美国乳腺癌临床实践指南更新（下）

　　时隔129天，美国国家综合癌症网络NCCN于2021年1月15日悄然将乳腺癌临床实践指南更新至2021年第1版，全文由238页增至240页，免费注册登录后仍可免费下载：

NCCN为非国立、非营利、全国综合癌症中心联盟组织，1993年11月成立，1995年1月31日正式宣布成为全国联盟，最初由13个美国知名综合癌症中心组成，目前已经增至30个：

前情提要

• NCCN乳腺癌临床实践指南2020年第6版（简体中文版）

• NCCN乳腺癌临床实践指南2020年第3版（简体中文版）

　　NCCN乳腺癌临床实践指南2021年第1版架构仍为临床路径＋循证解读＋参考文献，其依据仍来自权威学术期刊或学术会议最新发表的大样本多中心随机对照三期临床研究结果。由于本版更新内容太多，故分两集进行简介，以下为下集（下划线为新增内容，中划线为删除内容）

乳腺浸润癌（BINV-F 2 of 2）

• 第一项末行修改：对于特定疑难病例，常规再次切除之前应该进行临床判断并与患者讨论对于特定病例，应该进行临床判断，随后与患者讨论后，再次切除可能需要谨慎。

• First bullet, last line modified: For specifically challenging cases, clinical judgment and discussion with the patient should precede routine re-excision. Clinical judgment should be applied in specific cases for which following discussion with the patient, re-excision may be prudent.

• 第三项修改：对于乳腺浸润癌保乳术后显微镜下切缘局灶阳性患者，如果不存在广泛导管内成分，应该可以考虑剂量较高的瘤床追加放疗，因为对于复发风险较高患者通常推荐瘤床追加放疗。典型剂量为10～16戈瑞，分割为4～8次，每次2戈瑞参见BINV-I。

• Third bullet modified: For patients with invasive breast cancer, after BCS if margin is microscopically focally positive, in the absence of an EIC, the use of a higher radiation boost dose to the tumor bed should may be considered, since generally a boost to the tumor bed is recommended in patients at higher risk for recurrence. Typical doses are 10-16 Gy in 4-8 fractions at 2 Gy/fx. See BINV-I.

• 新增切缘分类表

• Margin table added.

乳腺浸润癌（BINV-G）

• 保乳放疗相对禁忌证，第三项修改：病理切缘持续阳性

• Relative, third bullet modified: Persistently positive pathologic margin

乳腺浸润癌（BINV-H 1 of 7）

• 修改脚注c：采用这些术式肿瘤整形技术可能减少对乳房切除术的需求并减少对二次手术重新切除的需求，同时以尽量减少乳房畸形。应该告知患者切缘阳性的可能性以及可能需要进行二次手术，可能包括分段再次切除，或可能需要乳房切除术伴或不伴乳头缺损。考虑应该对肿瘤整形手术切除标本进行系统定位标记、对乳腺组织移位重排情况予以详细具体记录。加强与肿瘤放疗团队与乳房重建团队的沟通，尤其考虑追加放疗时对于瘤腔定位追加放疗计划将是必要的。

• Footnote modified: An evaluation...Application of these oncoplastic techniques may reduce the need for mastectomy and reduce decrease the need for a secondary surgery for re-excision while to minimize breast deformity. Patients should be informed of the possibility of positive margins and potential need for secondary surgery, which could include either segmental re-excision resection, or could require mastectomy with or without loss of the nipple. Consider Systematic oncoplastic reduction specimen orientation as well as highly specific operative documentation regarding tissue rearrangement should be conducted. Enhance communication between the radiation oncology team and reconstructive team especially in instance will be necessary for boost cavity localization for RT treatment planning. of boost consideration

乳腺浸润癌（BINV-I）

• 放疗原则由1页拆分为3页，包括优化个体化治疗的实施、全乳放疗、胸壁放疗（包括乳房重建）、区域淋巴结放疗、术前术后全身治疗、部分乳房加速放疗（新增放疗剂量表）

• This section has been significantlty revised and updated.

