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根据澳洲乳癌与大肠直肠癌研究团队第12号研究（ABCSG-12），在接受内分泌治疗时并用zoledronic acid（Zometa，诺华药厂）可以预防停经后乳癌病患的骨质流失，这同时也可以改善治疗5年后的骨质密度；研究发表于8月20日的Lancet肿瘤学上。
过去发表于美国临床肿瘤学会第44届年会的ABCSG-12研究结果显示，相较于仅接受内分泌治疗，zoledronic acid合并内分泌治疗显著降低早期乳癌再发，使用Zoledronic acid女性乳癌再发的风险下降了36%，这项研究结果当时由Medscape肿瘤学报导。
在这项子研究中，研究者希望检验内分泌疗法对骨质密度的影响，同时评估合并zoledronic acid对骨质密度的效应；在接受内分泌治疗时使用zoledronic acid的病患，在治疗36个月后腰椎与股骨骨质密度呈现稳定状态。在60个月时，他们完成治疗后两年，相较于治疗前，他们的平均腰椎脊椎与股骨骨质密度显著改善。
主要作者、维也纳医学大学外科教授Michael Gnant医师表示，也接受内分泌治疗的停经后女性，骨质流失的情况相当显著，但这可以以简单且无害的治疗改善，对于和此研究一样的病患族群，我们建议使用辅助zoledronic acid。
ABCSG-12研究收纳1,803位停经前对内分泌治疗有反应的女性乳癌患者，研究者将这些受试者分为4个族群：tamoxifen 20 mg每天口服一次，加上goserelin (Zoladex，阿斯特捷利康药厂) 3.6 mg每28天皮下注射一次；anastrazole (Aridimex，阿斯特捷利康药厂)1 mg每天口服一次，加上goserelin 3.6 mg每28天皮下注射一次；anastrazole (Aridimex，阿斯特捷利康药厂)1 mg每天口服一次，加上goserelin 3.6 mg每28天皮下注射一次，加上zoledronic acid 4 mg静脉注射每六个月注射一次；tamoxifen 20 mg每天口服一次，加上goserelin (Zoladex，阿斯特捷利康药厂) 3.6 mg每28天皮下注射一次，加上zoledronic acid 4 mg静脉注射每六个月注射一次；为期3年。
针对404位病患的腰椎（L1-L4）与股骨进行骨质密度检测，于试验前以及接着在6、12、36与60个月时，以双能X射线吸收计（DEXA）共评估1,533次骨质密度；这项研究的试验终点为12个月时的骨密度变化。
在治疗三年后，接受内分泌治疗患者的腰椎骨密度相较于试验前下降了11.3%，而股骨骨密度下降了7.3%。研究者也观察到在36个月时，anastrazole相较于tamoxifen，下降骨密度程度更高。
在平均追踪60个月后，也就是结束治疗两年后，骨质密度显著改善但并未回到试验前的程度。没有使用zoledronic acid的病患，这两个部位的骨质密度相较于试验前，都是下降的，在腰椎下降了6.3%，在股骨下降了4.1%。
相形之下，接受zoledronic acid的女性，其骨质密度在36个月时仍然是稳定的；腰椎骨质密度增加了0.4%，股骨增加了0.8%。除此之外，他们的研究结果显示，相较于试验前的数值，这两个部位的骨质密度都是增加的：腰椎增加了0.4%，股骨增加了3.9%。
作者表示，仅五年的后续追踪不可能评估骨质流失病患是否可以恢复到试验前的程度，或是这些骨质增加是否足以预防未来的骨折。
Gnant医师向Medscape肿瘤学表示，病患将于最终回到试验前的程度；然而，特别是在anastrazole组，这得花上七、八年才能知道。目前，没有人可以真的说长期骨质密度下降将会对之后的骨完整度有什么影响。
这项研究由阿斯特捷利康与诺华药厂赞助。Gnant医师接受阿斯特捷利康、诺华、罗氏、赛诺菲安万特与安进药厂的研究赞助、顾问费、演讲费与谢礼。共同作者Gunther Steger医师，同样来自维也纳医学大学，接受阿斯特捷利康与诺华药厂赞助。
Zoledronic Acid Prevents Bone Loss During Breast Cancer Treatment
By Roxanne Nelson
Medscape Medical News
Concomitant zoledronic acid (Zometa, Novartis) that is given during adjuvant endocrine therapy can prevent bone loss in premenopausal breast cancer patients. It also improves bone-mineral density 5 years after treatment, according to the results of a substudy from the Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) that are published online August 20 in Lancet Oncology.
