Really scared please help

[ConcernedStu]

Hello, a loved one was diagnosed with locally advanced, possibly inflammatory breast cancer last march (IIIB er+ pr- Her2+). She had had stage one er+pr+ her2- bc dx in late 2007.This new cancer diagnoses came just after 5 years of Femara finished. She completed neoadjuvant ACTH, Mrm, and rads. Here's the problem I have: Ok so because a new primary formed the onc felt that the AI was ineffective. Due to this she decided to put her on tamoxifen, as it has a different mechanism of action than AIs. I thought this made sense. So she's been on tamoxifen and herceptin since completing all neoadjuvant chemo (since November). I thought nothing of this, but there are 1 or 2 studies saying tamoxifen and herceptin may not work well together (they may actually make the cancer more aggressive, but there are only one or two pre clinical studies of this out there). We are getting a second opinion within a moth, but by that point the year of herceptin is over 50% done. So is there anyone out here who have been on both at the same time and done well? A second less pressing question I have is that she received herceptin every 3 weeks with taxotere, not weekly like some others. Anyone else had herceptin every 3 weeks with neoadjuvant chemo? But please, if you were on tamoxifen and herceptin at the same time, let me hear you.


Adding this now: She is also pr- and tamoxifen was only found to reduce recurrence considerably in er+ and pr- cancer, while only having slight positive effects on er+ pr-. This second opinion is at a really good hospital, but I'm worried about the fact that if the second opinion onc disagrees and changes it to an AI, this 5 or 6 month period on tamoxifen will have really negative consequences, despite no really noticeable differences appearing until after a year or so. Someone please tell me I'm worrying too much lol.

[Aussie Girl]

Dear Concernedstu,

Very sorry to hear your loved one is having another encounter with breast cancer.

The combination of Herceptin and Tamoxifen is OK as far I can see on a quick literature search. They appear to be synergistic - they enhance the other's effect. Below in a link to a prior thread on this site.

http://www.breastcancer.org/treatment/hormonal

The 2013 European Society of Medical Oncology guidelines indicate the two can be used together safely. It also depends on the medical condition of your loved one. Her oncologist will have taken this into consideration. The Taxotere is the drug with the hardest side effects but has strong effects on breast cancer.

Some people on the forum are having Perjeta added to Taxotere and Herceptin, and some have carbiplatin too (TCH-P regimen). Perjeta has been available since October in the USA but is not easily available in some other countries. I would definitely ask about getting it.

I have the impression that many of them are doing the treatment 3 weekly for neoadjuvant, but hopefully they'll pick up this thread and provide an answer for you. Some of the ladies with Stage 4 may be able to add their experience.

Your loved one is lucky to have you looking out for her.

Wishing you both the best

Aussie Girl

[ConcernedStu]

Thanks Aussie Girl, she's already completed the neoadjuvant chemo though, so I don't know if there's a reason to ask about perjeta. Do the The 2013 European Society of Medical Oncology guidelines say that tamoxifen and herceptin are okay to be taken adjuvantly together (maybe you could post the site link?) From your post, it makes it seem like you think she's still on chemo, but she did finish it already (and boy was taxotere tough lol) She's currently only on herceptin as a monotherapy for a year and tamoxifen that's it. I'm not sure if the stage 4 ladies could help me as much only because they may be on a different protocol than she is since she's only stage 3. Thanks for your reply and maybe posting that link, hopefully others chime in.

[Aussie Girl]

First two links are example of in vitro data:


http://www.ncbi.nlm.nih.gov/pubmed/14977844

http://jme.endocrinology-journals.or.../41/5/367.full

Third link with key info about Tamoxifen and Herceptin
http://www.obgyn.net/breast-health/s...-breast-cancer

Trastuzumab Plus Hormones
Estrogen receptor (ER) biochemistry is complex due to multiple ligand/receptor species, interactions with signal transduction pathways, and interactions with transcriptional co-activators and co-repressors. Patients who are both ER+ and HER2 overexpressors may respond less well to tamoxifen, and the time to progression is shortened.17 Combined receptor blockade with antiestrogens and trastuzumab is a rational intervention approach, and a phase II trial of tamoxifen plus trastuzumab as first-line therapy for ER+ metastatic breast cancer is in progress. A similar comparative trial including the aromatase inhibitor anastrozole and the combination of letrozole plus trastuzumab in tamoxifen-resistant HER2 and ER+ and/or PR+ breast cancer is also planned.

