Progesterone therapy for stage 4 cancer

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Katzi17
Katzi17 Member Posts: 14

I put this on another board but I thought I’d try here . They say women with higher progesterone are better off so why is progesterone not a treatment ? I hear it makes cancer grow in some cases . Are there cases where it might actually slow it down ? Has that been studied ? It’s used in endometrial cancer so I’m wondering why not breast cancer . I’m sure it’s related to which receptors the tumors have but if anyone knows of any good currents studies let me know

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  • marijen
    marijen Member Posts: 3,731
    edited July 2018

    Katzi, I’m not supposed to be posting here but here’s a graphic and a link. Many people don’t believe the Truth About Cancer site and I have no idea about whether this is true or not but here you go. You can also read about progesterone in the book “What Your Doctor May Not Tell You About Breast Cancer”

    image

  • Daniel86
    Daniel86 Member Posts: 271
    edited July 2018

    When I started reading up about MBC, I came across this article that kind of made the role of PR clear to me.

    https://scienceblog.cancerresearchuk.org/2015/07/08/solving-a-breast-cancer-mystery-why-do-double-positive-women-do-better/

  • Cure-ious
    Cure-ious Member Posts: 2,626
    edited July 2018

    Thanks Marijen and Daniel to both of you for some excellent info! Sounds like progesterone could be mixed in, alone or with Faslodex or Femara, as part of anti-estrogen therapy. The metastatic cancers eventually mutate and escape ER-dependence anyway, but maybe PR will make the anti-estrogen therapies last longer. It would be interesting if the progesterone can inhibit the ER ESR1 mutation that commonly happens with progression on AIs..

  • marijen
    marijen Member Posts: 3,731
    edited July 2018

    If you are going to try using progesterone, be sure to get the natural, not the synthetic. Progest at Amazon is rated #1 by USP (whatever that is). I have used it but can forget for a while. But at stage IV I don’t think it should be the only treatment.


  • BellaTassie15
    BellaTassie15 Member Posts: 106
    edited July 2018

    When diagnosed I had a Mirena IUD, which is progesterone based. I'm triple positive and my (third) oncologist advised me to have it removed. They tried but it was stuck to the wall of the uterus. She wasn't that concerned about it though. As chemo put me into menopause I didn't need it so I wanted it removed. My fourth Oncologist wasn't worried about it either, every abdo scan noted it. But it has to be replaced every 5 years anyway so recently I had it removed using gas and brute force (ouchie 😬).

    I know it was only a small localised dosage, but wonder now if that had any influence on my mets being stable for the last 2 years?

  • JFL
    JFL Member Posts: 1,947
    edited July 2018

    The role of progesterone has always been unclear but I had understood that it was implicated in the programmed cell death / apoptosis phase of the cell cycle, which is how it benefits BC. I had heard that it can slow growth when given in the absence of estrogen but when given together (such as in the case of hormone replacement therapy), it does not have the same effect. I have always suspected it may have played a role in saving my life when I was in my 20s and experienced many delays before finally being diagnosed. From the age of 20-25, I was on progesterone for migraines.

    Before then, when I was 19 years old, I went to the doctor complaining of a suspicious lump that caused a dented area on my breast. I was seen by a nurse practitioner who laughed it off and sent me home, telling me I drank too much coffee causing fibrocystic breast tissue without running any tests. I felt relieved and didn't think twice about any of the other hard, fibrotic areas I felt over the years. At 28, I started experiencing advanced symptoms of BC (DVT in subclavian and brachial veins a few inches from the cancer). Although doctors now believe it was caused by the BC, they didn't suspect cancer at the time and ran every other test in the book for every rare disease but no tests for cancer, despite cancer being the #1 cause of DVT. At 29, I discovered another suspicious lump in another location and told my OB about the lump. He ordered a mammogram but his scheduling staff did not take me seriously and I waited nearly 3 months for an appointment. At 30, I was finally given a mammogram, ultrasound and biopsy and diagnosed with BC. At the time of dx, I had six 1cm tumors, including one tumor in the dented location where I felt the lump at 19 and another where I felt the lump at 29 and over half of my breast consisted of DCIS. Whether or not I had cancer back at 19, I did have abnormal changes in my breast tissue that ultimately progressed to cancer. Had I not taken progesterone from 20-25, I don't know if I would have fared so well when I was finally diagnosed.

  • Katzi17
    Katzi17 Member Posts: 14
    edited July 2018

    So what confuses me here is why isn't progesterone being studied as a therapy along with AI's if it clearly could have a role? I'm just so confused. I'll ask my oncologist as soon as my next appointment comes.

