Herceptin and Tamoxifen together

[Diane]

Can herceptin and tamoxifen be used together, does anyone have any info on this, or any site that has good information on herceptin? Thanks!

[Rich]

I don't have it handy but I have read that some are pursuing the idea that combining Tamoxifen with Herceptin can restore sensitivity to hormonal therapy in her-2+ patients. Tamoxifen is thought by some to actually increase her-2+ proliferation due to "estrogen agonism".

[Lani]

I had read several articles similar to those Rich referred to--will have to review them to see if they are in vitro studies , mice studies or whatever ie, not in vivo studies in humans as I recall. The most article I stumbled upon most recently (just last night) was this one:

1: Breast Cancer Res Treat. 2004 Jul;86(2):125-37. Related Articles, Links


Trastuzumab plus tamoxifen: anti-proliferative and molecular interactions in breast carcinoma.

Ropero S, Menendez JA, Vazquez-Martin A, Montero S, Cortes-Funes H, Colomer R.

Division of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain.

HER2 overexpression has been associated with anti-estrogen resistance in human breast cancer, and it has been suggested that the combined treatment of an anti-HER2 antibody plus tamoxifen has enhanced anti-cancer efficacy in breast cancer. The detailed anti-proliferative interactions between trastuzumab and tamoxifen were analyzed with the isobologram and Chou and Talalay methods, which assess the presence of synergy, addition or antagonism. We used the breast cancer cell lines that are estrogen receptor (ER)-positive and HER2-positive. We also analyzed the molecular changes on the HER2 and (ER) signaling pathways that are induced by trastuzumab plus tamoxifen. In terms of cancer cell proliferation, the simultaneous combination of trastuzumab and tamoxifen on BT-474 cells was more growth inhibitory (44%) than the treatment with trastuzumab (24%) or tamoxifen (31%) alone. Isobologram analysis of simultaneous trastuzumab plus tamoxifen exposure showed, however, that there were antagonistic interactions at an effect level of 30% (IC30). Using Chou and Talalay analysis we also observed antagonistic interactions at lower levels of cell kill, although there were additive effects at highest levels of cell kill. Trastuzumab followed by tamoxifen showed antagonism at all effects levels. Tamoxifen followed by trastuzumab showed antagonism at lower levels of cell kill, and additivity at higher levels of cell kill. Similar interactions were observed using T47D cells. The molecular effects of the combined treatment with trastuzumab plus tamoxifen on the levels of HER2 and ER signaling showed that, with respect to HER2 protein levels, trastuzumab downregulated HER2 by 27%, tamoxifen upregulated HER2 by 40%, and the combination of trastuzumab plus tamoxifen did not induce changes in HER2 respect to control. With respect to HER2 mRNA, trastuzumab upregulated HER2 mRNA to 367%, tamoxifen to 166%, and the combination to 401%. With respect to HER2 phosphorylation, trastuzumab upregulated HER2 phosphorylation to 352%, tamoxifen to 202% and the combination to 633%. Epidermal growth factor receptor levels were not changed by trastuzumab or tamoxifen alone, and were upregulated to 138% by the combination. The protein levels and activity of extracellular recptor kinase were not modified by trastuzumab, tamoxifen or the combination. Finally, estrogen receptor protein and mRNA levels were downregulated to about 50% by trastuzumab, tamoxifen or the combination. Taken together, our results show that in ER-positive breast cancer cells overexpressing HER2, trastuzumab plus tamoxifen have antagonistic interactions when used in combination, and that this antagonism may be related with an increase in HER2 signaling pathways that occurs when tamoxifen is added to trastuzumab. Copyright 2004 Kluwer Academic Publishers

PMID: 15319565 [PubMed - indexed for MEDLINE]

Will try to find the others if I have time, as obviously this is confusing. The bottom-line at the moment, is they just don't know...But let's push them to find out!

HOPE THIS HELPS,

Lani

[Lani]

here are the first 20 or so of the 509 articles cited in Pub Med when you enter herceptin, tamoxifen--listed from most recent to least recent:


