Relapse HISTORY for her2+S

[Becky]

Jen


I think you are right - about time to randomization except for one thing. I do personally know 2 women who participated in the Herceptin trial at my cancer center (I opted not to and can tell you why if interested).

These ladies were randomized after the 4 AC treatments. When they showed up for their first weekly taxol that's when they found out if it was taxol alone or taxol with Herceptin (both were randomized to the arm without Herceptin). I met these gals while getting Herceptin and found out everything about the trial and being in the trial because I was on my 3rd weekly Herceptin (started asap after ASCO 2005 when I was 4 1/2 months from my last chemo) but they were both on their 9th weekly. After asking how can this be - I jumped so fast to start as soon as I heard - they commented that since they were on the trial, they were given the option to start Herceptin (if they wanted it) sometime around April 20, 2005 when Genentech made a public announcement. Both ladies were about 7-8 months from their last chemo (but for this group of women, being 6 months or less from the last chemo did not matter).

So, randomization started 12 weeks after the beginning of AC (remember the trial used AC every 3 weeks and not the dense dose regime used now).

Best regards

Becky

[CherylS]

Boy, I have a hard time interpreting those graphs etc... Thanks to those of you with the ability that help us understand.

I remember that in a nutshell the other two US trials for early stage herceptin use indicated that after five years 15% of women had recurrence. That is simply stated. What I would like to know is 1) How many of the women who relapsed were ER+/ER- and 2) were their recurrences local or distant.

Anyone know?

Thanks!

[Becky]

I can't answer that question fully, Cheryl. But I will say that IN GENERAL (meaning all bc) the statistics say that 80% of recurrences are local. This is not broken out to Her2+ vs hormone only positive vs triple negative etc.

Kind regards

Becky

[CherylS]

Thanks Becky,

You are a wealth of knowledge. I love reading your posts. So then if I understand correctly, of this 15%, 3%, statistically speaking, would have had a distant episode, right? That's encouraging to us all, especially if we also have the benefit of hormone therapy such as AI or tamoxifen. We can always use that dose of encouragment. Wonder what HERA will end up showing us about 2 years of Herceptin vs. one. Anyone remember when that is due out?

[sassy]

My onc is thinking there may be something presented in December on two year use at San Antonio. Joe, any indications of this that you know of?
________
FlirtyCat cam

[Becky]

Sassy


It is well documented that the absolute earliest results of 2 yrs of Herceptin therapy vs one year will be the end of April 2007 but indications are that there will not be a release of data until 2008.

About 6 weeks ago, Eric Winer (of Dana Farber) visited our cancer center. My onc called me beforehand to make sure all the right questions were asked in regard to 2 yrs of therapy vs one year. Preliminary data suggest that 2 yrs gives absolutely no better results than one year. Statistically it is not better and may impact heart function down the road (this is the big fear - what happens to us 10 years down the road. This question is not addressed in the metastatic condition because most women might not survive with mets 10-15 years out and those that do, there is no statistical data).

However, there will be data in the long term on if 2 years of Herceptin delay or eliminate possible mets long term. For example, in the initial Tamoxifen studies, there were lots of trials to determine that 5 years of use gave the best benefit. And this was tested using 1 yr of use, 2 yrs, 5 yrs and 10 yrs (of which 10 yrs actually gave a worse outcome).

In the future, new members to this board will look at us and say "you used adjuvant Herceptin for a year. OMG!!" because I think they will find that less (let's say 3-6 months) works just as well as a year.

Unfortunately, it is difficult to get the funding to do these studies because everyone is awaiting the 2 yrs of Herceptin data. It is rationalized as "what if more is better then why test 3 months vs 6 months vs one year? But I personally think less will be the same as a year and probably have less long and short term side effects.

Kind regards

Becky

[RobinP]

http://www.what-is-cancer.com/papers...recurrence.htm


THE ABOVE LINK IS ANNUAL RISK OF RECURRENCE FOR VARIOUS GROUPS, NOT SPECIFICALLY ADDRESSING HER2 GROUPS. HOWEVER, STILL THIS GRAPH IS HELPFUL IN TERMS OF REFLECTING GENERAL HORMONAL POSITIVE AND NEGATIVE RELAPSE.

[stephanie59]

You all have me very confused. Let me see if I understand: statistically are you saying that HER2+ER-PR- relapses long term less than HER2+ER+PR- breast cancers? Or is it the other way around?

