Progesterone Questions

I saw pr- is usually poorly differentiated with a high mitotic score. Mine had the lowest mitotic score which apparently unusual for er+ pr- tumors I also fit the ILC/IDC mix one of each.

I think the anastrozole and exemestane I took helped prevent recurrence.

Being PR+ is a good thing as the progesterone our bodies make (endogenous progesterone) slows down the ER+ cancers. In fact, high levels of bio identical progesterone is actually used to treat ER+ cancer in some stage IV patients.

It's the man made progesterone that is not favorable in this scenario. When it comes to its action on the progesterone receptor it has the opposite effect and feeds the cancer. This would include progesterone containing HRT, birth control, and most of the progesterone creams. That's why the breast cancer warnings are on their label and usually in a box in bold print and docs won't prescribe it for us BC ladies. The ones that are in the know will prescribe alternatives like Intrarosa and bioidentical progesterone creams to help with the changes to our female parts after oophorectomy/anti-hormonal therapy.

The role of progesterone/progestins in breast cancer is complex, biphasic, and poorly understood. It has both proliferative and anti proliferative effects on breast cells depending on when it's administered, and in the case of breast cancer, possibly the specific receptor type. Medroxyprogesterone acetate when used, in conjunction with estrogen in the form of post menopausal HRT is implicated in a spike in breast cancer incidents in the late 90s/ early 2000s.

However medroxyprogesterone acetate has also been used with some success as a treatment for existing breast cancer, particularly before the existence of drugs like Tamoxifen. There is less information on the role of natural progesterone and it's relation to breast cancer. Some studies have found that it does not contribute to an increase in breast cancer risk as medroxyprogesterone does but interest in the effects of natural progesterone and breast cancer are recent.

While progesterone may slow the proliferation of hormone positive breast cancer via the mechanism proposed in the study others have mentioned, by interefering with the estrogen receptors, any benefit of progesterone might not extend to breast cancers that are hormone receptor positive cancers and also HER2 positive. HER2 receptors are triggered when HER3, HER4, and to some extent, HER1 is triggered and while I have not seen any studies on the effect of progesterone/progestins on HER2 positive breast cancer, progesterone stimulates the production of a compound called amphiregulin, which is a trigger (ligand) for HER1.

I guess the question would be, does triggering HER2 via HER1 via amphiregulin via progesterone stimulate proliferation more than inhibiting ER via PR via progesterone halts proliferation?

I don't think anyone has an answer to that right now.

Meow13:

I don't know much about ER+/PR- breast cancer, unfortunately.

I hope developments in immune therapy make this all irrelevent someday though.