中国乳腺癌新辅助治疗专家共识（2022年版）

doi:10.19401/j.cnki.1007-3639.2022.01.011

摘要/Abstract

摘要：

新辅助治疗已经成为乳腺癌综合治疗中非常重要的组成部分,2019年中国乳腺癌新辅助治疗专家组就新辅助治疗的目的、适应证、评估规范、手术治疗原则及新辅助系统治疗的策略进行了详细探讨和阐述,结合近两年新的循证医学证据和学术理念,对新辅助治疗临床实施规范和治疗原则予以更新和说明。

关键词: 乳腺癌, 新辅助治疗, 共识

Abstract:

Neoadjuvant therapy has become one of the standard treatments in early breast cancer. In 2019, China breast cancer neoadjuvant therapy expert group discussed and expounded the purpose, indication, evaluation criteria, surgical operation principles and the treatment strategy of neoadjuvant therapy. We further updated and discussed the clinical implementations and treatment principles of neoadjuvant therapy.

Key words: Breast cancer, Neoadjuvant treatment, Consensus

中图分类号:

R737.9

《中国乳腺癌新辅助治疗专家共识（年版）》专家组. 中国乳腺癌新辅助治疗专家共识（2022年版）[J]. 中国癌症杂志, 2022, 32(1): 80-89.

Expert group of expert consensus on neoadjuvant treatment of breast cancer in China ( edition) . Expert consensus on neoadjuvant treatment of breast cancer in China (2021 edition)[J]. China Oncology, 2022, 32(1): 80-89.

图/表 1

表 1

专家组投票结果"

