herceptin and tamoxifen

Kathy T · 02-22-2007, 08:31 AM

I remember reading on this site that Herceptin and Tamoxifen may not be synergistic--is there anyone who can provide info re: this? I'm not able to find anything in the articles. Thanks for your help.
Kathy T

sally · 02-22-2007, 06:08 PM

I was on Herceptin and Femara. My tumor markers went up consistantly. I stopped taking the Femara and started Tamoxifen with my Herceptin. My tumor markers have gone down my last two treatments. Hopefully they continue to do so. So far the combiniation is working for me but it has only been about 2 months. Only time will tell. Sally

heblaj01 · 02-23-2007, 06:24 AM

Kathy,
Some research shows that Tamoxifen may in some cases cause or enhance already present HER-2 positive cancer cells.
Also, I recall a paper stating that continuing to take Tamoxifen for 3 months after resistance leads to HER-2 positive tumors.
Here are articles which deal in part with this subject:
http://www.bcm.edu/fromthelab/vol03/is6/04aug_n4.htm
Researchers decode breast cancer mystery

http://cancerres.aacrjournals.org/cg...act/66/16/8266
Mechanisms of Tumor Regression and Resistance to Estrogen Deprivation and Fulvestrant in a Model of Estrogen Receptor–Positive, HER-2/neu-Positive Breast Cancer

http://japan.medscape.com/viewarticle/436131 Extract:
Interactions Between ER and Other Growth Factor Pathways

The estrogen receptor (ER) pathway is one of many growth factor pathways involved in breast cancer tumorigenesis, and these other pathways constitute novel therapeutic targets in themselves. Further, there are likely to be significant interactions between ER and other growth factor signaling pathways. Data to support this latter hypothesis were presented from murine models of breast cancer cell growth.[6] In this model system, the ER+ breast cancer cell line MCF-7 has been transfected with the HER2 gene, yielding cell line MCF-7/HER2-18. This cell line can be grown as a xenograft in mice to measure treatment effects.
Over time, growth of MCF-7/HER2-18 can be engineered to become resistant to tamoxifen, and in fact tamoxifen actually stimulates growth of the tumor. One question was whether other growth factor manipulations would affect tumor growth. To that end, the EGF-receptor (EGFR) tyrosine kinase inhibitor ZD1839 was used to see how EGF-based signaling might affect tamoxifen resistance. The major findings are summarized in Table 4.

Hopeful · 02-23-2007, 07:32 AM

Kathy,

Here is a link to a site with excellent information on bc and tamoxifen (among other topics): http://tamoxifen-issues.evidencewatch.com/

Hopeful

Debra · 02-23-2007, 07:58 AM

I am concerned about the # of women that are indeed on tamoxifen when it could actually be harming us if we are Her2 +. There must be many more Her2 women out there other then me, that are on tamoxifen and Her2 positive so I am wondering "who is missing the boat" on this one and how concerned I should be. One would think that the oncologists should be up on this matter. In addition, this should be a HUGE statement at cancer conferences as well. Why is it not? If something we are taking could actually stimulate HER2 cancer growth, this should be big news and I am not seeing it.

Frustrated today!!

Becky · 02-23-2007, 08:20 AM

As you can see from my pathology, I am only moderately ER+ and I am PR neg. Even if I didn’t know my Her2 status, it is well documented that Tamoxifen does not work in women who are not highly positive for BOTH hormone receptors. My first onc put me on Tamoxifen. We had strong discussions and he would not listen to my opinion. His reasoning (and I think the reasoning of many oncs) was that he had to do something (and I was premenopausal at the time). He did not encourage Zoladex or Lupron with an AI or oophorectomy. I got an oophorectomy, changed oncs and I am on Arimidex. I took the Tamoxifen prescription but never took the drug (opting instead for the path I chose). Discuss the issue with your onc and the facts you have. Mine first onc was a “I am the doctor” kind of guy and not good for me overall. In general, I think their best interests are at heart for “having to do something” if you are hormone positive. However, there are a lot of good options now and your Her2 status should be considered.

