Zometa news out of San Antonio....
Comments
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Voracious,
No, Gnant's study clearly states:
Among patients > 40 yr of age (n = 1,390) with presumed complete ovarian blockade, ZOL significantly reduced the risk of DFS events by 34% (HR = 0.66; Cox P = .014) and the risk of death by 49% (HR = 0.51; Cox P = .020); however, there were no significant DFS or OS benefits in patients <40 yr of age.
http://www.sabcs.org/PressReleases/Documents/Gnant.pdf (the details come after the press release part.)
The overall population benefitted, but when you separate out the olders and youngers, the youngers did not benefit (meaning the benefits of the olders were overwhelming the non-benefits to the youngers.)
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Beep... For ALL the women in the study the Reduced risk of recurrence was 28% and 36% reduction in death. Then the press release went on to say BUT in the OVER 40 crowd the improvement was even more significant. The press release is worded poorly.
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In other words... The results were STATISTICALLY significant for everyone... However, they "presume" that the 40 year and older women had an even better response because they think they had a more complete estrogen shutdown.
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Voracious,
The results paragraph (go to the pages that follow the press release portion) clearly states that there was no significant disease-free survival or overall survival benefits in patients under 40 years of age.
You're confusing the concept of averages. If there are 10 people, and 5 of them earn 20 percent more money this year, and 5 don't, then those 10 people will on average, earn more money this year. But when you separate them out, you see that 5 actually did not earn more money, but 5 did. Same concept here.
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I think if the under 40 crowd had no statistical benefit it would have said that in the first paragraph. That's also why they are referring to the more complete ovarian shutdown of the women over 40. The under 40 women had some benefit, but NOT significant and they surmise that the reason why the over 40 year old women did overwhelming better was due to the O/S doing a better job. I think you need to put all the pieces of the press release together because it is so poorly written.
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Argh.
In such studies, you always need to look at the details. If it says no significant benefit for women under 40, it means exactly that. "Significant" is a statistical term meaning that differences are big enough that they could not be due to chance (in other words, it is actually the treatment that is causing the benefits.)
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Also.... If you read the last paragraph the conclusion says the protocol should be given to ALL early stage ER+ women. It doesn't say just to the over 40 women..
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As far as I have been able to find, the actual data from the study has not yet been fully reported, so we don't know if there was *any* difference for the under 40s..."significant" or not.
Wish the news on Zometa were better for us younger ladies! But I still think the upside for us is that chemo is much more effective in younger women (possibly, in part, due to its endocrine effects).
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Beep... I agree we have to look closer at the details. But if you look at what we have right now... The conclusion says for women over 40.. The data is "highly" significant. The under 40 crowd are benefitting too! I believe this is positive knews for ALL ER + women!
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Btw.. I took Statistics in college. Probably the most important class that I ever took. That's why I think the press release stinks!
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Voracious,
We'll have to agree to disagree.
From this, and the other studies out there on Zometa, there's no evidence that it helps very young women with breast cancer. In fact, the AZURE trial showed that premenopausal women taking zometa did *worse* than those who did not get it. And that trial was much larger (and most of the women had chemo first).
Also, in this trial, none of the women got chemo. That's pretty significant. It may be that OS + tam or AI + zometa is better than OS with tam or AI but not Zometa (which is exactly the design of Gnant's study), but not better than chemo + hormonal therapy. That's an important question to address (not sure if it has been or if there are ongoing trials?)
Anyway, if I were a 30-something diagnosed with ER+ breast cancer tomorrow, depending on my nodal status, I would go with chemo + hormonals, but not zometa. The evidence just isn't there that it would help that person! Wish it would.
P.S. I took Statistics in college too.
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I too took Statistics in college...as well as Journalism...And that press release makes my head hurt. As a 30-something diagnosed with ER+ BC, at least my pre-existing condition makes Zometa a poor choice for me, or else I'd have to figure out somehow whether there would be a benefit, which still seems totally unclear to me.
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I would love to hear our oncs weigh in on this one. But I won't see mine for awhile. If anyone else is going to, please let us know what they say!
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Beeb.... Gnant published this a few weeks ago.... Notice how he says "subset analysis....showed GREATER benefits of zolendronic acid in patients over 40...."