Previous findings from the ABCSG-12 trial, presented at the American Society of Clinical Oncology 44th Annual Meeting, showed that zoledronic acid combined with endocrine therapy significantly reduced relapse in early breast cancer, as compared with endocrine therapy alone. Women taking zoledronic acid had a 36% lower risk for breast cancer recurrence, as reported at the time by Medscape Oncology.
In this substudy, the researchers attempted to quantify the long-term effects of endocrine therapy on bone-mineral density and to assess the effects of concomitant zoledronic acid on bone-mineral density. Patients who received zoledronic acid during endocrine therapy showed stable bone-mineral density at both the lumbar spine and trochanter bone after 36 months. At 60 months, 2 years after they ended treatment, their mean lumbar-spine and trochanter bone-mineral density had improved significantly, as compared with baseline.
"With endocrine therapy for premenopausal women, there is substantial bone loss," said lead author Michael Gnant, MD, professor of surgery at the Medical University of Vienna and president of the Austrian Breast and Colorectal Cancer Study Group. "But this can be corrected with an easy and harmless treatment. We do recommend adjuvant zoledronic acid for the exact patient group described in this trial."
The ABCSG-12 trial randomized 1803 premenopausal women with endocrine-responsive breast cancer to 4 treatment groups: tamoxifen 20 mg/day orally and goserelin (Zoladex, AstraZeneca) 3.6 mg subcutaneously every 28 days vs anastrozole (Aridimex, AstraZeneca) 1 mg/day orally and goserelin 3.6 mg subcutaneously every 28 days, both with or without zoledronic acid 4 mg intravenously every 6 months for a period of 3 years.
Of this group, a total of 1533 bone-mineral-density measurements were made by dual-energy X-ray absorptiometry (DEXA) at baseline and then at 6, 12, 36, and 60 months at the lumbar spine (L1–L4) and trochanter in 404 patients. The primary end point of this substudy was changes in bone-mineral density at 12 months.
After 3 years of treatment, patients who received endocrine therapy alone lost 11.3% of baseline lumbar spine bone density and 7.3% of trochanter bone density. The researchers also observed that at 36 months, anastrozole caused greater bone-mineral-density loss at the lumbar spine than tamoxifen.
At a median follow-up of 60 months, which was 2 years after treatment ended, bone-mineral density had improved but did not return to baseline levels. Patients who did not receive zoledronic acid still had decreased bone-mineral density at both sites compared with baseline; lumbar spine -6.3% and trochanter -4.1%.
In contrast, the women who received zoledronic acid had stable bone-mineral density at 36 months; lumbar spine +0.4% and trochanter +0.8%. In addition, they showed an increase in bone-mineral density at 60 months for both sites: lumbar spine +4.0% and trochanter +3.9%, as compared with baseline levels.
The authors note that after only 5 years of follow-up, it is not possible to assess whether the patients who suffered bone loss will ultimately regain their baseline density levels or if any improvements in bone-mineral density will be sufficient to prevent fractures in the future.
"Patients will eventually reach baseline levels," Dr. Gnant told Medscape Oncology. "However, particularly in the anastrozole group, this may take 7 or 8 years. Currently, nobody can realistically say what consequence a long-term period of reduced bone-mineral density will have on later bone integrity."
The study was sponsored by AstraZeneca and Novartis. Dr. Gnant has received research support, consulting fees, lecture fees, and honoraria from AstraZeneca, Novartis, Roche, Sanofi-Aventis, and Amgen. Coauthor Gunther Steger, MD, also from the Medical University of Vienna, has received honoraria from AstraZeneca and Novartis.
Lancet Oncol. 2008;9:840-849. Published online August 20, 2008.