Tamoxifin and Herceptin

[schoolteacher]

This Thursday I go back to the doctor to take my Herceptin and get my follow up blood work.

I really need advice about beginning Tamoxifin. I think I read one time about taking Tamoxifin and Herceptin together to get better results on this board. If any of you know any information about this, will you please let me know?

My oncologists said, "I could begin the Tamoxifin in December or I can wait until I finish the Herceptin in February." We don't know yet if I will stop the Herceptin in February since I was diagnosed as Stage IV in the beginning.

I do not really want to wait until February since my BC was estrogen driven.

I would greatly appreciate any advice that anyone can offer me concerning this next step in my journey. If there are any articles, I would greatly appreciate them too.

Thanks,
Amelia

[CindyE]

I don't have any knowledge about Tamoxifen and Herceptin but am taking both now. I started Tamoxifen about 2 weeks ago and am 6 months into my first year of Herceptin. So far just hot flashes, night sweats, and aches in my tumor area. I agree with you that I wanted to get going on Tamoxifen as I was ER+ and didn't want to feed my cancer. I too would love to hear from others on taking both of these drugs together.

[schoolteacher]

Cindy,

Thank you for your reply. Thanks for letting me know the side effects you have experienced. I did not realize that it would be possible to feel aches in the tumor area.

Some of the women I have talked too said, "The medicine made them mean."

If you gain any more knowledge about this combo, please let me know.

Amelia

[wtfsanjo]

there is a lot of data that says tamoxifen doesn't work nearly as well in Her2+ patients - some data says it doesn't work at all in Her2+ patients. however, the addition of herceptin interacts with the tamoxifen in Her2+ patients and makes the tamoxifen work better. i took tamoxifen during herceptin, and discontinued after the end of herceptin. at that point i strongly considering ovarian ablation (i was 28, premenopausal) and an aromatase inhibitor. if you are strongly hormone positive, i would definitely recommend an AI versus tamoxifen. oncologists are generally resistant to this idea of tamoxifen resistance in Her2+ patients - at this point the available data hasn't reached a critical point to change standard of care for Her2+ patients. most oncologists would agree, however, that tamoxifen doesn't work as well in Her2+ - if i had been more hormone positive that i was, my ovaries would be shut down already and i'd be on femara. no question.

katie

[Hopeful]

Amelia,

Here is a link to a thread that contains several excellent links on this topic: http://her2support.org/vbulletin/sho...eferrerid=1173

I agree with Katie's remarks above completely when she says, "oncologists are generally resistant to this idea of tamoxifen resistance in Her2+ patients - at this point the available data hasn't reached a critical point to change standard of care for Her2+ patients," and would add that those of us on this Board do a pretty good job of staying ahead of the curve in terms of reading papers and studies that apply to Her2+ patients, and often are the ones who bring this information to the attention of our doctors. IMO, it is always wise to keep asking questions until you get answers that make sense.

Hopeful

[schoolteacher]

Katie and Hopeful,

Thank you for your replies. I did have the Tamoxifin test about a month ago, and the results say that I am an extensive metabolizer of Tamoxifin.

Do either of you know if this fact will help? I am still premenopausal. My leave was still at 50. I have not had a period in three years.

Any additional advice I would greatly appreciate.

Amelia

[wtfsanjo]

as far as i know (and i've spent many hours trying to figure out this tamoxifen thing) it doesn't matter if you're a good metabolizer or not - even if you fully metabolize it, you cancer cells - because they are Her2+ - will still be resistant to the tamoxifen.

the only thing that menopausal status impacts is what sort of hormone therapies are available to you. tamoxifen can be used by both pre and post-menopausal women. aromatase inhibitors (femara, arimidex) are only for use in postmenopausal women. luckily, medical science can turn any premenopausal woman into a postmenopausal one through either ovarian suppression (shots to shut down your ovaries) or ovary removal (oopherectomy). aromatase inhibitors have been shown to be more effective than tamoxifen overall, and certainly are more effective in Her2+ patients.

