新英格兰：阿那曲唑延长两年足矣

　　激素受体阳性乳腺癌是最常见的乳腺癌分子亚型，大多数发生于绝经女性。对于早期患者，虽然术后连续5年内分泌治疗可显著减少复发，但是5年后超过一半病例复发。因此，延长术后内分泌治疗似乎是合理的。奥地利乳腺结直肠癌研究协作组ABCSG-6a研究证实，用芳香化酶抑制剂阿那曲唑延长术后内分泌治疗可继续减少复发。不过，内分泌治疗毕竟副作用较大、长期成本较高，不可能无限制延长，究竟延长多少时间最安全有效？

　　2021年7月29日，国际四大医学期刊之首、美国麻省医学会《新英格兰医学杂志》在线发表奥地利乳腺结直肠癌研究协作组ABCSG-16/SALSA研究报告，对激素受体阳性早期乳腺癌绝经女性完成连续5年内分泌治疗后再用阿那曲唑2年或5年的有效性和安全性进行了比较。该研究由阿斯利康提供资助。

ABCSG-16/SALSA (Secondary Adjuvant Long Term Study With Arimidex): A Prospective, Randomized, Open, Multicentre Phase III-study to Assess the Efficacy of Secondary Adjuvant Endocrine Anastrozole Therapy for 2 Further Yrs vs 5 Further Yrs in Patients With HR +ve Breast Cancer After 5-yr Primary Adjuvant Endocrine Therapy (NCT00295620)

　　该多中心前瞻非盲随机对照三期临床研究于2004年2月～2010年6月从75家奥地利医院入组完成术后5年内分泌治疗未复发的激素受体阳性早期乳腺癌绝经女性3484例，按1∶1的比例随机分为两组用阿那曲唑延长2年（1739例）或5年（1745例）。主要终点为无病生存，定义为随机分组至局部或远处复发、对侧乳腺癌、第二原发癌、死亡。对随机分组2年后（即2年组治疗结束时）未退出研究且未复发患者进行主要终点分析。次要终点包括总体生存、对侧乳腺癌、第二原发癌、临床骨折。

　　结果，随机分组2年后（即2年组治疗结束时）未退出研究且未复发患者共计3208例（2年组1603例、5年组1605例）。

　　中位随访118个月，2年组与5年组相比：

• 8年无病生存率相似：73.6%比73.9%（风险比：0.99，95%置信区间：0.85～1.15，P=0.90）

• 8年总体生存率相似：87.5%比87.3%（风险比：1.02，95%置信区间：0.83～1.25）

• 8年对侧乳腺癌相似：2.2%比2.1%（风险比：1.15，95%置信区间：0.75～1.77）

• 8年第二原发癌相似：6.2%比6.7%（风险比：1.06，95%置信区间：0.81～1.38）

• 5年临床骨折率较低：4.7%比6.3%（风险比：1.35，95%置信区间：1.00～1.84）

　　亚组分析未见任何特定亚组存在显著差异。

　　因此，该研究结果表明，对于完成术后5年内分泌治疗的激素受体阳性早期乳腺癌绝经女性，用阿那曲唑延长5年与2年相比，获益相似，但是副作用风险较高。不过，该研究乳腺癌T1期占3/4、T2期占1/4、N0期占2/3、N1占1/3、未化疗占3/4、化疗大多未用蒽环类或紫杉类、未放疗占1/5、保乳占4/5，复发风险本来就不高。对于复发风险较高的患者，术后内分泌治疗延长时间仍需个体化，具体请遵医嘱。而且，该研究仅针对阿那曲唑，并不包括其他芳香化酶抑制剂。

