In response to Alex’ post on DCIS:

The reoccurrence rate for DCIS is about 30% without radiation and 15% with radiation. Abeloff’s Clinical Oncology, Fourth Edition (2008) states; “No subsets of women have been identified who do as well following conservation surgery without radiation therapy as with it, although such subsets of patients have been aggressively sought. Current recommendations are to radiate the breast after lumpectomy to achieve the lowest possible recurrence rate. The only possible exception is elderly women with comorbid conditions”.
So radiotherapy is clearly appropriate, except for some older women. As far as using 3′-Diindolylmethane (DIM) instead of tamoxifen (TAM) there are no clear published results but that doesn’t preclude its use along with TAM.
DIM is a natural compound found in cruciferous vegetables that has antiproliferative and estrogenic activity. However, it is not clear whether the estrogenic effects are mediated through estrogen receptor (ER) α, ERβ, or both ER subtypes. It seems DIM is a new class of ERβ-selective compounds, because it does not bind to ERβ, but instead it selectively recruits ERβ and co-activators (Endocrinology 2009). DIM causes growth arrest and apoptosis of cancer cells in vitro. DIM disrupted Ca2+ homeostasis and alteration Ca2+ homeostasis in the ER and can induce cellular apoptosis by both calcium-dependent and calcium-independent mechanisms (Mol Cancer Ther 2006). Research indicates its usefulness in BCa, as DIM in estrogen dependent (MCF-7) and estrogen-independent (MDA-MB-231) human breast cancer cell lines showed that DIM treatment produced a marked increase (from 51 to 79%) in the proportion of cells in the G1 phase of the cell cycle, regardless of estrogen-receptor status (Carcinogenesis 2002). While this in vitro study is useful it doesn’t necessarily address the ER + issue.
This study shows the mechanism by which DIM affects the ER. DIM did not bind to the ER in this concentration range, as shown by a competitive ER binding assay, it activated the ER to a DNA-binding species. DIM increased the level of transcripts for the endogenous pS2 gene and activated the estrogen-responsive pERE-vit-CAT and pS2-tk-CAT reporter plasmids in transiently transfected MCF-7 cells (Biochemical Pharmacology 2000).
In another in vitro test DIM can induce apoptosis in breast cancer cells independent of estrogen receptor status by a process that is mediated by the modulated expression of the Bax/Bcl-2 family of apoptotic regulatory factors (Biochemical Pharmacology 2002).
DIM and TAM may act on different pathways, which may mean they do the same thing in the end or they don’t do the same. TAM inhibits a group of enzymes known as protein kinase C, while DIM increases ROS levels in cells, which affects kinases. DIM also activates IFN ϒ (Oncogene 2005). Using DIM and TAM together may give better results than either in isolation.
In another study I3C was shown to be effective. Studies showing that tamoxifen and DIM treatments increase the level of p21 associated with the CDK2 complex, thus rendering it inactive (The Journal of Biological Chemistry, 2001).
CDK2 kinase activity is significantly reduced in Indole-3-carbinol (I3C), DIM, and tamoxifen-treated cells compared with control cells (Me2SO or tryptophol). The reduced level of CDK2 enzymatic activity after I3C treatment is likely due to the formation of the larger 200 kDa inactive complex, whereas, in DIM or tamoxifen-treated cells, the reduction in CDK2 kinase activity correlated with the increase in p21 observed in fractions that correspond to the distribution of CDK2.
These results also show that I3C acts through a pathway that is distinct from either DIM or tamoxifen in regulating CDK2 enzymatic activity (The Journal of Biological Chemistry 2005).
There is also the issue of dosage and I believe, though I have no reference source, that DIM levels are generally too low. But that’s another letter.

Abeloff’s Clinical Oncology, Fourth Edition,Churchill Livingstone, USA 2008
Biochemical Pharmacology. Volume 60, Issue 2, 15 July 2000, Pages 167-177. doi:10.1016/S0006-2952(00)00307-5
Biochemical Pharmacology. Volume 63, Issue 6, 15 March 2002, Pp 1085-97. doi:10.1016/S0006-2952(02)00856-0
Carcinogenesis (2002) 23 (8): 1297-1305. doi: 10.1093/carcin/23.8.1297
Endocrinology Vol. 151, No. 4 Pp. 1662-7. doi:10.1210/en.2009-1028
Mol Cancer Ther 2006;5(3) Pp,556–63. doi: 10.1158/1535-7163.MCT-05-0355
Oncogene (2005) 24, 2343–2353. doi:10.1038/sj.onc.1208434 Published online 28 February 2005
The Journal of Biological Chemistry. November 2, 2001, 276 Pp.40888-95. DOI:10.1074/jbc.M106448200
The Journal of Biological Chemistry 2005 280, Pp.8756-64. doi: 10.1074/jbc.M407957200

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