题目	投票结果
题目	同意	不同意	弃权或无法确定
临床实践中,初诊不可手术患者,病灶穿刺明确病理学检查结果（浸润性癌）后,何时常规推荐等待IHC结果以制订后续治疗策略：
A.只要化疗方案选择合适（如先蒽环类药物序贯紫杉类药物）,不需等待IHC结果,后续调整即可;	7%	92%	0%
B.所有患者均需等待IHC结果后方制订方案。	84%	15%	0%
临床实践中,初诊可手术患者,拟行新辅助治疗,病灶穿刺明确病理学检查结果（浸润性癌）后, 具有以下特征时,推荐等待IHC结果：
A.只要化疗方案选择合适（如蒽环类药物序贯紫杉类药物）,所有患者均不需等待IHC结果;	12%	87%	0%
B.肿块超过2 cm但cN₀期;	59%	40%	0%
C.肿块超过5 cm但cN₃期;	79%	20%	0%
D.腋窝淋巴结阳性cN₁期;	96%	4%	0%
E.所有患者均需等待IHC结果后方制订方案。	92%	7%	0%
对于腋窝临床体检阴性的患者,新辅助治疗前仍建议进行超声评估腋窝状态	100%	0%	0%
如腋窝临床体检阴性但超声提示可疑腋窝淋巴结,建议超声引导下行穿刺明确	92%	7%	0%
新辅助治疗前,所有患者均需行基线的下述哪项检查,以完整评估原发灶范围：
A.超声;	100%	0%	0%
B.乳腺X线;	89%	7%	3%
C.乳腺磁共振。	86%	10%	3%
新辅助治疗前,哪些患者需行骨扫描：
A.全部患者;	23%	69%	7%
B.仅T₃期和（或）N₂期及以上患者;	67%	25%	7%
C.无需。	0%	96%	3%
新辅助治疗前,哪些患者需行PET/CT：
A.全部患者;	0%	100%	0%
B.仅T₃期和（或）N₂期及以上患者;	75%	17%	6%
C.无需。	11%	85%	3%
仅新辅助治疗前cN₁期及以下患者,新辅助治疗降期后才能进行前哨淋巴结活检（即cN_2-3期患者新辅助治疗降期后也不适合SLNB）。	72%	24%	3%
新辅助治疗降期后,行前哨淋巴结活检时建议常规采用双示踪（蓝染+核素）,其他的替代方法有：
A.采用荧光染料示踪替代核素示踪;	33%	48%	18%
B.对于有经验的操作者,可用蓝染单示踪。	56%	26%	17%
已确认新辅助治疗前,乳腺原发灶需进行标识（内标记marker & 外标记体表投影纹身）,若进行内标记,推荐marker放置的部位为：
A.病灶中央放置marker;	75%	17%	6%
B.病灶中央及边缘放置marker。	67%	21%	10%
已确认新辅助治疗前,乳腺原发灶需进行标识（内标记marker & 外标记体表投影纹身）,若无内标记,应该通过表面病灶投影如纹身或图示等方法外标记。	92%	7%	0%
ER⁺HER²⁺患者,哪些可采用靶向（双靶或单靶抗体药物）联合内分泌治疗：
A.所有患者,基于药敏尝试;	13%	81%	4%
B.高选择的不能耐受化疗患者;	100%	0%	0%
C.ER高表达、淋巴结阴性的绝经后患。	37%	50%	12%
ER^-HER²⁺患者,是否可采用仅用双靶治疗：
A.所有患者,基于药敏尝试;	3%	96%	0%
B.高选择的不能耐受化疗患者;	82%	13%	3%
C.淋巴结阴性的患者。	11%	88%	0%
TNBC患者,患者充分告知并且药物可及时,可推荐新辅助PD-1/PD-L1免疫治疗：
A.所有患者;	7%	88%	3%
B.仅PD-1/PD-L1阳性患者;	37%	51%	11%
C.不常规推荐。	80%	11%	7%
具有较重肿瘤负荷（cN₊期）的TNBC患者,新辅助治疗首选方案：
A.蒽环类药物联合/序贯紫杉类药物;	96%	3%	0%
B.蒽环类药物序贯紫杉类药物和铂类药物;	53%	38%	7%
C.紫杉类药物、铂类药物联合方案（后续序贯或不序贯蒽环类药物）;	66%	33%	0%
D.蒽环类药物、紫杉类药物方案+PARP抑制剂;	3%	88%	7%
E.蒽环类药物、紫杉类药物、铂类药物联合方案+PARP抑制剂。	0%	100%	0%
gBRCAmut患者,新辅助首选方案：
A.蒽环类药物联合/序贯紫杉类药物;	73%	26%	0%
B.蒽环类药物序贯紫杉类药物和铂类药物;	84%	11%	3%
C.紫杉类药物、铂类药物联合方案（后续序贯或不序贯蒽环类药物）;	76%	19%	3%
D.化疗联合PARP抑制剂;	17%	72%	10%
E.仅PARP抑制剂。	3%	96%	0%
Luminal型患者新辅助内分泌治疗适用于：
A.所有患者,基于药敏平台;	7%	92%	0%
B.不能耐受化疗的患者;	88%	7%	3%
C.ER高表达、cT_1-2N₀期患者;	37%	59%	3%
D.除临床试验外,不常规推荐。	59%	37%	3%
Luminal型患者如果使用新辅助内分泌治疗,推荐采用：
A.AI（绝经前+OFS）;	81%	18%	0%
B.氟维司群（绝经前+OFS）;	28%	60%	12%
C.CDK4/6抑制剂+AI（绝经前+OFS）。	42%	53%	3%
2个疗程评估退缩不佳的患者,需考虑治疗策略的改换（局部和或全身治疗）	57%	32%	10%
