faces near-certainty. The difference is their polygenic background.

This has direct implications for families going through IVF. Even if you already know your family carries a BRCA or PALB2 variant and you're planning to use PGT-M to screen for that specific mutation, the polygenic layer still matters. An embryo that doesn't carry the BRCA variant can still have high or low polygenic risk. And an embryo that does carry it will face very different odds depending on that same polygenic background.

The two types of genetic risk aren't competing. They're complementary.

What screening can actually measure

For IVF families, two tools address these two layers of risk.

PGT-M screens for known monogenic variants like BRCA1, BRCA2, PALB2, and CHEK2. If your family carries one of these, PGT-M can identify which embryos inherited it and which didn't. This has been standard practice for years, and a genetic counselor can help determine if your family history warrants testing.

Preimplantation genetic testing for polygenic conditions (PGT-P) does something different. It evaluates the aggregate polygenic risk from hundreds of common variants, producing a score that estimates each embryo's genetic predisposition to breast cancer relative to its siblings.

We've built what we believe is the strongest polygenic score for breast cancer currently available. Our score explains 14.3% of the variance in breast cancer risk, compared to 8.8% for Orchid and 3.3% for Genomic Prediction (Moore et al., 2025). And because embryos from the same IVF cycle are siblings, we validate our scores on sibling pairs, not unrelated individuals. That's the validation context that actually matches the decision you're making.

To be clear about what this does and doesn't do: a polygenic score isn't a diagnosis. It doesn't tell you whether a child will or won't develop breast cancer. It tells you where each embryo sits on the risk spectrum relative to its siblings. Some of that risk will also be shaped by environmental factors throughout life, things like physical activity, alcohol consumption, and hormone exposure. But the genetic baseline is the one piece parents can't change through lifestyle choices after birth. It's also the one piece that can be measured before embryo transfer.

For families where one parent has been affected by breast cancer, the baseline risk is already elevated. Our data shows that when one parent has had breast cancer, the family baseline risk is approximately 19.8%, compared to about 13% for the general population. PGT-P offers information about where each embryo falls within that family-specific range.

If you're interested in understanding your family's full genetic picture for breast cancer, or if you want to explore how PGT-M and PGT-P can work together, reach out to us.

This article is for informational purposes only and does not constitute medical advice. Herasight does not provide medical diagnoses or tell patients which embryo to transfer. All screening decisions should be made in consultation with your medical team.