BRCA risk factors: Making sense of the headlines

At the end of June, an article published in JAMA: The Journal of the American Medical Association[1] made headlines in the BRCA world.

The study provided data about risks for BRCA1 and BRCA2 mutation carriers, and the media reported exciting claims about pinpointing risk based on family history.

Jo Stanford, our Cancer Prevention Officer, breaks down the main findings to examine what the study’s results mean for BRCA+ women making health decisions today.

The key points regarding age were that for BRCA1, the number of breast cancer incidences per decade increased between the age 21-30 and 31-40 age bands, then remained relatively stable, with the peak incidences being in the 41-50 age group. It’s very important to note though that the p-value (which tells us about the statistical significance of the data) was .97, which is nowhere near statistically significant (a p-value of less than or equal to .05 is the standard measure of statistical significance). This trend therefore can only be described as an observation, but in no way a proven pattern.

For BRCA2 this was a similar story, with the peak of risk occurring in the 51-60 age bracket, with a slightly better p-value of .57 (but still not statistically significant).

In terms of age and ovarian cancer risks, the study suggests that the risk increases up to age 61-70 for both BRCA1&2, then plateaus, with the BRCA1 risk remaining higher than BRCA2 risk. BRCA1 risk looks to remain low until the age of 40, and BRCA2 risk until 50. However, there was only a small sample of ovarian cancer cases to make these judgements on.

These findings don’t change the general risk-reducing surgery recommendations that currently stand, but do highlight the need for decision-making to be based on your risks as they stand at the age you are now, to understand risk over the rest of your lifetime and not focus solely on that single risk figure given when you discovered you were BRCA+.

If you’re making choices about screening or surgery, please contact your genetic counsellor who’ll be able to help you understand your risk in more detail.

Some media coverage reported that the study demonstrated a family history of breast and ovarian cancer increased a BRCA+ woman’s risk of getting cancer themselves.

However, if we look in detail at the results of the study, the results showed only that having a family history of breast cancer increased the chances of developing breast cancer (in both BRCA1 and BRCA2).

However there was no significant increase in ovarian cancer risk for either BRCA1 or BRCA2 based on ovarian cancer family history.

The study did not report on whether there was an effect of breast cancer history on the chances of developing ovarian cancer, or vice versa.

Significantly, the researchers didn’t address the many reasons why a person with a genetic mutation may not report a family history of either breast or ovarian cancer. These may include:

• A BRCA+ person with a “male heavy” family who has inherited the mutation via the male line will not see cases of ovarian cancer - even though a BRCA2+ man’s risk of breast cancer is higher than an average man’s, it still low relatively speaking. It is likely therefore that they would not have cases of either cancer to report
•  The BRCA+ individual having a small family with fewer individuals to report on in the first place
•  The individual’s family members’ medical history being lost or not recorded properly over the generations, especially in the past when cancer diagnoses may not have been openly discussed.

It is worth noting that the patient population could’ve inherently biased the results - in the UK most people eligible for genetic testing on the NHS have had to pass the set threshold of risk, usually based on family history. The results could show that those with a family history of cancer are more likely to have a mutation and therefore develop cancer, because the study has not included those who haven’t got a family history.  

We also know from several studies that many BRCA+ women who are diagnosed with cancer have no family history. Indeed, of those women who are diagnosed with ovarian cancer and then find out they are BRCA+, 50% have no family history at all.

The key message from this is that for women with a genetic mutation, having no family history of ovarian cancer does not imply lower risk of developing the disease.

People are often very interested in where their mutation lies in terms of breast or ovarian cancer “clusters” in order to try and analyse their personal risk. In this study, the researchers found some differences in breast cancer risk based on mutation position for BRCA1 and 2 but no significant differences in ovarian cancer risk. This is surprising as there is much well-established data that has previously suggested different risks for ovarian cancer based on mutation position.

Simply put, knowing your mutation position isn’t enough to give you a personalised idea of risk in itself; there are many other factors that contribute to whether or not you get cancer. 

Although this research is exciting, the general guidelines for screening and risk reducing surgery are still correct. 

It’s incredibly important that you don’t attempt to apply the conclusions of any single research study to your personal risk, but instead consult your medical or genetics team to discuss your individual situation, risk and risk-reduction decisions regardless of your specific family history.

You can continue to contact your genetics clinic/ genetic counsellor when you are ready to discuss the next stage of your journey, or to find out more about your options, even years after you receive your test results. They will take into account the most up-to-date research and explain how it applies to your specific situation.

[1] Karoline B. Kuchenbaecker, PhD; John L. Hopper, PhD; Daniel R. Barnes, PhD; et al., Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers, JAMA. 2017;317 (23):2402-2416. Abstract