4个疗程评估退缩不佳的患者,需考虑治疗策略的改换（局部和或全身治疗）	96%	0%	3%
可手术乳腺癌,4个疗程临床评估SD时,HER2阳性,初始化疗+HP双靶治疗：
A.更改化疗方案+HP;	7%	80%	11%
B.更改化疗方案+TKI;	46%	53%	0%
C.更改化疗方案+TKI+曲妥珠单抗;	48%	51%	0%
D.手术;	75%	21%	3%
E.继续原方案。	0%	0%	0%
可手术乳腺癌,4个疗程临床评估SD时,TNBC,初始EC新辅助治疗：
A.继续序贯紫杉类药物方案;	61%	30%	7%
B.序贯紫杉类药物+铂类药物;	75%	20%	4%
C.手术。	69%	26%	3%
可手术乳腺癌,4个疗程临床评估SD时,TNBC,初始TEC新辅助治疗：
A.更改为含铂类药物方案;	50%	42%	7%
B.更改为NX方案;	30%	57%	11%
C.手术;	86%	13%	0%
D.继续TEC 2个疗程。	0%	96%	3%
可手术乳腺癌,4个疗程临床评估SD时,TNBC,初始PCb新辅助治疗：
A.更改为EC;	32%	64%	4%
B.手术;	92%	7%	0%
C.继续PCb 2个疗程。	0%	100%	0%
在规范的新辅助治疗评估,以及足疗程治疗后,初始cN₁期的TNBC或HER₂⁺患者新辅助治疗后cN₀期,前哨淋巴结活检仅获得2枚,均阴性,腋窝如何处理：
A.腋窝淋巴结清扫;	50%	41%	8%
B.腋窝区域放疗;	63%	18%	18%
C.腋窝不处理。	25%	70%	4%
在规范的新辅助治疗评估,以及足疗程治疗后,初始cN₁期的TNBC或HER²⁺患者,新辅助治疗后cN₀期,前哨淋巴结活检仅获得1枚,阴性,腋窝如何处理：
A.腋窝淋巴结清扫;	73%	23%	3%
B.腋窝区域放疗;	33%	58%	8%
C.腋窝不处理。	4%	84%	12%
在规范的新辅助治疗评估,以及足疗程治疗后,初始cN₁期患者,新辅助治疗后cN₀期,前哨淋巴结活检3枚及以上的石蜡包埋切片病理学检查仅1枚ITC时,后续腋窝如何处理：
A.腋窝淋巴结清扫;	50%	50%	0%
B.腋窝区域放疗。	60%	34%	4%
在规范的新辅助治疗评估,以及足疗程治疗后,初始cN₁期患者,新辅助治疗后cN₀期,前哨淋巴结活检3枚及以上的石蜡包埋切片病理学检查仅1枚微转移时,后续腋窝如何处理：
A.腋窝淋巴结清扫;	88%	12%	0%
B.腋窝区域放疗。	50%	41%	8%
在规范的新辅助治疗评估,以及足疗程治疗后,初始cN₁期患者,新辅助治疗后cN₀期,前哨淋巴结活检3枚及以上的石蜡包埋切片病理学检查仅1枚宏转移时,后续腋窝如何处理：
A.腋窝淋巴结清扫;	96%	3%	0%
B.腋窝区域放疗。	13%	78%	8%
初始不可保乳患者,新辅助治疗降期后,临床需慎重保乳的因素：
A.多灶病灶;	100%	0%	0%
B.TNBC;	15%	84%	0%
C.gBRCAmut。	57%	38%	3%
新辅助治疗后实施保乳手术,石蜡包埋切片病理学检查提示切缘不典型增生,后续除了放疗外的处理：
A.残腔广泛切除;	48%	48%	3%
B.全切;	0%	100%	0%
C.不处理。	63%	31%	0%
新辅助治疗后实施保乳手术,切缘阴性的定义：
A.No ink on tumor;	80%	16%	4%
B.1 mm;	48%	40%	11%
C.2 mm;	51%	44%	3%
D.5 mm;	12%	84%	4%
E.10 mm。	0%	96%	3%
HER2阳性,HP双靶+化疗,新辅助治疗后pCR,辅助治疗策略为：
A.继续完成满1年双靶;	100%	0%	0%
B.如新辅助治疗前肿瘤负荷较小（T₂N₀期）,仅使用曲妥珠单抗满1年;	39%	60%	0%
C.如新辅助治疗前肿瘤负荷较大[T₃期和（或）N₂期],辅助HP治疗后,继续TKI治疗1年。	40%	54%	4%
HER2阳性,HP双靶+化疗,新辅助治疗后non-pCR,T-DM1是当前标准的辅助治疗策略,以下情况：
A.残留肿瘤负荷较小时（MP4或RCB1）,可仅HP双靶治疗;	59%	36%	4%
B.残留肿瘤负荷较小时（MP4或RCB1）,可HP双靶治疗后,延长TKI治疗1年;	28%	60%	12%
C.退缩不明显、残留肿瘤负荷较大时（MP1-2或RCB3）可采用T-DM1后再延长TKI治疗1年。	20%	70%	8%
TNBC标准足疗程的新辅助治疗后,pCR,辅助强化治疗：
A.无需进行强化治疗;	91%	8%	0%
B.如新辅助治疗前肿瘤负荷较大[T₃期和（或）N₂期]继续卡培他滨节拍用法1年。	36%	52%	12%
TNBC标准足疗程的新辅助治疗后,non-pCR,卡培他滨是当前标准的辅助治疗策略。如采用PCb新辅助治疗6个疗程后,辅助强化治疗策略为：
A.EC3~4个疗程+/-卡培他滨;	40%	55%	5%
B.卡培他滨。	95%	4%	0%
Luminal（HER2^-）型标准足疗程的新辅助治疗后,non-pCR,辅助治疗策略除了标准内分泌治疗（AI+/-OFS）外：
A.卡培他滨;	37%	62%	0%
B.CDK4/6抑制剂。	77%	13%	9%

