Bisphosphonates as preventative

OzzieSue · 10-06-2008, 03:06 PM

Just came across this on OncologyStat. I'm sure I've seen threats asking about this option. Thought there might be some interested members.

A New Approach to Adjuvant Therapy for Breast Cancer

Dr. Clifford Hudis is Chief, Breast Cancer Medicine Service, Memorial-Sloan Kettering Cancer Center.

1. In your view, which development that has occurred since September 2007 could have the most significant impact on oncology in the area of breast cancer?
The development from this year that could have the biggest long-term impact on breast cancer is the observation that the bisphosphonates, widely used for treating and preventing osteoporosis, may have a role in adjuvant therapy for breast cancer.
2. What specific changes in oncology, specifically in the treatment of breast cancer, have you observed or do you foresee as a result of this development?
If the results of the Austrian Breast and Colorectal Cancer Study Group-12 trial, initially presented at the 2008 annual meeting of the American Society of Clinical Oncology (ASCO) by Dr. Michael Gnant, are confirmed by additional ongoing studies, the impact on breast cancer treatment could be profound. As was widely reported during the ASCO meeting, this randomized trial of approximately 1800 premenopausal women with stage I or II endocrine-responsive breast cancer found that the addition of zoledronic acid (Zometa) to endocrine therapy (tamoxifen or anastrozole) lowered the risk of relapse by 36% compared with endocrine therapy alone. This could mean that a large number of women who until now have been treated with direct anticancer drugs that prevent recurrence of early-stage breast cancer could, in addition, be treated with the bisphosphonates.
The reason this is so important is that the bisphosphonate drugs are relatively safe, comparatively speaking, and they have known health benefits related to osteoporosis. Now, they appear to have a direct anti−breast cancer effect. They may have anticancer effects against other tumors as well. The use of bisphosphonates as adjuvant therapy would represent a new frontier in preventing recurrence of early-stage breast cancer. Considering that breast cancer is such a common disease and is reasonably well treated in many parts of the world, the addition of bisphosphonate therapy would be an important incremental step toward improving overall outcomes.
3. Could you put this development into historical perspective for the practicing oncologist?
The treatment of breast cancer in its early stages is essentially directed at eradicating the primary tumor and any microscopic metastatic disease. These are 2 different objectives. For the first, we treat the breast with surgery and possibly radiation therapy; for the second, we treat the rest of the body with systemic therapy, which has conventionally involved chemotherapy or hormone manipulations. Recently, we have added trastuzumab for patients who are HER2 positive.
The reason that the bisphosphonate story is so interesting and potentially revolutionary is that it represents yet another separate treatment dimension. The bisphosphonates are a different class of drugs with a different purpose. After trastuzumab, this would be the next big step in breast cancer therapy, and one that is more broadly applicable than the narrowly targeted anti−HER2 approaches, which, of course, are also very important.
4. Would you sum up, in a few sentences, why you chose this development as the top story of the past year?
I chose the bisphosphonate story as a top story of the past year because it was somewhat unexpected, as we had not seen consistent prior evidence in this direction. So this really does represent a new approach to the adjuvant treatment of breast cancer. Also, bisphosphonate therapy is probably safer than many of the widely accepted, standard options already in use, and it may add another layer of protection for patients with a very common illness. For that reason, it could have a significant public health impact, and this is why I picked this development because of its potential for having a long-range impact on a common disease.
One caution, however, is that, to date, we only have the results from a single large study. Several other large trials of bisphosphonate therapy in breast cancer are nearing completion, and the results will be available soon. One of these is the phase III AZURE trial, which is assessing the addition of zoledronic acid to neoadjuvant or adjuvant chemotherapy and/or hormonal therapy in women with stage II or III breast cancer. Until the results of all of these large trials are in, it may be premature to implement adjuvant bisphosphonate therapy in regular clinical practice. As oncologists, we will be watching these developments closely.

Chelee · 10-06-2008, 11:58 PM

Sue, Your right...you have seen threads on this topic lately. It's interesting to see that Dr. Clifford Hudis of Sloan Kettering choose this as having one of the most significant impacts in the bc area since 2007.

My last two DEXA scans have not been very good which really concerns me. But three of my doctors don't want to start me on a bisphosphonate. My interest would be zometa since its shown to help prevent recurrance. I have an appointment coming up in two weeks and I plan on pushing this very issue. Maybe I'll take this article along with two others I have. Thanks Sue.

Chelee

BethC · 10-08-2008, 06:11 PM

Chelee,
I was reading your post and noticed on your signature that you're still producing estrogen after ooph! I had an ooph in May and was put on Femara but have never had any tests to confirm that my body isn't producing estrogen. Did they just test you routinely or what happened? Did you know you were producing estrogen? How would I know?

Thank you!