After reading posts for the last week or so, I started to worry about lower back pain I have been experiencing for the last few months. Have not had blood work since last November so have no indication if tumor marker is up. My oncologist is scheduling me for a bone scan asap. This is not the way I wanted to get Herceptin (not eligible before). Hope it's just old age catching up with me. Keep fingers crossed. Stephanie

[sassy]

My onc and I have discussed the possibility of long term heart impact, and the fact that statistical data is not available because previously long term use had not been expected due to underestimated effect of Herceptin. Could you share where I might find the documentation of 2 year info being available in April 2007, with release not scheduled until 2008? You are a wealth of information and I appreciate all your help and support!
________
SweetBlackAss3010

[sarah]

I've been on Herceptin 18 months. There's something about being ER+ and HER2+ that needs balancing or it up ticks the other, so it seems you need to take an AI with Herceptin? So I'm on Herceptin and Femara. Really not sure how well researched this is.
sarah

[Hopeful]

sarahdalton, here is a link to an article that explores the issue of her2/endocrine therapy: http://erc.endocrinology-journals.or.../full/11/4/623. I will be doing Femara + Herceptin, also; currently doing Rx + Herceptin.

Hopeful

[Lani]

since writing that article Dr. Nicholson has written 24 more. If there are any die-hards who really want to know all the latest before making up their minds (and these are only his articles and there are scores writing on it, but he and Dr. Dowsett seem to be the most interested in this, I supply the following list of references--due to technical problems (my computer ignorance). I will list about 4 and then about another 20 in a second post):
21: Vicent MJ, Greco F, Nicholson RI, Paul A, Griffiths PC, Duncan R. Related Articles, Links
Polymer therapeutics designed for a combination therapy of hormone-dependent cancer.
Angew Chem Int Ed Engl. 2005 Jun 27;44(26):4061-6. No abstract available.
PMID: 15912547 [PubMed - in process]
22: Nicholson RI, Hutcheson IR, Britton D, Knowlden JM, Jones HE, Harper ME, Hiscox SE, Barrow D, Gee JM. Related Articles, Links
Growth factor signalling networks in breast cancer and resistance to endocrine agents: new therapeutic strategies.
J Steroid Biochem Mol Biol. 2005 Feb;93(2-5):257-62. Epub 2005 Feb 8. Review.
PMID: 15860268 [PubMed - indexed for MEDLINE]
23: Taylor KM, Morgan HE, Johnson A, Nicholson RI. Related Articles, Links
Structure-function analysis of a novel member of the LIV-1 subfamily of zinc transporters, ZIP14.
FEBS Lett. 2005 Jan 17;579(2):427-32.
PMID: 15642354 [PubMed - indexed for MEDLINE]
24: Jones HE, Goddard L, Gee JM, Hiscox S, Rubini M, Barrow D, Knowlden JM, Williams S, Wakeling AE, Nicholson RI. Related Articles, Links
Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells.
Endocr Relat Cancer. 2004 Dec;11(4):793-814.
PMID: 15613453 [PubMed - indexed for MEDLINE]

[Lani]

