Progesterone blocking drugs?

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This is mostly a question...why are there no progesterone blocking drugs out there for hormonal treatment the way there are estrogen blockers? I was organizing stuff today and looked at my Oncotype info again and my PR score is very high...so blocking progesterone should be beneficial, in theory. Are they too toxic? Curious if anyone knows anything about this.

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  • doxie
    doxie Member Posts: 1,455
    edited June 2014

    With ER+ BC a high PR+ % is good.  Anti hormonals are more effective against these types of cancer.  The lower your PR is the higher your Oncotype score will be and more likely you'll need chemo.  I've not read of any research for an anti hormonal for PR.  

  • Lojo
    Lojo Member Posts: 303
    edited June 2014

    I did just see this about pr-antagonists. Most everything else I saw was about using PR blockers as contraception or to treat fibroids.

    http://www.bcrfcure.org/action_grantees_khan.html

  • mary625
    mary625 Member Posts: 1,056
    edited June 2014

    Doxie:  Can you explain a little bit more about why the PR+ is good?  I knew that ER+ was "good" because of Tamoxifen and AI's.  I'm very interested to know because I had a PR at 100% but was not eligible for Oncotype DX.  Thanks.  

  • sandilee
    sandilee Member Posts: 1,843
    edited June 2014

    "The lower your PR is the higher your Oncotype score will be and more likely you'll need chemo."

    I'd be interested in where this information came from. I have a negative PR, and I had a lowish onco score (18) and I didn't need chemo.  I still haven't had chemo, even with the cancer in my bones, and have been stable for three years with just hormonal drugs, as I'm ER+.  

      I've never heard that the progesterone marker really had much to do with one's treatments.  I'd love to read about that if you have a source.

  • lekker
    lekker Member Posts: 594
    edited June 2014

    The role of progesterone in breast cancer isn't very well understood from my research.  It does seem that having progesterone receptors is a good thing for prognosis, but I haven't been able to find a great explanation as to why.  The best I've found is that the presence of Progesterone Receptors indicates a functioning ER pathway (and therefore a target for tamoxifen) even in the absence of Estrogen Receptors.  I do know that Megace, which is an artificial progestin, is sometimes used as a treatment for advanced breast cancer that no longer responds to tamoxifen.  The description of Megace states that "it is not understood how it stops tumor growth, but it is assumed to interfere with estrogen". So it's interesting that a progestin is already given as a treatment, and now they're testing an anti-progesterone drug.  There is speculation that the synthetic progestins in some birth control (Mirena, Nuvaring, etc) increase breast cancer risk.  I'm sorry I'm not giving any answers, but this is something I've been wondering about for a while.  I do know that my progesterone level was quite low when I got pregnant with my second child almost 8 years ago and I exhibited signs of "estrogen dominance" for years before BC, but I don't know if it's related. I also wonder about the other hormones in our bodies that affect breast development and function - testosterone (they are finding Androgen Receptors in some BC), prolactin, oxytocin, etc.  I have a feeling that eventually they'll find there's more to this than ER/PR scores.

  • lekker
    lekker Member Posts: 594
    edited June 2014

    Sandlilee - the PR score is just one of the factors that goes into calculating the oncotype score. They break down the different genes into groups and multiply each group by a factor they somehow came up with to get the final score.  PR is in the "ER related genes" group which is the only group to have a negative multiplier - the higher that group's score, the more it lowers the final result.  So if you have low or absent PR expression, it will raise that part of the score.  If the scores from the other groups are low, you can still end up with a low score of course - PR is just one piece of the puzzle.  

    image

    The test was then validated using 675 node negative ER positive tamoxifen treated cases from NSABP B-14. In this analysis given classes of genes were given previously determined weighting factors and prognostic scores were calculated. The weightings would seem to make sense with proliferation, Her2 related, and invasion group genes increasing the score and ER related genes decreasing the score. The score was a continuous variable, but for the convenience of the presentation the patients were divided into 3 groups using cut points of 18 and 31.

    image

  • spendygirl
    spendygirl Member Posts: 231
    edited June 2014

    Thank you for raising this issue.  I've always wondered about the PR component.

