BC went from Er+Pr+Her2- to MBC that is Er-Pr+Her2-

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Anonymous
Anonymous Member Posts: 1,376
edited July 2021 in Stage IV/Metastatic Breast Cancer ONLY
BC went from Er+Pr+Her2- to MBC that is Er-Pr+Her2-
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  • DaughterOf
    DaughterOf Member Posts: 52
    edited July 2021

    Hello all,

    Does anyone here have experience with mets (especially liver) that are Er- but Pr+?

    My mum's oncologist wants to treat her with AI + Ibrance along with cyber knife and thomo therapy but mum and I are both very concerned whether AI and ibrance will work for her at all.

    She was Er+/Pr + (allred score 8) back in 2012 but her liver mets are Er- and Pr + (allred score 6).

    Is there any hope? She's already making funeral plans and I need to find light at the end of this dark tunnel and give her some hope and willpower to live.

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  • candy-678
    candy-678 Member Posts: 3,950
    edited July 2021

    DaughterOf- I posted to you on the liver met Thread. I was ER+/PR+/HER2- until recently when a new met popped up in the liver and we did a new biopsy. I am now ER-/PR+/HER2-. My MO said this is rare and that some studies have shown that the progesterone receptor plays a bigger role than they first thought. And that hormonals should still work with ER-/PR+. I am in the middle of deciding about possible local therapy--- Y90/ablation/etc--- and then I need to see if my MO is going to change systemic therapy.

    But I will be following this thread.


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  • DaughterOf
    DaughterOf Member Posts: 52
    edited July 2021

    Candy, thank you for being so lovely to post your reply twice for me. I am pretty new to this site (although I joined in 2017, I haven't used it) so I keep missing replies. Hopefully this thread will bring us more answers since this type of hormonal expression does seem to be very rare.

    My mum's oncologist seems to agree that hormonal therapy might still work, but I am still very concerned. My mum is taking all of this very roughly and I know that if she can avoid chemo (for now) she will accept this diagnosis easier.

    But with TNBC it seems that chemo is one of the best treatments, hence why I'm scared.

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  • buttonsmachine
    buttonsmachine Member Posts: 930
    edited July 2021

    DaughterOf, Like Candy, I am one of those who changed from ER+/PR+/Her2- to ER-/PR+/Her2- after my MBC diagnosis. I can also say that Ibrance did not work for me at all, but that just might have been me. Because of that we switched to Xeloda (a very tolerable pill chemo where you do not lose your hair), and that didn't work either. Unfortuantely I had to go on iv chemo which has been very hard from a quality of life perspective. I think for your Mom, it's best to try more tolerable therapies before resorting to harsher treatments. One other thing to check (which I may do also) is whether your Mom is AR+. There are some drugs like Enobosarm, which hasn't come out yet, that might be obtainable in the future. I hope that helps, best wishes to you both.

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  • Cure-ious
    Cure-ious Member Posts: 2,626
    edited July 2021

    Hi Daughter,

    This subtype is rare and was discussed in a Jan 2020 paper that reviewed survival data from 800K patients, comparing single hormone receptor-positive cases with double HR cancers or TNBC. Apparently it had been controversial as to whether the ER-PR+ classification was even real, in part because the fraction of patients given this diagnosis has dropped in recent years, from 5.45 to 1.6%, with no explanation (for comparison, 12.2% are ER+PR- and 19% are TNBC, with 67% double HR-positive). The analysis clearly showed that the ER-negPR-pos subtype is real, because there is a statistically significant survival difference for this group in comparison to the other subtypes, so it is its own molecular type.

    Basically, the survival stats showed ER+PR+> ER+PR- >ER-PR+> TNBC

    They conclude this is a distinct subgroup that needs to be studied because it has different signaling pathways than other subtypes and there needs to be therapies directed at it specifically.

    They also say it is still unclear if the ER-neg PR-pos group responds to anti-estrogen therapy, but the increased survival could result from such a difference, plus it should be noted that this cohort was analyzed from 1990-2015, meaning that none of these patients got a CDK4,6 inhibitor. The addition of Ibrance to anti-estrogen therapy helps most subtypes, but the degree of benefit is higher in some of the more risky cases, so it may be that CDK4,6 inhibitors will iron out some of this survival difference. I recall one of the early papers saying that adding Ibrance helps luminal B cancers even more than the luminal A ones...

    https://www.medpagetoday.com/hematologyoncology/br...

    https://www.breastcancer.org/research-news/er-neg-...



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  • Cure-ious
    Cure-ious Member Posts: 2,626
    edited July 2021

    There is an inhibitor of PR signaling (that also inhibits GR) called Mifepristone, which is being tested in a clinical trial (Chicago only) together with Keytruda on ER and/or PR-positive MBC, as well as TNBC. Mifepristone also improves the tumor microenvironment to make immunotherapy work better:

    "Antiprogestin therapy induces immunogenic tumor cell death in PR-overexpressing tumors, eliciting an adaptive immune memory response that protects mice from future tumor recurrence and increases sensitivity to PD-L1 blockade."

    https://clinicaltrials.gov/ct2/show/NCT03225547


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