Zoledronic Acid in the Treatment of Early-Stage Breast Cancer: Is There a Final Verdict?
Authors
Gnant M.Journal
Curr Oncol Rep. 2011 Nov 24. [Epub ahead of print]
Affiliation
Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria, michael.gnant@meduniwien.ac.at.
Abstract
Breast cancer, which preferentially metastasizes to bone, is the most common malignancy among women worldwide and is a leading cause of death. Clinical data from large, phase 3 trials (ie, ABCSG-12, ZO-FAST, and AZURE) demonstrate significantly improved disease-free survival with zoledronic acid in some patient populations with early breast cancer. Although the interim results from the AZURE trial did not show a disease-free survival benefit with zoledronic acid in the overall patient population, subset analyses showed that zoledronic acid significantly improved disease-free survival in women with established postmenopausal status at baseline. Similarly, subset analyses of the ABCSG-12 trial showed greater benefits from zoledronic acid in patients over 40 years of age who theoretically would have achieved more complete ovarian suppression. Together, these data support a potential role for zoledronic acid beyond bone health in breast cancer and suggest that the endocrine environment may influence the anticancer potential of zoledronic acid.
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Beeb, I have an appointment with my MO on Monday, and I will definitely ask for his take.
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Voracious,
"Greater" is only a comparative term, it doesn't really tell us anything about how the under-40 women did. They might have done awful and the over 40s had a "greater" benefit. They might have showed no change and the over 40s had a "greater" benefit. They might have showed a non-significant trend towards a benefit, and the over 40s had an even "greater" benefit. We just don't have the data.
I'd be guessing it's the last one...that the under-40s showed a numerical benefit, but not so large as to be "statistically significant."
Maybe with more time, it will be clear that Zometa helps the youngest women too. The evidence just doesn't seem to be there yet. And I would reallly like to know how the regimen studied by Gnant compares head-to-head with chemo+hormonal, since chemo is pretty much the standard-of-care for women under 40.
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For anyone reeeeeaaaaalllllyyyy interested in this topic, here's a podcast where the head of the AZURE trial, and Gnant, and a few other experts discuss their seemingly conflicting results.
The downloadable powerpoint slides are really interesting too:
Upshot: Zometa seems to prevent some BC recurrences and deaths in very low estrogen environments, which are not achievable by very young women (unless they have an ooph, maybe?). Secondly, it isn't clear that Zometa adds any benefit for women who've had chemotherapy.
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Beeb....We saw that video following last year's symposium....Thanks for posting it again. Here's a new video from Gnant:
http://www.youtube.com/watch?v=kFXsaNVv250Despite not having more data for us to parse, I did read one more thing that struck my attention. Gnant wrote (somewhere) that the strongest determining factor of Zometa effectiveness was AGE and not tumor size or other characteristics. He wrote that there is a powerful correlation between AGE and recurrence with women over 40 getting the best results.
Since we don't have the data which specifically breaks down the below 40 age bracket, we just have the first few paragraphs of the press release to go by that AVERAGES the entire group. Hopefully, when we see more data, we will know EXACTLY what benefit the under 40 group received. We shall see if there was a "statistically significant" benefit for women under 40. My guess is that the data IS "stastically significant" for the under 40 women, perhaps in the single digits.... We shall see... Stay tuned... AND....
1Athena1 and I have been having a discussion about why Gnant and Coleman got their differing results and Beeb...you touch on it. You mention that they believe that younger women who have oophs might have more "complete" ovarian suppression and that might help them achieve a VERY LOW estrogen environment. 1Athena1 and I believe, since LAST year, that they need to come up with a better way of defining and a measurement for a "very low" estrogen environment. That way, it might be able to determine who would benefit the most from the Zometa.