  • marijen
    marijen Member Posts: 3,731
    edited July 2018

    Easy Katzi, no money in it for the drug companies.


  • sandilee
    sandilee Member Posts: 1,843
    edited July 2018

    Megace is a synthetic progesterone that has been studied and has been shown to be of benefit to HR+ women. Some doctors do prescribe it, but not as an only therapy. My doc says women often don't like it because it increases your appetite and people tend to put weight on. He actually added it to my regimen because I really need to gain a few pounds.

    I just started taking it this month( I am also on Faslodex and Verzenio, which seem to be working) and I have noticed my appetite increasing already. I am enjoying my meals, which hasn't been the case for months while on chemos. I've also noticed an increase in my stamina- I don't feel lightheaded like I was after exercise or standing for awhile. Maybe because of blood sugar issues, or maybe I was just not getting enough nutrients- I don't know, but that problem has resolved. I also am feeling more relaxed than I was before, but who knows if it's because of the Megace. I am strongly ER+ and have weak PR (barely positive as of recent liver biopsy.)

    All in all, I think this is a good additional drug for me.

  • Lula73
    Lula73 Member Posts: 1,824
    edited July 2018

    Why no/so little research? It was recently discovered that the cells respond differently to the synthetic vs bioidentical progesterone. It’s a timing thing.

  • marijen
    marijen Member Posts: 3,731
    edited July 2018

    Lula, so that means there may be more studies in the future?


  • Lula73
    Lula73 Member Posts: 1,824
    edited July 2018

    I’m pretty confident that studies are going on now. We just have to wait for the results which could be years coming. With the studies we already have there are docs who will run with it to help give ladies with stage IV every chance they can. That’s the kind of doc I would want...

  • marijen
    marijen Member Posts: 3,731
    edited July 2018

    This is helpful..

    Hormone Balance and Imbalance

    http://www.immunesystemetc.com/Hormones.html

  • WC3
    WC3 Member Posts: 1,540
    edited July 2018

    If the mods don't mind, here it the reply I posted on Katzi's other thread on the same topic in case people find something informative in it.


    Progesterone and breast cancer is an interest of mine. I've discovered that it's a complex subject that is not yet very straight forward.

    Certain progestins had been used in the past to treat breast cancer but I can find little information on it. One of them was medroxyprogesterone acetate, which is ironic because that is the progestin implemented in an increase of breast cancer rates in post menopausal women who took HRT to alleviate symptoms of menopause.

    Here is one of the few studies I found on the use of medroxyprogesterone in the treatment of breast cancer.

    Oral medroxyprogesterone acetate in the treatment of metastatic breast cancer.

    As an aside...it seems that not all progestins affect breast cancer risk and breast cancer proliferation equally. Unfortunately many studies do not differentiate between different progestins, but here is a study that sought to distinguish the risk from micronized progesterone (bio identical) from synthetic progestins if you are interested.

    The impact of micronized progesterone on breast cancer risk: a systematic review

    It should be noted they are talking about risk of developing breast cancer, and not the actual effect on already existing breast cancer.

    To continue with using progestins to treat breast cancer...

    There is renewed interest in treating ER+/PR+ breast cancer with progestins, this time I believe bio identical progesterone and there are three clinical trials planned or already under way. The idea is that in hormone receptor positive breast cancer, the progesterone receptors are attached to the estrogen alpha receptors, and when activated, interfere with the ability of the estrogen alpha receptors to be activated.

    Progesterone receptor modulates ERα action in breast cancer

    Here is a nice article on that paper.

    Solving a breast cancer mystery – why do 'double-positive' women do better?

    Here is a link to one of the clinical trials involving progesterone therapy in breast cancer. They are not including people with stsge IV in it but those running the trial might have some information or resources that could be of help.

    A trial looking at progesterone to treat early breast cancer in premenopausal women

    I should mention something though concerning progesterone and HER2 positive status. I am by no means an authority on this matter, I just came across this in my own personal research...HER2 receptors are activated and cause tumor proliferation by the activation of other HER receptors, particularly HER1 which is also called EGFR. One of the things that activates HER1 is a compound called amphiregulin, and one of the things that causes the expression of/interacts with amphiregulin is progesterone. I cannot say what the implications are of this, but being HER2 positive, I would be concerned that activation of HER2 receptors by this mechanism, in the presence of exogenous progesterone use, would negate any anti proliferative effects that the progesterone exerts through alpha progesterone receptor inhibition. I would love to find someone who could give me an answer to this someday.

