What to do about Zometa??

Let-It-Be · February 2011

I don't know what to do? My 3rd infusion is due end of Feb.

I was pre-meno at diagnosis. My onc. basically said I can do it if I like, but there's no benefit as a result of this dread Azure trial. Is anyone else continuing who is pre-menopausal?

My thoughts are that this is just one trial...what if it is beneficial?

I'm inclined to continue, but would like to know what others are doing?

Christine

KerryMac · February 2011

I'm due #4 in March...I am seeing my Onc beforehand, so I will see what her opinion is. I too am inclined to continue, at the very least for my bones. I think if she says that it is up to me, I might keep on it, I am assuming Norvatis will still do the infusion...?? (they withdrew their FDA approval for early-stage)

I also have that nagging thought, this is just one study - what if it really is beneficial for me??

Let-It-Be · February 2011

Hey Kerry! I'm glad you pitched in your thoughts on this dilemma. I had a really bad day my last appt. when a substitute onc told me of the "azzure" trial. Since she spelled it wrong I had trouble googling. I just called my onc's office and they are like bricks. I talk only to the assistant. They offer no opinion.

My Access nurse called last night that's what got me going. If she's on the ball, assuming Novartis is still carrying on. I just had the blood work booked with the assistant.

Ouch they withdrew FDA approval for early stage. That royally sucks!

One thing, it is a low dose. I think I am going to keep at it.

chinablue · February 2011

I am quitting! I have read all about it, discussed it with my onclolgist and checked with two other doctors.

clariceak · February 2011

I need it for my bones, so not much of a dilemna for me. I am curious to hear what other oncs have to say about it. There is a part of me that still hopes it can be beneficial, although I was in peri-menopause when I was dxed.

Let-It-Be · February 2011

Interesting. Now I truly don't know what to do...

Kerry, do share what your onc thinks. Sherri why was your onc so against it?

Can it really hurt us? arghhh. Damn Azure results!

kim40 · February 2011

I just had my infusion #3 on the 4th of January. I'm still on the fence for the next one. I agree with Kerry, what if it is benefical to me?

KerryMac · February 2011

I'm seeing my Onc March 3rd, so I will let you know her input....

kimber3006 · February 2011

I went ahead with mine at the end of December. I'm still pre-menopausal and getting Eligard (like Lupron) injections. I didn't see anything in the Azure trial that directly applied to me, but I would think that due to the shots physically I'd be more likely to be classified with the 5 years post-menopausal group, for whom a benefit was still seen. Who knows? I wanted to err on the side of caution while they sort it all out.

everyminute · February 2011

I am still getting it. Next infusion is in April.

My onc was never big on the trial but got the insurance to cover it as a "preventative" for osteporosis since I got a hysterectomy in Dec 09. So my onc let me have it every 6 months for two years and told me no more after that. I wanted at least 3 years, she said no. I even sent her a bunch of research (pre azure results).

Ironically she sent me for a dexa scan and after 2 years on tamoxifen (easy on bones) and zometa ("bone builder") - I come back as osteopenia and osteoporosis) SO I get to continue on Zometa because of that.

But I still believe that it is only one study and that more will come of it. I have to - it keeps me sane.

1Athena1 · February 2011

I went ahead and got the Zometa a few days after the study was publicized. My onc's reaction was to shrug his shoulders, which has been my reaction after the initial shock.

I read the Azure trial results carefully and they do not directly contradict the Austrian study. The study subjects have important differences. We can say that, based on these two studies, the evidence supporting Zometa is mixed, favoring women in menopause for more than five years, BUT early stage premenopausal women who did not do chemo but did take Tamoxifen found some benefit too. Both studies were well designed. It is comparing apples to oranges. See previous discussion:

http://community.breastcancer.org/forum/108/topic/761791?page=2#post_2154378

(Sorry - using Google chrome)

Welcome to the world of cancer treatment research findings, where everything is a "maybe" and yesses become nos in a heartbeat. I changed my signature when the Azure study came out.

AgentMo · February 2011

Actually, the biggest difference between Azure and Austria is that premenopausal women where chemically sent into menopause in Austria. That fits well with the Azure fact that postmenopausal women benefitted from Zometa. So my take is as long as you are postmenopausal however induced it is well worth to have Zometa. It is not doing you any harm anyway, so the only thing that can happen is that it actually prevents your cancer.