With regard to Zometa and chemo...Gnant was NOT looking at that population at all. In fact, I applaud his study design because we know that many ER+ sisters are OVER treated with chemo and for women with excellent prognostics, including low Oncotype DX scores, many doctors are looking for other means of protecting them from future recurrence. That's why his study and the SOFT study that looks at ovarian suppression as opposed to chemo are good studies. That's also why I think it's worth repeating what Dr. Adam Brufsky said about Gnant's work:
"The problem with studies of this nature is that people do so well for so long
with the standard of care. You need to wait a long time, beyond 5 years, to
actually see a difference in relapse rate. Actually, these curves started to
grow apart, so the data are nothing new. But what is surprising to everybody, is
that only with 3 years of therapy, there is now a survival benefit. This has
been shown in many trials. I have a hard time understanding why people don't
accept the fact that bisphosphonates have an antitumor effect. The problem is
that they can't explain it, so they don't want to believe it. There are several
trials going in this direction. There are more data to support this than there
are to support dose-dense chemotherapy, which is commonly used. If there is as
much data to support this treatment, which is not as toxic, we ought to be using
it in postmenopausal women."- Adam Brufsky, MD, PhD
HemOnc Today
Editorial Board member -
http://www.youtube.com/watch?v=twlFII2YtBo
Above is a recent video of Coleman discussing AZURE.
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No, Voracious, we shall not see....we already know. We have more than the press release, we have the abstract from Gnant's study. It follows the press release on the same document. Have you seen it? The abstract is written by the investigators, not by a press person. In the abstract, Gnant writes:
"there were no significant DFS or OS benefits in patients <40 yr of age"
What more can I say?
The link is here:
http://www.sabcs.org/PressReleases/Documents/Gnant.pdf
At last year's symposium, Gnant presented the same evidence in his slides regarding the lack of benefit for the under-40s.
The consensus seems to be that Zometa only adds benefit in a very low estrogen environment, which is unacheivable for very young women (under 40) on ovarian suppression.
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Thanks for the additional videos, Voracious.
What concerns me about the AZURE update video is that Coleman reports that Zometa actually had an *adverse* effect on younger women. Meaning they actually did worse in terms of disease-free and overall survival if they got Zometa.
Also, as an aside, I've heard that women who hope to become pregnant should be cautious about taking bisphosphonates, because it can affect the developing bones of a fetus, even years after you take it.
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beeb...The issue with Coleman's AZURE group is that the younger women may NOT have had complete ovarian suppression....Some may have had ovarian suppression due to the chemo, so that may have contributed to the "adverse" effects.... That's why Athena and I think it is important that the researchers develop a test to determine what exactly a low estrogen environment is. Recall that in Coleman's sample population the women underwent chemo and were stages 1 through 3. Gnant's study group is COMPLETELY different. No chemo and ovarian suppression.
I am going to stand firm until I see further data because the sentence that you keep quoting from Gnant is taken OUT OF CONTEXT. I will not debate the semantics. Here's another statement by Gnant from the latest findings:
WEDNESDAY, Dec. 7 (HealthDay News) -- A drug developed to treat osteoporosis appears to boost survival in women with certain types of breast cancer, according to two new studies.
These preliminary findings regarding the bone-building drug zoledronic acid potentially give scores of women more options to battle their tumors. The studies are slated for presentation at the San Antonio Breast Cancer Symposium this week.
The first looked at premenopausal women with estrogen receptor-positive breast cancer receiving either the bone drug plus hormone therapy or a placebo plus hormone therapy for three years.
Earlier data from this study were encouraging, and this update -- 84 months after the trial's start -- provides further evidence of improved disease-free survival and recurrence rates among women receiving zoledronic acid. The drug is known by the brand names Reclast and Zometa.
The new research shows that women receiving zoledronic acid had a 28 percent reduced risk for recurrence and a 36 percent reduced risk for dying.
Women over the age of 40 received the most benefit, the researchers said.
"In general, the overall survival is excellent, which demonstrates that treating these patients without adjuvant chemotherapy is a very good approach," said study author Dr. Michael Gnant, a professor of surgery at the Medical University of Vienna, Austria. He said the study received academic and not pharmaceutical funding.
Many women were still seeing the benefit four and five years after their treatment stopped. "This means we've changed something in the beginning in terms of the disease," Gnant said."
Beeb....As you can see from Gnant's statement he singles out the women who are over 40 and receiving the most benefit. Then he goes on to say, "IN GENERAL," which I believe is referring to the entire group, "THE OVERALL SURVIVAL IS EXCELLENT...."