Beth

katcdale@yahoo.com · 10-08-2008, 11:32 PM

hi Chel...and all,

I have been in a time warp ..and it looks l am near you,CHel, with Time according to the BC. My Onc gave me some Zometa for osteopenia borderline.. But after the 4th (every 3 mos or less) Treatment I asked him to quit. Now I see that it may have helped me....BUT WATCH OUT FOR TEETH, gums....
What else did that MD say or has anyone of your ONCs mentioned exercise or what to eat as a preventative option ?

just wondering,

Kat in the delta

Chelee · 10-09-2008, 11:47 PM

Beth, I was peri-meno when dx. So after finishing chemo my onc insisted I start on an AI verse's Tamox. I wanted to make sure I was really menopausal before starting the AI so I pushed for labs. Both FSH & estradiol showed I was in "chemopause". So I started Femara.

About 3 months afterwards I was concerned because I felt like I was going to get my monthly friend back? So I requested my FSH & estradiol be checked again? When we did...it showed I was right...I was very peri-meno. So I started on zoladex monthly and it barely put me in menopause? So since I had a cyst on one ovary I requested to have it removed and have an ooph at the same time. (figuring with the ooph of course that would put me in menopause!) (NOT!) Well over a yr later labs still say peri-meno. I was checked out by two Endo's...and had a battery of tests and they can't find a reason for it. (My own research says ovarian remants syndrome?)

So then it was decided even though I had an ooph I would go back on zoladex. ARGH! But even with the ooph & zoladex my FSH & estradiol still stay peri-meno.

So regardless of the mess I've been dealing with...I would suggest you request labs to check your FSH and estradiol at least once. I see your young. The ooph probably did it's job for you so I wouldn't worry. Beth...after my ooph I never noticed any changes that one should experience with menopause. No hotflashes, dryness, nothing? That's what made me keep asking to have my labs checked. But there are a few strange things that can keep estrogen running through your body...unusal things like a 3rd ovary and as I mentioned the ovarian remants syndrome. But this is NOT the norm. I am sure your fine.

Chelee

harrie · 10-10-2008, 12:11 AM

I will be having my DEXA done tomorrow. It will be interesting to see if my osteopenia is stabilized or worsened. Have been on AI for about a yr now. Am also working with my ins co to have my DEXA covered since I need to have it done annually now that I am on Femara.
The article was intereting. Thanks for posting.

Chelee · 10-10-2008, 12:19 AM

Kat, Yes my doctors have mentioned weight bearing exercises and increasing my vitamin D3. My Endo just added 5000 IU's once per wk to my regular amount of D I take. But I'm still concerned that is not near enough. My last labs that checked my vitamin D level was low. (24). Which the lowest it should be for our reference range is 30. I've heard others on her have their doctors add 50.000 IU's. So I'm wondering why I only had 5000 iu's once per wk added? My Endo seems to think adding the vitamin D is going to help my increase my bone density. He just keeps telling me he's working on it while by bones get worse! I just requested a new endo when I went to my primary doc's office this wk. This endo is NOT doing enough for me.

My last two DEXA scans shows a significant decrease in bone density. The most recent scan was pretty worrisome. I am aware of all the possible side affects and especially the osteonecrosis of the jaw. If nothing else I thought I could have a few infusions the first year and see how that goes? Just doing nothing is worrying me.

Kat, you said the zometa may of helped. Did you have a recent DEXA to compare with your first baseline dexa? Are you going to go back on it? And did you have any problems with it after your infusions?

Chelee

10-10-2008, 11:17 AM

HI,
The Zometa's 1st infusion make me have terrrible flulike symptoms....I did not know about this and neither did my onc. It lasted maybe 4 days.. WIth each infusion it got better... but my gums began to swell and my teeth got loose...so I know my body the best.. so I asked him to quit... I went for a 2nd opinion.... and that onc gives it at most 2x/yr unless it is in your bones..then,,,, you'd get it more often... hang in there....

what are you taking now??

I think the best any one of us can do id to EXERCISE and eat fruit and vegetables daily.. with some added vitamins... but do not get all vitamins from pills. I try to buy Organic whenever I can ...I add juice plus+ from Dr. Kim Dalzell. Look her up and tell her I told you to call her... she doesn't mind... RSVP ....gotta run.. I am 3hrs late for an apt.... Kat in the delta.

ps... not much change but not worse on bone density..... It may have helped me not get it in my BONES!! so you decide..... let me know.. kat

harrie · 10-11-2008, 11:43 PM

Unregistered:
Now you don't have to answer this if you don't want to, but may I ask if you had any pre-existing periodontal conditions prior to starting the Zometa?