  • doxie
    doxie Member Posts: 1,455
    edited June 2014

    lekker,  thanks for doing a good job of answering the high and low PR+ question.  When my BS talked about my pathology report he said "we like the PR % to be higher" so I did a lot of research on it.  I too read that high PR+ makes Tamoxifen more effective.  I'm on an AI, so the better treatment with for the BC I have.  Sorry but that was 2.5 years ago now.  I'll post this and look to see if I can find what I read.  Looking at my oncotype report, if my PR had been as high as my ER, I would have had a more difficult decision to make about chemo.  

    Here are a couple.

    http://jco.ascopubs.org/content/early/2012/12/04/J...

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684553/

  • Johanne76
    Johanne76 Member Posts: 6
    edited June 2014

    I am new to this site and let's just say I am now becoming a member of this club. I have been diagnosed with ILC, grade 1, 13 mm, ER+ PR -.   I recently had a MRI and they possibly found another tumor 9 mm. I am hoping that it is a false positive. 

    At any rate, the astonishing thing for me is women that initially had a 1cm tumor had a lumpectomy and shortly thereafter had a mastectomy. I am hoping for just a lumpectomy.  I am confused why there are so many mastectomies when the tumors are grade 1 and 1cm. Everything I have been told is that I have an excellent prognosis with just a lumpectomy but will require constant surveillance every 6 mos.

    I would appreciate some input on this issue. Thank you.  

    Johanne

  • MsPharoah
    MsPharoah Member Posts: 1,034
    edited June 2014


    Hi Johanne76.  I am so sorry that you are on this site, but glad you found this site.  I also had ILC and had an MRI before surgery to assess if there was any other cancer.  That is very common with ILC as it is often mult focal or multi centric.   MRI's are notorious for finding lots of things that are not cancer and that happened to me.  I hope that your biopsy comes out B9 as mine did.

    You should be fine having a lumpectomy/radiation, but many women may need a mastectomy if the pathology from their lumpectomy surgery show positive margins (cancer at the edge of the tumor tissue) and they are not candidates for another try to get clear margins.    And some women just change their minds for all kinds of reasons, fear or not wanting to have as close surveillance in the future, or they change their mind about radiation.

    My surgeon recommended that I have a mastectomy only if I was BRCA+ (I was not) or the MRI detected additional cancer (It did not)....or if he was unable to get clear margins. (He did!)

    I wish you the best as you begin this process. 

    Hugs, MsP

  • muska
    muska Member Posts: 1,195
    edited June 2014


    Hi Johanne, location of the tumor(s) matters too. If there are more than one tumors and they are in different quadrants mastectomy may be in order even if the tumors are small. Surgeon needs to get clear margins.

  • Johanne76
    Johanne76 Member Posts: 6
    edited June 2014

    Thank you so much for your responses.   Of course, I am just a nervous wreck. This waiting game takes it toll.  I have another question:  I was told by my the oncologist that I interviewed that the ONCO test is not given to  ILC patients.  Is that correct?   MSP thanks for telling me about the BRAC+ test. 

    Johanne

  • mary625
    mary625 Member Posts: 1,056
    edited June 2014

    Johanne--many women are frustrated or lack confidence in the surveillance methods.  My ILC was not picked up by mammogram.  Even when I found it, it did not appear clearly on the mammo.  Therefore, when I found out that even with what I had gone through, I would not qualify for an MRI routinely on the good breast, I took their strong advice to have a bilateral mastectomy.  I was not a candidate for lumpectomy due to tumor size, which started at about 7 cm.  But even in cases like those you've seen with much smaller tumors and lower stages, women just don't feel confidence with the current modes of detection, and in many cases rightfully so.