    The only thing I have right now are a few papers on amphiregulin, progesterone, estrogen, and breast development and a paper the concluded that amphiregulin confers herceptin resistance in HER2 positive breast cancer.

    Amphiregulin confers trastuzumab resistance via AKT and ERK activation in HER2-positive breast cancer.

    I think we will see studies that better investigate the relation between these things in the future though.

    One more thing. One study I found observed a bi phastic effect of progesterone on breast cancer. In some instance they observed cell proliferation and in other inhibition.

    Biphasic Regulation of Breast Cancer Cell Growth by Progesterone: Role of the Cyclin-Dependent Kinase Inhibitors, p21 and p27Kip

    A general disclaimer for the general public: As always, take these studies with a grain of salt. We aren't mice or petri dishes. Research is a discover process. Conclusions are tentative and sometimes subjective. Biology is complex. And researchers aren't infallible. And make sure your doctor is aware of and onboard with any treatments, medical or alternative that you embark on.

    Edit: I just noticed that the website the paper on medroxyprogesterone as a treatment for metastatic breast cancer has links to more papers on the matter. One details it's use in ER+/PR+ breast cancer specifically.

    Edit 2: Estrogen alpha receptor = estrogen receptor alpha.

    Edit 3: HER2 heterodimerizes with HER3 more than HER1 but HER1 is still a concern.

  • marijen
    marijen Member Posts: 3,731
    edited July 2018

    WC 3, well that’s A LOT to read and thank you! I wonder if I have low progesterone? As I think it was about 50% and Estrogen was 90%. Would you know?


  • marijen
    marijen Member Posts: 3,731
    edited July 2018

    Also, it would be nice if the Mods could combine the two threads started by Katzi. It would be less confusing. I don’t think they mind about cross posting.


  • WC3
    WC3 Member Posts: 1,540
    edited August 2018

    marijen:

    I'm sorry I don't really know unfortunately. I do know, however, that estrogen and progesterone levels are not routinely monitored in women even when they are experiencing symptoms of hormone problems, and I think they should be.

    I think a few times in a woman's life, a hormone profile should be constructed. This would entail taking blood or possibly saliva samples every day or every few days but this is not an accepted idea in the medical community. In fact when women have signs of female hormone problems that do not entail the development of masculine features or inappropriate lactation, and no structural reasons can be found, they often remain undiagnosed and untreated, are referred to a mental health professional, or are blindly treated with hormones in the form of birth control pills without the actual problem ever being determined.

    It's like the dark ages.

  • marijen
    marijen Member Posts: 3,731
    edited August 2018

    The dark ages is correct! My pcp doesn’t says they don’t normally check vitd3 and she’s head of the dept, I had to talk her into it. Unbelievable in the NW. Agree that once in a while through out our lives hormones should be checked. Why don’t they want to help us remains the question. Too expensive? But they are happy to run extra scans.



  • Lula73
    Lula73 Member Posts: 1,824
    edited August 2018

    marijen- the percentages associated with ER & PR don’t have anything to do with your estrogen and progesterone levels. Rather the percentages refer to the percentage of cancer cells that had ERs and PRs in the biopsy/excision sample. So 90% of the cell’s in your cancer tissue sample had estrogen receptors and 50% of them had progesterone receptors. On the Vitamin d topic-it’s hard to believe there are still docs out there who don’t routinely test Vit D. Even in areas of the country that get plenty of sun year round, many people are wearing sunscreen, wearing sun blocking clothing, and driving behind UV blocking windshields. Vit D is an essential building block for normal cell replication. Low levels can lead to errors in cell DNA and if those cells aren’t identified by the body’s immune system or they grow/replicate faster than the body can clear them you end up with cancer-perhaps malignant or perhaps benign. Note that just because a doc is head of a department does not mean they’re any better than any other doc at that facility. The job is often given to the doc who will agree to the extra admin work and meetings after several have already passed on it. The doc usually accepts it for the prestige/ego boost. Just one more misleading misnomer in the medical world that we have to figure out for ourselves. You’re doc on the subject of Vit D being case in point. Have you gotten the Vit D results back?

  • marijen
    marijen Member Posts: 3,731
    edited August 2018

    Yes Lula, 41 at 5000 iu per day. I’m going to increase even though my MO said not to. The thing is with head of the dept. I’m thinking she determines what goes and what does not? Not happy with this one at all. Too bad for her if she’s not checking her own. PNW

    It’s a darned shame we have to figure all this out by ourselves too. There should be a Black Warning Box with the first biopsy pathology report! :)

    Thanks for the info on the progesterone. I’m doing one dime size of Progest all natural daily.