i know it sounds scary to "shut down" your ovaries, but even at 28 with no kids i was 100% on board until my onc decided that 10% progesterone positivity wasn't enough to merit such aggressive care.

like hopeful said - ask a lot of question of your onc - and of people on this board. i hang out primarily at the young survival coalition board, and as knowledgeable as those women are - the women over here on Her2support are like scientists!

k

[basset girl]

Amelia, I was in the same situation last year. I took Tamoxifin while I was finishing up my Herceptin but after the Herceptin was finished (I got one year) I had my ovaries out so I could take Arimidex. My onc agreed that he thought the Arimidex worked better for Her2 patients. Having the ovaries out was so simple, just out patient surgery and I was back to work in 3 days. The Arimidex does cause alot of aches and pains but so far I can tolerate it. When I was on the Tamoxifin I didn't notice much side effects except the hot flashes.

Nancy

[Hopeful]

Amelia,

My understanding is that in Her2+ ER+ patients, the "cross talk" as they call it allows for stimulation of the cancer in multiple ways, whereas there are fewer stimulation pathways in Her2- patients. Using Tamoxifen to block ER stimulation can push the Her2+ cells to more active signaling, to give the cancer an alternate pathway to grow through. One of the studies I cited in the link above said that this force was so strong in some patients, if clinical trials utilizing Tamoxifen were to be designed, it might be prudent to treat even Her2- patients with a Her2 blocker, to prevent this alternate signaling from occurring.

Whether or not to take Tamoxifen is a decision you need to make with your doctor. For myself, all of the reading I have done on this topic has made me leery of not just Tamoxifen, but anything (foods included) that can act like a SERM.

Hopeful

[dlaxague]

Hi all,

When the adjuvant AI data first started appearing, there was a lot of talk about AI's being better in HER2+ cancer because HER2+ cancer was Tamoxifen resistant. But I think that over the last few years the thinking has changed a bit. Yes, HER2+ cancers tend to derive less benefit from hormonal treatment. That is probably in part because the levels of hormone receptors tend to be lower, and in part because of resistance to hormonal treatment. But it's looking as if that resistance is similar for AI's. It's not just Tamoxifen.

And alas, the jury is still out on the whole issue. It's interesting to me that the garden-variety community oncs are the ones who'll tell us that they know these answers: "AI's are more effective for HER2+", or "Tamoxifen is fine for HER2+", or "Herceptin makes Tamoxifen work better". Any or all of these statements may be true, or not. We do not (yet) know enough to make such broad statements.

I think that these docs make these silly statements for several reasons. One, they know that we like to hear that it's all under control. They, too, like to feel that it's all under control. So they tend toward giving answers that sound more secure or absolute than they really are. Secondly, these busy community oncs probably do not read all there is to read about breast cancer. They may be hanging their hat on one or two studies, when there are 10 studies and the results are contradictory. You can find one or two studies to support almost anything you'd like to support. The experts in the field of hormone treatment and hormone resistance will be the first to say that they do not (yet) know enough to make such statements.

There's a lot of information going to appear next week at SABCS. In the meantime, here's a recent (2008), long, and complicated discussion:

http://www.medscape.com/viewarticle/580741_3

You may have to register to see this but Medscape registration is free. The link is to page 3 of 7, so scroll through it all. If you're like me, you'll skim the details of the complicated discussion of pathways and crosstalk but still be able to get the gist of it. I'll copy/paste some relevant snips (broken up for readability) below. Remember that they are talking about hormonal treatment in the absence of Herceptin or other HER2 targeted therapy (although if you follow the link, page 4 and 5 do bring in Herceptin and friends).

