Zometa news out of San Antonio....

Cookiegal... Hmmmm.... Not sure if when they were randomized if the women who weren't given the ZOMETA were receiving anything. All it says was that they were randomized. It wasn't a blinded test so I assume if they were randomly chosen NOT to receive the Zometa, then they just didn't get it and were spared a mock infusion.



I would like to know if they broke out the data of which women had surgical ovarian suppression and if that mattered. It speaks to Athena and my question about how to measure a complete response to estrogen suppression. Could those younger women who had their ovaries removed have a better response?

voraciousreader --- I looked but haven't found anything in the way of research as to Zometa and ILC.  I would like to know if ILC makes a difference because my onc suggested Zometa as a way to address the bone deterioration I've experienced while on anastrozole.  I balked because of some looming dental issues but if Zometa would also be beneficial in reducing recurrence risk I would want to consider it.

voraciousreader -- I already know what my dentist thinks of the idea.  She is strongly opposed to bisphosphonates under any circumstances, not just mine.  I backburnered a possible implant until I'm done with cancer treatment (in the middle of radiation right now) so that's the main issue.  Thanks for your advice.

Sue -- Thanks.  I took HRT also but it doesn't seem to have helped avoid bone loss (although my onc thinks I might be in even worse shape if I hadn't been on HRT).  I didn't do chemo so I am interested in other ways to reduce recurrence risk (well, aren't we all).  I hope the Zometa works for you.   

The number of women over age 40 was 1,390. The total was 1,800 +. That means only about 400 women were younger than 40. Yes, it is correct to say that overall there is benefit because the over 40 way outnumber the under 40. But if the subset analysis says there is no significant benefit then there's no way around that. Anyway it's hard to reach a definitive conclusion with 400 people. And I don't think it's by accident that they have way more over 40 women. We are not just talking about diarrhea but metastasis as a possible side effect (based on Coleman).

Thank you for posting this. I met with my onc in Sept and he sited a study that contradicted this and took me off Zometa (I had 3 left). I am 51 and seem to fit the criteria for the benefit. I just sent him a note requesting that decision be reversed. I'll let you know what he says.

Those of you on Zometa, how often do you get treatment? My onc is willing to give it to me but he mentioned administering it twice a year for three years. Does that sound right? Thanks.

Hi posy1: Yes, that was my schedule, every 6 months for 3 years.

When I developed osteopenia on Femara I was given Zometa twice per year for 3 years. This past August was my last dose. There was a research article (I'll see if I can find it) that reversing osteopenia while on Zometa was more effective in patients whose Vitamin D was not deficient.  From what I recall of the article Vitamin D made the Zometa show better bone results - reverse bone loss. 

This might tickle your brain:

The Lancet Oncology, Volume 12, Issue 11,  Pages 991 - 992, October 2011 <Previous Article|Next Article>doi:10.1016/S1470-2045(11)70252-2Cite or Link Using DOI

Adjuvant zoledronic acid for breast cancer: mechanism of action?

