早期乳腺癌局部治疗与全身治疗的进展与展望

doi:10.19401/j.cnki.1007-3639.2025.02.007

摘要/Abstract

摘要：

乳腺癌是女性最常见的恶性肿瘤。早期乳腺癌指病灶局限在乳房和区域淋巴结，并无远处转移的乳腺癌，其治疗策略包括术前新辅助治疗、局部治疗[手术和（或）放疗]以及术后辅助治疗。早期乳腺癌具有高度异质性，因此需要根据不同的分子亚型以及临床病理学特征制定对应治疗策略。目前将乳腺癌根据雌激素受体、孕激素受体和人表皮生长因子受体2（human epidermal growth factor receptor 2，HER2）的表达，进一步划分为激素受体阳性型、三阴性乳腺癌（triple-negative breast cancer，TNBC）、HER2阳性型等亚型，伴随着不同分子分型的生物学特性的深入探索，一系列新药的推陈出新，譬如针对激素受体阳性型的CDK4/6抑制剂、针对HER2阳性的抗HER2靶向治疗药物、针对TNBC的免疫治疗药物、针对BRCA突变的多腺苷二磷酸核糖聚合酶[poly (ADP-ribose) polymerase，PARP]抑制剂及新一代的抗体药物偶联物（antibody-drug conjugates，ADC）相继进入临床实践。结合精确的个体化治疗策略的实施，目前早期乳腺癌的预后不断提升，局部治疗也从“最大可耐受”模式更新至“最小最有效”模式。曾经绝大多数乳腺癌患者接受了全乳切除联合腋窝淋巴结清扫手术，而目前保乳手术和前哨淋巴结活检术已成为早期乳腺癌标准的手术方式。近20年来新辅助治疗促使肿瘤降期，更是为原本不可保乳、不可保腋窝的患者提供了外科降阶梯的可能。近年来，如何缩小手术范围，在保障治疗效果的同时减轻患者的身体、心理及经济负担的降阶梯局部治疗理念也不断普及。本文就早期乳腺癌局部和系统性治疗的现状、研究进展及展望予以综述，旨在为广大临床工作者提供参考。

关键词: 乳腺癌, 保乳手术, 前哨淋巴结活检, 新辅助治疗, 辅助治疗

Abstract:

Breast cancer is the most common malignant tumor in women. Early breast cancer refers to primary lesion localized in the breast and regional lymph nodes, and without distant metastasis. Treatment strategies include preoperative neoadjuvant therapy, local treatment (surgery and/or radiotherapy), and postoperative adjuvant therapy. Early breast cancer is highly heterogeneous, hence currently treatment strategies need to be formulated according to different molecular subtypes and pathology stages. At present, breast cancer is further divided into hormone receptor positive, triple negative breast cancer (TNBC), human epidermal growth factor receptor 2 (HER2) positive and other undefined subtypes. With the in-depth exploration of the biological characteristics of different molecular types, a series of new drugs have been developed, such as CDK4/6 inhibitors for hormone receptor positive, anti HER2 targeted therapy for HER2 positive, immunotherapy for TNBC, poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA mutations, and new generation of antibody-drug conjugates (ADCs) drug have entered clinical practice. Combined with the implementation of precision individualized treatment strategy, the prognosis of early breast cancer is also constantly improving, and local treatment is also updated from the "most tolerable" mode to the "least effective" mode, also known as “less is more”. Breast conserving surgery and sentinel lymph node biopsy have become the standard surgical methods for early breast cancer. The neo-adjuvant treatment has promoted the tumor down-staging, and it has also provided the possibility of surgical step-down for patients who could not have breast conserving surgery or sentinel lymph node biopsy. In recent years, the concept of reducing the scope and trauma of surgery, ensuring treatment effectiveness while reducing the physical, psychological, and economic burden on patients through local treatment, has been increasingly popular. This article reviewed the updated research progress and future prospects of local and systematic treatment of early breast cancer aimed to provide reference for clinical workers.

Key words: Breast cancer, Breast conserving surgery, Sentinel lymph node biopsy, Neoadjuvant therapy, Adjuvant therapy

中图分类号:

R737.9

李俊杰. 早期乳腺癌局部治疗与全身治疗的进展与展望[J]. 中国癌症杂志, 2025, 35(2): 205-212.

LI Junjie. Progress and future prospects in local and systemic treatment of early breast cancer[J]. China Oncology, 2025, 35(2): 205-212.

