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AI or targeted therapy failure?


Hi there,

Just wondering how one knows which medication failed if you are taking a targeted therapy and an AI?

My sister is on Ibrance and Letrazole and MRI was clear on spine in November and now a 19 mm spot on T2. Her tumour markers have also been slowly rising.

Her cancer is lobular, estrogen positive, progesterone negative and Her2 negative

Previously (6 yrs ago) it was progesterone positive.

She was on Kisqali for a short time but could not tolerate side effects.

Thanks for any insights you may have.



  • moderators
    moderators Posts: 8,081

    Hi @barnswallow25, and welcome to our Community!

    We're so sorry to hear of your sister's diagnosis, but we're really glad you've found us. You're sure to get a wealth of advice, information, encouragement, and support here — we're all here for you both!

    We do hear that sometimes medications that once worked on MBC stopped having an effect on the cancer and a new medication then becomes an option. You can read more about What Happens If Metastatic Breast Cancer Treatment Stops Working? for more. But, in a nutshell, typically there is another CDK4/6 Inhibitor and/or hormonal therapy combination one could try if the previous treatment fails the patient.

    Please let us know how else we can help support you and your sister. Others will surely be by soon to weigh in!

    —The Mods

  • arissasmom
    arissasmom Member Posts: 4

    They don't know. That's why they typically change both the AI and the CDK4/6.

  • aprilgirl1
    aprilgirl1 Member Posts: 768

    Barnswallow25, I am sorry your sister is experiencing some progression. There are some oncologists that will radiate a new "cancer" spot if there is progression and stay on the same treatment. However, if tumor markers are rising and she has a new spot, it might be time to have a new biopsy and look for any acquired mutations?

    I have read about the importance of FES Petscans for Lobular breast cancer stage IV patients as the regular scans don't always show lobular breast cancer well. You can do a search on the topics for FES Petscan or stage IV ILC and see if you can find more info.

    Hope this helps!

  • cure-ious
    cure-ious Member Posts: 2,745

    barnswallow, It is more common just a failure of the endocrine therapy- early study found around a third of women remained sensitive to the same CDK4,6i, and nowadays I think many MOs just switch to a different ET and different CDK4,6i, and see if it works. Lobular especialy is sensitive to anti-estrogens.

  • foxymoron
    foxymoron Member Posts: 4

    hi. I started on ribociclib and letrozole. Had nine mets. 7 months later I developed spots on my liver. Once moved me straight onto capecitabine. She is hopeful this will blast my liver. Maybe then I can go back to targeted therapy. Awaiting genetic tests.
    Onco says she doesn’t know whether the ribo or letrozole stopped working.

  • amel_83
    amel_83 Member Posts: 145

    Same as @foxymoron...

    After 14 months ribociclib and letrozole fail and had liver mets active again. My MO just put me on Capecitabine. But as I still 90% ER+ they will consider another EI and may another cdk4/6i or Everonimus...may be with a biopsy they can have a better idea, sometimes the cancer loose his ER+, but other times ER+ still there, but the EI in my case.