蒙特菲奥里奥医疗中心Joseph A. Sparano研究组取得一项新突破。他们研究了临床和基因组风险指导乳腺癌辅助治疗的使用。 这一研究成果发表在2019年6月20日出版的国际学术期刊《新英格兰医学杂志》上。

课题组研究人员开展了一个前瞻性的试验方法，包括对激素受体阳性、人类表皮生长因子受体2阴性、腋窝淋巴结阴性的9427名女性乳腺癌患者，进行21个基因检测。课题组研究人员基于肿瘤大小和组织学分级，对临床乳腺癌的复发风险低或高进行分析。利用Cox比例危险模型计算远处复发的危险比，评估临床风险的效果。 最初的内分泌治疗是在大多数50岁或更年轻的绝经前妇女中单独使用它莫西芬。临床风险水平在女性中间远处复发的预后已复发11到25分(0到100的规模，得分越高表明糟糕的预后或受益于化疗上表现出更大的潜能)被随机分配到内分泌治疗(风险率高与低的比较临床风险,2.73;95%置信区间[CI]， 1.93 ~ 3.87，或化疗加内分泌(化疗-内分泌)治疗(危险比2.41;95% CI(1.66 ~ 3.48)，复发率高的女性(26 ~ 100)，均采用化学内分泌治疗(危险比3.17;95% CI, 1.94 - 5.19)。 50岁或更年轻的女性中间,仅接受内分泌治疗,远处复发的估计(±SE)率在9年不到5%(≤1.8±0.9%)复发得分较低(0到10分)，无论临床风险，和一个中间4.7±1.0%复发评分和较低的临床风险。在这一年龄组中，单纯接受内分泌治疗的临床风险高、复发程度中等的女性(12.3±2.4%)和接受化疗内分泌治疗的复发程度高的女性(15.2±3.3%)在9岁时远处复发的估计超过10%。临床风险分层提供了预后信息，当增加到21个基因复发评分时，可以用来确定绝经前妇女谁可以受益于更有效的治疗。

乳腺癌患者辅助化疗的使用可能受到临床病理因素和基于21个基因检测的评分的指导，以确定复发风险。 乳腺癌复发的临床风险水平是否会增加复发评分的预后信息尚不清楚。

附：英文原文

Title: Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer

Author: Joseph A. Sparano, M.D., Robert J. Gray, Ph.D., Peter M. Ravdin, M.D., Della F. Makower, M.D., Kathleen I. Pritchard, M.D., Kathy S. Albain, M.D., Daniel F. Hayes, M.D., Charles E. Geyer, Jr., M.D., Elizabeth C. Dees, M.D., Matthew P. Goetz, M.D., John A. Olson, Jr., M.D., Ph.D., Tracy Lively, Ph.D., Sunil S. Badve, M.B., B.S., M.D., Thomas J. Saphner, M.D., Lynne I. Wagner, Ph.D., Timothy J. Whelan, B.M., B.Ch., M.S.C., Matthew J. Ellis, M.B., B.Chir., Ph.D., Soonmyung Paik, M.D., William C. Wood, M.D., Maccon M. Keane, M.D., Henry L. Gomez Moreno, M.D., Pavan S. Reddy, M.D., Timothy F. Goggins, M.D., Ingrid A. Mayer, M.D., M.S.C.I., Adam M. Brufsky, M.D., Ph.D., Deborah L. Toppmeyer, M.D., Virginia G. Kaklamani, M.D., D.Sc., Jeffrey L. Berenberg, M.D., Jeffrey Abrams, M.D., and George W. Sledge, Jr., M.D.

Issue&Volume: VOL.380，NO.25， 2019

Abstract:

BACKGROUND
The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known.

METHODS
We performed a prospective trial involving 9427 women with hormone-receptor–positive, human epidermal growth factor receptor 2–negative, axillary node–negative breast cancer, in whom an assay of 21 genes had been performed, and we classified the clinical risk of recurrence of breast cancer as low or high on the basis of the tumor size and histologic grade. The effect of clinical risk was evaluated by calculating hazard ratios for distant recurrence with the use of Cox proportional-hazards models. The initial endocrine therapy was tamoxifen alone in the majority of the premenopausal women who were 50 years of age or younger.

RESULTS
The level of clinical risk was prognostic of distant recurrence in women with an intermediate 21-gene recurrence score of 11 to 25 (on a scale of 0 to 100, with higher scores indicating a worse prognosis or a greater potential benefit from chemotherapy) who were randomly assigned to endocrine therapy (hazard ratio for the comparison of high vs. low clinical risk, 2.73; 95% confidence interval [CI], 1.93 to 3.87) or to chemotherapy plus endocrine (chemoendocrine) therapy (hazard ratio, 2.41; 95% CI, 1.66 to 3.48) and in women with a high recurrence score (a score of 26 to 100), all of whom were assigned to chemoendocrine therapy (hazard ratio, 3.17; 95% CI, 1.94 to 5.19). Among women who were 50 years of age or younger who had received endocrine therapy alone, the estimated (±SE) rate of distant recurrence at 9 years was less than 5% (≤1.8±0.9%) with a low recurrence score (a score of 0 to 10), irrespective of clinical risk, and 4.7±1.0% with an intermediate recurrence score and low clinical risk. In this age group, the estimated distant recurrence at 9 years exceeded 10% among women with a high clinical risk and an intermediate recurrence score who received endocrine therapy alone (12.3±2.4%) and among those with a high recurrence score who received chemoendocrine therapy (15.2±3.3%).

CONCLUSIONS
Clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy.

DOI: 10.1056/NEJMoa1904819

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1904819