There was some initial enthusiasm that HER2+ tumors would be more sensitive to AIs than to tamoxifen.[76] Careful analysis of published data, however, suggests that even with AIs, patients with HER2+ disease have a poor response.[83,84,85,86,87,88]

For example, a phase III trial of 916 patients[17] with advanced breast tumors and an unknown HER2 status treated with first-line endocrine therapy showed superiority of letrozole over tamoxifen in terms of TTP (9.4 months versus 6.0 months; P <0.0001) and overall response rate (ORR; 32% versus 21%; P = 0.0002).

Nevertheless, subsequent analysis of HER2 status[83] revealed that in HER2+ patients there was no significant difference between those treated with letrozole and those treated with tamoxifen in terms of ORR (17% versus 13%; P = 0.45) or clinical benefit[89] (33% versus 26%; P = 0.31), although a strong trend towards a longer duration of response with letrozole was observed (6.1 months versus 3.3 months; P = 0.0596).[83] These poor results in the HER2+ subpopulation contrast with the median TTP observed in the HER2-negative subgroup (12.2 months in letrozole-treated patients and 8.5 months in tamoxifen-treated patients).

Finally, early preliminary reports from the Breast International Group 1-98 Study (BIG 1-98) and the Arimidex or Tamoxifen Alone or in Combination (ATAC) trial, which compared tamoxifen with either letrozole or anastrozole, revealed that HER2+ status is associated with a significantly higher relapse rate, regardless of whether an AI or tamoxifen is administered.[86,88]

Taken together, these studies strongly suggest that HR+/HER2+ breast cancer may be less responsive to tamoxifen and estrogen-deprivation therapies with AIs than cancer negative for HR and HER2 expression, which could be an indication than HER2 overexpression and/or amplification results in a dominant phenotype in ER+/HER2+ tumors.

Are you still reading? There's LOTS more - that's only a portion of page 3, and he goes on to discuss Herceptin and other targeted therapies in conjunction with hormonal treatment, etc. Let me know if you have trouble with the link.

Debbie Laxague

[Hopeful]

The difference I see between AI's and Tamoxifen is that Tamoxifen is both an angonist and an antagonist for ER receptors. While it is supposed to be strictly an antagonist for bc, in Her2+ patients in particular, it has the capacity to act as an agonist, to actually promote the growth of the cancer. The GUNN study from Naples was the first to recognize this, when their data showed that ER+ Her2+ bc patients fared worse on Tamoxifen than those that received no hormonal treatment.

I have not yet read any papers that intimate that AI's have a similar result. I think this is most likely because they work by removing ER rather than manipulating it.

Hopeful

[schoolteacher]

I really appreciate all the information that everyone has supplied. I have your posts and the articles to discuss this with my doctor tomorrow.

Thanks to all.

Amelia

[wtfsanjo]

thanks for bringing up all the contradictions; i am aware of many conflicting studies. bearing that in mind, how do you (or anyone else) conceptualize the "real world" decision-making process around AIs versus Tamoxifen for Her2+ women? (full disclosure: i am a phd student at johns hopkins doing research in patient-centered decision making in chemoprevention.)

the clinical answer can't be "do neither" for various reasons. and it's neither safe nor pragmatic to put women on herceptin for the entirety of their hormone therapy. the options are limited, but a choice must be made. the glut of information that exists on the internet (published and unpublished) and beyond complicates such a decision to the point of total paralysis for a patient.

so: what is a marginally well-educated Her2+ and hormone positive patient to do? if a person can't reliably look at outcome data, should we instead be focusing solely on the risks and side effects of each particular hormone therapy to guide decisions?

[Rich66]

"they tend toward giving answers that sound more secure or absolute than they really are"

Ha! I have felt this way about things on many occassions...paired with the sense they are overworked and unable to stay as updated as they might be. I have had to correct oncs on basic info suggesting they were incorporating info from the previous patient. Scary.
Any thoughts on Fulvestrant which seems to be a different approach, obliterating the receptor itself.