图/表 2

表1

乳腺癌AJCC分期"

T stage	Criteria	N stage	Criteria		M stage	Criteria
T stage	Criteria	N stage	Clinical	Pathology	M stage	Criteria
T0	No evidence of primary tumor	N0	No regional lymph node metastases (by imaging or clinical examination)	No regional lymph node metastasis identified or ITCs only	M0	No clinical or radiographic evidence of distant metastases
Tis	Ductal carcinoma in situ /Paget's	/
T1	T1mi: ≤ 1 mm; T1a: >1 mm, but ≤ 5 mm; T1b: >5 mm, but ≤ 10 mm; T1c: >10 mm, but ≤ 20 mm	N1	Metastases to movable ipsilateral level Ⅰ and Ⅱ axillary lymph node(s)	pN1mic: Micrometastases (>0.2 mm,<2.0 mm); pN1a: Metastases in 1-3 axillary lymph nodes, at least one metastasis >2.0 mm; pN1b: Metastases in ipsilateral internal mammary sentinel lymph nodes, excluding ITCs; pN1c: pN1a and pN1b combined	M1	Clinical or radiographic evidence of distant metastases
T2	>20 mm, but ≤ 50 mm	N2	cN2a: Metastases in ipsilateral level Ⅰ and Ⅱ axillary lymph nodes fixed to one another (matted) or to other structures; cN2b: Metastases only in ipsilateral internal mammary lymph nodes in the absence of axillary lymph node metastases	pN2a: Metastases in 4-9 axillary lymph nodes; pN2b: Metastases in clinically detected internal mammary lymph nodes with or without microscopic confirmation; with pathologically negative axillary lymph nodes
T3	>50 mm	N3	cN3a: Metastases in ipsilateral infraclavicular lymph node(s); cN3b: Metastases in ipsilateral internal mammary lymph node(s) and axillary lymph node(s); cN3c: Metastases in ipsilateral supraclavicular lymph node(s)	pN3a: Metastases in 10 or more axillary lymph nodes (at least one tumor deposit larger than 2.0 mm) or metastases to the infraclavicular; pN3b: pN1a or pN2a in the presence of cN2b or pN2a in the presence of pN1b; pN3c: Metastases in ipsilateral supraclavicular lymph nodes
T4	T4a: Extension to the chest wall; T4b:Ulceration and/or ipsilateral macroscopic satellite nodules and/or edema of the skin; T4c: Both T4a and T4b; T4d: Inflammatory carcinoma

