美国乳腺癌临床实践指南第二版更新

　　时隔56天，美国国家综合癌症网络NCCN于2021年3月12日悄然将乳腺癌临床实践指南更新至2021年第2版，全文由240页增至244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2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，具体更新如下（下划线为新增内容，中划线为删除内容）

整体修改

• 全部标题：复发性无法切除（局部或区域）或四期（M1）病变

• Headings modified throughout: Recurrent Unresectable (local or regional) or Stage IV (M1) Disease

乳腺浸润癌术后全身治疗：HR阳性HER2阴性病变（BINV-6）

• 标题修改：pN0改为绝经后患者伴pT1-3和pN0或pN+肿瘤

• pN0 → POSTMENOPAUSAL PATIENTS with pT1-3 AND pN0 or pN+ TUMORS

• 修改分支：肿瘤≤0.5厘米、肿瘤>0.5厘米改为肿瘤≤0.5厘米且pN0、肿瘤>0.5厘米或pN1微转移（腋窝转移淋巴结≤2毫米）或pN1（1～3枚淋巴结阳性）、pN2/pN3（≥4枚同侧淋巴结转移>2毫米）

• Branches modified: Tumor ≤0.5 cm and pN0; Tumor >0.5 cm or pN1 mi (≤2 mm axillary node metastases) or pN1 (1-3 positive nodes); pN2/pN3 (≥4 ipsilateral metastases >2 mm)

• 新增前提：如有化疗指征，强烈考虑21基因RT-PCR检测（1类证据）

• Modified: Strongly consider 21-gene RT-PCR assay if candidate for chemotherapy (category 1)

• 修改治疗：合并复发评分26～30和≥31为复发评分≥26；复发评分<26术后内分泌治疗改为1类证据；复发评分≥26术后化疗→内分泌治疗改为1类证据。

• Treatment: Replaced pathways for recurrence score 26-30 and ≥31 with a single pathway for recurrence score ≥26. Recurrence score <26: Adjuvant endocrine therapy changed to a category 1 recommendation. Recurrence score ≥26: Adjuvant chemotherapy followed by endocrine therapy changed to a category 1 recommendation.

• 修改脚注z：对于正在接受术后治疗的绝经后（自然或诱发）自然或诱发停经患者，考虑术后双膦酸盐治疗

• Footnote modified: Consider adjuvant bisphosphonate therapy in postmenopausal patients with natural or induced menopause. receiving adjuvant therapy.

乳腺浸润癌术后全身治疗：HR阳性HER2阴性病变（BINV-7）

• 标题修改：pN+改为绝经前患者伴pT1-3和pN0肿瘤

• pN+ → PREMENOPAUSAL PATIENTS with pT1-3 AND pN0 TUMORS

• 新增前提：如有化疗指征，强烈考虑21基因RT-PCR检测（1类证据）

• Modified: Strongly consider 21-gene RT-PCR assay if candidate for chemotherapy (category 1) (Also on BINV-7)

• 修改脚注z：对于正在接受术后治疗的绝经后（自然或诱发）自然或诱发停经患者，考虑术后双膦酸盐治疗

• Footnote modified: Consider adjuvant bisphosphonate therapy in postmenopausal patients with natural or induced menopause. receiving adjuvant therapy.

• 新增脚注kk：对于复发评分<26的患者，内分泌治疗±化疗相比，远处复发率较低，不过尚不明确该获益是否由于化疗促进卵巢抑制作用所致。

• Footnote added: In premenopausal patients with RS <26, the addition of chemotherapy to endocrine therapy was associated with a lower rate of distant recurrence compared with endocrine monotherapy, but it is unclear if the benefit was due to the ovarian suppression effects promoted by chemotherapy.

乳腺浸润癌术后全身治疗：HR阳性HER2阴性病变（BINV-8）

• 标题修改：pN+改为绝经前患者伴pT1-3和pN+肿瘤

• pN+ → PREMENOPAUSAL PATIENTS with pT1-3 AND pN+ TUMORS

• 修改脚注z：对于正在接受术后治疗的绝经后（自然或诱发）自然或诱发停经患者，考虑术后双膦酸盐治疗

• Footnote modified: Consider adjuvant bisphosphonate therapy in postmenopausal patients with natural or induced menopause. receiving adjuvant therapy.

