Early stage BC and Zometa

Kathy, thanks for the information.  I am going to ask my oncologist.  I am just curious why it was never brought up to me.  I hope you are feeling better today.  Susan

Is anyone concerned that Zometa will make their bones brittle?

So glad you are feeling better Kathylev!

Future infusions, if you have the same SE as me, will be almost nothing--a little tired and maybe a headache the next day, but not at all like the first infusion.

My rheumetologist (sp?) also  thought there would be no issues with only two infusion a year for three years. 

Does anyone know about in the zometa study above, what does early initiation vs delayed mean?  Does that mean if you didn't get zometa right after chemo that you're not going to see those lower recurrence rates?  Or do they mean that delayed is by several years?  I'm a year out from chemo and still waiting to start zometa.  That's why I'm wondering.

Wow, that is interesting re: biopsy vs. pathology results.

According to my biopsy, I was 90 percent er+ but my pathology only had me at 10 percent.

Which one is more reliable?? I assumed it was the pathology, since that is what my bs and onc went with, but maybe not?

Yes, that is true--the pathology is usually the more reliable one as lago said above.  The biopsy only samples the tumor.  (Well, Actually the pathology only samples the biopsy as well, but it is much more concise and systematic cuts, rather than random.)  When I went for my 2nd opinion at UCLA, the onc there also agreed with the estrogen receptor loss theory I mentioned in one of my last posts.  I asked her then how do they know if someone is truly a triple negative?  And she said that usually the difference wouldn't be that much, and in triple negs, it is usually at 0% with absolutely no estrogen receptors present, so the chances of every single one breaking off would be like winning the lottery. 

My surgery was done late on a Friday afternoon as well.  I looked at my report and it was not done till that following Monday.  Kathylev, I don't think that would account for your whole change in estrogen receptivity, as it was quite different, but maybe a little bit???  Anyways, though, both oncs I saw said that weakly positive is still treated the same as strongly positive.

I know my onc just came back from San Antonio yesterday. It will be interesting to hear what she has to say. Unfortunately I won't be seeing her at my next infusion so I will have to wait till January.

Hi,

Kathy..I go when available to the monthly BC support group at Gilda's Club. Nice group of ladies..I also go once a month to the book club. Tomorrow evening I will go to the Christms party. All events are free at Gilda's Club and all are really so nice. Just curious about why you got chemo. Was it your oncotype score?I too am interested in the findings from San Antonio. No visit till March I believe.

Hugs,

Francine

I happened to be reading your discussion and it reminded me of an article I read.  It is from the College of American Pathologists where they discuss the new guidelines labs will follow beginning 2011 to be sure the ER and PR measurements are accurate and standardized.  Very interesting discussions are within the article if you don't mind plowing through it.  The people here are the leaders in the field and it's interesting to read what they say.  I'll copy some of it here.

"And, says University of Michigan oncologist Daniel Hayes, MD, another co-author of the guideline, the benefit seen from hormonal therapy seems to level off at about 30 percent to 50 percent positivity. “A patient is not more likely to benefit if her tumor has 100 percent positive cells versus 50 versus 30.” "

This is where you can read it.  Sorry I am unable to paste a link.

http://www.cap.org/

Making ER/PgR practices toe the line

Feature Story 

ABCSG-12 Shows Benefit for Zoledronic Acid in Early Breast Cancer

By: KERRI WACHTER, Internal Medicine News Digital Network

12/17/10
 | 

SAN ANTONIO - Despite the negative results overall of the AZURE trial, it may not be time to put the final nail in coffin of adjuvant zoledronic acid for the treatment of hormone-positive breast cancer.

[Zoledronic Acid Sinks as Breast Cancer Therapy in AZURE Trial]

Updated results for the ABCSG (Austrian Breast and Colorectal Cancer Study Group) Trial 12 continue to show disease-free and overall survival benefits 2 years after stopping adjuvant endocrine treatment with zoledronic acid (Zometa), according to an update presented at the annual San Antonio Breast Cancer Symposium.

The positive Austrian trial randomized 899 premenopausal women on goserelin (Zoladex) to 3 years of zoledronic acid with either tamoxifen or anastrozole (Arimidex) and 904 comparators to endocrine therapy alone (N. Engl. J. Med. 2009;360:679-91).

At a median follow-up of 62 months (2 years after treatment completion), zoledronic acid reduced the risk of disease-free survival events by 32%, compared with endocrine therapy alone (hazard ratio, 0.68; P = .008). Better disease-free survival was seen whether the women were on tamoxifen (HR, 0.67) or anastrozole (HR, 0.68). A trend toward reduced risk of death with zoledronic acid also endured (HR, 0.67; P = .09).

"We observed persistence of benefit with adjuvant zoledronic acid in the ABCSG-12 trial," said Dr. Michael Gnant, president of the ABCSG, at the press briefing where Dr. Robert Coleman reported no disease-free survival benefit overall (adjusted HR, 0.98; P = .79) from adjuvant zoledronic acid in the AZURE (Adjuvant Treatment With Zoledronic Acid in Stage II/III Breast Cancer) trial.