表1

表2

参考文献 28

[1]	SIEGEL R L, GIAQUINTO AN, JEMAL A. Cancer statistics, 2024[J]. CA Cancer J Clin, 2024, 74: 12-49.
[2]	中国抗癌协会乳腺癌专业委员会, 中华医学会肿瘤学分会乳腺肿瘤学组. 中国抗癌协会乳腺癌诊治指南与规范(2024年版)[J]. 中国癌症杂志, 2023, 33(12): 1092-1187. doi: 10.19401/j.cnki.1007-3639.2023.12.004
	The Society of Breast Cancer China AntiCancer Association, Breast Oncology Group of the Oncology Branch of the Chinese Medical Association. Guidelines for breast cancer diagnosis and treatment by China Anti-cancer Association(2024 edition)[J]. China Oncol, 2023, 33(12): 1092-1187.
[3]	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.
[4]	SLAMON D, LIPATOV O, NOWECKI Z, et al. Ribociclib plus endocrine therapy in early breast cancer[J]. N Engl J Med, 2024, 390(12): 1080-1091.
[5]	HE M, JIANG Y Z, GONG Y, et al. Intensive chemotherapy versus standard chemotherapy among patients with high risk, operable, triple negative breast cancer based on integrated mRNA-lncRNA signature (BCTOP-T-A01): randomised, multicentre, phase 3 trial[J]. BMJ, 2024, 387: e079603.
[6]	LOIBL S, JASSEM J, SONNENBLICK A, et al. Adjuvant pertuzumab and trastuzumab in early human epidermal growth factor receptor 2-positive breast cancer in the APHINITY trial: third interim overall survival analysis with efficacy update[J]. J Clin Oncol, 2024, 42(31): 3643-3651. doi: 10.1200/JCO.23.02505 pmid: 39259927
[7]	GEYER C E Jr, GARBER J E, GELBER R D, et al. Overall survival in the OlympiA phase Ⅲ trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer[J]. Ann Oncol, 2022, 33(12): 1250-1268.
[8]	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.
[9]	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: S1470-2045(18)30570-9 pmid: 30413379
[10]	GHOSSAIN A, GHOSSAIN M A. History of mastectomy before and after Halsted[J]. J Med Liban, 2009, 57(2): 65-71.
[11]	FISHER B, WOLMARK N, REDMOND C, et al. Findings from NSABP protocol No. B-04: comparison of radical mastectomy with alternative treatments. Ⅱ. The clinical and biologic significance of medial-central breast cancers[J]. Cancer, 1981, 48(8): 1863-1872.
[12]	WAN A D, LIANG Y, CHEN L, et al. Association of long-term oncologic prognosis with minimal access breast surgery vs conventional breast surgery[J]. JAMA Surg, 2022, 157(12): e224711.
[13]	FISHER B, ANDERSON S, BRYANT J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer[J]. N Engl J Med, 2002, 347(16): 1233-1241.
[14]	MORAN M S, SCHNITT S J, GIULIANO A E, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages Ⅰ and Ⅱ invasive breast cancer[J]. J Clin Oncol, 2014, 32(14): 1507-1515.
[15]	BUNDRED J R, MICHAEL S, STUART B, et al. Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis[J]. BMJ, 2022, 378: e070346.
[16]	BOUGHEY J C, ROSENKRANZ K M, BALLMAN K V, et al. Impact of breast conservation therapy on local recurrence in patients with multiple ipsilateral breast cancer-results from ACOSOG Z11102 (alliance)[J]. Cancer Res, 2023, 83(5_Suppl): GS4-1-GS4-01.
[17]	Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials[J]. Lancet Oncol, 2018, 19(1): 27-39. doi: S1470-2045(17)30777-5 pmid: 29242041
[18]	《中国乳腺癌新辅助治疗专家共识2022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. doi: 10.19401/j.cnki.1007-3639.2022.01.011
	Expert group of expert consensus on neoadjuvant treatment of breast cancer in China (2022 edition). Expert consensus on neoadjuvant treatment of breast cancer in China (2022 edition)[J]. Chin Oncol, 2022, 32(1): 80-89. doi: 10.19401/j.cnki.1007-3639.2022.01.011
[19]	LYMAN G H, GIULIANO A E, SOMERFIELD M R, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer[J]. J Clin Oncol, 2005, 23(30): 7703-7720. doi: 10.1200/JCO.2005.08.001 pmid: 16157938
[20]	VERONESI U, PAGANELLI G, VIALE G, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer[J]. N Engl J Med, 2003, 349(6): 546-553.
[21]	GIULIANO A E, BALLMAN K V, MCCALL L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (alliance) randomized clinical trial[J]. JAMA, 2017, 318(10): 918-926.
[22]	BARTELS S A L, DONKER M, PONCET C, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS trial[J]. J Clin Oncol, 2023, 41(12): 2159-2165.
[23]	DE BONIFACE J, TVEDSKOV T F, RYDÉN L, et al. Omitting axillary dissection in breast cancer with sentinel-node metastases[J]. N Engl J Med, 2024, 390(13): 1163-1175.
[24]	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.
[25]	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 pmid: 24101169
[26]	GENTILINI O D, BOTTERI E, SANGALLI C, et al. Sentinel lymph node biopsy vs no axillary surgery in patients with small breast cancer and negative results on ultrasonography of axillary lymph nodes: the SOUND randomized clinical trial[J]. JAMA Oncol, 2023, 9(11): 1557-1564.
[27]	KUERER H M, SMITH B D, KRISHNAMURTHY S, et al. Eliminating breast surgery for invasive breast cancer in exceptional responders to neoadjuvant systemic therapy: a multicentre, single-arm, phase 2 trial[J]. Lancet Oncol, 2022, 23(12): 1517-1524.
[28]	中国抗癌协会乳腺癌专业委员会, 中国医师协会外科医师分会乳腺外科医师委员会, 上海市抗癌协会乳腺癌专业委员会. 乳腺肿瘤整形与乳房重建专家共识(2022年版)[J]. 中国癌症杂志, 2022, 32(9): 836-924. doi: 10.19401/j.cnki.1007-3639.2022.09.011
	Committee of Breast Cancer Society, Chinese Anti-Cancer Association; Breast Surgeons Committee of Surgeons Branch, Chinese Medical Doctor Association; Committee of Breast Cancer Society, Shanghai Anti-Cancer Association. Expert consensus on oncoplastic surgery of breast tumor and breast reconstruction (2022 edition)[J]. Chin Oncol, 2022, 32(9): 836-924. doi: 10.19401/j.cnki.1007-3639.2022.09.011

Subtype	Based on IHC
Subtype	ER	PR	HER2	Ki-67 proliferation index
Luminal A	Positive	High expression	Negative	Low
Luminal B
HER2^-	Positive	Low expression	Negative	High
HER2⁺	Positive	All	Positive	All
HER2⁺	Negative	Negative	Positive	All
TNBC	Negative	Negative	Negative	All