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乳腺导管原位癌俗称零期乳腺癌，主要治疗方法为保乳手术＋放疗。临床前研究结果表明，曲妥珠单抗可增强HER2阳性乳腺癌放疗效果。不过，对于HER2阳性乳腺导管原位癌保乳术后放疗患者，曲妥珠单抗的临床意义尚不明确。 2021年3月19日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表NRG（NSABP＋RTOG＋GOG）肿瘤学协作组、拉什大学、匹兹堡大学、西北大学、弗吉尼亚联邦大学、科罗拉多大学、凯萨医疗中心、凯斯西储大学、托马斯杰斐逊大学、西密歇根癌症研究联盟、佛罗里达大学的NSABP B-43研究报告，对HER2阳性乳腺导管原位癌保乳术后全乳放疗±曲妥珠单抗的同侧乳腺癌复发率进行了比较。 NSABP B-43 (NCT00769379): A Phase III Clinical Trial Comparing Trastuzumab Given Concurrently With Radiation Therapy and Radiation Therapy Alone for Women With HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy 该多中心随机对照三期临床研究于2008年12月10日～2014年12月8日从全国入组体力状态评分为0或1、已知雌激素受体和/或孕激素受体状态、集中检测HER2为阳性的乳腺导管原位癌保乳术后患者2014例，按1∶1随机分为两组：全乳放疗组1008例、全乳放疗＋曲妥珠单抗组1006例。根据绝经状态、术后内分泌治疗计划、肿瘤分级进行亚组分析。当发生同侧乳腺癌复发事件163例或全部入组患者随访≥5年时，进行意向治疗初步分析。 结果，截至2019年12月31日，中位随访79.2个月，同侧乳腺癌复发114例，全部入组患者随访≥5年，全乳放疗组、全乳放疗＋曲妥珠单抗组分别失访3例、13例，其余1005例全乳放疗与993例全乳放疗＋曲妥珠单抗的患者相比：
根据亚组分析，对于绝经后、未计划术后内分泌治疗、肿瘤分级较高的患者，全乳放疗±曲妥珠单抗相比，同侧乳腺癌复发风险较低，不过亦无统计学意义。 因此，该研究结果表明，对于HER2阳性乳腺导管原位癌保乳术后患者，全乳放疗±曲妥珠单抗相比，同侧乳腺癌复发风险减少19%，虽有临床意义，但无统计学意义，故该研究结果为阴性。 J Clin Oncol. 2021 Mar 19. Online ahead of print. Comparison of Radiation With or Without Concurrent Trastuzumab for HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy: A Phase III Clinical Trial. Cobleigh MA, Anderson SJ, Siziopikou KP, Arthur DW, Rabinovitch R, Julian TB, Parda DS, Seaward SA, Carter DL, Lyons JA, Dillmon MS, Magrinat GC, Kavadi VS, Zibelli AM, Tiriveedhi L, Hill ML, Melnik MK, Beriwal S, Mamounas EP, Wolmark N. NRG Oncology, Pittsburgh, PA; University of Pittsburgh, Pittsburgh, PA; Allegheny Health Network, Pittsburgh, PA; UPMC Hillman Cancer Center, Magee Womens Hospital, Pittsburgh, PA; Rush University Medical Center, Chicago, IL; Northwestern University Feinberg School of Medicine, Chicago, IL; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; University of Colorado Cancer Center, Aurora, CO; Rocky Mountain Cancer Centers, Aurora, CO; Kaiser Permanente Cancer Research Program, Vallejo, CA; US Oncology, The Woodlands, TX; University Hospitals Seidman Cancer Center, Cleveland, OH; Harbin Clinic, Rome, GA; Cone Health Center, Greensboro, NC; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA; Mercy Clinic Cancer and Hematology, Springfield, MO; Mission Cancer and Blood, Des Moines, IA; Cancer Research Consortium of West Michigan, Grand Rapids, MI; Orlando Health UF Health Cancer Center, Orlando, FL. PURPOSE: Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS). PATIENTS AND METHODS: Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years. RESULTS: There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; P value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; P value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; P value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years. CONCLUSION: Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy. PMID: 33739848 DOI: 10.1200/JCO.20.02824
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