"Why are the ABCSG-12 results so different from the premenopausal [women] in AZURE?" asked Dr. Gnant, professor of surgery at the Medical University of Vienna. "I believe that when you look closely, there is minimal overlap in patient selection and treatment," he said.

"All of them [in the ABCSG-12 trial] were put into artificial menopause for 3 years with the use of goserelin. None of these patients had adjuvant chemotherapy. I think that's an important difference from the AZURE trial," said Dr. Gnant.

In the AZURE trial, 96% of patients had adjuvant chemotherapy, and none got ovarian function-suppression treatment. Also, in the ABCSG-12 trial, about 70% of patients had low-risk, stage I breast cancer. Patients in the AZURE trial had stage II or III breast cancer.

Patients in the ABCSG-12 trial were randomized to one of four treatment groups: 20 mg/day tamoxifen; 20 mg/day tamoxifen plus 4 mg zoledronic acid every 6 months; 1 mg/day anastrozole; or 1 mg/day anastrozole plus 4 mg zoledronic acid every 6 months. Treatment lasted for 3 years. All patients received 3.6-mg subcutaneous goserelin every 28 days.

In all, 1,803 patients were enrolled between 1999 and 2006. As of May 18, 2010, 186 disease-free survival events and 73 deaths were recorded: 45 locoregional relapse events, 100 distant relapse events (including 53 bone metastasis events), and 14 contralateral breast cancer events. Adding zoledronic acid to endocrine therapy was associated with a continued reduction in recurrences inside and outside bone.

[FDA: Bevacizumab Should No Longer Be Indicated for Breast Cancer]

Adverse events associated with zoledronic acid treatment (arthralgia, bone pain, and pyrexia) were generally mild and consistent with the established safety profile. Zoledronic acid did not increase the occurrence of serious adverse events, compared with endocrine therapy alone. Importantly, there was no significant renal toxicity and no confirmed cases of osteonecrosis of the jaw.

"I find it quite intriguing and actually reassuring that with this therapeutic intervention that lasted 3 years - just an infusion every 6 months - you can change something in the long-term outcome of these patients," said Dr. Gnant. "When we break it down according to additional preplanned subgroups, actually we see that ... adjuvant bisphosphonate treatment works in every subgroup, at least if you look at the tumor-derived parameters."

The addition of adjuvant zoledronic acid may not make much difference in patients younger than 40 years, he suggested: "It's exactly that group of patients where we cannot assume that the goserelin treatment will lead to full suppression of ovarian function and to very low estrogen levels," he said.

Among patients aged 40 years or older in ABCSG-12, however, there was a roughly 40% difference in disease-free survival, which translated into a 40% reduction in the risk of dying from breast cancer, although this did not reach statistical significance.

[Dual Anti-HER2 Blockade Called the Future of Breast Cancer Therapy]

The AZURE researchers also did extensive planned subgroup analyses. "One clearly stands out from all the others. That is the treatment effect on disease-free survival according to menopausal status," observed Dr. Coleman, a professor of medical oncology at the University of Sheffield (England). There was a clear overall survival benefit for women at least 5 years out from menopause on zoledronic acid. These women had a 29% reduction in the risk of death (P = .017).

"While obviously it's fair to say that the overall result of AZURE is a little bit disappointing, scientifically it makes perfect sense," said Dr. Gnant. "Perfect suppression - or a natural lack of estrogen - in combination with adjuvant zoledronic acid leads to significant disease-free and overall survival benefit."

To put the results in practical terms, Dr. Gnant noted that for the past 2 years, he would have put his 42-year-old wife on zoledronic acid if she developed ER-positive breast cancer, but not his 83-year-old mother. "This has changed this afternoon. Now, my 83-year-old mother would also receive zoledronic acid," he said.

The ABCSG-12 trial was sponsored by Austrian Breast & Colorectal Cancer Study Group, with support from AstraZenaca (which makes Arimedex) and Novartis Pharmaceutical (which makes Zometa). Dr. Gnant disclosed that he has significant financial relationships with several pharmaceutical companies, including Novartis.

[Women's Health Initiative: New Findings on Big-Three Cancer Rates]

The AZURE trial was sponsored by the University of Sheffield. Dr. Coleman disclosed that he receives grant support from Novartis and is a speaker for Novartis and Amgen.

Gee, I'm only "weakly" ER+ (which I'm guessing is only 5-10%) but both oncs I saw (Kaiser and UCLA) said that positive is positive--it's like being pregnant--you either are or you aren't.  Soooo....I'm on an AI and going through all these side effects (I hope not for nothing!)  My onc at Kaiser said herceptin can influence the estrogen receptivitiy and the onc at UCLA said that we just don't know what turns a cell in remission back on so we cover all the bases even when only slightly ER+. I guess again, it all goes back to, NO ONE REALLY KNOWS!  Sigh, sigh.  . .