美国临床肿瘤学会和安大略省癌症医疗委员会临床实践指南：乳腺癌术后双膦酸盐和其他骨调节剂的使用

　　2017年3月6日，美国临床肿瘤学会官方期刊《临床肿瘤学杂志》在线发表美国（密歇根大学、哈佛医学院、麻省总医院、列克星敦医院、哈滨医院）和加拿大（伦敦健康科学中心、金斯顿总医院、温莎地区癌症中心、渥太华医院、森尼布鲁克健康科学中心、森尼布鲁克奥德特癌症中心、麦克马斯特大学、朱拉文斯基癌症中心）联合起草的美国临床肿瘤学会和安大略省癌症医疗委员会临床实践指南：乳腺癌术后双膦酸盐和其他骨调节剂的使用。

• 安大略省：简称安省，位于加拿大东部，是加拿大首都渥太华所在省份，也是加拿大人口最多的省份，知名城市还包括多伦多、渥太华、哈密尔顿、金斯顿、伦敦、温莎、滑铁卢，与美国密歇根州隔湖相望，由于历史和地缘关系，与美国东北部各州的文化教育医疗卫生交流密切。

• 安大略省癌症医疗委员会：安大略省政府机构，负责改善癌症服务，其前身为1943年成立的安大略省癌症治疗研究基金会，1995年由安大略省省长李博（鲍勃·雷）根据《癌症法案》提议创建，并于1997年正式启动。

　　为了对双膦酸盐和其他骨调节剂辅助治疗乳腺癌患者提出推荐意见，安大略省癌症医疗委员会和美国临床肿瘤学会召集了一个工作组和专家组，通过文献系统回顾，制定循证推荐意见。

　　结果发现：对于非转移性乳腺癌绝经后患者，双膦酸盐辅助治疗可以减少骨复发并改善生存。该指南中，绝经后包括自然绝经、卵巢抑制或切除所致。复发风险较高的患者绝对获益较大，几乎所有研究都在接受全身疗法的患者中进行。大多数研究评价了唑来膦酸或氯膦酸盐，其他双膦酸盐的数据极其有限。虽然发现地诺单抗减少骨折，但是仍然需要长期生存数据。

　　推荐意见：建议考虑（如果可用）唑来膦酸（每6个月4mg静脉注射）或氯膦酸盐（每天1600mg口服）用于符合全身辅助疗法指征的绝经后乳腺癌患者。需要进一步研究比较不同的骨调节剂、剂量、给药间隔、持续时间。颌骨坏死和肾损伤的风险因素应被评定，并且应在开始治疗之前处理任何未解决的牙齿或口腔健康问题。地诺单抗辅助治疗数据虽然看好，但是目前不足以提出任何推荐意见。在骨矿物质密度低的患者中使用这些药物减少脆性骨折超出本指南范围。推荐意见并不意味着在这些情况下限制骨修复剂的此类使用。

J Clin Oncol. 2017 Mar 6. [Epub ahead of print]

Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: A Cancer Care Ontario and American Society of Clinical Oncology Clinical Practice Guideline.

Sukhbinder Dhesy-Thind, Glenn G. Fletcher, Phillip S. Blanchette, Mark J. Clemons, Melissa S. Dillmon, Elizabeth S. Frank, Sonal Gandhi, Rasna Gupta, Mihaela Mates, Beverly Moy, Ted Vandenberg, Catherine H. Van Poznak.

Juravinski Cancer Centre; McMaster University, Hamilton, Ontario; Sunnybrook Odette Cancer Centre; Sunnybrook Health Sciences, Toronto, Ontario; The Ottawa Hospital Cancer Centre, Ottawa, Ontario; Windsor Regional Cancer Program, Windsor, Ontario; Kingston General Hospital, Kingston, Ontario; London Health Sciences Centre, London, Ontario, Canada; Harbin Clinic, Rome, GA; Lexington; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; University of Michigan, Ann Arbor, MI.

PURPOSE: To make recommendations regarding the use of bisphosphonates and other bone-modifying agents as adjuvant therapy for patients with breast cancer.

METHODS: Cancer Care Ontario and ASCO convened a Working Group and Expert Panel to develop evidence-based recommendations informed by a systematic review of the literature.

RESULTS: Adjuvant bisphosphonates were found to reduce bone recurrence and improve survival in postmenopausal patients with nonmetastatic breast cancer. In this guideline, postmenopausal includes patients with natural menopause or that induced by ovarian suppression or ablation. Absolute benefit is greater in patients who are at higher risk of recurrence, and almost all trials were conducted in patients who also received systemic therapy. Most studies evaluated zoledronic acid or clodronate, and data are extremely limited for other bisphosphonates. While denosumab was found to reduce fractures, long-term survival data are still required.

RECOMMENDATIONS: It is recommended that, if available, zoledronic acid (4 mg intravenously every 6 months) or clodronate (1,600 mg/d orally) be considered as adjuvant therapy for postmenopausal patients with breast cancer who are deemed candidates for adjuvant systemic therapy. Further research comparing different bone-modifying agents, doses, dosing intervals, and durations is required. Risk factors for osteonecrosis of the jaw and renal impairment should be assessed, and any pending dental or oral health problems should be dealt with prior to starting treatment. Data for adjuvant denosumab look promising but are currently insufficient to make any recommendation. Use of these agents to reduce fragility fractures in patients with low bone mineral density is beyond the scope of the guideline. Recommendations are not meant to restrict such use of bone-modifying agents in these situations.

DOI: 10.1200/JCO.2016.70.7257