  • Lula73
    Lula73 Member Posts: 1,824
    edited August 2018

    to some extent she does. But primarily she is responsible for handling anything between the higher ups at the hospital and the staff working under her. She handles going to department head meetings, escalating complaints from employees, reprimanding employees, identifying areas of overspend, etc. A lot of managerial admin things. She does not control whether or not a dr in her department routinely orders tests she may not agree need to be done or treatments ordered. My Vit D was 10 when my PCP humored me and drew the labs. That was about 5 years ago now. I take 10,000IU 5 days a week. Solgar makes a 10,000IU softgel so I just have to take 1.

  • marijen
    marijen Member Posts: 3,731
    edited August 2018

    Mine was 10 too. Thank goodness she wasn’t my first pcp. I was getting the impression she’s there to please the bosses and the guidelines. Thanks for the Solgar tip. How high is your D now? The trouble with supplements is we don’t know their effectiveness without the tests, that I explained to her as well as it’s important for breast cancer and many other things. I know for sure it has helped my muscle and bone pain. But I shouldn’t have to tell her this!



  • Murfy
    Murfy Member Posts: 342
    edited August 2018

    The Women's Health Initiative shows that E+P resulted in 24% more cases of BC vs placebo. The P in this large study was medroxyprogesterone. And yet, natural progesterone may temper estrogen's ability to increase breast cancer cell proliferation?

    *sigh*

    I am overwhelmed by how little we actually know about this disease. When research findings are contradictory, how do we know what to believe?

  • Lula73
    Lula73 Member Posts: 1,824
    edited August 2018

    medroxyprogesterone is not the same as bioidentical or natural progesterone. It’s what is in depo-provera. So it would make sense that it would have higher rate of BC vs placebo. Treating stage 4 should be done with bioidentical/natural progesterone.

  • Becca953
    Becca953 Member Posts: 99
    edited August 2018

    I find this thread very interesting. I was wondering about the fact that my tumor was ER 95% and PR 0%, but HER 2 +++. MO said this is "classic" HER2 disease due to the inverse relationship between HER2 and ER. So, I wonder how the info WC3 posted regarding amphiregulin plays into this? I think medicine is getting to the point, where all tumors can be analyzed for mutations, and other factors besides hormone positive and HER2, but the research is not quite there for it to be standard across the board when diagnosed. One day this may help us all obtain better personalized treatment.

    The vitamin D relationship is fascinating. I was low in Vitamin D for years, but had been taking it for at least two years before the cancer developed. My levels were 57 at diagnosis. So, did the low previous vitamin D contribute to the cancer, or was I predisposed to cancer anyway due to dense breasts, and the vitamin D controlled the growth? Interestingly, the growth factor, mitotic rate was rated as slow growing, especially for HER2, which made me question how much chemo was going to help. Yet another worry! Are we putting a square peg in a round hole?

    This dang disease has so many faucets and variables, and sometimes the science is contradictory.

  • Murfy
    Murfy Member Posts: 342
    edited August 2018

    These review articles helped explain the conundrum that is progesterone. Each review had a small section on progesterone (P4) and breast cancer. FYI, medroxyP and P4 both act through the PR, eliciting the same response. MedroxyP also weakly binds the androgen and glucocorticoid receptor, but then so does P4 in high enough doses. I love learning....


    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC35651...

    Synopsis: "These data demonstrate that progesterone can be pro-proliferative and pro-tumorigenic; however, the actions of progesterone are dependent on the cellular context. Its action in normal mammary cells and in breast cancer of various stages can be quite different. As with other reproductive tissues, differences in the tissue microenvironment may explain the variety of observed responses to progesterone in normal mammary tissue and breast cancer."

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC33189...

    Synopsis: "Progesterone is a risk factor for breast cancer and promotes pre-neoplastic progression by stimulating cyclical proliferation of the mature breast epithelium and by activating mammary stem cell pools or occult tumor initiating cells. Alterations in the progesterone/PR signaling axis, including a switch from a paracrine to an autocrine regulation of proliferation, contribute to progression. In more advanced stage breast cancer PR, either independent of P4 or in response to P4, suppresses tumor invasion and metastasis through maintaining epithelial cell phenotype and impeding the epithelial-mesencyhmal transition (EMT)."


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