• 治疗修改：如无化疗指征，术后内分泌治疗＋卵巢抑制/切除；如有化疗指征，考虑进行基因表达检测，根据预后选择术后化疗→内分泌治疗或术后内分泌治疗＋卵巢抑制/切除。

• Treatment options modified: Not a candidate for chemotherapy: Adjuvant endocrine therapy + ovarian suppression/ablation. If candidate for chemotherapy consider gene expression assay to assess prognosis: Adjuvant chemotherapy followed by endocrine therapy or adjuvant endocrine therapy + ovarian suppression/ablation

• 新增脚注kk：对于复发评分<26的患者，内分泌治疗±化疗相比，远处复发率较低，不过尚不明确该获益是否由于化疗促进卵巢抑制作用所致。

• Footnote added: In premenopausal patients with RS <26, the addition of chemotherapy to endocrine therapy was associated with a lower rate of distant recurrence compared with endocrine monotherapy, but it is unclear if the benefit was due to the ovarian suppression effects promoted by chemotherapy.

乳腺浸润癌术后内分泌治疗（BINV-K）

• 修改脚注c：对于正在接受术后芳香化酶抑制剂治疗的绝经后（自然或诱发）患者，考虑术后双膦酸盐或地舒单抗治疗。对于接受术后芳香化酶抑制剂治疗的绝经后（自然或诱发）患者，可选双膦酸盐（口服/静脉注射）或地舒单抗，以维持或改善骨密度并减少骨折风险。

• Footnote modified: Consider adjuvant bisphosphonate therapy or denosumab in postmenopausal (natural or induced) patients receiving adjuvant aromatase inhibitor therapy. The use of a bisphosphonate (oral/IV) or denosumab is acceptable to maintain or to improve bone mineral density and reduce risk of fractures in postmenopausal (natural or induced) patients receiving adjuvant aromatase inhibitor therapy.

乳腺浸润癌术前/术后治疗方案（BINV-L 1 of 7）

• 修改脚注h：将给药顺序改为紫杉醇紫杉类（±HER2靶向治疗）→剂量密集AC或许是可以接受的。

• Footnote h modified: It would be is acceptable to change the administration sequence to paclitaxel taxane (with or without HER2 targeted therapy) followed by dose-dense AC.

乳腺浸润癌术前/术后治疗方案（BINV-L 2 of 7）

• 修改脚注h：将给药顺序改为紫杉醇紫杉类（±HER2靶向治疗）→剂量密集AC或许是可以接受的。

• Footnote h modified: It would be is acceptable to change the administration sequence to paclitaxel taxane (with or without HER2 targeted therapy) followed by dose-dense AC.

乳腺浸润癌基因表达检测指导术后全身治疗（BINV-N 1 of 5）

• 根据2020年圣安东尼奥乳腺癌大会（SABCS）21基因检测复发评分<25、1～3枚淋巴结阳性、激素受体阳性且HER2阴性乳腺癌患者术后标准分泌治疗±化疗的RxPONDER（SWOG S1007）研究摘要，对表格进行更新。

• Table has been updated based on Kalinsky K, Barlow WE, Meric-Bernstam F, et al. First results from a phase III randomized clinical trial of standard adjuvant endocrine therapy (ET) +/- chemotherapy (CT) in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) < 25: SWOG S1007 (RxPonder). SABCS 2021;81(4): Abstract GS3-00.

• 修改表格：21基因（Oncotype Dx）检测对于pN+pN1（1～3枚淋巴结阳性）患者具有预测和预后作用：是 N/A 仍在等待RxPONDER研究结果，绝经后（1类证据）绝经前（2A类证据）

• Assay modified: 21-gene (Oncotype Dx) for pN+pN1 (1-3 positive nodes) Predictive: Yes N/A awaiting results of RxPONDER study NCCN Category of Preference/Evidence and Consensus: Postmenopausal: Preferred; 1. Premenopausal: Other; 2A.

• 修改脚注a：基因表达检测可对TNM分期和生物标志信息进行补充，有助结局预后和疗效预测。对于分期，这些检测并非必须。21基因检测（Oncotype Dx）被NCCN乳腺癌专家组首选用于淋巴结阴性乳腺癌预后和化疗获益预测。其他预后基因表达检测可为1～3枚淋巴结阳性患者提供更多预后信息，不过尚不明确能否预测1～3枚淋巴结阳性患者化疗获益的能力。

• Footnote modified: Gene expression assays provide prognostic and therapy-predictive information that complements T,N,M and biomarker information. Use of these assays is not required for staging. The 21-gene assay (Oncotype Dx) is preferred by the NCCN Breast Cancer Panel for node-negative breast cancer prognosis and prediction of chemotherapy benefit. Other prognostic gene expression assays can provide additional prognostic information in patients with 1-3 positive lymph nodes but are unknown if the ability to predict chemotherapy benefit is unknown. in 1-3 positive lymph nodes.

