三阳性乳腺癌内分泌治疗联合靶向治疗的研究进展

doi:10.19401/j.cnki.1007-3639.2023.03.013

摘要/Abstract

摘要：

三阳性乳腺癌（triple-positive breast cancer，TPBC）是指雌激素受体、孕激素受体和人表皮生长因子受体2（human epidermal growth factor receptor 2，HER2）表达均为阳性的乳腺癌，占所有乳腺癌病理学类型的5%~10%。TPBC是Luminal B型乳腺癌亚型的一种特殊类型，既可以接受内分泌治疗，又可以接受靶向治疗。目前国内外指南推荐TPBC的治疗首选抗HER2靶向治疗联合化疗，但TPBC新辅助治疗的病理学完全缓解率却低于激素受体阴性/HER2阳性乳腺癌，且雌激素受体表达>30%的患者从抗HER2靶向治疗联合化疗中获益较小。目前随着多种抗HER2靶向药物不断问世，以及细胞周期蛋白依赖性激酶4和6抑制剂的临床应用，使得临床上对于高选择的患者首选靶向治疗联合内分泌治疗成为可能。本文就TPBC内分泌治疗联合靶向治疗的最新研究进展进行综述。

关键词: 三阳性乳腺癌, 内分泌治疗, 靶向治疗

Abstract:

Triple-positive breast cancer (TPBC) refers to breast cancer with positive expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2), accounting for 5%-10% of all pathological types of breast cancer. TPBC is a special subtype of Luminal B breast cancer, which can receive both endocrine therapy and targeted therapy. TPBC is a special subtype of Luminal B breast cancer, which can receive both endocrine therapy and targeted therapy. The current guidelines recommend that anti-HER2-targeted therapy combined with chemotherapy is the first choice for TPBC treatment. However, the pathological complete response rate of TPBC is lower than that of hormone receptor negative/HER2-positive breast cancer. Moreover, patients with estrogen receptor expression >30% benefit less from anti-HER2-targeted therapy combined with chemotherapy. With the advent of various anti-HER2 targeted drugs and the clinical application of cyclin-dependent kinase 4 and 6 inhibitors, the combination of targeted therapy and endocrine therapy becomes possible for highly selected patients. This article reviewed the research progress of TPBC endocrine therapy combined with targeted therapy.

Key words: Triple-positive breast cancer, Endocrine therapy, Targeted therapy

中图分类号:

R737.9

曹晓珊, 丛斌斌. 三阳性乳腺癌内分泌治疗联合靶向治疗的研究进展[J]. 中国癌症杂志, 2023, 33(3): 288-292.

CAO Xiaoshan, CONG Binbin. The research progress of endocrine therapy combined with targeted therapy for triple-positive breast cancer[J]. China Oncology, 2023, 33(3): 288-292.

