Mutations become Targets

A little while ago, I wrote a post for about genetic and genomic mutations, exploring some of the information we learned about my original breast tumor in 2017 and highlighting the differences between genetic and genomic testing. You can access that article here. As an aside SBC is a great resource for those newly diagnosed and beyond!

As we learn more about the results from my liver biopsy, there are more and more avenues of treatment because of the new mutations. First, an overview of what we knew before the recent progression.

  • I inherited a germline or genetic mutation called ATM. If you are interested, you can learn more about it from the amazing Facing our Risk of Cancer Empowered (FORCE) here. This mutation is something that I will always have because it is in my DNA. There are no FDA approved treatments for breast cancer caused by the ATM germline mutation like there are for the BRCA mutations. Watching closely as different cohorts are studied.
  • Based on the genomic testing (different from genetic testing, see the article at SBC noted above) of the tumor removed from my breast back in 2017, we saw four (4) different somatic (meaning acquired by cancer cells mutating, not from inherited DNA changes) mutations, only one of which was actionable: PIK3CA. Based on that biopsy, I was on alpelisib/Piqray for several years. There are some differences in how entrenched a mutation is when it is in the original tumor versus acquired by the metastases as they mutate over time.
  • Based on liquid biopsy reports before the recent progression, there are multiple somatic ATM mutations. The PIK3CA mutation that showed up in the tissue biopsy didn’t show up in the liquid biopsies. At some point perhaps some of these mutations will become actionable. For now, we just watch those.

Generally, liquid biopsies (usually testing on 2 vials of blood) are less reliable than tissue biopsies because the technology is still relatively new and there is no way to test every single blood cell in one’s body; however, these liquid biopsies also might show different mutations than tissue biopsies in light of tumor heterogeneity (probably a topic for another post). Prior to having soft tissue mets in my liver, the only way we could determine what was going on with the cancer in my body mutating was the liquid biopsy or a bone biopsy. As some of you may remember, we tried a bone biopsy on that pesky met in my pelvis, but that wasn’t successful for a variety of reasons. Repeated the liquid biopsies several times, but didn’t get more information. One thing that might have affected the ability to get information was that I hadn’t had a significant progression, just a few new mets each time I changed treatments. The volume of circulating tumor DNA in the blood makes it more or less likely that there will be something to find in the those two vials.

Fast forward to 2022 and the liver biopsy in January. I wrote about the different receptors and how those have changed since the original pathology report back in 2017 and you can read about that here. We also repeated the liquid biopsy and sent off the tissue recovered from my liver for genomic testing to find out if there are other somatic mutations that can be targeted. Interestingly, the liquid biopsy came back with those same four (4) ATM mutations, a PIK3CA mutation (albeit a different one from the original biopsy), a small BRCA1 mutation, and a few others that aren’t actionable yet. The genomic testing will hopefully tell us even more about these somatic or acquired mutations.

But, how to interpret these findings?

  1. The reports from the various companies are not always clear or understandable and every single one is substantially different. The reports from the company my doctor prefers for the liquid biopsy is now something I know how to interpret after seeing several, but the first time I get a report from a new company, it takes me some time to understand it. I utilize the company’s website, other online information from trusted sources, and my doctor to help me learn what the reports mean.
  2. It may seem counterintuitive, but the more mutations there are, the better. While it is true that the cancer learns from the treatments to be able to beat what we have to throw at it, it it also true that the more the cancer acquires mutations, the more likely it is that we have something to target that specific pathway. For example, acquiring a BRCA mutation means that I may be able to utilize a PARP inhibitor like Lynparza/olaparib in the future. So far, the trial data showed that PARP inhibitors are NOT effective for ATM mutated breast cancer (but was effective for ATM mutated prostate cancer), so those drugs haven’t been an option for me up until now.
  3. Context is important. Findings from the various tests affect how we proceed differently and it is important to understand how each is ranked and the context for the findings. Different doctors do tend to utilize different methods of analysis and I have found that having input from doctors outside of my primary team is very helpful. I utilize the patient portals to ensure that each doctor is fully briefed on the thoughts of the others, which does take a fair amount of time and effort.
  4. Feeling overwhelmed is more than normal, it’s expected. The subtype or receptor status of our cancer becomes a bit like the sorting hat in Harry Potter because the treatments and experiences and life expectancy of the different subtypes are often very different. To suddenly find oneself in a different group, to open up possibilities for treatment that were never possible before, to close the door on treatments that one might have expected, to have to shift thinking about different types of mets or side effucks … it’s all very disorienting. It takes time to adjust, to shift, to re-focus.
  5. While everyone’s experience is unique, learning from others who have been on the same medication is extremely helpful in setting expectations and ensuring that you have the right remedies on hand just in case. Any medical professional can read or provide to you the full list of all the side effects of a particular medication. It is those who have lived experience with that medication who know far more about what to expect.

And so, we keep moving forward. The genomic testing on that liver biopsy may confirm the information we know or give us different information. Until we know more, we proceed as planned, adjusting as needed once further information is available.

7 thoughts on “Mutations become Targets

  1. You lost me for a minute there when I thought I read something about a Pikachu mutation. 🤦🏽‍♀️🥴 🤷🏽‍♀️😂

    I love what you said about how doctors can review information about side effects that are listed, but people living with the medication are a much better barometer of more specific and additional Information!

    I am always telling my doctors, “Ok, but at least this many people in a group of people with this very rare condition are experiencing the same thing. That can’t be a coincidence. Prove me wrong!” Lol


Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s