Stan, Most of the references that you gave were from the late 70's, early 80's. Clinical protocols are out of my area and I haven't had a chance to look up specific references, so I'll just post a general impression that I have, subject to modification by me or others.
Estrogen, like the molecules that LGND synthesize for use in their IR technology, is a small molecule that acts by first binding to it's receptor(s) which are inside cells, including breast. The binding can stimulate the cells to divide, and in some cases, breast cancers is thought to be due to such a stimulation that is out of control. Tamoxifen can also bind to this receptor and block estrogen from binding, so it is considered an anti-estrogen for breast. However, it has the undesired property of binding to the receptor in uterine cells and causing them to divide, resulting in endometrial cancer.
Breast cancer cells can lose their estrogen receptor and therefore they can be classified as ER+ (still have the receptor) or ER- (lost the receptor). I believe that Tamoxifen was initially recommended for ER+ tumors (because the above model would predict that it was ineffective in ER- tumors because there was no receptor). I believe that it was also recommended for use as adjuvant therapy after surgery and radiation and/or chemotherapy, because it was more effective on residual tumor cells than primary treatment for a large or many smaller tumors.
However, more recent studies (earlier 90's) indicated that Tamoxifen could also be effective against ER- tumors, so the target population was changed to all breast cancer, regardless of ER status. Recently, a long term study indicated that Tamoxifen produced no measurable benefit when used for more than 5 years. |