KerryMac · February 2011

Actually, that is my thinking too - removing my Ovaries has hopefully put my Estrogen levels to that of someone well into menopause....and all the women on the Austrian trial had Lupron too, if I am not mistaken. So I am thinking (hoping) that I would (or at the very least could) still benefit. 30% is nothing to sneeze at.

voraciousreader · February 2011

This appears on the Breastcancer.org website. The first is a press release from the 2010 San Antonio Breast Symposium where the Azure study was presented. The second article is Breastcancer.org's spin on the Azure and Austrian study.

Press Release:

SAN ANTONIO (MedPage Today) -- Women with stage II/III breast cancer derived no survival benefit when the bisphosphonate zoledronic acid (Zometa) was added to adjuvant chemotherapy and hormonal therapy, results of a large multicenter study showed.

Disease-free survival (DFS), overall survival, and recurrence rates did not differ significantly between patients who received the bisphosphonate and those who did not.

A prespecified subgroup analysis showed significant interaction between treatment and menopausal status, Robert Coleman, MD, said here at the San Antonio Breast Cancer Symposium. Postmenopausal patients had a 29% reduction in the mortality hazard when treated with zoledronic acid, whereas premenopausal patients did not benefit.

"A highly significant heterogeneity of effect by menopausal status was seen, with improved DFS and overall survival in those more than five years post-menopause," Coleman, of the University of Sheffield in England, said at a news briefing.

"Adjuvant bisphosphonate efficacy may be dependent on a low estrogen concentration within the bone microenvironment."

Updated results of another study of adjuvant zoledronic acid showed a 32% improvement in DFS in premenopausal patients with early-stage breast cancer, treated with adjuvant hormonal therapy after surgery.

Comparison of patient populations from the two studies showed substantial differences that might have accounted for the different results.

Coleman reported findings from the Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE) trial, the largest-ever study of adjuvant bisphosphonate therapy in breast cancer.

The primary objective of the study was to determine whether the bisphosphonate would reduce breast cancer patients' risk of recurrence. The rationale for the study came from preclinical evidence that the agents may affect the microenvironment that permits cancer cell growth.

Investigators at 174 centers in England enrolled 3,360 patients with stage II/III breast cancer. All patients had surgery, adjuvant chemotherapy, and/or adjuvant hormonal therapy and were randomized to either zoledronic acid or placebo.

The primary endpoint was disease-free survival, determined after 940 qualifying events. Secondary endpoints included invasive DFS, overall survival, and bone metastasis-free survival.

After a median follow-up of five years, the two treatment groups had virtually identical DFS and invasive DFS, as both outcomes were associated with hazard ratios of 0.98.

Additionally, 243 deaths had occurred in the zoledronic acid arm compared with 276 in the control arm, resulting in a trend favoring the bisphosphonate (HR 0.85, P=0.07).

A prespecified analysis of DFS by menopausal status showed distinctly different results in pre- and postmenopausal patients (P=0.001 for heterogeneity).

The DFS hazard was increased in women who were premenopausal or menopausal for less than five years. The hazard was decreased in postmenopausal women.

Analysis of survival by menopausal status showed no difference in survival among premenopausal patients (HR 1.01) but a statistically significant reduction in the hazard for postmenopausal women (HR 0.71, P=0.017).

Commenting on the results, Sharon Giordano, MD, of the University of Texas MD Anderson Cancer Center in Houston, said the outcome difference by menopausal status is intriguing but not definitive.

"Routine adjuvant use of zoledronic acid to prevent recurrence is not indicated," said Giordano.

"Bisphosphonates continue to have an important role in treating bone loss among women with breast cancer," she added.

The results differed substantially from those of the Austrian Breast Cancer Study Group (ABCSG) XII trial, which showed a 36% improvement in the hazard for DFS after 48 months (N Engl J Med 2009; 360: 679-691). After an additional 14 months of follow-up, adjuvant endocrine therapy plus zoledronic acid maintained a significant advantage over endocrine therapy alone, Michael Gnant, MD, of Medical University of Vienna, reported at the news briefing.

That trial involved 1,808 premenopausal women with stage I/II breast cancer. Following surgery, the patients were randomized to adjuvant hormonal therapy alone or with zoledronic acid. The primary endpoint was DFS.

After a median follow-up of 62 months, 76 qualifying events had occurred in the zoledronic acid arm compared with 119 events in the patients randomized to endocrine therapy alone. The difference translated into a 32% reduction in the hazard in favor of zoledronic acid (HR 0.68, P=0.008).

Analysis of overall survival demonstrated a trend in favor of the zoledronic acid arm (HR 0.67, P=0.143).

"Adding zoledronic acid to endocrine therapy for three years produced durable disease-free survival benefits and a strong trend towards improved overall survival," said Gnant.