Henny · 10-14-2008, 07:49 PM

I saw my onc today for a followup. When I asked, he recommended Zometa and gave me the abstract from Dr Gnant. Since I "only" have osteopenia and not osteoporosis and don't have bone mets my insurance is unlikely to cover it.
The cost is $2000/dose-twice a year for 3 years. Think I might raid my 401k for Zometa money (401k's are on my mind right now)

Henny

sassy · 10-14-2008, 08:23 PM

Henny,

My insurance paid when osteopenia was evident, so maybe yours will also. (401K--don't sell, buy low)

Henny · 10-14-2008, 08:34 PM

I'll check with the ins tomorrow. And I am really going to leave my 401k alone-I have a lot of retiring to do-and a lot of places to see
H

harrie · 10-14-2008, 11:56 PM

Good idea Henny,...follow thru with your ins co and fight if you have to. Right now is really best to leave that 401K alone.

BethC · 10-15-2008, 01:22 AM

Henny,
I wanted to let you know that it took about 5 months and lots and lots of phone calls, faxing, etc. from my doctor's office to finally get my insurance to cover it. However, they finally said that it did not have to be preapproved and they reserved the right to review any charges. So that was really lame and I may still end up getting billed for it, but I will appeal it if that happens. Also, Novartis has a patient help program, which I contacted, and they try to get insurance to pay for the medicine. If they won't, they may help pay for the medicine. I got nowhere until I contacted Novartis and then they started faxing paperwork, which seemed to get the ball rolling.

Good luck!
Beth

suzan w · 10-17-2008, 10:05 AM

I was dx'd with osteoporosis in 1994. Took hormone replacements ( gut feeling said "NO NO NO") for more than 10 years...stopped 2 months before breast cancer diagnosis. Also took Fosomax for those 10 years. So, did the hormone replacements cause the BC? Did Fosomax add anything to the picture? My osteoporosis did not improve while on the Fosomax. It actually got a little worse! My doc at the time kept saying that without the hormone replacements and Fosomax, that my osteop. would get MUCH worse...although my scores were -3+ and worse. One doc even told me that she was shocked that I didn't crumble before her very eyes! Anyhow...just my 2 cents worth! I have been on daily injections of Forteo for 9 months (2 year plan) and my last Dexa showed improvement!!!

harrie · 10-17-2008, 10:37 AM

Suzan, what is Forteo?

RobinP · 10-17-2008, 11:03 AM

Harry Forteo is a long term acting injectable bisphophonate used for severe bone loss. I hope you folks that are using bisphosphonates are getting at least 800mg of vitamin D3 and 1500 mg of calcuim citrate per day. If you are not, you may be making bone density worse.

Bisphosphonates have long been thought to help prevent bone mets by decreasing bone turn-over. I took them for four years, but have since been on a drug holiday, as there are safety issues beyond four years of use concerning osteonecrosis of the jaw and concerns over the extreme long half life of the drug, where it is thought to terminally be in the bone and not broken down and lost.

Now I wonder if bisphosphonates really help prevent her2+ bc mets since it usually spread to the central nervous system as a first spread. Becky, any comments on this, that is how often does her2 bc spread to the bones?

Henny · 10-18-2008, 09:43 AM

Does Her2 go to the CNS first in most cases?
I will be starting Zometa in the next week. The insurance co said it was covered as an infused medication by the onc but the onc office said that just means they can decide whether or not to pay later. I decided to go ahead and deal with the ins co when I need to.
Sounds like flu-like symptoms and gum discomfort are the main side effects. Anything else?
Thanks everyone for your input and encouragement

Henny

Henny · 11-02-2008, 08:04 PM

Well, I had the first zometa dose for prevention last week. I was expecting just a few aches and pains that ibuprofen would take care of but it was a bit nastier than that and I had to resort to Vicodin at night. One week of whining every 6 months is pretty darn easy after the last year and a half and certainly nothing compared to what some of us have to put up with.
Hope you all had an exciting Halloween

Henny

dlaxague · 11-02-2008, 08:29 PM

Hi, I think that the studies that are reporting zoledronic acid results are on ERPR+ premenopausal women with ovarian suppression. And it's impressive - I'm thinking that it was 34% relative reduction of recurrence, and not just bone recurrence. I don't think they were HER2+. This doesn't mean that there wouldn't be the same effect in other categories of breast cancer - just that we don't have that information, yet.

Okay, it's 36%. And no mention of HER2.

http://www.medscape.com/viewarticle/575394

Here's what Eric Winer said in the above article
:
"Breast cancer expert Eric Winer, MD, from Harvard Medical School, in Boston, Massachusetts, who moderated the press conference at which the results were presented, agreed that zoledronic acid should now be considered an appropriate therapy. He emphasized, however, that the results apply only to the patient population in this trial — premenopausal women with endocrine-responsive early breast cancer who have undergone ovarian suppression with goserelin and who are receiving endocrine treatment. This is the standard of care (with tamoxifen) in about one third of premenopausal breast cancer patients, he explained to journalists. Another third are treated with endocrine therapy without goserelin, and the last third are treated with chemotherapy and tamoxifen."