1: Sarwar N, Kim JS, Jiang J, Peston D, Sinnett HD, Madden P, Gee JM, Nicholson RI, Lykkesfeldt AE, Shousha S, Coombes RC, Ali S. Related Articles, Links
Phosphorylation of ER{alpha} at serine 118 in primary breast cancer and in tamoxifen-resistant tumours is indicative of a complex role for ER{alpha} phosphorylation in breast cancer progression.
Endocr Relat Cancer. 2006 Sep;13(3):851-61.
PMID: 16954434 [PubMed - in process]
2: Jones HE, Gee JM, Barrow D, Tonge D, Holloway B, Nicholson RI. Related Articles, Links
Inhibition of insulin receptor isoform-A signalling restores sensitivity to gefitinib in previously de novo resistant colon cancer cells.
Br J Cancer. 2006 Jul 17;95(2):172-80. Epub 2006 Jul 4.
PMID: 16819546 [PubMed - in process]
3: Cui Y, Parra I, Zhang M, Hilsenbeck SG, Tsimelzon A, Furukawa T, Horii A, Zhang ZY, Nicholson RI, Fuqua SA. Related Articles, Links
Elevated expression of mitogen-activated protein kinase phosphatase 3 in breast tumors: a mechanism of tamoxifen resistance.
Cancer Res. 2006 Jun 1;66(11):5950-9.
PMID: 16740736 [PubMed - indexed for MEDLINE]
4: De Martino G, Edler MC, La Regina G, Coluccia A, Barbera MC, Barrow D, Nicholson RI, Chiosis G, Brancale A, Hamel E, Artico M, Silvestri R. Related Articles, Links
New arylthioindoles: potent inhibitors of tubulin polymerization. 2. Structure-activity relationships and molecular modeling studies.
J Med Chem. 2006 Feb 9;49(3):947-54.
PMID: 16451061 [PubMed - indexed for MEDLINE]
5: Hiscox S, Morgan L, Green TP, Barrow D, Gee J, Nicholson RI. Related Articles, Links
Elevated Src activity promotes cellular invasion and motility in tamoxifen resistant breast cancer cells.
Breast Cancer Res Treat. 2006 Jun;97(3):263-74. Epub 2005 Dec 7.
PMID: 16333527 [PubMed - in process]
6: Greco F, Vicent MJ, Penning NA, Nicholson RI, Duncan R. Related Articles, Links
HPMA copolymer-aminoglutethimide conjugates inhibit aromatase in MCF-7 cell lines.
J Drug Target. 2005 Sep-Nov;13(8-9):459-70.
PMID: 16332571 [PubMed - indexed for MEDLINE]
7: Yee SW, Jarno L, Gomaa MS, Elford C, Ooi LL, Coogan MP, McClelland R, Nicholson RI, Evans BA, Brancale A, Simons C. Related Articles, Links
Novel tetralone-derived retinoic acid metabolism blocking agents: synthesis and in vitro evaluation with liver microsomal and MCF-7 CYP26A1 cell assays.
J Med Chem. 2005 Nov 17;48(23):7123-31.
PMID: 16279770 [PubMed - indexed for MEDLINE]
8: Britton DJ, Hutcheson IR, Knowlden JM, Barrow D, Giles M, McClelland RA, Gee JM, Nicholson RI. Related Articles, Links
Bidirectional cross talk between ERalpha and EGFR signalling pathways regulates tamoxifen-resistant growth.
Breast Cancer Res Treat. 2006 Mar;96(2):131-46. Epub 2005 Oct 27.
PMID: 16261397 [PubMed - in process]
9: Dowsett M, Nicholson RI, Pietras RJ. Related Articles, Links
Biological characteristics of the pure antiestrogen fulvestrant: overcoming endocrine resistance.
Breast Cancer Res Treat. 2005;93 Suppl 1:S11-8. Review.
PMID: 16247595 [PubMed - indexed for MEDLINE]
10: Nicholson RI, Johnston SR. Related Articles, Links
Endocrine therapy--current benefits and limitations.
Breast Cancer Res Treat. 2005;93 Suppl 1:S3-10. Review.
PMID: 16247594 [PubMed - indexed for MEDLINE]
11: Rampaul RS, Pinder SE, Nicholson RI, Gullick WJ, Robertson JF, Ellis IO. Related Articles, Links
Clinical value of epidermal growth factor receptor expression in primary breast cancer.
Adv Anat Pathol. 2005 Sep;12(5):271-3. Review.
PMID: 16210923 [PubMed - indexed for MEDLINE]
12: Gee JM, Robertson JF, Gutteridge E, Ellis IO, Pinder SE, Rubini M, Nicholson RI. Related Articles, Links
Epidermal growth factor receptor/HER2/insulin-like growth factor receptor signalling and oestrogen receptor activity in clinical breast cancer.
Endocr Relat Cancer. 2005 Jul;12 Suppl 1:S99-S111. Review.
PMID: 16113104 [PubMed - indexed for MEDLINE]
13: Staka CM, Nicholson RI, Gee JM. Related Articles, Links
Acquired resistance to oestrogen deprivation: role for growth factor signalling kinases/oestrogen receptor cross-talk revealed in new MCF-7X model.
Endocr Relat Cancer. 2005 Jul;12 Suppl 1:S85-97.
PMID: 16113102 [PubMed - indexed for MEDLINE]
14: Nicholson RI, Hutcheson IR, Hiscox SE, Knowlden JM, Giles M, Barrow D, Gee JM. Related Articles, Links
Growth factor signalling and resistance to selective oestrogen receptor modulators and pure anti-oestrogens: the use of anti-growth factor therapies to treat or delay endocrine resistance in breast cancer.
Endocr Relat Cancer. 2005 Jul;12 Suppl 1:S29-36. Review.
PMID: 16113097 [PubMed - indexed for MEDLINE]
15: Duncan R, Vicent MJ, Greco F, Nicholson RI. Related Articles, Links
Polymer-drug conjugates: towards a novel approach for the treatment of endrocine-related cancer.
Endocr Relat Cancer. 2005 Jul;12 Suppl 1:S189-99. Review.
PMID: 16113096 [PubMed - indexed for MEDLINE]
16: Jones HE, Gee JM, Taylor KM, Barrow D, Williams HD, Rubini M, Nicholson RI. Related Articles, Links
Development of strategies for the use of anti-growth factor treatments.
Endocr Relat Cancer. 2005 Jul;12 Suppl 1:S173-82. Review.
PMID: 16113094 [PubMed - indexed for MEDLINE]
17: Agrawal A, Gutteridge E, Gee JM, Nicholson RI, Robertson JF. Related Articles, Links
Overview of tyrosine kinase inhibitors in clinical breast cancer.
Endocr Relat Cancer. 2005 Jul;12 Suppl 1:S135-44. Review.
PMID: 16113090 [PubMed - indexed for MEDLINE]
18: Gee JM, Howell A, Gullick WJ, Benz CC, Sutherland RL, Santen RJ, Martin LA, Ciardiello F, Miller WR, Dowsett M, Barrett-Lee P, Robertson JF, Johnston SR, Jones HE, Wakeling AE, Duncan R, Nicholson RI. Related Articles, Links
Consensus statement. Workshop on therapeutic resistance in breast cancer: impact of growth factor signalling pathways and implications for future treatment.
Endocr Relat Cancer. 2005 Jul;12 Suppl 1:S1-7. Review.
PMID: 16113086 [PubMed - indexed for MEDLINE]
19: Hiscox S, Jiang WG, Obermeier K, Taylor K, Morgan L, Burmi R, Barrow D, Nicholson RI. Related Articles, Links
Tamoxifen resistance in MCF7 cells promotes EMT-like behaviour and involves modulation of beta-catenin phosphorylation.
Int J Cancer. 2006 Jan 15;118(2):290-301.
PMID: 16080193 [PubMed - indexed for MEDLINE]
20: Knowlden JM, Hutcheson IR, Barrow D, Gee JM, Nicholson RI. Related Articles, Links
Insulin-like growth factor-I receptor signaling in tamoxifen-resistant breast cancer: a supporting role to the epidermal growth factor receptor.
Endocrinology. 2005 Nov;146(11):4609-18. Epub 2005 Jul 21.
PMID: 16037379 [PubMed - indexed for MEDLINE]
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Hope this helps!