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© 2011 by American Society of Clinical Oncology
Can We Predict Who's at Risk for Developing Bone Metastases in Breast Cancer?Larissa A. Korde and Julie R. Gralow⇓+ Author AffiliationsUniversity of Washington School of Medicine, Seattle, WACorresponding author: Julie R. Gralow, MD, University of Washington/Seattle Cancer Care Alliance, 825 Eastlake Avenue East, G3-630, Seattle, WA 98116, 206-288-7722 (206-288-2054); e-mail: pink@u.washington.eduBone metastases are common in patients with advanced breast cancer. Bone is the first site of distant disease in 25% to 40% of patients with metastatic breast cancer, and up to 60% to 80% of patients with recurrent breast cancer eventually show evidence of skeletal involvement.1 The process of breast cancer metastasis, including tumor cell seeding, tumor dormancy, and metastatic growth, is only partly understood. Circulating breast cancer cells have been shown to demonstrate affinity for bone and exhibit chemotactic responses to areas of bone undergoing resorption.2 Disseminated tumor cells have been reported in the bone marrow of 30% to 40% of patients with early-stage breast cancer at the time of diagnosis.3 The majority of these disseminated tumor cells die, but some are capable of micrometastatic proliferation or remain dormant, only to grow later. The development of established bone metastases involves complex, reciprocal interactions between cancer cells and the bone microenvironment, with a resultant vicious cycle of tumor cell growth and bone destruction.4 The rich supply of mitogenic factors released during bone resorption can lead to increased survival and proliferation of disseminated breast cancer cells.5 It is possible that elevated rates of bone remodeling during early breast cancer growth and dissemination could increase the risk of bone metastases, and that adjuvant antiosteoclast therapy, through reduction of bone turnover and interference with tumor cell-bone microenvironment interaction, could decrease cancer recurrence. Based in part on this hypothesis, several large, randomized clinical trials of adjuvant osteoclast-targeted therapies have been undertaken in early-stage breast cancer, with conflicting results reported to date and no definitive conclusion as to which patients might benefit from such a strategy.6-11 A better understanding of the interaction between breast cancer, bone turnover, and the skeletal microenvironment could provide useful insights in determining which patients and which cancers are at increased risk for developing bone metastasis, and in tailoring therapy to prevent or reduce the occurrence of bone metastases. Several studies have explored patient and primary tumor factors associated with bone-specific distant recurrence in breast cancer. Disseminated tumor cells found in the bone marrow of patients with early-stage breast cancer without other clinically detectable metastatic disease appear to have prognostic importance, but these patients do not appear to be at higher risk of future bone recurrence versus all sites of relapse.3,12-15 The International Breast Cancer Study Group analyzed recurrence data in over 6,000 patients treated in seven adjuvant breast cancer trials to identify patients at high risk for bone metastases.16 Factors associated with higher rates of bone recurrence included higher numbers of involved lymph nodes, larger tumor size, and tumor estrogen receptor (ER) expression. In a study of the distribution of organ site-specific relapse within the intrinsic breast cancer molecular subtypes, an association was seen between the ER-positive luminal subtypes and bone as a site of relapse.17 Interestingly, when bone relapse occurred in the human epidermal growth factor receptor 2 subtype, the genes upregulated were entirely different from those in luminal tumors, suggesting that metastasis to bone occurs via different processes in different intrinsic subtypes. In addition to ER, many genes and proteins associated with the primary tumor have been studied as predictors of bone metastasis, including parathyroid hormone-related protein and its receptor, osteopontin, ostenectin, several interleukins including IL-8, receptor activator of nuclear factor kappa beta (RANK) and RANK ligand, C-X-C chemokine receptor type 4, bone sialoprotein, tumor cell surface integrins, and Fas/Fas-ligand.16-32 Recently, several groups have published microarray multigene expression profiles that are predictive for bone metastases in breast cancer.33-35 We are clearly gaining an increased understanding of factors associated with osteotropic metastases in early-stage breast cancer, but there is still no validated, reliable marker or assay to predict an elevated risk of future bone metastasis. Biochemical markers of bone turnover, released as a result of normal bone maintenance and repair as well as malignant bone involvement, can provide insight into ongoing rates of bone metabolism.36 Bone markers have the potential