　　对此，加拿大多伦多大学西奈山医院发表同期评论：激素受体阳性乳腺癌延长芳香化酶抑制剂。

相关链接

• 最近十五年乳腺癌患者生存状况

• 早期乳腺癌五年内分泌治疗结束后二十年复发风险仍然持续增加

• 来曲唑和他莫昔芬单药或序贯辅助治疗乳腺癌绝经后女性的长期随访

• 芳香酶抑制剂辅助疗法延长至10年显著降低乳腺癌复发风险

• 乳腺癌术后芳香酶抑制剂哪家强

• 乳腺癌辅助内分泌治疗，规范与精准并重

• 来曲唑与阿那曲唑辅助治疗激素受体和淋巴结阳性早期乳腺癌绝经后患者的有效性和安全性相似

• 来曲唑对早期乳腺癌并不优于阿那曲唑

• 如何避免乳腺癌内分泌辅助疗法研究得出阴性结果

N Engl J Med. 2021 Jul 29;385(5):395-405.

Duration of Adjuvant Aromatase-Inhibitor Therapy in Postmenopausal Breast Cancer.

Gnant M, Fitzal F, Rinnerthaler G, Steger GG, Greil-Ressler S, Balic M, Heck D, Jakesz R, Thaler J, Egle D, Manfreda D, Bjelic-Radisic V, Wieder U, Singer CF, Melbinger-Zeinitzer E, Haslbauer F, Sevelda P, Trapl H, Wette V, Wimmer K, Gampenrieder SP, Bartsch R, Kacerovsky-Strobl S, Suppan C, Brunner C, Deutschmann C, Soelkner L, Fesl C, Greil R; Austrian Breast and Colorectal Cancer Study Group.

Austrian Breast and Colorectal Cancer Study Group, Medical University of Vienna, Hanusch Hospital, Hospital Hietzing, Karl Landsteiner Institute for Gynecological Oncology and Senology, Vienna; Paracelsus Medical University Salzburg, Salzburg; Medical University Graz, Graz; Ordensklinikum Linz, Linz; Klinikum Wels-Grieskirchen, Wels; Medical University Innsbruck, Innsbruck; Hospital Wolfsberg, Wolfsberg; Hospital Vocklabruck, Vocklabruck; General Hospital Baden, Baden; Sankt Veit an der Glan, Austria; University Hospital Helios, University Witten Herdecke, Wuppertal, Germany.

BACKGROUND: For postmenopausal women with hormone-receptor-positive breast cancer, the most effective duration for adjuvant therapy with an aromatase inhibitor remains unclear.

METHODS: In this prospective, phase 3 trial, we randomly assigned postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy to receive the aromatase inhibitor anastrozole for an additional 2 years (2-year group, receiving a total of 7 years) or an additional 5 years (5-year group, receiving a total of 10 years). The primary end point was disease-free survival. The primary analysis included all the patients who were still participating in the trial and who had no recurrence 2 years after randomization (i.e., when treatment in the 2-year group had ended). Secondary end points were overall survival, contralateral breast cancer, second primary cancer, and clinical bone fracture.

RESULTS: Among the 3484 women who were enrolled in the trial, 3208 remained in the trial without disease progression after the first 2 years of extended anastrozole treatment following randomization. Among these women, disease progression or death occurred in 335 women in each treatment group in the primary-analysis set at 8 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P = 0.90). No between-group differences occurred in most secondary end points, and subgroup analyses did not indicate differences in any particular subgroup. The risk of clinical bone fracture was higher in the 5-year group than in the 2-year group (hazard ratio, 1.35; 95% CI, 1.00 to 1.84).

CONCLUSIONS: In postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy, extending hormone therapy by 5 years provided no benefit over a 2-year extension but was associated with a greater risk of bone fracture.

Funded by AstraZeneca and the Austrian Breast and Colorectal Cancer Study Group

ABCSG-16/SALSA ClinicalTrials.gov number: NCT00295620

PMID: 34320285

DOI: 10.1056/NEJMoa2104162

N Engl J Med. 2021 Jul 29;385(5):462-463.

Extended Aromatase Inhibitors in Hormone-Receptor-Positive Breast Cancer.

Goodwin PJ.

Lunenfeld-Tanenbaum Research Institute, Sinai Health System, University of Toronto, Toronto.

PMID: 34320293

DOI: 10.1056/NEJMe2109356