[RobinP]

Hi Steph,

You said above that , "You all have me very confused. Let me see if I understand: statistically are you saying that HER2+ER-PR- relapses long term less than HER2+ER+PR- breast cancers? Or is it the other way around?"

I will try to clarify your question for you. We do not have long term data on her2 relapse beyond five years from any prospective studies yet. However, we do know the relapse history bc relapse based on hormonal status. From this data, we know that hormonal negatives usually relapse more in the first five years or relapse less after five years than hormonal positives.

Hope this helps. Also, hope your back pain is nothing serious. Take care.

[Becky]

However, I would like to add...

Her2+ women who are also hormone positive relapse less (overall) than those who are hormone negative. The natural progression of the two diseases could be slightly different (with perhaps a blip after hormone therapy is completed) but we just don't really know for sure because Her2s weren't separated out of that hormone positive data. However, it would make sense that the blip is stronger for those who are only hormone positive (but not Her2) because they tend to be very, very strongly positive for ER and PR whereas Her2s who are also hormone positive tend to not be as hormone positive.

It is ALWAYS good to be hormone positive.

Kind regards

Becky

[RobinP]

Just to clarify for others, Becky, in the HERA trial and adjuvant Herceptin NCI trials, the hormonal receptors were separated out. It was found that Her2+ women who are also hormone positive relapse less in the first few years compared to hormonal negatives. However, it was not clear, because the data is not available yet, if these women will acutally relapse later than sooner. It is too soon to fully comment on the hormonal positive, her2 combination long term relapse history, beyond five years, unitl the long term data from the HERA trial is revealed.

http://content.nejm.org/cgi/data/353/16/1673/DC1/1

Just to add, from the above link, the relapse data for hormonal negatives and postives that are her2+ also are grapphed out in the lower last panels for five years out.

[penelope]

Although the hormonal status and DFS is mapped out it does not say if these patients were node positive or negative in the context of hormonal status. IE both graphs could be a conglomeration of node + and - patients.

[atdec05]

penelope,

I questioned that too. If you notice panel A only goes out 2 years. I believe that's because node negative women were included only recently in the trials, so there is no data beyond 2 years for them. Hence the panels that show DFS for hormone Positive/negative women probably are based on node positive women.
- Anna

[RobinP]

Oh, no you guys still don't see it? Okay,please try again. Click on the website I provided above. Then scroll down below panel A and B and look at fig. 3, for panel E and F which sites hormonal negative and positive data.Got it? I hope so.

[RobinP]

PS. To further help you:

Panel E and F are labeled HR negative and HR positive, the HR stands for hormonal receptor. The data does go out to five years.Once again, here is the link:

http://content.nejm.org/cgi/data/353/16/1673/DC1/1