• 新增脚注c：在RxPONDER研究全部患者中，10.3%为高分级、9.2%有3枚淋巴结阳性。

• Footnote added: In the overall study population of the RxPONDER trial, 10.3% had high grade disease and 9.2% had 3 involved nodes.

乳腺浸润癌基因表达检测指导术后全身治疗（BINV-N 2 of 5）

• 根据TAILORx和RxPONDER研究结果，对表格进行更新。

• Page has been significantly revised.

• 修改脚注a：基因表达检测可对TNM分期和生物标志信息进行补充，有助结局预后和疗效预测。对于分期，这些检测并非必须。21基因检测（Oncotype Dx）被NCCN乳腺癌专家组首选用于淋巴结阴性乳腺癌预后和化疗获益预测。其他预后基因表达检测可为1～3枚淋巴结阳性患者提供更多预后信息，不过尚不明确能否预测1～3枚淋巴结阳性患者化疗获益的能力。

• Footnote modified: Gene expression assays provide prognostic and therapy-predictive information that complements T,N,M and biomarker information. Use of these assays is not required for staging. The 21-gene assay (Oncotype Dx) is preferred by the NCCN Breast Cancer Panel for node-negative breast cancer prognosis and prediction of chemotherapy benefit. Other prognostic gene expression assays can provide additional prognostic information in patients with 1-3 positive lymph nodes but are unknown if the ability to predict chemotherapy benefit is unknown. in 1-3 positive lymph nodes.

乳腺浸润癌基因表达检测指导术后全身治疗（BINV-N 3 of 5）

• 修改脚注a：基因表达检测可对TNM分期和生物标志信息进行补充，有助结局预后和疗效预测。对于分期，这些检测并非必须。21基因检测（Oncotype Dx）被NCCN乳腺癌专家组首选用于淋巴结阴性乳腺癌预后和化疗获益预测。其他预后基因表达检测可为1～3枚淋巴结阳性患者提供更多预后信息，不过尚不明确能否预测1～3枚淋巴结阳性患者化疗获益的能力。

• Footnote modified: Gene expression assays provide prognostic and therapy-predictive information that complements T,N,M and biomarker information. Use of these assays is not required for staging. The 21-gene assay (Oncotype Dx) is preferred by the NCCN Breast Cancer Panel for node-negative breast cancer prognosis and prediction of chemotherapy benefit. Other prognostic gene expression assays can provide additional prognostic information in patients with 1-3 positive lymph nodes but are unknown if the ability to predict chemotherapy benefit is unknown. in 1-3 positive lymph nodes.

乳腺浸润癌基因表达检测指导术后全身治疗（BINV-N 4 of 5）

• 修改脚注a：基因表达检测可对TNM分期和生物标志信息进行补充，有助结局预后和疗效预测。对于分期，这些检测并非必须。21基因检测（Oncotype Dx）被NCCN乳腺癌专家组首选用于淋巴结阴性乳腺癌预后和化疗获益预测。其他预后基因表达检测可为1～3枚淋巴结阳性患者提供更多预后信息，不过尚不明确能否预测1～3枚淋巴结阳性患者化疗获益的能力。

• Footnote modified: Gene expression assays provide prognostic and therapy-predictive information that complements T,N,M and biomarker information. Use of these assays is not required for staging. The 21-gene assay (Oncotype Dx) is preferred by the NCCN Breast Cancer Panel for node-negative breast cancer prognosis and prediction of chemotherapy benefit. Other prognostic gene expression assays can provide additional prognostic information in patients with 1-3 positive lymph nodes but are unknown if the ability to predict chemotherapy benefit is unknown. in 1-3 positive lymph nodes.

乳腺浸润癌基因表达检测指导术后全身治疗（BINV-N 5 of 5）

• 更新参考文献

• References have been updated.