Fourth Link is ESMO
http://annonc.oxfordjournals.org/con...nc.mdt284.full

In general, chemotherapy should not be used concomitantly with ET [II, D] [62]. Trastuzumab may routinely be combined with non-anthracycline-based chemotherapy and ET [I, A]; concomitant use with anthracyclines is not routinely recommended outside of clinical trials, although may be considered in selected patients treated in experienced centres. For most patients, the use of a sequential anthracycline-based followed by taxane-trastuzumab- based regimen is the preferred choice. RT may be delivered safely during trastuzumab, ET and non-anthracycline-based chemotherapy [III, B].

I hope that info helps. I would still ask about Perjeta, and other drugs such as Tykerb, Kadcyla. It won't hurt to ask because her disease is quite locally advanced. It is worth getting to know a little about the weapons that may be called on later, so to speak.

The senior members on the site who are often Stage 3b to stage 4 have the best understanding of the chemo regimens. I've only joined the crew in June 2013, so I am a relative newbie.

Cheers

Aussie Girl

[ConcernedStu]

I'm not sure how active this forum is, but I'll bump this thread. On the breastcancer.org triple positive forum, there's been people on both at the same time in the non metastatic setting, anyone here? Thanks

[Coux92]

I'm triple positive, finished chemo (TCH) in Oct. Rad in Dec. doing solo Herceptin now and started tamoxifen in Jan.... Oh dear God, I hope they are safe to take together! I like aussiegirls take on things.
Best wishes.

[Debbie L.]

Argg, I just wrote a long reply and there was an error when I submitted it. It was probably too long, anyway (smile).

First of all, does it help to know that premenopausal women with ER+ HER2+ cancer routinely take Tamoxifen adjuvantly (unless they remove or suppress their ovaries)?

Second of all, I think your doc's conclusion that the issue was that the AI "didn't work" because it didn't prevent the second primary could be argued. Perhaps the addition of Herceptin TO the AI, rather than necessarily a switch to Tamoxifen, would make just as much sense, especially if you're feeling an AI is important.

If you're in the US, it might be a good time for a real (as opposed to online forum, smile) second (3rd, 4th) opinion, from an NCI-designated Comprehensive Cancer Center.

My take on this (just an opinion, and not an expert one, either) is that much of the discussion about HER2+'ivity and Tamoxifen comes from the early days when they were just beginning to tease out some of the peculiarities of HER2+ cancer behavior. They saw that ER+ HER2+ cancer tended to be less responsive to endocrine therapy -- and at that time, endocrine tx was, by default, Tamoxifen. By the time the AIs were coming to the forefront, so was Herceptin, and we now know that Herceptin (or some anti-HER2 agent) improves response to endocrine therapy. Probably any endocrine therapy. Most of the negative stuff about Tamoxifen and HER2 doesn't seem relevant today, as it's without Herceptin, and it's often Tamoxifen vs. nothing rather than Tamoxifen vs an AI (plus Herceptin) -- which is what we really want to know.

I see differing amounts of enthusiasm from the experts about the small improvements in efficacy that AIs seem to offer in most studies (generic use of AIs, not specific to HER2+). Some say it's not enough to make a decision on and one should go with what's best tolerated or most appropriate. Others say that for those at high risk of recurrence, even a small improvement in benefit is important and so AIs are a strong first choice, even going to the point of rendering someone artificially postmenopausal specifically so they can take an AI (an approach I don't think we have much evidence for).

Debbie Laxague

[Debbie L.]

Sorry, in trying to remember what I'd said in the post that I lost, I forgot one of the most important parts. Are you sure you found evidence that it's Herceptin and Tamoxifen that may be a bad idea? Or is it HER2+ and Tamoxifen that was getting a bad rap?