    I did not receive the Oncotype DX test because I had a positive lymph node at diagnosis.  It is my understanding that the Oncotype can be used on any type of breast cancer that is not lymph node positive.  

  • MsPharoah
    MsPharoah Member Posts: 1,034
    edited June 2014

    Johanne, the oncotype test does not exclude ILC.  I am not sure why your onc said that.  The oncotype test is ordered for patients with hormone receptor positive breast cancer.  Node status is not necessarily a criteria.  This test examines your tumor's characteristics and helps you understand your risk of recurrence so you can make good decisions about things that can lower that risk.  Most women use it to make a decision about chemo or no.

     Genomics has a web site with more information on this test.  Take a look. 

    MsP

  • Johanne76
    Johanne76 Member Posts: 6
    edited June 2014

     Just to clarify:  In my initial message I meant to say my doctor would have me under constant surveillance of my breast cancer every 6 mos for 5 years!!  

    My mind has been a bit foggie these days..

    Johanne

  • rettemich
    rettemich Member Posts: 369
    edited June 2014

    This is really interesting. I am er really high and pr really low. From everything I have researched balancing the two is the ideal. Not 50/50 but balance so they work together. I wish the Dr.'s would tell us more about things like this but i don't think they even really know. I want to see if there is a way even with the Tamox to up the pr.

  • mary625
    mary625 Member Posts: 1,056
    edited June 2014

    I believe that Oncotype has changed since 2011 to allow node positive patients, but I wonder if oncs are offering it.  I could not get it from my onc in September 2011.  

    Regarding upping the progesterone, you really can't do that.  The PR+ % refers to how many of the receptors on the cancer cells were sensitive to progesterone.  There's no way to change that.  

  • rettemich
    rettemich Member Posts: 369
    edited June 2014

    Mary, Thanks for clarifying that.

  • Lojo
    Lojo Member Posts: 303
    edited June 2014

    Johanne,

    I also have ILC (though mine was larger and I had very close margins), node negative, ER/PR+. I had the oncotype test (and yes, I know they're now doing it for some women with one positive node). My score came back low, which meant no chemo. As far as I understand, oncotype can be used for both ILC and IDC. 

    I did have a double mastectomy (one side prophylactic) even though I am BRCA1/2 negative. The reasoning was, despite testing negative for the BRCA1/2 mutations, I have a strong family history (mom had pre-menopausal BC and she had a contralateral recurrence). 

    So... some of the reason you're seeing ILC with so many mastectomies is because ILC doesn't form defined tumors the same way that IDC does, doesn't show up on mammograms as often, and hence tends to be diagnosed later/larger. There is also some suggestion (though not definite) that ILC has a higher contralateral recurrence rate, or that at a minimum it is harder to detect than IDC. See if you can push for the oncotype, as it can give you one more piece of information about your tumor (especially since your PR status is negative, which I think is a little more unusal for ILC).

    If your doctor is recommending a lumpectomy, rads and surveillance, that sounds like a good plan to me, and all the studies show similar survival rates with lump+rads vs mastectomy - but do look into whether alternating MRIs with mammograms is the plan for surveillance, as MRIs can detect things that mammograms miss, etc. 

    Best,

    Lojo

  • mkkjd60
    mkkjd60 Member Posts: 583
    edited July 2014

    When my mom had bc, I contacted a dr at Sloan who had a trial for a drug used in prostate cancer called "MDV"  .  I don't know much more about it except that my FIL was on the same drug for prostate cancer and it kept his advanced cancer at bay for over a year and a half.

  • Lojo
    Lojo Member Posts: 303
    edited August 2014

    Trial for a SPRM (like tamoxifen is a SERM)

    http://clinicaltrials.gov/show/NCT01800422

  • Meow13
    Meow13 Member Posts: 4,859
    edited August 2014

    My ER was 94% and PR < 10% so maybe that was one factor of why my Oncodx was 34. However the cancer was a very slow growing one, maybe the HER2 (+2) negative?

