好风险乳腺导管原位癌要不要放疗

　　乳腺导管原位癌（0期）与浸润癌（I～IV期）相比，肿瘤切除保乳术后复发风险极低。不过，正所谓螺蛳壳里做道场，低风险又被进一步分为坏风险（肿瘤较大、分级较高、有症状）和好风险（肿瘤较小、分级较低、无症状、发现于乳腺钼靶筛查）。对于坏风险乳腺导管原位癌，术后辅助放疗可进一步减少复发风险。对于好风险乳腺导管原位癌，2015年发表的NRG肿瘤放疗协作组（RTOG）9804研究短期随访结果已经证实，肿瘤切除保乳术后全乳放疗与单纯观察相比，7年同侧乳腺癌局部复发风险减少89%。那么，长期随访结果如何？

NRG/RTOG 9804 (NCT00003857): Phase III Trial of Tamoxifen Alone vs. Tamoxifen Plus Radiation Therapy for Good Risk Duct Carcinoma In-Situ (DCIS) of the Female Breast

　　2021年8月18日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表美国纽约纪念医院斯隆凯特林癌症中心、NRG肿瘤统计数据管理中心、德克萨斯大学MD安德森癌症中心、哈佛大学麻省总医院癌症中心、达特茅斯学院希区柯克医疗中心、卡罗来纳东部癌症中心、亨利福特医院罗杰尔癌症中心、东南临床肿瘤研究联盟、密歇根大学、萨克拉门托放射学会、夏威夷大学癌症中心、俄亥俄州立大学综合癌症中心、加拿大多伦多大学森尼布鲁克医院奥德特癌症中心、拉瓦尔大学魁北克医院中心的NRG/RTOG 9804研究长期随访结果，对好风险乳腺导管原位癌肿瘤切除保乳术后全乳放疗或单纯观察的15年同侧乳腺癌局部复发风险进行了比较。

　　该国际多中心随机对照三期临床研究于1999年12月～2006年7月从美国和加拿大将近200家医院入组乳腺钼靶检出乳腺导管原位癌大小≤2.5厘米、细胞核核分级低或中、乳腺肿瘤切除保乳手术最终切缘≥3毫米的女性患者636例，按1∶1随机分入放疗组（322例）或观察组（314例）。大约各三分之二的患者服用他莫昔芬。通过对数秩检验和竞争风险回归模型，对放疗组与观察组的同侧乳腺癌复发累计发生比例进行比较。

　　结果，636例患者中位年龄58岁，乳腺导管原位癌术后病理检查平均大小0.60厘米。中位随访13.9年，放疗组与观察组相比：

• 他莫昔芬意向治疗比例：70%比69%

• 他莫昔芬实际治疗比例：58%比66%（P=0.05）

• 15年同侧乳腺癌复发比例：7.1%比15.1%（95%置信区间：4.0～11.5、10.8～20.2）

• 15年同侧乳腺癌复发风险：减少63%（风险比：0.36，95%置信区间：0.20～0.66，P=0.0007）

• 15年局部浸润癌复发比例：5.4%比9.5%（95%置信区间：2.7～9.5、6.0～13.9)

• 15年局部浸润癌复发风险：减少56%（风险比：0.44，95%置信区间：0.21～0.91，P=0.027）

　　根据多因素分析，无论其他影响因素如何，同侧乳腺癌复发风险减少的显著独立相关因素：

• 术后放疗：风险减少66%（风险比：0.34，95%置信区间：0.19～0.64，P=0.0007）

• 他莫昔芬：风险减少55%（风险比：0.45，95%置信区间：0.25～0.78，P=0.0047）

　　因此，该研究长期随访结果表明，放疗可显著减少好风险乳腺导管原位癌术后15年同侧全部癌和浸润癌复发。不过，这些结果并非放疗的绝对指征，而是有助于医患共同决定乳腺导管原位癌乳腺肿瘤切除保乳术后减少长期同侧乳腺癌复发风险的治疗方案，以尽可能减少乳腺癌复发风险，尤其长期浸润癌风险。当然，毕竟多数患者即使不放疗亦未复发、少数患者即使放疗仍然复发，对于不愿放疗且知情同意的患者也可长期观察。

J Clin Oncol. 2021 Aug 18. Online ahead of print.

Randomized Phase III Trial Evaluating Radiation Following Surgical Excision for Good-Risk Ductal Carcinoma In Situ: Long-Term Report From NRG Oncology/RTOG 9804.

