The study reviewed here found that Zometa (chemical name: zoledronic acid) didn't destroy or slow the growth of breast cancer cells when it was given before surgery to post-menopausal women diagnosed with early-stage, hormone-receptor-positive breast cancer. These results were reported at the 2009 San Antonio Breast Cancer Symposium.
Zometa is a medicine used to strengthen bones in women diagnosed with breast cancer that has spread to the bone. Zometa is given intravenously and can reduce bone pain and the risk of fractures. Zometa is a bisphosphonate. Bisphosphonates are most commonly used to strengthen bones and to treat osteoporosis in post-menopausal women who haven't been diagnosed with cancer, but are sometimes used to strengthen bones in women diagnosed with breast cancer.
Besides improving bone health, other research has shown that Zometa can:
Based on these results, researchers wanted to know if treatment with Zometa before breast cancer surgery would kill breast cancer cells or slow the cancer's growth. Doctors call treatment given before surgery neoadjuvant therapy.
In this study, 110 post-menopausal women diagnosed with early-stage, hormone-receptor-positive breast cancer got one of three treatments before surgery:
After the cancer tumors were removed, the researchers looked at the cancer cells for any signs that the cells were dying (called apoptosis) or weakened from the treatment given before surgery. Cell weakening was measured by tests called Ki67, progesterone receptor expression, and cell turnover index score.
The researchers compared cancer cells from women who got Zometa plus Femara or Femara alone before surgery to cells from women who got the placebo to see if the neoadjuvant treatments made a difference.
This study looked at breast cancer cells in the lab to see if Zometa was killing them or slowing their grow. Even though the study didn't seem to show any benefits from Zometa, it could be that Zometa has effects on other mechanisms in the cells that weren't measured in this study and are more positive. More research is needed to look at this possibility.
The results of studies like this -- even if they don't show a benefit -- help doctors better understand the behavior of breast cancer and give us hope for better ways to treat breast cancer. Stay tuned to Breastcancer.org for the latest news on breast cancer research that can make a difference, today or tomorrow.
SAN ANTONIO (MedPage Today) -- A preoperative dose of bone-building zoledronic acid (Zometa) did not kill breast cancer cells or halt their proliferation, British researchers found.
The same strategy using the aromatase inhibitor letrozole (Femara) reduced proliferation (indicated by its marker Ki67) by 52% with a similar benefit for cell turnover rates (both P≤0.001) in a randomized trial led by Nigel Bundred, MD, of the University Hospital of South Manchester and University of Manchester.
But zoledronic acid had no additive impact (P=0.26), Bundred reported here at the San Antonio Breast Cancer Symposium.
Recent studies have created intense interest in adjuvant use of bisphosphonates for benefits beyond osteoporosis or bone metastasis treatment, noted program committee member Peter M. Ravdin, MD, PhD, of the University of Texas Health Sciences Center in San Antonio.
At last year's SABCS meeting, zoledronic acid was reported to have a direct impact on breast cancer, shrinking tumors by at least a third and doubling pathologic complete response when added to neoadjuvant chemotherapy.
An Austrian trial reported at the American Society of Clinical Oncology (ASCO) meeting earlier that year suggested improved survival when breast cancer patients got zoledronic acid along with their adjuvant endocrine therapy.
But the new results, rather than disproving an effect outside of bone, suggest instead that the mechanism is not proliferation or apoptosis, Bundred said.
"The bottom line is what happens in patients," he told MedPage Today, and given the clinical trial findings, he's not discouraged.
"It doesn't mean there isn't an effect," he said at a press conference. "It may just be we're not picking up what it's affecting."
One possibility is macrophage activity -- a possibility Bundred said his group is in a position to rapidly study along with other potential markers now that they already have the prospectively collected tumor samples to examine.
The researchers' Let-Zol trial included 110 post menopausal women with estrogen receptor-positive, invasive breast cancer randomized to 14 days of pre-operative treatment with placebo, letrozole (2.5 mg) alone, or letrozole in combination with a single dose of zoledronic acid (4 mg) given two to four days before surgery.
The effect on apoptosis measured by absolute change in the marker activated Capase 3 was greatest with letrozole alone, followed by its combination with zoledronic acid, but neither was significantly different compared with placebo (0.4%, 0.2% and, 0.1% versus baseline).
For proliferation measured by Ki67, the absolute change from baseline was significant for letrozole alone (-8.6%, 95% CI -4.6 to -14.7) and in combination with zoledronic acid (-12.9%, 95% CI -6.9 to -17.5).
Both were significantly better than placebo's +0.8% change in Ki67 (P≤0.001) but without any difference between the letrozole arms, suggesting no added effect from the bisphosphonate.
Progesterone receptor expression -- a marker of "switch-off" of the tumor -- fell about an absolute 15% with letrozole compared with baseline, but slightly less at about 10% with addition of zoledronic acid. The placebo group also had about a 5% reduction from baseline but none of the groups differed significantly from each other.
The absolute change in Cell Turnover Index scores was -18.9% with letrozole alone, -17.7% with the combination, and +0.3% with placebo, again significant for both letrozole arms compared with placebo (P≤0.001), but not between letrozole groups.
Bundred said the negative study could only be considered exploratory.
The study was supported by Novartis, the maker of zoledronic acid. Bundred reported having consulted for AstraZeneca, Pfizer, and Novartis.
Guise reported being on the advisory board for Amgen, Novartis, Lilly, and Roche. Ravdin reported no conflicts of interest.
Primary source: San Antonio Breast Cancer Symposium Source reference: Bundred NJ, et al "Randomised Placebo Controlled Trial Studying Short Term Biological Effects of the Combination of Letrozole and Zoledronic Acid on Invasive Breast Cancer" SABCS 2009; Abstract 2009.
Breastcancer.org 7 East Lancaster Avenue, 3rd Floor Ardmore, PA 19003
Learn more about our commitment to your privacy
© 2010 Breastcancer.org - All rights reserved.
Breastcancer.org is a non-profit organization dedicated to providing information and community to those touched by this disease. Learn more about our commitment to providing complete, accurate, and private breast cancer information.