for use in assessing overall skeletal health, osteoporotic fracture risk, and monitoring response to antiresorptive therapies in managing osteoporosis.37 In patients with cancer, markers of bone turnover have been evaluated in screening for development of bone metastases, predicting risk of skeletal-related events and survival in patients with bone metastases, and monitoring response to antiosteoclast therapy.38-41 Several serum and urine tests for bone resorption and formation have been used to evaluate and follow bone remodeling activity. Most markers of bone metabolism have diurnal, and in some cases seasonal, variations. Many are significantly influenced by sex, age, and renal function, and most bone resorption markers are increased in postmenopausal women with osteopenia or osteoporosis.42Based on preclinical studies demonstrating that increased bone resorption creates an environment that promotes growth of breast cancer cells, and that substances released from resorbing bone have a chemotactic effect on these tumor cells, it has been hypothesized that circulating markers of bone turnover may help identify patients with early-stage breast cancer at increased risk for development of bone metastasis.2,5 In an early study of this association, Diel et al43 showed a relationship between high preoperative serum levels of bone sialoprotein and the future development of bone metastases. In the article that accompanies this editorial, Lipton et al44 ask whether it is possible to identify a subset of patients with breast cancer with a predilection to bone as a first site of distant recurrence by using a serum assay for the carboxyterminal peptide of type I collagen (CTx), a marker of bone turnover released during bone resorption. The authors examined the association between CTx and bone as a first site of relapse on the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) adjuvant phase III MA.14 study. Six hundred sixty-seven postmenopausal patients with stage I/II, predominantly ER-positive breast cancer enrolled on the MA.14 study between 1996 and 2000, and were randomly assigned to adjuvant tamoxifen alone or in combination with octreotide. The study reported no benefit in event-free or recurrence-free survival for the addition of octreotide to tamoxifen.45 In order to explore whether increased bone resorption creates an environment that promotes development of breast cancer bone metastases, serum CTx concentrations before initiation of endocrine therapy were determined for 621 of 667 patients. Ninety-two patients (15%) were found to have elevated bone resorption, as determined by high serum CTx levels. At 8 years of follow-up, there were a total of 123 relapses (approximately 20% of patients), of which 19 (3.1% of patients, 15% of recurrences) were within the bone only, and 47 (7.5%) were within bone plus other sites. The investigators report that higher serum CTx predicted for bone-only relapse, but not for bone plus other sites of recurrence, or relapse in general. While this study is interesting and hypothesis-generating, the strength of the findings is limited by several factors. The number of patients with bone-only relapse was quite small, and the number of patients with elevated serum CTx was much larger, indicating that many patients with elevated CTx did not relapse in the bone. Because the NCIC MA.14 study did not require evaluation of site of recurrence in a systematic way at the time of relapse (by mandating bone scans in all relapsed patients, for example), the strength of the classification of recurrence sites is limited. For the group categorized as having relapse in "bone plus other sites," it's not clear how many had bone-predominant disease (with perhaps minimal additional distant or locoregional disease) and how many had visceral-dominant disease (with minor bone involvement). These are likely different groups of patients. Elevated bone resorption at the time of study entry, as reflected in baseline serum CTx levels, could have been due to normal physiologic forces associated with bone loss, such as osteoporosis, or alternatively it could have been due to early bone metastases. Evaluation for metastatic disease at the time of trial enrollment included a chest x-ray and routine blood work, and did not include a specific bone metastasis work-up. Osteoporosis and bone density were not specifically assessed at baseline or while on study, and data on bisphosphonate use, which was permitted at enrollment and during follow-up and which could have affected CTx level, was not collected by the study. If validated in future studies, the exciting possibility suggested by Lipton et al44 that elevated bone turnover markers can predict which patients with early-stage cancer are at increased risk for bone-specific relapse could lead to the selective addition of antiresorptive therapies to the adjuvant breast cancer treatment plan. Bisphosphonates and RANK ligand inhibitors have been shown to reduce both normal physiologic bone loss