McCormick B, Winter KA, Woodward W, Kuerer HM, Sneige N, Rakovitch E, Smith BL, Germain I, Hartford AC, O'Rourke MA, Walker EM, Strom EA, Hopkins JO, Pierce LJ, Pu AT, Sumida KNM, Vesprini D, Moughan J, White JR.

Memorial Sloan Kettering Cancer Center, New York, NY; NRG Oncology Statistics and Data Management Center, Philadelphia, PA; The University of Texas MD Anderson Cancer Center, Houston, TX; Odette Cancer Centre-Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Massachusetts General Hospital Cancer Center, Boston, MA; CHU de Quebec-L'Hotel-Dieu de Quebec, Quebec City, QC, Canada; Dartmouth-Hitchcock Medical Center, Lebanon, NH; Greenville CCOP-Cancer Centers of The Carolinas-Eastside, Greenville, SC; Henry Ford Hospital Rogel Cancer Center, Detroit, MI; Southeast Clinical Oncology Research (SCOR) Consortium NCORP, Winston-Salem, NC; University of Michigan, Ann Arbor, MI; Radiological Associates of Sacramento, Sacramento, CA; University of Hawaii Cancer Center MBCCOP, Honolulu, HI; Ohio State University Comprehensive Cancer Center, Columbus, OH.

PURPOSE: To our knowledge, NRG/RTOG 9804 is the only randomized trial to assess the impact of whole breast irradiation (radiation therapy [RT]) versus observation (OBS) in women with good-risk ductal carcinoma in situ (DCIS), following lumpectomy. Long-term results focusing on ipsilateral breast recurrence (IBR), the primary outcome, are presented here.

PATIENTS AND METHODS: Eligible patients underwent lumpectomy for DCIS that was mammogram detected, size ≤ 2.5 cm, final margins ≥ 3 mm, and low or intermediate nuclear grade. Consented patients were randomly assigned to RT or OBS. Tamoxifen use was optional. Cumulative incidence was used to estimate IBR, log-rank test and Gray's test to compare treatments, and Fine-Gray regression for hazard ratios (HRs).

RESULTS: A total of six hundred thirty-six women were randomly assigned from 1999 to 2006. Median age was 58 years and mean pathologic DCIS size was 0.60 cm. Intention to use tamoxifen was balanced between arms (69%); however, actual receipt of tamoxifen varied, 58% RT versus 66% OBS (P = .05). At 13.9 years' median follow-up, the 15-year cumulative incidence of IBR was 7.1% (95% CI, 4.0 to 11.5) with RT versus 15.1% (95% CI, 10.8 to 20.2) OBS (P = .0007; HR = 0.36; 95% CI, 0.20 to 0.66); and for invasive LR was 5.4% (95% CI, 2.7 to 9.5) RT versus 9.5% (95% CI, 6.0 to 13.9) OBS (P = .027; HR = 0.44; 95% CI, 0.21 to 0.91). On multivariable analysis, only RT (HR = 0.34; 95% CI, 0.19 to 0.64; P = .0007) and tamoxifen use (HR = 0.45; 95% CI, 0.25 to 0.78; P = .0047) were associated with reduced IBR.

CONCLUSION: RT significantly reduced all and invasive IBR for good-risk DCIS with durable results at 15 years. These results are not an absolute indication for RT but rather should inform shared patient-physician treatment decisions about ipsilateral breast risk reduction in the long term following lumpectomy.

KEY OBJECTIVE: To identify a group of women with good-risk ductal carcinoma in situ (DCIS) whose risk of local recurrence after breast conservation surgery was so low, to justify the omission of breast radiation.

KNOWLEDGE GENERATED: The local recurrence risk in good-risk patients without radiation, last reported with a median follow-up of 7 years, to be 1% per year, continued at that rate through 15 years of follow-up. The addition of whole breast radiation after surgery delayed and decreased the risk of both invasive and noninvasive local events significantly.

RELEVANCE: Widespread use of screening mammography identifies good-risk DCIS in many thousands of women each year. This information supports the decision to treat patients with good-risk DCIS, who want to minimize their in-breast recurrence, and particularly invasive risk in the long term. The results of this trial provide critical information that can inform shared patient-physician treatment decisions.

PMID: 34406870

DOI: 10.1200/JCO.21.01083