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Why only in HR-? Maybe because not sequenced 24hrs after chemo. No mention of Her2 status but here it is:
From Reuters Health Information
Bisphosphonates May Prolong Survival in Metastatic Breast Cancer Patients
By David Douglas
NEW YORK (Reuters Health) Jun 15 - IV bisphosphonate in addition to chemotherapy or hormonal therapy has an anti-tumor effect on hormone receptor (HR)-negative breast cancer patients with bone metastases, who may gain a survival advantage, according to Korean researchers.
Because of the retrospective nature of the study, investigator Dr. Jungsil Ro told Reuters Health, "we cannot strongly claim prolonged survival. However, the data appear encouraging enough to design a prospective study to confirm the anti-tumor activity of IV bisphosphonate."
In a May 20th paper published in BMC Cancer, Dr. Ro and colleagues at the National Cancer Center, Goyang-si point out that bisphosphonates have become the standard therapy for breast cancer patients with bone metastasis. This treatment reduces the symptoms and complications of bone involvement. However, the clinical relevance of their anti-tumor effect has not been established.
To gain more information, the researchers studied data on 230 patients with HR-positive tumors and 87 with HR-negative tumors. All had bone metastasis at diagnosis and known breast cancer subtypes.
Most of the women (n=262; 82.6%) received therapy with bisphosphonates during follow-up. The median number of cycles of treatment was 17.7 and the median interval between cycles was 31 days.
No survival benefit was seen in HR-positive patients, but HR-negative patients receiving bisphosphonates showed significantly improved survival (hazard ratio, 0.56). Median overall survival was 1.7 years in HR-negative patients who received bisphosphonates compared with 1.3 years in HR-negative patients who did not receive bisphosphonates.
Multivariate analysis showed that in HR-negative patients, bisphosphonate was a significant overall survival factor. More bisphosphonate-treated HR-negative women also had disease-free intervals of more than 2 years and fewer than three metastatic sites.
The researchers conclude that bisphosphonate treatment "may give a survival benefit in metastatic breast cancer patients, particularly in patients with HR-negative tumors, which are known to have a poorer prognosis."
"We have designed a prospective study in metastatic breast cancer patients without bone metastasis to see whether IV bisphosphonate -- zoledronic acid -- in combination with chemo- or hormone therapy as a first-line therapy will show an anti-tumor effect... or decrease bone metastasis," Dr. Ro added.
BMC Cancer 2009;9.
From a researcher regarding relevancy of ER status:
I am afraid I will not be able to scientifically resolve this. All I can say is that the Korean study was done in patients with bone metastases, and neither ZA treatment nor receptor status served as a prospectively defined factor in any way. This limits the power of that report to support its conclusion, and - as always in such retrospective investigations - the result they obtained may well be observed just by chance. I would not draw the conclusion that ZA is not effective in HR-positive breast cancer.
In fact, in the early disease setting, the contrary appears to be true. As we have shown in the ABCSG-12 trial you are refering to (NEJM Feb 12, 2009), ZA can decrease the risk of relapse in the aduvant setting in a trial of endocrine responsive premenopausal breast cancer patients by about 36 per cent. This report was confirmed by the 3-year results of the bone protection ZO-FAST trial in postmenopausal patients, also exclusively done in patients with endocrine-responsive breast cancer. We are currently lacking data on receptor-negative breast cancer in the adjuvant setting. This patient population is studied in the AZURE trial, which is due to report by the end of 2010.
In summary, I dont think that currently we have any reason to believe that ZA would be less effective in endocrine-responsive breast cancer. As far as I know, all data on preventing and delaying SREs in patients with bone metastases by ZA have been obtained in a receptor-unstratified patient population
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