乳腺浸润癌（BINV-J 1 of 2）

• 标题修改：男性（出生时被认定为男性）乳腺癌特殊注意事项

• Title modified: Special Consideration for Breast Cancer in Men (Sex Assigned Male at Birth)

• 第二项第七点修改：早期乳腺癌治疗后的随访：男性早期乳腺癌患者治疗后不需要常规乳腺钼靶检查。支持对男性进行乳腺癌筛查的数据有限。

• Second bullet Seventh sub-bullet modified: Follow-up after treatment for earlystage disease: Routine mammography is not required after treatment for early breast cancer in men. There are only limited data to support screening for breast cancer in men.

• 第二项第八点修改：男性晚期乳腺癌患者的化疗、HER2靶向治疗、免疫治疗和PARP抑制剂适应证和推荐意见与女性晚期乳腺癌患者相似。

• Last sub-bullet, last line modified: Indications for and recommendations regarding chemotherapy, HER2-targeted therapy, immunotherapy, and PARP inhibitors for advanced breast cancer in men are similar to those for advanced breast cancer in women.

乳腺浸润癌（BINV-J 2 of 2）

• 新增参考文献

• Reference added: Gao Y, Goldberg JE, Young TK, et al. Breast Cancer Screening in High-Risk Men: A 12-year Longitudinal Observational Study of Male Breast Imaging Utilization and Outcomes. Radiology 2019;293(2):282-291.

乳腺浸润癌（BINV-K）

• 对于芳香酶抑制剂5年＋卵巢抑制或切除的绝经前患者，新增：考虑再用芳香酶抑制剂3～5年

• Arrow added for an additional 3-5 y of AI for premenopausal patients who received AI for 5y + ovarian suppression.

• 新增脚注c：对于接受芳香酶抑制剂辅助治疗的绝经后（自然或诱发）患者，考虑双膦酸盐或地舒单抗辅助治疗

• Footnote added: Consider adjuvant bisphosphonate therapy or denosumab in postmenopausal (natural or induced) patients receiving adjuvant aromatase inhibitor therapy.

乳腺浸润癌（BINV-L 2 of 7）

• 以下从“首选方案”移至“某些情况下有用”：

• Moved from "Preferred Regimens" to "Useful in Certain Circumstances":

• AC→TH（多柔比星＋环磷酰胺→紫杉醇＋曲妥珠单抗，各种疗程）

• AC followed by T + trastuzumab (various schedules)

• AC→THP（多柔比星＋环磷酰胺→紫杉醇＋曲妥珠单抗＋帕妥珠单抗，各种疗程）

• AC followed by T + trastuzumab + pertuzumab (various schedules)

• 删除脚注：回顾研究证据表明，对于HER2阳性肿瘤患者，蒽环类化疗方案可能优于非蒽环类方案

• Footnote reoved: Retrospective evidence suggests that anthracyclinebased chemotherapy regimens may be superior to non-anthracyclinebased regimens in patients with HER2-positive tumors

• 修改脚注e：由于医学原因（例如过敏反应），对于某些患者，紫杉类（例如多西他赛、紫杉醇、白蛋白结合紫杉醇）可以互相替代。纳米颗粒白蛋白结合紫杉醇可以替代紫杉醇或多西他赛。如果替代每周紫杉醇或多西他赛，那么白蛋白结合紫杉醇每周剂量不应超过125mg/m²。（同BINV-L 1 of 7、BINV-Q 1/2 of 7）

• Footnote modified: Alternative taxanes (ie, docetaxel, paclitaxel, albumin-bound paclitaxel) may be substituted for select patients due to medical necessity (ie, hypersensitivity reaction). Nab-paclitaxel may be substituted for paclitaxel or docetaxel. If substituted for weekly paclitaxel or docetaxel, then the weekly dose of albumin-bound paclitaxel should not exceed 125 mg/m². (Also on BINV-L 1 of 7, and BINV-Q 1/2 of 7)

乳腺浸润癌（BINV-L (5 of 7)

• 修改：AC或剂量密集AC→THP

• Modified: AC or Dose-Dense AC followed by T + trastuzumab + pertuzumab

• AC疗程，新增：剂量密集：每个周期14天×4个周期

• Under AC dosing, added: For dose-dense: Cycle every 14 days for 4 cycles

乳腺浸润癌（BINV-L 7 of 7）

• 新增参考文献

• Reference added: Swain SM, Ewer MS, Viale G, et al. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, openlabel, multicenter, multinational cardiac safety study. Ann Oncol 2018;29(3):646-653.