Debbie again

[ConcernedStu]

Debbie, there were one or two preclinical trials done on labs showing tamoxifen and Herceptin together may have a negative affect, but this has not been proven in actual trials at all. You said you often see premenopausal people on tamoxifen when her2+, but are they also on their year of herceptin when on tamoxifen (have you ever seen this?) Adding this now (also put it in original post): She is also pr- and tamoxifen was only found to reduce recurrence considerably in er+ and pr- cancer, while only having slight positive effects on er+ pr-. This second opinion is at a really good hospital, but I'm worried about the fact that if the second opinion onc disagrees and changes it to an AI, this 5 or 6 month period on tamoxifen will have really negative consequences, despite no really noticeable differences appearing until after a year or so. Someone please tell me I'm worrying too much lol. By the way do people often get 3rd and 4th opinions? I'm pretty sure this second opinion is all I will need, but the fact that it is a month away is why I'm worrying so much in the mean time. I think I am overworrying, but this 5 or 6 months shouldn't make a big difference in the grand scheme of things right?

[Debbie L.]

You're worrying too much. (friendly smile, we ALL worry too much, and you asked us to tell you that, right?)

>>You said you often see premenopausal people on tamoxifen when her2+, but are they also on their year of herceptin when on tamoxifen (have you ever seen this?)

Yes, all the time. I think that's exactly standard of care. Premenopausal women who have adjuvant or neoadjuvant standard-of-care chemo/Herceptin go on to receive a year of Herceptin and if ER+, Tamoxifen. There are some who will have their ovaries removed or suppress ovarian function -- and some of those will also take Tamoxifen while others will use an AI. You could reference the NCCN guidelines on that (I will do that eventually but don't have time right now).

I'm glad you're getting another opinion because although it's possible the new opinion may "prefer" an AI, I'm almost certain they will reassure you that the Tamoxifen is also a fine choice.

Debbie Laxague

[Debbie L.]

NCCN endocrine tx guidelines, which are linked from the HER2+ tx ones:

Hmm, 'can't seem to link directly to, nor copy/paste from, the actual guidelines. If you go here: http://www.nccn.org/professionals/ph...nes.asp#breast

And click on the guidelines link (not the one for patients, but the first one), and then in the table of contents choose "BINV5" under adjuvant therapy, it should take you to the HER2+ page, which again has an option to link to the "adjuvant endocrine therapy" BINV-J page. Where again no distinction is made among the available endocrine therapies, as regards HER2+ disease.

I think you have to attest to being a medical professional, to enter this part of the guidelines. But I don't think there are any website police currently working to control this "problem" of fraudulent access.

Debbie L.

[ConcernedStu]

Update: I messaged 2 MD Anderson oncs, and they both said Herceptin and Tamoxifen is a very common combo for er+. The fact that the cancer was pr- means it may be less effective, but the mda oncs didn't even say that even though I mentioned that the cancer was er+ pr- her2+. My main worry was that tamoxifen and Herceptin could have a negative effect on the cancer, which it can't. Whew!

[katmaloo]

I read a study that said HER2 cancers did not always do well with tamoxifen, but that this negative interaction was actually mitigated by herceptin--so the herceptin was a good thing. I asked my oncologist about this, since you continue tamoxifen for several years after you stop the herceptin, she said she had seen the studies, but that this problem has not been seen outside of the research setting. Basically, she said to stop worrying. I haven't, but I thought I'd stop worrying until I stopped the herceptin…I hope your concern is also unfounded; I haven't run across anything to contraindicate herceptin and tamoxifen…it seems pretty standard.

[Laurel]

Hey there, Concerned!

Welcome to our merry band of good folks here! Sorry you had to join, but now that you have please stick around and ask all the questions you like. I am triple positive (er, pr, & Her2) and took Tamoxifen for several months in conjunction with my Herceptin. Once confirmed to be in menopause I switched and did 3 years of Femara, so 2 years of Tamoxifen, and 3 of an A.I. for a total of 5 years. In October with my annual visit, it was suggested that I continue on Tamoxifen for another 5 years as long as I tolerate it well. I had tendon problems with the Femara.

[conomyself]

In January I spoke to a top notch breast cancer only oncologist, my second opinion specialist.

I am on Herceptin and Perjeta and it is keeping me stable. I have been avoiding starting Tamoxifen even though it is standard of care just because I was worried I would not like the side effects.

She urged me to start Tamoxifen. She said in her experience all of the stage 4 patients she has had who have gone more than 10 years have been on Herceptin and an anti-hormonal.

Based on this visit, and another last year to a major cancer center where the onc told me to start Tamoxifen (I can be stubborn), I started last week. So far so good.

Rachael