"Zoledronic acid's anticancer benefits are consistent with the 'seed and soil' hypothesis. Bisphosphonates may modify the bone marrow microenvironment and thereby contribute to the disease-free survival results seen in and outside of bone."

"Combining zoledronic acid with adjuvant endocrine therapy should be considered for premenopausal women with early-stage endocrine-responsive breast cancer," Gnant added.

The studies were supported by Novartis.

Coleman disclosed relationships with Novartis and Amgen.

Gnant disclosed a relationship with Novartis.

Giordano had no disclosures.

Primary source: San Antonio Breast Cancer Symposium Source reference: Coleman RE, et al "Adjuvant treatment with zoledronic acid in stage II/III breast cancer. The AZURE Trial (BIG 01/04)" SABCS 2010; Abstract P5-11-02

Breastcancer.org's website discussion of the results:

SABCS: Bone Drug Fails to Stop Breast Cancer

Zometa (chemical name: zoledronic acid) is used to strengthen bones and lower the risk of fractures or other bone complications in women diagnosed with metastatic breast cancer that has spread to the bones. Earlier studies suggested that Zometa also might help stop breast cancer from spreading to the bones by making it harder for breast cancer cells to grow in bones.

Two studies are reviewed here. They both wanted to see if Zometa could reduce the risk of the cancer coming back in women diagnosed with early-stage breast cancer.

One study, called the Austrian Breast Cancer Study Group (ABCSG) XII trial, suggested that treatment with Zometa and hormonal therapy after surgery could reduce the risk of recurrence in premenopausal women diagnosed with early-stage, hormone-receptor-positive breast cancer.

The other study, called the Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE) trial, found that treatment with Zometa after surgery didn't really reduce the risk of recurrence of in premenopausal women diagnosed with early-stage breast cancer. Still, the AZURE study did suggest that Zometa might reduce the risk of recurrence in post-menopausal women.

Because of these conflicting results, doctors don't agree on whether Zometa treatment makes sense for some women to reduce the risk of recurrence of early-stage breast cancer.

In the ABCSG trial, 1,808 premenopausal women diagnosed with stage I or II hormone-receptor-positive breast cancer had surgery and then hormonal therapy to reduce recurrence risk. Half the women got Zometa with hormonal therapy and half got only hormonal therapy.

About 4 years after surgery, the women who got Zometa and hormonal therapy had a 36% improvement in disease-free survival compared to the women who got only hormonal therapy. Doctors call the time a woman lives without the cancer coming back disease-free survival. After another year of follow-up, disease-free survival was 32% better in the women who got Zometa and hormonal therapy.

Overall survival in the ABCSG trial -- the time a woman lived whether or not the cancer came back -- was 33% better in women who got Zometa and hormonal therapy. But this difference wasn't statistically significant, which means that it could have been due to chance and not because of the difference in treatments.

In the AZURE trial, 3,360 women diagnosed with stage II or III breast cancer had surgery and then hormonal therapy and/or chemotherapy to reduce the risk of recurrence. Half of the women also got Zometa and the other half did not.

About 5 years after surgery, the women who got Zometa and the women who didn't get Zometa had the same risk of recurrence overall. So Zometa didn't seem to affect disease-free survival in the AZURE trial.

Still, when the researchers looked at premenopausal and post-menopausal women as separate groups, there were different results. Post-menopausal women who got Zometa had a 29% improvement in disease-free survival compared to post-menopausal women who didn't get Zometa. But this difference wasn't statistically significant, which means that it could have been due to chance and not because of the difference in treatments. There was no difference in disease-free survival in premenopausal women, whether or not they got Zometa.

There were some important differences in these two studies, which may be why there are different results:

The women in the ABSCG trial were all premenopausal. The women in the AZURE trial were both pre- and post-menopausal.
The ABSCG trial studied only hormone-receptor-positive, stage I or II cancers. The AZURE trial included both hormone-receptor-positive and hormone-receptor-negative cancers that were stage II or III.

Because doctors aren't sure if Zometa can improve disease-free survival in women diagnosed with early-stage breast cancer, it's not routinely used for that purpose at this time.

Still, using Zometa and other bisphosphonates may make sense for post-menopausal women to strengthen bones that may be weakened by some breast cancer treatments.

Bisphosphonates used to prevent or treat osteoporosis include:

Actonel (chemical name: risedronate)
Boniva (chemical name: ibandronate)
Fosamax (chemical name: alendronate)
Reclast (chemical name: zoledronic acid -- the same active ingredient as Zometa)

Reclast is given intravenously once a year. The others are pills taken by mouth.