乳腺浸润癌（BINV-M 1 of 2）

• 修改：根据疗效可提供患者个体水平重要预后信息，尤其对于三阴性乳腺癌和HER2阳性乳腺癌患者

• Provides important prognostic information at an individual patient level based on response to therapy, particularly in patients with triple negative (TNBC) and HER2-positive breast cancer. Treatment response provides important prognostic information at an individual patient level, particularly in patients with TNBC or HER2-positive breast cancer.

• 修改：允许存在残留病变的HER2阳性和三阴性乳腺癌患者修改或增加辅助治疗方案。确定复发风险较高的残留病变患者以允许增加辅助治疗方案，尤其对于三阴性乳腺癌或HER2阳性乳腺癌患者。

• Allows the modification or addition of adjuvant regimens among patients with HER2-positive and TNBC with residual disease. Identifies patients with residual disease at higher risk for relapse to allow for the addition of supplemental adjuvant regimens, particularly in patients with TNBC or HER2-positive breast cancer.

• 新增：允许有时间延迟根治手术决策。

• Allows time for delayed decision-making for definitive surgery.

• 修改：如果治疗后腋窝转阴，可能允许单纯前哨淋巴结活检。如果治疗后由cN+变为cN0，可能允许单纯前哨淋巴结活检。

• May allow SLNB alone if a positive axilla is cleared with therapy. May allow SLNB alone if initial cN+ becomes cN0 after preoperative therapy.

• 修改：如果腋窝淋巴结病变清除，可能缩小放疗范围或减少放疗。对于术前治疗后cN+变为cN0/pN0的患者，可能允许较局限的放疗范围。

• May allow for smaller radiotherapy ports or less radiotherapy if axillary nodal disease cleared. May allow for more limited radiation fields in patients with cN+ who become cN0/pN0 after preoperative therapy.

• 适合术前全身治疗的患者：N2、N3、T4、T≥2或N≥1、淋巴结阳性、淋巴结阴性，改为cN2、cN3、cT4、cT≥2或cN≥1、cN+、cN0

• Candidates for Preoperative Systemic Therapy

• 项目修改：根治手术可能延迟的患者。如果需要时间决定手术方案。

• Bullet modified: Patients in whom definitive surgery may be delayed. If time needed to decide surgical options.

乳腺浸润癌（BINV-M 2 of 2）

• 修改第四项：根据合并症或低风险管腔型生物学特征，根据临床特征和/或基因组特征，雌激素受体阳性乳腺癌患者可考虑术前单纯内分泌治疗。

• Fourth bullet modified: Preoperative endocrine therapy alone may be considered for patients with ER-positive disease based on comorbidities or low-risk luminal biology based on clinical characteristics and/or genomic signatures.

• 修改第七项：首选术前完成给予完整的标准治疗方案。如果术前未完成全部计划治疗，其余可以辅助治疗形式给予术后可进行额外化疗以完成治疗方案。对于术前全身治疗期间出现肿瘤进展的可手术乳腺癌患者，可考虑更换全身治疗方案或如果认为可切除那么立即进行手术。

• Last bullet modified: Tumor...It is preferred that the standard regimen is completed standard regimen should be given prior to surgery. If all intended treatment is not completed prior to surgery, the remainder additional chemotherapy to complete the regimen may be given after surgery in the adjuvant setting. Patients with operable breast cancer experiencing progression of disease during preoperative systemic therapy may be given an alternate systemic regimen or proceed to surgery if deemed resectable.

乳腺浸润癌（BINV-N）

• 标题修改：根据基因表达指导术后内分泌治疗是否加用全身辅助化疗

• Title modified: Gene Expression Assays for Consideration of Adjuvant Systemic Therapy Addition of Adjuvant Systemic Chemotherapy to Adjuvant Endocrine Therapy

• 乳腺癌指数（BCI）预测作用不明确可预测延长术后内分泌治疗的获益

• Breast Cancer Index Predictive, modified: Not determined Predictive of benefit of extended adjuvant endocrine therapy

乳腺浸润癌（BINV-N 4 of 5）

• 根据最新文献，将乳腺癌指数（BCI）单列一页

• BCI recurrence risk and treatment implications significantly revised/updated.

