are you ready for something completely different? It may be progesterone,not estrogen

[Lani]

at fault in the majority of breast cancers.

Well, here us a paper causing the issue to be reexamined:
Endocr Relat Cancer. 2006 Sep;13(3):717-38. Links
Progesterone metabolites in breast cancer.

Wiebe JP.
Department of Biology, Hormonal Regulatory Mechanisms Laboratory, University of Western Ontario, London, Ontario, Canada N6A 5B7.
In the 70 years since progesterone (P) was identified in corpus luteum extracts, its metabolism has been examined extensively in many tissues and cell lines from numerous species. In addition to the reproductive tissues and adrenals, every other tissue that has been investigated appears to have one or more P-metabolizing enzyme, each of which is specific for a particular site on the P molecule. In the past, the actions of the P metabolizing enzymes generally have been equated to a means of reducing the P concentration in the tissue microenvironment, and the products have been dismissed as inactive waste metabolites. In human breast tissues and cell lines, the following P-metabolizing enzymes have been identified: 5alpha-reductase, 3alpha-hydroxysteroid oxidoreductase (3alpha-HSO), 3beta-HSO, 20alpha-HSO, and 6alpha-hydroxylase. Rather than providing diverse pathways for inactivating and controlling the concentration of P in breast tissue microenvironments, it is proposed that the enzymes act directly on P to produce two types of autocrines/paracrines with opposing regulatory roles in breast cancer. Evidence is reviewed which shows that P is directly converted to the 4-pregnenes, 3alpha-hydroxy-4-pregnen-20-one (3alpha-dihydroprogesterone; 3alphaHP) and 20alpha-dihydroprogesterone (20alphaHP), by the actions of 3alpha-HSO and 20alpha-HSO respectively and to the 5alpha-pregnane, 5alpha-pregnane-3,20-dione(5alpha-dihydroprogesterone; 5alphaP), by the irreversible action of 5alpha-reductase. In vitro studies on a number of breast cell lines indicate that 3alphaHP promotes normalcy by downregulating cell proliferation and detachment, whereas 5alphaP promotes mitogenesis and metastasis by stimulating cell proliferation and detachment. The hormones bind to novel, separate, and specific plasma membrane-based receptors and influence opposing actions on mitosis, apoptosis, and cytoskeletal and adhesion plaque molecules via cell signaling pathways. In normal tissue, the ratio of 4-pregnenes:5alpha-pregnanes is high because of high P 3alpha- and 20alpha-HSO activities/expression and low P 5alpha-reductase activity/expression. In breast tumor tissue and tumorigenic cell lines, the ratio is reversed in favor of the 5alpha-pregnanes because of altered P-metabolizing enzyme activities/expression. The evidence suggests that the promotion of breast cancer is related to changes in in situ concentrations of cancer-inhibiting and -promoting P metabolites. Current estrogen-based theories and therapies apply to only a fraction of all breast cancers; the majority (about two-thirds) of breast cancer cases are estrogen-insensitive and have lacked endocrine explanations. As the P metabolites, 5alphaP and 3alphaHP, have been shown to act with equal efficacy on all breast cell lines tested, regardless of their tumorigenicity, estrogen sensitivity, and estrogen receptor/progesterone receptor status, it is proposed that they offer a new hormonal basis for all forms of breast cancer. New diagnostic and therapeutic possibilities for breast cancer progression, control, regression, and prevention are suggested.
PMID: 16954427 [PubMed - in process]

[Joy]

Thanks Lani, I was very interested to read this (not that I'm smart enough to get all of it). If I'm interpreting this right, then this is very relevant for me personally (although that is a big 'IF'). When I switched from Taxol/Carbo cause it plateaued in efficacy to Megace (progesterone) my liver lesions tripled and doubled in 6 weeks time and I'm wondering if there is a connection between that and this article's info. In the past estrogen manipulating treatments have worked REALLY well for me. We thought that Megace would work well too. I could be really wrong, but it just seems crazy that I had SO much progression while on a progestriogenic drug. Do you have any thoughts?

By the way I love all of your articles and insights. I just hope that YOU are doing well and feeling great, cause we are here for you, too.

[RobinP]

Let's remember, in the WHI studies, HRT increased risk of bc to a much greater degree when Progesterone plus estrogen was used, as opposed to estrogen alone. So yes, Progesterone is a bad player.

[Bev]

Are there any treatments that would target P? BB

[Kaye]

This is really not new. Dr. John Lee had been talking about this for awhile and, in fact, published a book around 4+/- yrs ago in which this was discussed. Interestingly, at time of my dx my PR was not reported--only ER. I was told that whatever PR level was I'd still be treated the same. However, I do wonder if reason for not reporting it was because it was atypical and info re such was available then.

[R.B.]

Another tantilising link between reproductive factors and cancers.

RB

[jhandley]

I have read Dr Lee's book which made a lot of sense to me. Be careful about confusing progesterone and progestin which is chemically altered progesterone.
According to Dr Lee (natural) progesterone is OK and he provides evidence to show it slows down cell proliferation whereas synthetic progestin (used in contraceptives) is not OK.
After reading his book I got my salivary hormones tested and I was low in progesterone. Women who are low in progesterone have a higher rate of BC.
Symptoms of low progesterone include fibroids, fibrocystic breasts, endometriosis amongst others ..I had all these.
I use natural progesterone cream to mimic normal physiological levels as per his instructions..it apparently also normalises the p 53 tumour suppressor gene if it is faulty. My onc. doesnt have aproblem with this ( my tumour was er/pr -.)

Regards
Jackie