If you've been diagnosed with early-stage breast cancer, you may want to ask your doctor if a bisphosphonate makes sense for you. If you're a post-menopausal woman, your doctor may recommend a bisphosphonate to strengthen your bones or treat osteoporosis. Whether Zometa also can lower your risk of recurrence is unclear. If you're prescribed a bisphosphonate, know that some of them need to be taken in a specific way and all may cause serious side effects; make sure you and your doctor talk about how to take the medicine.

voraciousreader · February 2011

For the record, I'm stage 1. I was expecting my second Zometa infusion on the Monday following the Azure study announcement. I postponed my infusion while my physician, who was attending the conference, gathered more information. I am pre-menopausal and also receive Lupron which puts me in a menopausal state. Ultimately, my physician and my niece who is also an oncologist, agreed that I should continue with the Zometa. What Dr. Gnant, who led the Austrian study said, following the results of the Azure study was that he didn't see any conflict in the results. He said, now he would not only give Zometa to his 42 year old wife, but he'd also give it to his 80 something year old mother. The way my oncologist explained it to me was that as long as you were in a menopausal state, he believed the Zometa was helpful.

Let-It-Be · February 2011

voraciousreader, thank you for that review. My dilemma is, I was diagnosed at 40, I am now 42. I have not been offered lupron shots or an oomph. My onc is against both (as well as my natruopath).

I take tamoxifen, as well as I3C to reduce estrogen. My periods have become irregular and lasting 1-2 days only. They seem to be disappearing slowly.

I seem to be on that cusp of pre-meno and peri-meno. I am getting mixed advice and I don't know where I fit in. If I continue zometa, shouldn't I have my ovaries shut down? I don't understand why my onc would say do it if you like and not make a better recommendation? Is it because they simply don't know, and perhaps I could still be benefitting even though I am still menstruating? Ugh! It seems like all the Austian women had their ovaries shut down.

Should I address this option of ovary oblation for better zometa results?

Is anyone still taking zometa who has not had lupron shots or and oomph?

I feel like I've left out a major component!

lago · February 2011

My onc was going to put me on it prior to the San Antonio conference. I am slightly osteopenic and will be going on Anastrozole soon. I was peri menopausal prior to chemo. Never got my period on chemo so my onc believes (and me too) that I am done.

So no zometa or any bisphosphonates unless my bones get worse. Will be tested in a year. My internist is monitoring this now.

voraciousreader · February 2011

Let it be - Just today, over at the Johns Hopkins Breast Center's Ask The Expert addresses the question you ask and Lillie Shockney gives the answer regarding adding Lupron:

Replied	JHU's Breast Center Reply
Premenopausal 54 year old woman on tamoxifen and have added monthly injections of Lupron. I know Arimidex is slightly more beneficial in postmenopausal women, but in my case, where I am premenopausal (or was before I started Lupron 5 months ago), is there any reason that I should switch to Armidex? In other words is Arimidex more effective than Tamoxifen in premenopausal women with ovarian suppression via Lupron? Plan in my case is to remain on Tamoxifen/Lupron for two years until I will be in natural menopause and then switch to Arimidex for 5 years. Just wondering if there's any benefit in switching to Arimidex sooner while on Lupron for ovarian suppression. Thank you.
2/5/2011	We don't know the answer to your question yet and that is the basis of several trials. In fact we are not even sure adding lupron to tamoxifen is more effective though biologically it makes sense. All of these questions are being addressed, but for now, no definitive data. Hang in there!

voraciousreader · February 2011

The takeaway message from Shockney's reply is that ovarian suppression is still being studied. Perhaps you wish to discuss it further with your physician or get a second opinion. My physician is a proponent of ovarian suppression with either tamoxifen or an AI. There is no right or wrong answer right now. I'm grade 1 and have a "favorable" subtype of breast cancer and think I'm being over treated. I agreed to the Lupron AND Zometa unless I got side effects. So far, I have a new uterine polyp, since my others were removed shortly before being diagnosed with the breast cancer and I have a fibroid. I've been going for 6 month check ups and so far, everything is "stable." If you check with some other posts here on breastcancer.org, you'll see many different opinions. Some women discontinued Lupron because of the side effects, while others breezed through oopherectimies.

All of these treatments have potential side effects and benefits. If you're looking for the correct approach, I would have to say, until the results of the trials are known about ovarian suppression, the answer is elusive. However, until then, you really have to go with your gut with which oncologist's opinion you trust the most. Remember, we can only make a decision based on the best available information at the time. No reason why you can't be reconsidering adding Lupron.

Good luck. My prayers and thoughts are with you.