• 新增参考文献：Clin Cancer Res. 2021;27(1):311-319.

• Reference added: Noordhoek I, Treuner K, Putter H, et al. Breast Cancer Index predicts extended endocrine benefit to individualize selection of HR+ early stage breast cancer patients for 10 years of endocrine therapy. Clin Cancer Res 2020 Oct 27. doi: 10.1158/1078-0432.CCR-20-2737. Online ahead of print.

乳腺浸润癌（BINV-O）

修改：对于治疗诱发停经的女性，如果考虑采用芳香酶抑制剂作为内分泌治疗的一部分，或需要卵巢切除术，或连续测定FSH和/或雌二醇水平，以确认患者处于绝经后状态。

Last line modified: For patients with therapy-induced amenorrhea, or oophorectomy or serial measurement of FSH and/or estradiol are needed to ensure postmenopausal status. if the use of aromatase inhibitors is considered as a component of endocrine therapy.

乳腺浸润癌（BINV-P）

• 某些情况下有用：

• Useful in certain circumstances

• 删除：氟甲睾酮

• Fluoxymesterone removed.

• 修改：乙炔雌二醇

• Modified: Ethinyl Estradiol

• 新增脚注a：推荐对接受芳香酶抑制剂且有骨质疏松风险（例如年龄>65岁、家族史、长期用类固醇）患者进行骨密度基线评定。

• Footnote added: Baseline assessment of bone density recommended for patients receiving an aromatase inhibitor who are at risk of osteoporosis (eg, age >65, family history, chronic steroids).

• 修改脚注c：如果CDK4/6或PI3K抑制剂治疗期间疾病进展，支持采用其他CDK4/6或PIK3CA治疗方案进行下一线治疗的数据有限

• Footnote modified: If there is disease progression while on a CDK4/6 or PI3K inhibitor therapy, there are limited data to support an additional line of therapy with another CDK4/6- or PIK3CA-containing regimen.

乳腺浸润癌（BINV-Q 2 of 7）

• 其他推荐方案：恩美曲妥珠单抗（T-DM1）改为1类推荐意见

• Other recommended regimen: Ado-trastuzumab emtansine (T-DM1) changed to a category 1 recommendation.

乳腺浸润癌（BINV-R 1 of 3)

• HR阳性/HER2阴性病变

• HR-positive/HER2-negative disease

• 生物标志修改：PIK3CA活化突变

• Biomarker modified: PIK3CA activating mutation

• HR阴性/HER2阴性病变

• HR-negative/HER2-negative disease

• 生物标志新增：PD-L1表达阳性临界值为联合阳性评分≥10

• Biomarker added: PD-L1 expression- Threshold for positivity combined positive score ≥10

• 新增药物：帕博利珠单抗＋化疗（白蛋白结合紫杉醇，紫杉醇，或吉西他滨和卡铂）。此为1类推荐意见

• Agent added: Pembrolizumab + chemotherapy (albuminbound paclitaxel, paclitaxel, or gemcitabine and carboplatin). This is a category 1 recommendation.

• 阿替利珠单抗＋白蛋白结合紫杉醇由2A类改为1类推荐意见

• Atezolizumab + albumin-bound paclitaxel changed from a category 2A to a category 1 recommendation.

• HR阴性/HER2阴性病变NCCN首选分类修改：首选一线治疗

• NCCN Category of Preference modified for the options for HR-negative/HER2-negative disease: Preferred first-line therapy

• 新增脚注h：虽然一线治疗已有数据，但是如果以前未用PD-L1抑制剂治疗，那么这些方案可用于二线及其后续治疗。如果PD-L1抑制剂治疗时疾病进展，那么没有数据支持采用其他PD-L1抑制剂进行下一线治疗。

• Footnote added: While available data are in the first-line setting, these regimens can be used for second and subsequent lines of therapy if PD-L1 inhibitor therapy has not been previously used. If there is disease progression while on a PD-L1 inhibitor, there are no data to support an additional line of therapy with another PD-L1 inhibitor.