PubMed Central
Display Show
All: 59
Review: 34
[Click to change filter selection through My NCBI.]
Items 1 - 20 of 59

of 3
Next
1: Emens LA. Related Articles, Links
Abstract Trastuzumab: Targeted Therapy for the Management of HER-2/neu-Overexpressing Metastatic Breast Cancer.
Am J Ther. 2005 May-Jun;12(3):243-53.
PMID: 15891269 [PubMed - in process]
2: Vazquez-Martin A, Colomer R, Ropero S, Abel Menendez J, Argiris A, Wang CX, Koay DC, Digiovanna MP. Related Articles, Links
No abstract Growth and molecular interactions between tamoxifen and trastuzumab.
Clin Cancer Res. 2005 May 1;11(9):3597; author reply 3597-9. No abstract available.
PMID: 15867265 [PubMed - in process]
3: Kim R, Tanabe K, Emi M, Uchida Y, Toge T. Related Articles, Links
Abstract Modulation of tamoxifen sensitivity by antisense Bcl-2 and trastuzumab in breast carcinoma cells.
Cancer. 2005 May 15;103(10):2199-207.
PMID: 15830342 [PubMed - in process]
4: Emens LA, Reilly RT, Jaffee EM. Related Articles, Links
Abstract Breast cancer vaccines: maximizing cancer treatment by tapping into host immunity.
Endocr Relat Cancer. 2005 Mar;12(1):1-17.
PMID: 15788636 [PubMed - in process]
5: Stebbing J, Glassman R. Related Articles, Links
No abstract Breast cancer (metastatic).
Clin Evid. 2004 Jun;(11):2266-99. Review. No abstract available.
PMID: 15652111 [PubMed - indexed for MEDLINE]
6: Ropero S, Menendez JA, Vazquez-Martin A, Montero S, Cortes-Funes H, Colomer R. Related Articles, Links
Abstract Trastuzumab plus tamoxifen: anti-proliferative and molecular interactions in breast carcinoma.
Breast Cancer Res Treat. 2004 Jul;86(2):125-37.
PMID: 15319565 [PubMed - indexed for MEDLINE]
7: Senkus-Konefka E, Jassem J. Related Articles, Links
Abstract Report on the 4th European Breast Cancer Conference, Hamburg, Germany, 16-20 March 2004.
Breast Cancer Res. 2004;6(4):148-52. Epub 2004 May 18.
PMID: 15217485 [PubMed - indexed for MEDLINE]
8: Hayes DF. Related Articles, Links
No abstract Tamoxifen: Dr. Jekyll and Mr. Hyde?
J Natl Cancer Inst. 2004 Jun 16;96(12):895-7. No abstract available.
PMID: 15199102 [PubMed - indexed for MEDLINE]
9: Yang Z, Barnes CJ, Kumar R. Related Articles, Links
Abstract Human epidermal growth factor receptor 2 status modulates subcellular localization of and interaction with estrogen receptor alpha in breast cancer cells.
Clin Cancer Res. 2004 Jun 1;10(11):3621-8.
PMID: 15173068 [PubMed - indexed for MEDLINE]
10: Ellis M. Related Articles, Links
Free Full Text Overcoming endocrine therapy resistance by signal transduction inhibition.
Oncologist. 2004;9 Suppl 3:20-6. Review.
PMID: 15163844 [PubMed - indexed for MEDLINE]
11: Kaklamani V, O'Regan RM. Related Articles, Links
Abstract New targeted therapies in breast cancer.
Semin Oncol. 2004 Apr;31(2 Suppl 4):20-5. Review.
PMID: 15124130 [PubMed - indexed for MEDLINE]
12: Petit T, Claude L, Carrie C. Related Articles, Links
Abstract [Sequencing of adjuvant treatment after surgery for invasive breast cancer]
Cancer Radiother. 2004 Feb;8(1):54-8. Review. French.
PMID: 15093202 [PubMed - indexed for MEDLINE]
13: Argiris A, Wang CX, Whalen SG, DiGiovanna MP. Related Articles, Links
Free Full Text Synergistic interactions between tamoxifen and trastuzumab (Herceptin).
Clin Cancer Res. 2004 Feb 15;10(4):1409-20.
PMID: 14977844 [PubMed - indexed for MEDLINE]
14: Jhabvala-Romero F, Evans A, Guo S, Denton M, Clinton GM. Related Articles, Links
Abstract Herstatin inhibits heregulin-mediated breast cancer cell growth and overcomes tamoxifen resistance in breast cancer cells that overexpress HER-2.
Oncogene. 2003 Nov 6;22(50):8178-86.
PMID: 14603258 [PubMed - indexed for MEDLINE]
15: Ali SM, Harvey HA, Lipton A. Related Articles, Links
Abstract Metastatic breast cancer: overview of treatment.
Clin Orthop Relat Res. 2003 Oct;(415 Suppl):S132-7. Review.
PMID: 14600603 [PubMed - indexed for MEDLINE]
16: Gradishar WJ, O'Regan RM. Related Articles, Links
Abstract Progress in systemic adjuvant therapy of early-stage breast cancer.
Int J Clin Oncol. 2003 Aug;8(4):239-47. Review.
PMID: 12955580 [PubMed - indexed for MEDLINE]
17: Atalay G, Cardoso F, Awada A, Piccart MJ. Related Articles, Links
Abstract Novel therapeutic strategies targeting the epidermal growth factor receptor (EGFR) family and its downstream effectors in breast cancer.
Ann Oncol. 2003 Sep;14(9):1346-63. Review.
PMID: 12954573 [PubMed - indexed for MEDLINE]
18: Sayer HG, Hoffken K. Related Articles, Links
Abstract [Hormone therapy, chemotherapy and immunotherapy in breast carcinoma. The best strategy for your patient]
MMW Fortschr Med. 2003 Jun 12;145(24):40-2. German.
PMID: 12866298 [PubMed - indexed for MEDLINE]
19: Galleshaw J. Related Articles, Links
No abstract New options in the prevention and treatment of breast carcinoma.
J Med Assoc Ga. 2003 Winter-Spring;92(1):19-22. Review. No abstract available.
PMID: 12743901 [PubMed - indexed for MEDLINE]
20: Crino L, Franceschi E, Scopece L. Related Articles, Links
No abstract HER-2 inhibitors: clinical results.
Suppl Tumori. 2002 Nov-Dec;1(6):S3-4. Review. No abstract available.
PMID: 12658892 [PubMed - indexed for M