表 1

参考文献 31

[1]	中国乳腺癌新辅助治疗专家组. 中国乳腺癌新辅助治疗专家共识(2019年版)[J]. 中国癌症杂志, 2019, 29(5): 390-400.
	China Breast Cancer Neoadjuvant Therapy Expert Group. Expert consensus on neoadjuvant therapy for breast cancer in China (2019 edition)[J]. China Oncol, 2019, 29(5): 390-400.
[2]	KORDE L A, SOMERFIELD M R, CAREY L A, et al. Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO guideline[J]. J Clin Oncol, 2021, 39(13): 1485-1505. doi: 10.1200/JCO.20.03399
[3]	BURSTEIN H J, CURIGLIANO G, THÜRLIMANN B, et al. Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021[J]. Ann Oncol, 2021, 32(10): 1216-1235. doi: 10.1016/j.annonc.2021.06.023
[4]	中国抗癌协会乳腺癌专业委员会. 中国抗癌协会乳腺癌诊治指南与规范(2021年版)[J]. 中国癌症杂志, 2021, 31(10): 954-1040.
	The Society of Breast Cancer China Anti-Cancer Association. Guidelines for breast cancer diagnosis and treatment by China Anti-Cancer Association (2021 edition)[J]. China Oncol, 2021, 31(10): 954-1040.
[5]	BOUGHEY J C, SUMAN V J, MITTENDORF E A, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (alliance) clinical trial[J]. JAMA, 2013, 310(14): 1455-1461. doi: 10.1001/jama.2013.278932
[6]	BRACKSTONE M, BALDASSARRE F G, PERERA F E, et al. Management of the axilla in early-stage breast cancer: Ontario health (cancer care Ontario) and ASCO guideline[J]. J Clin Oncol, 2021, 39(27): 3056-3082. doi: 10.1200/JCO.21.00934
[7]	JUNG S Y, HAN J H, PARK S J, et al. The sentinel lymph node biopsy using indocyanine green fluorescence plus radioisotope method compared with the radioisotope-only method for breast cancer patients after neoadjuvant chemotherapy: a prospective, randomized, open-label, single-center phase 2 trial[J]. Ann Surg Oncol, 2019, 26(8): 2409-2416. doi: 10.1245/s10434-019-07400-0
[8]	MAMTANI A, BARRIO A V, KING T A, et al. How often does neoadjuvant chemotherapy avoid axillary dissection in patients with histologically confirmed nodal metastases? Results of a prospective study[J]. Ann Surg Oncol, 2016, 23(11): 3467-3474. doi: 10.1245/s10434-016-5246-8
[9]	《乳腺癌新辅助治疗的病理诊断专家共识2020版》编写组. 乳腺癌新辅助治疗的病理诊断专家共识(2020版)[J]. 中华病理学杂志, 2020, 49(4): 296-304.
	Writing Group of Expert Panel Consensus on Pathological Diagnosis of Breast Cancer with Neoadjuvant Therapy, the 2020 Version . Expert panel consensus on pathological diagnosis of breast cancer with neoadjuvant therapy, the 2020 version[J]. Chin J Pathol, 2020, 49(4): 296-304.
[10]	EL-DIDI M H, MONEER M M, KHALED H M, et al. Pathological assessment of the response of locally advanced breast cancer to neoadjuvant chemotherapy and its implications for surgical management[J]. Surg Today, 2000, 30(3): 249-254. doi: 10.1007/s005950050054
[11]	HARBECK N, GLUZ O, CHRISTGEN M, et al. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): final analysis of the west German study group adjuvant dynamic marker-adjusted personalized therapy trial optimizing risk assessment and therapy response prediction in early BC HER2^- and hormone receptor-positive phase Ⅱ randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET[J]. J Clin Oncol, 2017, 35(26): 3046-3054. doi: 10.1200/JCO.2016.71.9815
[12]	PÉREZ-GARCÍA J M, GEBHART G, RUIZ BORREGO M, et al. Chemotherapy de-escalation using an ¹⁸F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): a multicentre, randomised, open-label, non-comparative, phase 2 trial[J]. Lancet Oncol, 2021, 22(6): 858-871. doi: 10.1016/S1470-2045(21)00122-4
[13]	LOIBL S, UNTCH M, BURCHARDI N, et al. A randomised phase Ⅱ study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study[J]. Ann Oncol, 2019, 30(8): 1279-1288. doi: 10.1093/annonc/mdz158
[14]	MITTENDORF E A, ZHANG H, BARRIOS C H, et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial[J]. Lancet, 2020, 396(10257): 1090-1100. doi: 10.1016/S0140-6736(20)31953-X