Latte · February 2011

I've also been trying to decide what to do - I haven't had zometa yet as I am still finishing up with rads and then have an ooph scheduled (I am BRCA1+). Before Azure was out, my onc said she didn't think zometa was a great idea, but she would support me if i wanted to take it. but after azure came out, she was against it. i still have a couple of months to decide what to do (I need to finish up with active tx and also get my wisdom teeth out first).

Let-It-Be · February 2011

Thanks everyone for your input. I will make a call on Monday to my onc and bring up lupron or further ovary suppression.

It is all a crapshoot and my gut says it can't hurt to do it...

KerryMac · February 2011

Christine, it is standard of care in Toronto-area hospitals to give ovarian suppression for Stage 3. I am a bit surprised actually that they didn't recommend it for you.

My Onc originally said Lupron and Tamox. I was the one who asked about an ooph, but she jumped on it - no one ever tried to tell me it wasn't necessary. I know that there is no evidence blah blah blah, but in my gut it felt right, and I can honestly say I have not regretted it for a second.

Let-It-Be · February 2011

Thanks Kerry, now I'm really wondering what has been skipped over in my treatment (!)

I'll call her Monday for more information and at least demand why she's against lupron/ooph?? I followed what you did and when you had an ooph, but I guess I've been in denial not wanting more surgery...
$hit, time to wake up and really start asking questions!!!

KerryMac · February 2011

It is so strange that there doesn't seem to be any concensus on this. I know Kim has had a huge fight trying to get her ovaries removed, she can't find anyone in Halifax who will do it for her. It really makes me wonder. Every other type of treatment is more or less the same for everyone - surgery/chemo/rads, but then there seems to be 1000 different opinions on what to do with the hormonals.

The fact is I really don't know if there is any benefit having the ovaries out or not, but I feel better for doing it. So, if it is something that would make you rest a bit easier, i would really piush for it. You could even try Lupron for a bit, its not so "final". BTW the surgery really was not bad at all.

kim40 · February 2011

Kerry is right. I have been fighting tooth and nail to have them removed, but no one will touch me with a ten foot pole. Letters have been written from my GP to all the gynos in Halifax, but nothing. They all said no. I just recently received a name of a gyno that is 4 hours away from where I live. I had my GP send a referral to him. I haven't heard back yet, but I am keeping my fingers crossed. If I don't hear anything by the end of March, then I'm going to Toronto. I'm already planning a vacation up that way this summer, so if I can get my ovaries out at the same time, then I will. I just don't understand why the standard of care is so different from one place to the next. I am doing the ovarian suppression in the meantime, but come on, a needle every three months for the next five years! Drug companies love me!!!

Let-It-Be · February 2011

Hey Kim, at least you were offered Lupron! I called my onc today, of course, had to leave a message and no reply yet. I know she is against an ooph, but I don't exactly remember why...I was in a daze at the time and was just relieved not to have more surgery.

I think Lupron was up in the air like zometa, with the "you can do it if you like.." !!?

arghhhh!!

kim40 · February 2011

My oncologist didn't want to give the Zoladex. I basically had to go in there and stomp my feet and demand that I wanted it! He originally told me that because I was young (41), he just wanted to me to go on Tamoxifin. I felt that wasn't enough for me. I wanted more. I did a lot of research and seeing how I couldn't get my ovaries out, this was the next best thing.

I don't get it why the standard of care, especially for Stage 3, is so different from one province to the next, or from one city to the next. It rots my socks!

Beverly11 · February 2011

The medical system flip/flops constantly. When I was going through treatment, I was trying to get approval for zometa and was prepared to fight the system/do whatever I had to do to get the drug. My oncologist was not very interested in zometa at one point and then completely changed over a 3 week period. I am seeing him next week and have an infusion as well. I am on a trial for 3 years. It is one trial. I want to stay on it. Helps keep me sane too.

Marion · February 2011

Hello Let-it-be,

I was part of the Zometa clinical trial.

After I found out about the Azure trial results, I talked to the research nurse and my onc. and decided to drop out. My onc did not really give me any advice on whether I should quit or not. He thinks I've already done more than enough to avoid recurrence.

I dropped out and so far I do not regret it. I was on the trial for 11 months total. The research study actually paid for a bone scan after I dropped out and still said they want to continue following me.

Let-It-Be · February 2011

Hey Beverly, did your onc advise lupron shots or an ooph? Have you done either of these?

I left my really long messages and now have an appt. to discuss my concerns on the 22nd. In the meantime, I did bloodwork today for going ahead. Interesting though, Novartis faxed my onc's office with a note saying "this patient has withdrawn from treatment". Which I didn't do...

What to do about Zometa??

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