in osteoporotic patients, and cancer treatment-related bone loss in postmenopausal patients with breast cancer receiving aromatase inhibitor therapy and premenopausal women undergoing ovarian suppression or experiencing chemotherapy-induced premature ovarian failure.46-55 In patients with breast cancer with established bone metastases, these antiosteoclast therapies can reduce complications of malignant bone involvement, including the incidence of skeletal-related events.56-61 In early-stage breast cancer, conflicting data from several randomized clinical trials suggest that adjuvant bisphosphonate treatment may reduce recurrence risk, at least in a subset of patients.6-11 Recent reports suggest that adjuvant bisphosphonate benefit may be restricted to women with the lowest estrogen state, those who are most likely to have the highest rates of ongoing physiologic bone resorption at the time of their breast cancer diagnosis and treatment. The promising, yet somewhat contradictory, results of three older adjuvant clodronate studies suggested that bisphosphonates might impact disease recurrence, but were inconclusive.6-8 More recent results from several large adjuvant trials of zoledronic acid have also been conflicting. The Austrian Breast Cancer Study Group (ABCSG) -12 study investigated the adjuvant use of zoledronic acid in premenopausal patients with ER-positive breast cancer receiving ovarian suppression for 3 years in combination with either tamoxifen or anastrozole. The study reported an improvement in disease-free survival in the group receiving zoledronic acid (given every 6 months for 3 years), in addition to favorable benefits on bone mineral density.10,53 Interestingly, and somewhat contrary to the hypothesis that adjuvant bisphosphonates would preferentially reduce bone-specific metastases, the ABSCG-12 study reported decreases not only in bone but also in visceral and locoregional recurrences, as well as contralateral disease. While the primary mechanism of action of bisphosphonates is on the osteoclast, there is some evidence of direct antitumor effects of amino-bisphosphonates in laboratory models.62 A recent subgroup analysis of ABCSG-12 suggested that the disease-free survival benefit of adjuvant zoledronic acid appeared to be driven by patients who were older than 40 years of age. Although all patients got ovarian suppression in this study, patients older than 40 years at baseline likely achieved more substantial estrogen deprivation, which would be expected to be associated with more significant rates of bone loss.63 The Zometa-Femara Adjuvant Synergy Trials (Z-FAST, ZO-FAST, and EZO-FAST) enrolled postmenopausal women with ER-positive tumors receiving letrozole, an aromatase inhibitor known to increase bone loss due to its antiestrogen effects, and randomized to immediate versus delayed zoledronic acid. A combined analysis showed lower recurrence rates in the group receiving upfront zoledronic acid.11 The large, phase III Adjuvant Treatment with Zoledronic Acid in Stage II/III Breast Cancer (AZURE) study randomly assigned women with stage II or III breast cancer receiving standard adjuvant therapy to zoledronic acid or not for 5 years, given at a more intensive dosing schedule than that used in ABSCG-12.9 For the overall study population there was no significant difference in disease-free or overall survival in the two study arms. In a planned subset analysis, women who were older than 60 years of age or known to be postmenopausal for longer than 5 years had a significant improvement in overall survival with the addition of zoledronic acid. This supports the hypothesis that adjuvant bisphosphonates might be most effective at reducing breast cancer recurrence in a low estrogen, high bone resorptive environment. We await the results of several additional large, randomized trials of adjuvant bisphosphonates and the RANK ligand inhibitor, denosumab. The Southwest Oncology Group (SWOG) S0307 trial, comparing adjuvant clodronate, ibandronate, and zoledronic acid in patients with early-stage breast cancer, collected baseline serum and primary tumor blocks for correlative studies aimed at defining who is at risk for developing bone metastases and most likely to benefit from adjuvant bisphosphonate therapy. This study, and others soon to report, will provide additional information to help us better understand the relationship between breast cancer cells, the bone microenvironment, and antiosteoclast therapy. The hypothesis and data presented by Lipton et al44 are intriguing. While it is unlikely that a single marker will hold all the answers, this study highlights the possibility of moving toward a more tailored approach to predicting metastatic behavior. Data presented in this study do not conclusively tell us that we should be using bone turnover markers at the time of breast cancer diagnosis to define the anticancer treatment plan. There is no question, however, that many patients with breast cancer are at increased risk