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Aug 30, 2014 07:54PM
Mike, it appears that bazedoxifene (without CEE) may be useful in the inhibition of both Tamoxifen (used most often in pre-menopausal cases) and Aromatase Inhibitor (used in post-menopausal cases)-resistant tumors alike. One study quotes:
"Breast cancer remains the most commonly diagnosed cancer among women and the leading cause of cancer mortality in women worldwide. While targeted therapies such as tamoxifen and aromatase inhibitors are effective in treating estrogen receptor (ER) positive tumors, de novo and acquired resistance remain an impediment to durable clinical responses. However, ERα remains a therapeutic target in breast cancers that are resistant to both first and second line endocrine interventions. Evaluation of the molecular pharmacology of clinically relevant ER modulators revealed that the third generation selective estrogen receptor modulator (SERM) bazedoxifene had a unique mechanism of action and inhibited the growth of both tamoxifen sensitive and resistant ERα positive breast cancer xenografts. These findings provide strong support for the clinical evaluation of bazedoxifene in breast cancer patients who relapse while undergoing treatment with tamoxifen and/or an aromatase inhibitor."
This is BZA only. Major studies have yet to be done on the BZA/CEE combo, or SERC.
But again, numerous studies (one, quoted below) seem to show that the other part of the combo (CEE) has an unexpected ability to inhibit breast tumors after a certain interval of estrogen deprivation:
"The paradoxical reduction of breast cancer incidence in women receiving estrogen alone is consistent with a model that this hormone causes apoptosis in women deprived of estrogen long term as a result of the cessation of estrogen production after the menopause. Understanding of the kinetics of occult tumors suggests that breast cancer "prevention" with anti-estrogens or aromatase inhibitors represents early treatment rather than a reduction in de novo tumor formation."
I believe that this means that Tamox and AIs treat existing tumors effectively, but new (de novo) tumors threaten several years later because they may never have really prevented by these agents. New growth may not be a resistance to the drugs at all, but a misunderstanding of how these drugs actually work (and when they do not). If this is so, hope remains, or so it seems. -Same study, new quote:
"Our in vivo data suggest that the combination of a SERM, bazedoxifene (BZA), with conjugated equine estrogen (CEE) acts to block maturation of the mammary gland in oophorectomized, immature mice. This hormonal combination is defined by the generic term, tissue selective estrogen complex or TSEC. Xenograft studies with the BZA/CEE combination show that it blocks the growth of occult, hormone dependent tumors in nude mice. These pre-clinical data suggest that the BZA/CEE TSEC combination may prevent the growth of occult breast tumors in women."
Here we see true prevention of new tumors. Could it be that the preventive tool that Tamox/AIs may not be, BZA/CEE is? -Even with the estrogen in it?
Could it be that after Tamox/AIs have cleared the body of existing tumors, a sufficient time of estrogen deprivation can be identified, after which BZA/CEE can be introduced to begin the work of prevention by targeting those sleeping estrogen receptors for destruction? Intriguing questions, for sure. -Would that we had more answers.
Oncotype DX DCIS score:13, VNPI score: 5
6/12/2013, DCIS, Right, <1cm, Stage 0, Grade 1, 0/0 nodes, ER+/PR+
6/12/2013 Lumpectomy: Right
6/28/2015, DCIS, Right, 1cm, Stage 0, Grade 2, 0/3 nodes, ER+/PR-
8/18/2015 Prophylactic mastectomy: Left, Right; Reconstruction (left): Tissue expander placement; Reconstruction (right): Tissue expander placement