乳腺浸润癌：ER和/或PR阳性复发性无法切除（局部或区域）或四期（M1）病变全身治疗方案（BINV-P）

• 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抑制剂进行下一线治疗的数据有限。如果PI3K抑制剂治疗期间疾病进展，支持采用包含PIK3CA方案进行下一线治疗的数据有限。

• Footnote c clarified: If there is disease progression while on a CDK4/6 inhibitor, there are limited data to support the use of another CKD4/6 inhibitor. If there is progression while on a PI3K inhibitor, there are limited data to support another line of therapy with a PIK3CA-containing regimen.

乳腺浸润癌：HER2阳性复发性无法切除（局部或区域）或四期（M1）病变全身治疗方案（BINV-Q 2 of 8）

• 按一线、二线、三线及以上，对表格所列治疗方案进行重新排列组合。

• Table reorganized to list regimens by setting/line of therapy.

• 三线及以上治疗方案新增：马格妥昔单抗＋化疗（卡培他滨、艾立布林、吉西他滨或长春瑞滨）

• Third-line therapy and beyond: Regimen added: Margetuximab-cmkb + chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine)

• 新增脚注j：一线治疗缓解后曲妥珠单抗/帕妥珠单抗维持（如果ER阳性，同时给予内分泌治疗）

• Maintenance trastuzumab/pertuzumab after response (with concurrent endocrine therapy if ER+ and HER2+ metastatic breast cancer).

• 新增脚注k：该治疗方案可用于三线或四线选择；三线及以上治疗最佳顺序尚不明确。

• Regimen may be used as a third- or fourth-line option; the optimal sequence for third-line therapy and beyond is not known.

• 新增脚注l：妥卡替尼＋曲妥珠单抗＋卡培他滨被推荐用于恩美曲妥珠单抗治疗期间全身和中枢神经系统进展患者。

• Tucatinib + trastuzumab + capecitabine is preferred in patients with both systemic and CNS progression on ado-trastuzumab emtansine.

• 新增脚注m：德鲁曲妥珠单抗被推荐用于恩美曲妥珠单抗治疗期间进展的内脏转移患者。

• Fam-trastuzumab deruxtecan-nxki is preferred in patients with visceral metastases if progression on ado-trastuzumab emtansine.

• 新增脚注o：多线化疗同时抗HER2治疗（曲妥珠单抗或酪氨酸激酶抑制剂）可为复发性不可切除HER2阳性转移性乳腺癌提供临床获益，并且已被2或3期试验进行研究。临床经验表明，此类治疗方案通常可带来临床获益。不过，对于曾经帕妥珠单抗＋化疗、恩美曲妥珠单抗、德鲁曲妥珠单抗、曲妥珠单抗＋卡培他滨＋妥卡替尼方案治疗的患者，此类治疗方案缺乏任何有意义的数据。因此，治疗的最佳顺序或真正获益尚不明确。

• Multiple lines of concurrent chemotherapy with anti-HER2 therapy (trastuzumab or a TKI) offer clinical benefit for recurrent unresectable HER2+ metastatic breast cancer and have been studied in phase 2 or 3 trials. Clinical experience suggests frequent clinical benefit for such treatment. However, there are no meaningful data for use of any of these regimens among patients previously treated with pertuzumab-based chemotherapy, ado-trastuzumab emtansine, fam-trastuzumab deruxtecan-nxki, or trastuzumab/capecitabine/tucatinib regimens. Thus, the optimal sequence or true benefit of therapy is not known.

• 该页部分脚注移至下页：正在接受全身HER2靶向治疗患者的其他注意事项

• Select footnotes were moved from this page to BINV-Q (3 of 8) under: Additional Considerations for Those Receiving Systemic HER2-Targeted Therapy.

乳腺浸润癌：HER2阳性复发性无法切除（局部或区域）或四期（M1）病变全身治疗方案（BINV-Q 6 of 8）

• 新增用法：马格妥昔单抗＋卡培他滨、马格妥昔单抗＋艾立布林、马格妥昔单抗＋吉西他滨、马格妥昔单抗＋长春瑞滨

• Dosing added for: Margetuximab-cmkb + capecitabine, Margetuximab-cmkb + eribulin, Margetuximab-cmkb + gemcitabine, Margetuximab-cmkb + vinorelbine

乳腺浸润癌：HER2阳性复发性无法切除（局部或区域）或四期（M1）病变全身治疗方案（BINV-Q 8 of 8）

• 更新参考文献

• References have been updated.

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