Rising ESR1 Mutations During Aromatase Inhibitor and Palbociclib Therapy

[Hazelgreen]

From Oncology October 15, 2022:

Published in The Lancet Oncology 29.09.2022

"This phase III trial evaluated the use of blood ESR1 mutational burden to guide the change of therapy in patients with oestrogen receptor–positive HER2-negative breast cancer. Patients in whom an increase in blood ESR1 mutation levels was detected with no synchronous disease progression were randomised to either continue treatment with first-line aromatase inhibitors and palbociclib or switch to fulvestrant and palbociclib. Patients who switched to fulvestrant-based therapy had significantly longer median progression-free survival than those who remained on the original treatment. Adverse effects were similar between the treatment groups.

These results suggest that circulating tumour DNA may serve as a tool to predict tumour resistance and allow for earlier optimisation of therapy."

[Mumberly]

thanks for always sharing these research links. They are typically over my head, but sometimes I can garner a question or two for my oncologist.

I also appreciate knowing how much work is being done on our behalf in the lab ♥️🙏🤞🏻

K

[Bettybuckets]

thank you very helpful. I had my lymph node assessed for mutations and didn’t have ESRI so we switched from Ibrance to Verzenio ti try ti extend the use of this class of drugs before jumping ship to next therapy. Nice to know that can get the info from a blood draw as that node biopsy was no picnic!

[OneLump22]

Wow! Thanks for your hard work & research & posting that article.

Incidentally, my Onc office sent recent blood test back & my Phosphorus levels show slightly elevated.

[Hazelgreen in reply to OneLump22]

Interesting, what did your oncologist suggest you do? According to Medline Plus, you may wish to avoid many processed foods...

[OneLump22 in reply to Hazelgreen]

I did get a craving for hotdogs last week, but the blood samples were taken on the 7th. I messaged dr.'s office, but no response yet. Usually takes 2 or 3 days.

[Merma]

Thanks for sharing this!

[Beryl71]

does this mean changing when the first line if treatment fails or changing anyway? X

[Hazelgreen in reply to Beryl71]

This study was done with patients who had "no synchronous disease progression" so I assume their treaments hadn't failed. It does suggest there is an advantage to changing treatment when ESR1 mutations are detected.

[Beryl71 in reply to Hazelgreen]

what kind of test does that require?

[Hazelgreen in reply to Beryl71]

In response to the question, "How do you test for ESR1 mutation?", the Internet indicates, "There are many technologies for detecting ESR1 mutations in MBC. Sample sources include solid tissue biopsy, CTCs, and cell-free DNA (cfDNA); detection assays include next-generation sequencing (NGS) and droplet digital PCR (ddPCR), with ddPCR the most sensitive [21]."

My own PIK3CA mutation was determined when a tissue sample from my liver was biopsied.

[love2golfwell]

Thank you for sharing what you learn from your research. Very helpful. Maybe this is something doctors will start testing for along with our regular bloodwork and tumor markers.

[DDIL1]

I was just diagnosed with an ESR1 mutation and I had slight progression. They found it with a blood test. Switching treatment to Kisquali and Fulvestrant from Ibrance and Letrozole.

[Wintervt in reply to DDIL1]

How are you doing on Kisquali and Fulvestrant? My oncologist suggested this combo for me even though I had progression with Fulvestrant only. Instead we are going to try Elacestrant.

[DDIL1 in reply to Wintervt]

I just started only been a month. My onc just suggested elecestrant as well. But did say if the side effected me I can’t go back on Fulvestrant. So I don’t know if I just go for the new drug or stay a bit on Fulvestrant. It would be nice to take a pill vs. shots. Sorry you had progression. This makes me think I should switch to elecestrant since it is a SERD/SERM and may be a better blockade.

[Wintervt in reply to DDIL1]

Is your oncologist suggesting that you go on Elacestrant and Fulvestrant or Elacestrant only. When I was on Fulvestrant it was by itself, I think if we had coupled it with a CDK4/6 it would have helped keep things stable.

[DDIL1 in reply to Wintervt]

He has me on Kisquali and Fulvestrant. I’m lobular so it’s a sneaky thing.