[15]	SCHMID P, CORTES J, PUSZTAI L, et al. Pembrolizumab for early triple-negative breast cancer[J]. N Engl J Med, 2020, 382(9): 810-821. doi: 10.1056/NEJMoa1910549
[16]	POGGIO F, BRUZZONE M, CEPPI M, et al. Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis[J]. Ann Oncol, 2018, 29(7): 1497-1508. doi: 10.1093/annonc/mdy127
[17]	ELLIS M J, SUMAN V J, HOOG J, et al. Ki-67 proliferation index as a tool for chemotherapy decisions during and after neoadjuvant aromatase inhibitor treatment of breast cancer: results from the American College of Surgeons Oncology group Z1031 trial (alliance)[J]. J Clin Oncol, 2017, 35(10): 1061-1069. doi: 10.1200/JCO.2016.69.4406
[18]	NITZ U, GLUZ O, KREIPE H H, et al. The run-in phase of the prospective WSG-ADAPT HR+/HER2- trial demonstrates the feasibility of a study design combining static and dynamic biomarker assessments for individualized therapy in early breast cancer[J]. Ther Adv Med Oncol, 2020, 12: 1758835920973130.
[19]	SCHNEEWEISS A, CHIA S, HICKISH T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase Ⅱ cardiac safety study (TRYPHAENA)[J]. Ann Oncol, 2013, 24(9): 2278-2284. doi: 10.1093/annonc/mdt182
[20]	HURVITZ S A, MARTIN M, JUNG K H, et al. Neoadjuvant trastuzumab emtansine and pertuzumab in human epidermal growth factor receptor 2-positive breast cancer: three-year outcomes from the phase Ⅲ KRISTINE study[J]. J Clin Oncol, 2019, 37(25): 2206-2216. doi: 10.1200/JCO.19.00882
[21]	VAN RAMSHORST M S, VAN DER VOORT A, VAN WERKHOVEN E D, et al. Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial[J]. Lancet Oncol, 2018, 19(12): 1630-1640. doi: 10.1016/S1470-2045(18)30570-9
[22]	NCCN Clinical Practice Guidelines in Oncology-Breast Cancer (Version 8 2021)[M]. 2021.
[23]	MASUDA N, LEE S J, OHTANI S, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy[J]. N Engl J Med, 2017, 376(22): 2147-2159. doi: 10.1056/NEJMoa1612645
[24]	VON MINCKWITZ G, HUANG C S, MANO M S, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer[J]. N Engl J Med, 2019, 380(7): 617-628. doi: 10.1056/NEJMoa1814017
[25]	VON MINCKWITZ G, BLOHMER J U, COSTA S D, et al. Response-guided neoadjuvant chemotherapy for breast cancer[J]. J Clin Oncol, 2013, 31(29): 3623-3630. doi: 10.1200/JCO.2012.45.0940
[26]	CROSHAW R, SHAPIRO-WRIGHT H, SVENSSON E, et al. Accuracy of clinical examination, digital mammogram, ultrasound, and MRI in determining postneoadjuvant pathologic tumor response in operable breast cancer patients[J]. Ann Surg Oncol, 2011, 18(11): 3160-3163. doi: 10.1245/s10434-011-1919-5
[27]	GIANNI L, EIERMANN W, SEMIGLAZOV V, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort[J]. Lancet, 2010, 375(9712): 377-384. doi: 10.1016/S0140-6736(09)61964-4
[28]	GIANNI L, PIENKOWSKI T, IM Y H, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial[J]. Lancet Oncol, 2016, 17(6): 791-800. doi: 10.1016/S1470-2045(16)00163-7
[29]	JOHNSTON S R D, HARBECK N, HEGG R, et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR⁺, HER2^-, node-positive, high-risk, early breast cancer (monarchE)[J]. J Clin Oncol, 2020, 38(34): 3987-3998. doi: 10.1200/JCO.20.02514
[30]	MAYER I A, ZHAO F M, ARTEAGA C L, et al. Randomized phase Ⅲ postoperative trial of platinum-based chemotherapy versus capecitabine in patients with residual triple-negative breast cancer following neoadjuvant chemotherapy: ECOG-ACRIN EA1131[J]. J Clin Oncol, 2021, 39(23): 2539-2551. doi: 10.1200/JCO.21.00976
[31]	LOIBL S, MARMÉ F, MARTIN M, et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer-the Penelope-B trial[J]. J Clin Oncol, 2021, 39(14): 1518-1530. doi: 10.1200/JCO.20.03639