  • QuinnCat
    QuinnCat Member Posts: 3,456
    edited August 2014

    Meow13 - it's remarkable how similar or dx is.  Moi - IDC 1.4 cm , Grade 3, 0/1 node, ER+ but barely PR (90% ER and 5% PR based on IHC) and Her2 negative.  Oncotype score 39.   The barely PR or negative PR with ER+ makes it luminal B, a bit more aggressive than luminal A breast cancer, but not as bad as a triple negative or her2+, though some would dispute her2+ being worse because there is herceptin for that.

    It is curious that you didn't do chemo.  But I'm more curious why you say the cancer was a "slow growing one?"  My Ki67 (based on the biopsy) and a component in the Oncotype, was 60%, which indicates fast dividing cells.  Were you ever given your Ki67??

    I've seen a lot of journal articles mentioning much lower % of chemo or hormone blockers working for Luminal B, so you may have picked right on the chemo, at least for that reason.

  • JohnSmith
    JohnSmith Member Posts: 651
    edited December 2014

    My wife's PR score was also high at 95%.

    I was also wondering why there aren't any therapies that exploit the progesterone receptor.

    What's the deal here?

  • luckypenny
    luckypenny Member Posts: 150
    edited December 2014

    I had 70% er 6% pr and her2 negative. 6 nodes positive large tumor so no oncotype. I had to get chemo. No option there. No oncotype score but my ki-67 very low 9% and was a grade 2 My ki67 doesn't seem to correlate with a poorer prognosis. I did have the mirena removed a year before my breast cancer diagnosis. Funny that I had low pr after having the mirena for 6 years.

    To lower my recurrency- I had full hysterectomy ( I am not brca positive) , take Metformin and zometa and arimidex. I am 44. Honestly- I have no idea what the numbers truly mean and figure I have done everything I possibly could to prevent it from coming back.

  • JohnSmith
    JohnSmith Member Posts: 651
    edited December 2014

    What are the drugs that exploit high progesterone receptor (PR) activity?

  • doxie
    doxie Member Posts: 1,455
    edited December 2014

    The benefits of being high PR+ is somewhat counterintuitive. Actually the higher the PR+ % generally the better the prognosis. Tamoxifen is not as effective with low PR % tumors, thus women are encouraged to take AIs and if necessary with ovarian suppression. Tumors with ER+, low PR, and high Ki67 are Luminal B. Generally chemo is suggested for these and there is a poor prognosis.

    Somewhere on these boards there was a discussion on PR blocking drugs. Not sure where it is, but it may have been within the last 6 months or so.

  • JohnSmith
    JohnSmith Member Posts: 651
    edited December 2014

    After a bit of research, PR & ER are tied to each other. In a broad sense, it appears PR is a subset of ER. It sounds like PR is an estrogen regulated protein, so Tamoxifen not only blocks the Estrogen receptor (it's primary target), but also blocks the progesterone receptor in the process.

    If your estrogen receptor isn't working (or is low), you'll have an inactive progesterone receptor as well.

    My interpretation is that there is no need to PR specific drugs. Tamoxifen (if it's working properly and you don't have resistance) will work on the PR component as well.

  • Lojo
    Lojo Member Posts: 303
    edited June 2016

    https://www.sciencedaily.com/releases/2016/06/1606...

    Cross talk between hormone receptors has unexpected effects

    Finding suggests novel ways to improve breast cancer care

    Date:
    June 24, 2016
    Source:
    University of Chicago Medical Center
    Summary:
    Although the estrogen receptor is considered dominant in breast cancer, the progesterone receptor assumes control when both receptors are present and exposed to estrogens and progestins. Then, the progesterone receptor drives estrogen receptor activity. Treating tumor-bearing mice with an estrogen antagonist and a progestin antagonist caused rapid tumor regression, report scientists at the conclusion of their study.

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