of bone loss due to their age and menopausal status, as well as their anticancer therapies, leading to increased rates of osteoporosis and associated fracture. That fact, in and of itself, is reason enough to monitor and maintain the bone health of our patients with early-stage breast cancer, including assessment of bone mineral density, supplementation with adequate calcium and vitamin D, and, in selected cases, initiation of antiresorptive drug therapy.64There is complicated interplay between breast cancer cells and the bone microenvironment. Accurately teasing out which patient and tumor characteristics can be used to predict who is likely to recur in the bone, and which patients are most likely to benefit from bone-targeted therapy, will require more complex analyses. If adjuvant bisphosphonates and other antiosteoclast therapies are found to be effective in reducing bone recurrences in breast cancer, they will likely be of benefit in only a subset of patients, since the majority of women with early-stage breast cancer will not develop bone or other distant metastases and will not die of their disease. Identifying predictors of bone metastases will allow for selective use of bone-targeted therapy in patients who would benefit from them most, while avoiding the adverse effects and cost in patients unlikely to benefit. We are entering an era in which we will be increasingly tailoring therapy to individual tumor and patient characteristics. Identifying which patients and which tumors are at highest risk for bone recurrence holds great promise in the management of early-stage breast cancer. Next SectionAUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTAlthough all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.Employment or Leadership Position: None Consultant or Advisory Role: None Stock Ownership: None Honoraria: None Research Funding: Larissa A. Korde, Amgen; Julie R. Gralow, Amgen, Roche, Novartis Expert Testimony: None Other Remuneration: None Previous SectionNext SectionAUTHOR CONTRIBUTIONS
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Here's the full context of Gnant's info for women under 40:
Results: At median follow-up of 76 mo, patients receiving ZOL had a significant 27% reduction in the risk of DFS events (HR = 0.73; Cox P = .022) and a significant 41% reduction in the risk of death (HR = 0.59; Cox P = .027) vs no ZOL. Multivariate analyses showed a strong interaction between ZOL and patient age, but did not show any interactions between ZOL and ANA/TAM or any classic tumor parameter (eg, T, N, grade, ER). Among patients > 40 yr of age (n = 1,390) with presumed complete ovarian blockade, ZOL significantly reduced the risk of DFS events by 34% (HR = 0.66; Cox P = .014) and the risk of death by 49% (HR = 0.51; Cox P = .020); however, there were no significant DFS or OS benefits in patients <40 yr of age. Currently, all patients have completed 3 yr of ZOL and are in the follow-up phase with no reported cases of osteonecrosis of the jaw or renal failure. Additional analyses at a median follow-up of approximately 84 mo are planned for late 2011 and will be presented, providing additional insights into disease recurrence patterns with and without ZOL.
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Voracious,
You say "Then he goes on to say, "IN GENERAL," which I believe is referring to the entire group, "THE OVERALL SURVIVAL IS EXCELLENT....""
I agree that he is referring to the entire group, but my interpretation is that he is saying the overall survival is good for early stage patients using only hormonal treatment with or without Zometa, so maybe women in this group do not need chemo. I'd likely agree.
The question I'm getting at is simply, does Zometa help women under 40, and all the available data thus far says: No, it does not (whether they get chemo or instead only do ovarian suppression + tam or AI). Wish it were different.
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beeb...I sent you a PM.
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beeb...To answer your question, "Does Zometa help women under 40?" The answer is, "Yes...BASED ON GNANT'S STUDY...just NOT AS MUCH AS WOMEN OVER 40."
So, if you are Stage 1 or 2 and DID NOT RECEIVE CHEMO AND you are ER+ and are doing Tamoxifen or an AI, AND doing ovarian suppression and taking Zometa 2X a year for three years, you will benefit.
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Is there any research as to the benefits of Zometa for post-menopausal patients with ILC? I ask because ILC can have a different metastatic pattern.
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JSwan... That is a great question. Folks like you and I, who don't have traditional type of bc often wonder if the data applys to our specific types. At first blush, that type of data isn't usually broken down. Usually in retrospective analysis we get our answers. You might try doing a search at pubmed.org to see if there is some data. I'd be curious to know.