Debra · 02-23-2007, 09:17 AM

Just curious if anyone can tell me what is considered to be "highly" ER or PR positive. I am 19% ER + and 20% PR + and am wondering if this is the "average" or considered low for being positive. According to my first oncologist, positive is positive and regardless of the percentage, one takes an estrogen blocker. It appears one wants to be in the 50 and above percentage range for tumor receptive to the hormones. I have not found any info on the net regarding the % of receptive tumors being a plus or minus. If anyone can shead some light for me that would be great!

Becky · 02-23-2007, 09:56 AM

Low is 10% - 30%. Moderate is 31 - 60 and high is 60%+. Ranges vary accordingly article to article but you are in the low range. However, your onc is right - positive is positive.

Hopeful · 02-23-2007, 10:56 AM

I actually have a theory that the Taxomifen resistance is part of the reason the Oncotype scores come back high for Her2+ ER+ patients. The one thing they know about Oncotype is that it is extremely sensitive to Tamoxifen - if you look at the form upon which your score is reported, under "Results," it reads:

"Test results should be interpreted using the information in the Clinical Experience section below, which applies only to patients consistent with this experience."

The "Clinical Experience" section referred to in the "Results" section above, reads:

"The following results are from a clinical validation study with defined endpoints involving 666 patients. The patients enrolled in the study were female, stage I or II, node negative, ER-positive, and treated with tamoxifen" (emphasis added)

My thinking is if this test is projecting what would happen to me if I did nothing after surguery and radiation except take Tamoxifen, and my tumor, due to Her2+, was at best Tamoxifen resistant and at worst Tamoxifen was demonstrated to cause my tumor to grow, of course my recurrence score is going to be high. That is one of the reasons I have not put a great deal of confidence in my score. It just didn't appear consistent with the pathology.

Hopeful

Rupali · 02-23-2007, 11:37 AM

This confuses me .

I was diagnosed in December 2004 and had mastectomy, chemo(4AC+4 TAxol) followed by 2 years of Herceptin (2nd year ends in May 2007) plus they started me on Tamoxifen in June 2005. I was just 10% ER+ and 10% PR+.
I am being followed by a community oncologist and another Oncologist at a big cancer center in Boston, namely MGH. I am really confused why they have put me on Tamoxifen , zoladex and Herceptin together.
What do you think I should do? Please advice.

heblaj01 · 02-23-2007, 11:41 AM

I remember an article about a group of French researchers who studied in the lab the metabolism of Tamoxifen & the possible impact of its metabolites one of which had agonist properties on cancer cells while others were antagonist.
They warned about possible risks. But this was years before Tamoxifen was found to increase the risk of endometrial cancer. I don't know if subsequently they found a relation between this metabolite & the risk in patients.

Rupali · 02-23-2007, 11:48 AM

http://clincancerres.aacrjournals.or...full/10/4/1409

Read this article . This says the following:
Conclusions: The combination of tamoxifen and Herceptin is formally demonstrated to result in synergistic growth inhibition and enhancement of G0-G1 cell cycle accumulation. In vitro, the individual drugs or combination produces a cytostatic effect. These results suggest that combined inhibition of ER and HER-2/neu signaling may represent a powerful approach to the treatment of breast cancer.

Becky · 02-25-2007, 02:34 PM

Rupali

I agree with your last post. My disagreement would start when Herceptin treatment is over in the adjuvant setting and one is on Tamoxifen alone. I have grave reservations on the use of tamoxifen alone in those who are Her2+ and are not strongly positive for both ER and PR.

Hopeful · 03-07-2007, 09:06 AM

http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

Hopeful

Emelie · 03-07-2007, 09:26 AM

Possible relocation..
My husband has been offered a terrific job in Denver and I am more than a little overwhelmed with the thought of a move right now. I have completed 3 tx AC, 7(of 12 scheduled) tx Taxotere with Herceptin and will have a MRM on the left breast after that. Radiation is recommended by both the oncologist and surgeon. I have told my husband that I just need him to take care of me immediately after surgery and that I will be fine by myself to do radiation. They want him to start his job asap. Both of my daughters are away at college, so can not ask them for help. On top of that we will have insurance issues. How hard is the post-surgery and is it wise to be all alone for radiation treatments? I am Stage III with node positive. Tumor 4 cm. er-/hr- Her 2 ++. Also, how do I create my signature so I don't have to re-enter my info each time?
Any input is greatly appreciated and thank you to all you wonderful ladies who share your comments, insights, and messages. It really helps to know I am not completely alone.
Emelie