参考文献 21

[1]	JOHNSTON S R D, HEGG R, IM S A, et al. Phase Ⅲ, randomized study of dual human epidermal growth factor receptor 2 (HER2) blockade with lapatinib plus trastuzumab in combination with an aromatase inhibitor in postmenopausal women with HER2-positive, hormone receptor-positive metastatic breast cancer: updated results of ALTERNATIVE[J]. J Clin Oncol, 2021, 39(1): 79-89.
[2]	CORTAZAR P, ZHANG L J, UNTCH M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis[J]. Lancet, 2014, 384(9938): 164-172. doi: 10.1016/S0140-6736(13)62422-8 pmid: 24529560
[3]	DIECI M V, GUARNERI V. Should triple-positive breast cancer be recognized as a distinct subtype?[J]. Expert Rev Anticancer Ther, 2020, 20(12): 1011-1014. doi: 10.1080/14737140.2020.1829484
[4]	MONTEMURRO F, ROSSI V, COSSU ROCCA M, et al. Hormone-receptor expression and activity of trastuzumab with chemotherapy in HER2-positive advanced breast cancer patients[J]. Cancer, 2012, 118(1): 17-26. doi: 10.1002/cncr.26162 pmid: 21598238
[5]	CROESSMANN S, FORMISANO L, KINCH L N, et al. Combined blockade of activating ERBB2 mutations and ER results in synthetic lethality of ER⁺/HER2 mutant breast cancer[J]. Clin Cancer Res, 2019, 25(1): 277-289. doi: 10.1158/1078-0432.CCR-18-1544
[6]	KAUFMAN B, MACKEY J R, CLEMENS M R, et al. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase Ⅲ TAnDEM study[J]. J Clin Oncol, 2009, 27(33): 5529-5537. doi: 10.1200/JCO.2008.20.6847
[7]	JOHNSTON S, PIPPEN J Jr, PIVOT X, et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer[J]. J Clin Oncol, 2009, 27(33): 5538-5546. doi: 10.1200/JCO.2009.23.3734 pmid: 19786658
[8]	OZAKI Y, AOYAMA Y, MASUDA J, et al. Trastuzumab and fulvestrant combination therapy for women with advanced breast cancer positive for hormone receptor and human epidermal growth factor receptor 2: a retrospective single-center study[J]. BMC Cancer, 2022, 22(1): 36. doi: 10.1186/s12885-021-09128-1 pmid: 34983437
[9]	STATLER A B, HOBBS B P, WEI W, et al. Real-world treatment patterns and outcomes in HR⁺/HER2⁺ metastatic breast cancer patients: a national cancer database analysis[J]. Sci Rep, 2019, 9(1): 18126. doi: 10.1038/s41598-019-54402-9
[10]	HUA X, BI X W, ZHAO J L, et al. Trastuzumab plus endocrine therapy or chemotherapy as first-line treatment for patients with hormone receptor-positive and HER2-positive metastatic breast cancer (SYSUCC-002)[J]. Clin Cancer Res, 2022, 28(4): 637-645. doi: 10.1158/1078-0432.CCR-21-3435
[11]	BASELGA J, CORTÉS J, KIM S B, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer[J]. N Engl J Med, 2012, 366(2): 109-119. doi: 10.1056/NEJMoa1113216
[12]	RIMAWI M, FERRERO J M, DE LA HABA-RODRIGUEZ J, et al. First-line trastuzumab plus an aromatase inhibitor, with or without pertuzumab, in human epidermal growth factor receptor 2-positive and hormone receptor-positive metastatic or locally advanced breast cancer (PERTAIN): a randomized, open-label phase Ⅱ trial[J]. J Clin Oncol, 2018, 36(28): 2826-2835. doi: 10.1200/JCO.2017.76.7863
[13]	HUOBER J, RIBI K, WEDER P, et al. Pertuzumab (P) + trastuzumab (T) with or without chemotherapy both followed by T-DM1 in case of progression in patients with HER2-positive metastatic breast cancer (MBC) - The PERNETTA trial (SAKK 22/10), a randomized open label phase Ⅱ study (SAKK, UNICANCER, BOOG)[J]. Ann Oncol, 2019, 30: iii47-iii64.
[14]	CIRUELOS E, VILLAGRASA P, PASCUAL T, et al. Palbociclib and trastuzumab in HER2-positive advanced breast cancer: results from the phase Ⅱ SOLTI-1303 PATRICIA trial[J]. Clin Cancer Res, 2020, 26(22): 5820-5829. doi: 10.1158/1078-0432.CCR-20-0844
[15]	TOLANEY S M, WARDLEY A M, ZAMBELLI S, et al. Abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in women with hormone receptor-positive, HER2-positive advanced breast cancer (monarcHER): a randomised, open-label, phase 2 trial[J]. Lancet Oncol, 2020, 21(6): 763-775. doi: S1470-2045(20)30112-1 pmid: 32353342
[16]	ZHANG J, MENG Y C, WANG B Y, et al. Dalpiciclib combined with pyrotinib and letrozole in women with HER2-positive, hormone receptor-positive metastatic breast cancer (LORDSHIPS): a phase Ⅰb study[J]. Front Oncol, 2022, 12: 775081.
[17]	GUARNERI V, DIECI M V, BISAGNI G, et al. De-escalated therapy for HR⁺/HER2⁺ breast cancer patients with Ki-67 response after 2-week letrozole: results of the PerELISA neoadjuvant study[J]. Ann Oncol, 2019, 30(6): 921-926. doi: 10.1093/annonc/mdz055
[18]	GIANNI L, BISAGNI G, COLLEONI M, et al. Neoadjuvant treatment with trastuzumab and pertuzumab plus palbociclib and fulvestrant in HER2-positive, ER-positive breast cancer (NA-PHER2): an exploratory, open-label, phase 2 study[J]. Lancet Oncol, 2018, 19(2): 249-256. doi: S1470-2045(18)30001-9 pmid: 29326029
[19]	NIU N, QIU F, LIU T, et al. Primary analysis of MUKDEN 01: a multicenter, single-arm, prospective, phase 2 study of neoadjuvant treatment with pyrotinib and letrozole plus dalpiciclib in triple-positive breast cancer[J]. J Clin Oncol, 2022, 40(16_suppl): 588. doi: 10.1200/JCO.2022.40.16_suppl.588
[20]	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
[21]	CHAN A, DELALOGE S, HOLMES F A, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet Oncol, 2016, 17(3): 367-377. doi: S1470-2045(15)00551-3 pmid: 26874901