Original TextVolker Kunzmann a, Martin Wilhelm bThe ABCSG-12 trial1 reported a sustained disease-free survival (DFS) benefit of endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer. Taken together with two other trials of zoledronic acid in premenopausal and postmenopausal patients with breast cancer (webappendix p 1),2, 3 this trial raises important questions about which patients might benefit most from adjuvant treatment.By contrast with the positive outcomes of ABCSG-12 and the ZO-FAST study,3 investigators reported no DFS benefit with zoledronic acid in the total AZURE trial population.2 On the basis of post-hoc subgroup analyses, the ABCSG-12 investigators proposed that zoledronic acid might be most effective in a low-oestrogenic environment, suggesting that the anticancer effect of bisphosphonates is mediated by age-dependent or oestrogen-dependent changes to the bone microenvironment. However, although subgroup analyses in adjuvant trials seem to support an anticancer effect of zoledronic acid in a low oestrogenic environment (by either natural menopause or ovarian suppression), preclinical data supporting a greater anticancer effect of zoledronic acid in a low oestrogenic environment are lacking.Preclinical studies suggest that nitrogen-containing bisphosphonates such as zoledronic acid might have many anticancer properties including direct induction of tumour-cell apoptosis, synergy with cytotoxic chemotherapy, inhibition of angiogenesis or tumour-cell invasion, modification of the cancer-cell microenvironment, effects on disseminated tumour cells, and induction of immunomodulatory effects by selective stimulation of γδ T cells. By contrast with these proposed effects in vitro, only the unique immunomodulatory effect of nitrogen-containing bisphosphonates by selective stimulation of phosphoantigen-reactive γδ T cells has been repeatedly validated in vivo with standard dosing schedules.4-6 Benzaid and colleagues7 provide further evidence for an immunosurveillance function of bisphosphonate-activated γδ T cells against human breast cancer cells by showing that only oestrogen-receptor (ER)-positive and HER2-negative breast cancer cells producing high concentrations of intracellular phosphoantigen after zoledronic acid treatment are sensitive to an immune-mediated attack by γδ T cells.In view of these data, we propose a different explanation for the conflicting results from the adjuvant trials. Because previous chemotherapy greatly affects the reactivity of bisphosphonate-activated γδ T cells,5 the large proportion of women receiving neoadjuvant or adjuvant chemotherapy in the AZURE trial (95% vs 6% in the ABCSG-12 trial) might also affect DFS by suppressing γδ T-cell-mediated immunomodulatory effects (webappendix p 1). This assumption is strengthened by the fewer acute phase reactions-as assessed by the incidence of pyrexia-which are γδ T-cell-mediated,4 in the AZURE trial than in the ABCSG-12 trial (2·2% vs 10%). Additionally, the proportion of ER-positive breast cancers-which are more sensitive to γδ T-cell-mediated cytotoxicity than are ER-negative breast cancers-was smaller in the AZURE trial than in the ABCSG-12 trial (78% vs 94%). The significant DFS and overall survival improvements in the AZURE subset of women who had been postmenopausal for longer than 5 years at study entry (aged >60 years) might be explained by less frequent (or less intensive) previous chemotherapy, or a higher incidence of ER-positive tumours, although this issue has not been reported in detail. On the basis of the interpretation that adjuvant zoledronic acid might be most effective in chemotherapy-naive ER-positive breast cancer, the non-detectable DFS benefit in the ABCSG-12 subset of women younger than 40 years (23% of the overall ABCSG-12 population) might not only be explained by incomplete oestrogen deprivation, but also by more women receiving neoadjuvant chemotherapy and fewer tumours with high ER expression. A reanalysis of completed and ongoing (eg, SWOG 0307) adjuvant trials stratified by previous chemotherapy, rate of acute phase reactions, and ER expression in different age groups would be necessary to clearly define the mechanism of action behind the effects of zoledronic acid, and might help to define the patient subsets who will benefit most.We declare that we have no conflicts of interest.       

I am surprised that you are having a hard time getting it since you have broken bones, have ovaries out etc.  I have an HMO (kaiser) and had NO trouble at all--I just had to get a bone scan that said "oesteopenia with increased risk of fractures due to young menopausal status (my ovaries removed also) and aromatose inhibitor (femara) use."  I expected a bigger fight because o fthe HMO thing, but nope, I get zometa every 6 months,but I think I only get 2 years on it, not 3 like I see others writing about.

Also, Onc did advise me to take extra vitamin D while on zometa.  Glad I am after reading the paper above!

Posy1 - I'm getting Zometa every 3 months for 2 years. My Onc. said that is a low dose but seems high to me compared to what others are getting. And I'm low risk, too. Hmmm...

Is anyone doing the Monthy injections? I was told that is an option for me if I wanted but his office is over an hour away so every 3 months for the infusion is more convenient.

Seashelley:  I am following the  protocol  used in the Austrian study.(Zo-fast, Dr Gnant)  Infusions every 6 months for 3 years. There is a clinical trial running that doses more frequently. You are low risk.  You could ask your doctor why you are getting it more often.

Sherryc:  The worst side effect from Zometa is osteonecrosis of the jaw (Very nasty, indeed)  It is rare, however, and not experienced by women in the recent trial results presented at San Antonio.  Have your dentist examine your teeth for any potentialproblems before starting.  Some women experience fever, muscle aches or bone pain after infusion. Best to have your infusion over 30 minutes and drink lots of water. (my experience was no SE's). 

Hey Ladies

I just came from my onc appt and he advised gave me a choice of either coming off it or staying on it but extending it from three years to five.  I chose the five year option.  If it is going to help a little percentage than I'll take it.

My new onc, who just got out of med school, will not let me go on Zometa until I have a recurrence. Those were her words. She said that bone density and bone scans were normal, even though I just broke two bones recently. I finish Femara in August. She said do not continue after that. I thought since I was stage 3C that the drs would throw whatever they could at me so I wouldn't get a recurrence, not wait for it to happen. I am changing oncs and hospitals, I am going to drs at Dr. Weiss' hospital. I've just decided.....