Hope this helps!
Lani

[PS]

I believe I did read however that Iressa may reverse tamoxifen resistance. Try putting herceptin and iressa into pub med and see if you can find that! Good luck, Lani

[Diane]

Wow, many thanks, i've got alot of reading to do. It does seem very confusing. It almost sounds like I need to choose between the tamoxifen or the herceptin,

[LANI]

Not at all!

Are you pre-,peri- or postmenopausal?

Her2 neu people would appear to do best with an aromatase inhibitor --in the neoadjuvant setting Matthew Ellis (I believe it is one of the articles in the list of 20) gave letrozole with herceptin to her2positive estrogen receptor positive patients before surgery and saw it work rather well.

Aromatase inhibitors are not given in pre-or peri-menopausal women, because their effect is to
rob the body of whatever estrogen it still produces after the ovaries no longer make estrogen.

If you are pre or perimenopausal, your doctor may insist you have your ovaries removed or
that you take shots of a compound that makes your pituitary no longer send messages to your ovary to make estrogen (and other things), before giving you an aromatase inhibitor. If you do either of those, you will be a candidate to take aromatase inhibitors, which seem to work better than tamoxifen and with fewer side effects (although they haven't been used by large numbers of people for as long as tamoxifen has).

Herceptin monotherapy (that is, when it is given alone) is generally much less effective when it is given with something else. So far the only something else they give it with is chemotherapy.

You did not say if you have positive nodes, a large tumor, or metastases so I assumed you had early breast cancer and were looking into these things to prevent it from coming back.

I also assumed that you were her2positive AND estrogen and or/progesterone receptor
positve. It is felt that even when her2positive tumors are estrogen positive, that they are only weakly estrogen positive with a small number of receptors, even if they might be a rather larger percentage of receptors. (ARTICLE BY KOPECNY). It remains unclear what is the best treatment for them. I hope the ASCO meeting will address this group of patients.

Hope this helped,
Lani

[*_sally_*]

I am getting Letrozole, Herceptin and Lupron to shut down the ovaries. I was told that the treatment was more effective if you went the post menopausal route. I recieved 2 lupron shots and decided to get my ovaries out instead. Your hormones are on a rollercoaster with lupron. I am 37 years old dx 03/04 HER2+++ estrogen+ 8/16 nodes + mets to the liver. I hope some of this helps. Sally

[Rozebud]

I am on herceptin and tamoxifen. I tried to talk my oncologist into switching to AIs (I still plan to force the issue this summer) but she said that all the evidence that they are contraindicated is antedotal. Meaning, there have been no conclusive studies that say there is interference. That being said....if you can push for AIs (with lupron shots to put you into menopause or an oopherectomy) I think that is superior.

[Diane]

Forgot to put in my stats, 2.3 tumour, Her2+++, er+pr-, grade 3. One more AC (agggghhhhh) tomorrow and 4 taxol after that. I hope my oncologist will start me on herceptin with the taxol. It really sounds like the way to go, but no doubt will have to fight with insurance co. Does anyone know when this conference is over, I know my Dr. went to it.

[lor]

Diane,

You have asked a very good question. I have been thinking about the tamoxifen versus AIs issue. I also have one more AC to go, then taxol with herceptin. I had a 3cm tumor, 8/18 nodes +, Her2+, er+pr+ grade 3 and pre-meno. If you find any helpful info. please post to keep me updated. Good luck with your last AC...I am soooooo glad that phase of treatment is almost over.

Thank you!