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I wish they had a sub set with ovaries out under 40....then we could pin down whether it is age or hormonals.
It's tricky because we really don't know how much of the chemo benefit is actually because of the hormonal impact.
At some point I wish they could have that trial as well, but I am betting a decent number of women with ovaries out may end up getting zometa for bone reasons.
I also wonder about the placebo, was it a pill or an infusion. I would be grumpy if I was getting a placebo infusion.
The studies presented back in 09 pointed to a lower risk of local disease as well as bone mets.
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- 204 Breast Cancer with Another Diagnosis or Comorbidity
- 4K DCIS (Ductal Carcinoma In Situ)
- 79 DCIS plus HER2-positive Microinvasion
- 529 Genetic Testing
- 2.2K HER2+ (Positive) Breast Cancer
- 1.5K IBC (Inflammatory Breast Cancer)
- 3.4K IDC (Invasive Ductal Carcinoma)
- 1.5K ILC (Invasive Lobular Carcinoma)
- 999 Just Diagnosed With a Recurrence or Metastasis
- 652 LCIS (Lobular Carcinoma In Situ)
- 193 Less Common Types of Breast Cancer
- 252 Male Breast Cancer
- 86 Mixed Type Breast Cancer
- 3.1K Not Diagnosed With a Recurrence or Metastases but Concerned
- 189 Palliative Therapy/Hospice Care
- 488 Second or Third Breast Cancer
- 1.2K Stage I Breast Cancer
- 313 Stage II Breast Cancer
- 3.8K Stage III Breast Cancer
- 2.5K Triple-Negative Breast Cancer
- 13.1K Day-to-Day Matters
- 132 All things COVID-19 or coronavirus
- 87 BCO Free-Cycle: Give or Trade Items Related to Breast Cancer
- 5.9K Clinical Trials, Research News, Podcasts, and Study Results
- 86 Coping with Holidays, Special Days and Anniversaries
- 828 Employment, Insurance, and Other Financial Issues
- 101 Family and Family Planning Matters
- Family Issues for Those Who Have Breast Cancer
- 26 Furry friends
- 1.8K Humor and Games
- 1.6K Mental Health: Because Cancer Doesn't Just Affect Your Breasts
- 706 Recipe Swap for Healthy Living
- 704 Recommend Your Resources
- 171 Sex & Relationship Matters
- 9 The Political Corner
- 874 Working on Your Fitness
- 4.5K Moving On & Finding Inspiration After Breast Cancer
- 394 Bonded by Breast Cancer
- 3.1K Life After Breast Cancer
- 806 Prayers and Spiritual Support
- 285 Who or What Inspires You?
- 28.7K Not Diagnosed But Concerned
- 1K Benign Breast Conditions
- 2.3K High Risk for Breast Cancer
- 18K Not Diagnosed But Worried
- 7.4K Waiting for Test Results
- 603 Site News and Announcements
- 560 Comments, Suggestions, Feature Requests
- 39 Mod Announcements, Breastcancer.org News, Blog Entries, Podcasts
- 4 Survey, Interview and Participant Requests: Need your Help!
- 61.9K Tests, Treatments & Side Effects
- 586 Alternative Medicine
- 255 Bone Health and Bone Loss
- 11.4K Breast Reconstruction
- 7.9K Chemotherapy - Before, During, and After
- 2.7K Complementary and Holistic Medicine and Treatment
- 775 Diagnosed and Waiting for Test Results
- 7.8K Hormonal Therapy - Before, During, and After
- 50 Immunotherapy - Before, During, and After
- 7.4K Just Diagnosed
- 1.4K Living Without Reconstruction After a Mastectomy
- 5.2K Lymphedema
- 3.6K Managing Side Effects of Breast Cancer and Its Treatment
- 591 Pain
- 3.9K Radiation Therapy - Before, During, and After
- 8.4K Surgery - Before, During, and After
- 109 Welcome to Breastcancer.org
- 98 Acknowledging and honoring our Community
- 11 Info & Resources for New Patients & Members From the Team