Fisher Bernard, Bryant John, Dignam James J, Wickerham D Lawrence, Mamounas Eleftherios P, Fisher Edwin R, Margolese Richard G, Nesbitt Lois, Paik Soonmyung, Pisansky Thomas M, Wolmark Norman
National Surgical Adjuvant Breast and Bowel Project Biostatistical Center, Division of Pathology, and Breast Committee, Pittsburgh, PA, USA.
J Clin Oncol. 2002 Oct 15;20(20):4141-9. doi: 10.1200/JCO.2002.11.101.
This trial was prompted by uncertainty about the need for breast irradiation after lumpectomy in node-negative women with invasive breast cancers of </= 1 cm, by speculation that tamoxifen (TAM) might be as or more effective than radiation therapy (XRT) in reducing the rate of ipsilateral breast tumor recurrence (IBTR) in such women, and by the thesis that both modalities might be more effective than either alone.
After lumpectomy, 1,009 women were randomly assigned to TAM (n = 336), XRT and placebo (n = 336), or XRT and TAM (n = 337). Rates of IBTR, distant recurrence, and contralateral breast cancer (CBC) were among the end points for analysis. Cumulative incidence of IBTR and of CBC was computed accounting for competing risks. Results with two-sided P values of.05 or less were statistically significant.
XRT and placebo resulted in a 49% lower hazard rate of IBTR than did TAM alone; XRT and TAM resulted in a 63% lower rate than did XRT and placebo. When compared with TAM alone, XRT plus TAM resulted in an 81% reduction in hazard rate of IBTR. Cumulative incidence of IBTR through 8 years was 16.5% with TAM, 9.3% with XRT and placebo, and 2.8% with XRT and TAM. XRT reduced IBTR below the level achieved with TAM alone, regardless of estrogen receptor (ER) status. Distant treatment failures were infrequent and not significantly different among the groups (P =.28). When TAM-treated women were compared with those who received XRT and placebo, there was a significant reduction in CBC (hazard ratio, 0.45; 95% confidence interval, 0.21 to 0.95; P =.039). Survival in the three groups was 93%, 94%, and 93%, respectively (P =.93).
In women with tumors </= 1 cm, IBTR occurs with enough frequency after lumpectomy to justify considering XRT, regardless of tumor ER status, and TAM plus XRT when tumors are ER positive.
本试验的开展是由于对于肿瘤直径≤1cm的腋窝淋巴结阴性浸润性乳腺癌女性患者在保乳手术后是否需要进行乳房放疗存在不确定性；有人推测他莫昔芬（TAM）在降低此类女性同侧乳腺肿瘤复发（IBTR）率方面可能与放射治疗（XRT）同样有效或更有效；还有一种观点认为两种治疗方式联合使用可能比单独使用任何一种更有效。
1009名女性在保乳手术后被随机分为三组，分别接受TAM治疗（n = 336）、XRT联合安慰剂治疗（n = 336）或XRT联合TAM治疗（n = 337）。IBTR、远处复发和对侧乳腺癌（CBC）发生率是分析的终点指标。计算IBTR和CBC的累积发生率时考虑了竞争风险。双侧P值≤0.05的结果具有统计学意义。
XRT联合安慰剂组的IBTR风险率比单纯TAM组低49%；XRT联合TAM组的风险率比XRT联合安慰剂组低63%。与单纯TAM组相比，XRT联合TAM组的IBTR风险率降低了81%。TAM组8年的IBTR累积发生率为16.5%，XRT联合安慰剂组为9.3%，XRT联合TAM组为2.8%。无论雌激素受体（ER）状态如何，XRT均可将IBTR发生率降至单纯TAM治疗所达到的水平以下。远处治疗失败情况不常见，且各组之间无显著差异（P = 0.28）。与接受XRT联合安慰剂治疗的女性相比，接受TAM治疗的女性CBC发生率显著降低（风险比，0.45；95%置信区间，0.21至0.95；P = 0.039）。三组的生存率分别为93%、94%和93%（P = 0.93）。
对于肿瘤直径≤1cm的女性，保乳手术后IBTR的发生率足以证明无论肿瘤ER状态如何都应考虑进行XRT，而对于ER阳性肿瘤应考虑TAM联合XRT。