[caya]

I am also triple positive, started Herceptin in June 2007 (after completing 3 x FEC, then 3 X Taxotere), started Tamoxifen in July 2007. I am still taking Tamoxifen, my onc. and one second opinion onc. have both advised me to stay on Tamox. for at least a couple of years as I already have osteopania, and Tamox. is good for the bones, AIs supposedly are not.
My onc. and I have discussed this matter of Tamox. vs. AIs, taking my ovaries out - he just does not recommend it for now, probably because many of the studies are not definitive as pointed out here.
I am investigating doing Zometa infusions, I have an appointment with a rheumatologist and will discuss all this with her as well. My onc. thinks it could be a good thing for me.
Yes, what is a triple+ girl to do? (and I am highly ER+/PR+).

all the best
caya

Hi Amelia,

May I be so forward as to suggest that you get a second opinion at a major cancer center. While others have focused on the portion of your post regarding Tamoxofin, I am more concerned about your statement that you might stop Herceptin, although you are Stage IV. If you are currently on Herceptin and your cancer is still under control, I think it would be a big mistake to discontinue the Herceptin after only a year or on the drug. I am not sure why your onc is even talking about possibly stopping it, unless you have progression.

I would also be quite concerned about taking Tamoxifin without Herceptin, for the reasons discussed by others.

I also was diagnosed as stage IV, and I currently am on Herceptin, Zoladex, and Femara, as well as Zometa.

Good luck!

Jill

[AlaskaAngel]

Hi,

To add to the decision-making process in regard to the real world...

What about the HR-positive premeno HER2 patients who:

1) missed out on trastuzumab (by virtue of being diagnosed and treated before it was available as adjuvant therapy)

2) might be able to access a pill form of treatment, but are economically or logistically unable to access an IV form

They may not be commonly accessing the internet or this forum, but they also are part of the picture. Due to the concern about not taking tamoxifen without Herceptin, they are are particularly at risk, aren't they?

My "feeling" (not scientific) is that docs are groomed to offer a pill as a solution for diseases, and the patients pressure them for something to use as a reassurance, and psychologically it makes docs feel like they are doing something and allows them to play the all-knowing role of a hero who has "done all he can", and so they avoid dealing with specific splinter groups like HER2's any differently for the most part than general bc as much as possible partly out of convenience. Habits formed are hard to break. Thus the continuing physician endorsement of tamoxifen for HER2's continues.

At the same time, these wise men give zero emphasis at patient visits to the importance of balancing fats, or to promoting exercise, or to encouraging weight loss, or to avoiding the foods that are created through the use of supplemental hormones and pesticides. I feel their net credibility is rather limited.

AlaskaAngel

[Hopeful]

New information on line today about tamoxifen posted in the articles forum: http://her2support.org/vbulletin/sho...eferrerid=1173

Hopeful

[schoolteacher]

I really appreciate all the information about Tamoxifen and Herceptin. Some of you posted last night after I left school, so I was unable to read your post until this afternoon.

He gave me the prescription today for the Tamoxifen. I do know at this point if I take the tamoxifen, I will definitely be taking the Herceptin with it. He told me I can stay on the Herceptin after February if I want to.

I also asked him about having my ovaries out like Caya did, and he said, "He did not know if he would recommend doing this at this point." My estrogen level was 50 three weeks ago, and I do not understand why it is still at this level. I have not had a period in over three years. I am not overweight, and I walk some. I have started eating some foods with soy in them, and I wonder if this is affecting my estrogen level.

He did do an Elisa test to check the Her2 today. The last one was 11.9, so I am praying that it is still in the normal range.

I am reading the latest article that Hoepful has posted.

I am wondering if you can be tested for the being deficit in E-cadherin (absencee of good cell-cell adhesion)?

I have thought about getting him to do a phone consultation with Dr. Slamon to see what he thinks.

Amelia

Please stay on the Herceptin, if you are still stable on it!! I wonder why your doctor doesn't recommend that you stay on it, rather than just saying that you "may" stay on it. Although I do much more than my fair share of researching, I expect my oncologist to provide her recommendations for treatment and the bases for these recommendations rather than just offering choices.

Take care,