• 帕博利珠单抗单药生物标志及其检测，新增：肿瘤突变负荷高（每百万碱基突变>10），由大规模并行测序（NGS）检出

• Biomarker and detection options added for single agent pembrolizumab: TMB-H (>10 muts/mb); detected by NGS

• 修改脚注g：帕博利珠单抗适用于治疗不可切除或转移、微卫星不稳定性高（MSI-H）或错配修复缺陷 (dMMR)、或肿瘤突变负荷高（TMB-H）既往治疗后出现进展且替代治疗方案不理想的患者。

• Footnote modified: Pembrolizumab is indicated for the treatment of patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, or TMB-H tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.

• 新增脚注e：参见NCCN免疫治疗相关毒性管理指南指南

• Footnote added: See NCCN Guidelines for Management of Immuotherapy-Related Toxicities.

乳腺浸润癌（BINV-R 2 of 3)

• 新增给药方案：帕博利珠单抗＋化疗（白蛋白结合紫杉醇，紫杉醇，或吉西他滨和卡铂）

• Dose schedule added for pembrolizumab + chemotherapy (albuminbound paclitaxel, paclitaxel, or gemcitabine and carboplatin)

• 新增参考文献：晚期三阴性乳腺癌一线化疗＋免疫治疗

• Reference added: Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020 Dec 5;396(10265):1817-1828.

乳腺浸润癌（BINV-S 3 of 3)

• 化疗期间肝功能检测、全血细胞计数建议随访间隔：每个周期之前，如有必要

• LFTs, CBC, interval modified for chemotherapy: Prior to each cycle, as indicated

• 化疗期间骨扫描建议随访间隔：每4～6个周期

• Bone scan, interval modified for chemotherapy: Every 4-6 cycles

• PET/CT建议随访间隔：由“可选”改为“临床如有必要”

• PET/CT intervals changed from "Optional" to "As clinically indicated"

• 肿瘤标志建议随访间隔：由“可选”改为“临床如有必要”

• Tumor Markers intervals changed from "Optional" to "As clinically indicated"

叶状肿瘤（PHYLL-1）

• 切除活检结果修改：

• Findings modified after excisional biopsy

• 纤维腺瘤或良性叶状肿瘤

• Fibroadenoma or benign Phyllodes tumor

• 叶状肿瘤，包括良性、交界性或和恶性

• Phyllodes tumor including benign, borderline or and malignant

• 粗针活检结果修改：

• Findings modified after core needle biopsy

• 纤维腺瘤或不确定或良性叶状肿瘤

• Fibroadenoma or Indeterminate or benign Phyllodes tumor

• 叶状肿瘤包括良性、交界性或和恶性叶状肿瘤

• Phyllodes tumor includes benign, Borderline or malignant Phyllodes tumor

妊娠期乳腺癌（PREG-1）

• 修改脚注d：尚无足够安全性数据支持推荐在妊娠期常规使用紫杉类。紫杉类用于妊娠期间的数据有限。如果要用，NCCN专家组推荐：根据病情，如有临床指征，妊娠前三个月后可予每周紫杉醇。

• Footnote d modified: There are insufficient safety data to recommend general use of taxanes during pregnancy. There are limited data on the use of taxanes during pregnancy. If used, the NCCN Panel recommends weekly administration of paclitaxel after the first trimester if clinically indicated by disease status.

炎性乳腺癌（IBC-1）

• 对检查项目进行重新组织（钼靶、CT、骨扫描、FDG-PET/CT、磁共振成像归入影像学检查）

• Workup reorganized.

• 新增磁共振成像：胸部/腹部/±盆腔增强CT或磁共振成像（由2B类改为2A类推荐意见）

• Added MRI as option: Abdominal ± pelvic diagnostic CT with contrast or MRI with contrast

• 骨扫描由2B类改为2A类推荐意见

• Bone scan changed from category 2B to category 2A recommendation.

• FDG-PET/CT删除“可选”

• Removed "optional" from FDG-PET/CT

• 删除：氟化钠PET/CT

• Removed: Sodium fluoride PET/CT

志谢：复旦大学附属肿瘤医院余科达教授对部分官方直译提供了修改意见，特此致谢！