[1]柴效科,卫翀羿,程晓成,等.激素受体阳性/人类表皮生长因子受体2阴性乳腺癌靶向治疗研究进展[J].新乡医学院学报,2023,40(5):490-496.[doi:10.7683/xxyxyxb.2023.05.017]
　CHAI Xiaoke,WEI Chongyi,CHENG Xiaocheng,et al.Research progress on targeted therapy of hormone receptor positive/human epidermal growth factor receptor 2 negative breast cancer[J].Journal of Xinxiang Medical University,2023,40(5):490-496.[doi:10.7683/xxyxyxb.2023.05.017]
点击复制

激素受体阳性/人类表皮生长因子受体2阴性乳腺癌靶向治疗研究进展
分享到：

《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
40卷
期数:
2023年5
页码:
490-496
栏目:
综述
出版日期:
2023-05-05

文章信息/Info

Title:
Research progress on targeted therapy of hormone receptor positive/human epidermal growth factor receptor 2 negative breast cancer
作者:
柴效科; 卫翀羿; 程晓成; 周海存; 隆建萍
(甘肃省妇幼保健院乳腺三科，甘肃　兰州　730050)
Author(s):
CHAI Xiaoke; WEI Chongyi; CHENG Xiaocheng; ZHOU Haicun; LONG Jianping
（The Third Department of Breast,Gansu Provincial Maternity and Child-Care Hospital,Lanzhou 730050,Gansu Province,China）
关键词:
乳腺癌; 内分泌治疗; 靶向治疗
Keywords:
breast cancer; endocrine therapy; targeted therapy
分类号:
R737.9
DOI:
10.7683/xxyxyxb.2023.05.017
文献标志码:
A
摘要:
激素受体阳性（HR+）/人类表皮生长因子受体2阴性（HER2-）乳腺癌是最常见的乳腺癌亚型。随着分子生物学的发展及个体化精准治疗理念认识的深入，HR+/HER2-乳腺癌的治疗由单一内分泌治疗转变为内分泌联合靶向治疗模式。近年来，HR+/HER2-乳腺癌靶向治疗药物的研发取得了突破性进展，如细胞周期蛋白依赖性激酶4/6、磷脂酰肌醇-3-激酶、雷帕霉素靶蛋白抑制剂等靶向药物得到了广泛的研究并被应用于临床。为进一步了解靶向治疗药物的临床疗效和安全性，本文就HR+/HER2-型乳腺癌靶向治疗方面的研究进行综述，以期为乳腺癌患者的精准治疗提供理论基础。
Abstract:
Hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer is the most common subtype of breast cancer.With the development of molecular biology and the indepth understanding of the concept of individualized precision therapy,the treatment model of HR+/HER2- breast cancer has changed from single endocrine therapy to endocrine combined targeted therapy.In recent years,breakthroughs have been made in the research and development of HR+/HER2- breast cancer targeted therapy drugs.Targeted drugs such as cyclin-dependent kinase4/6,phosphatidylinositol-3-kinases,mammalian target of rapamycin inhibitors and other targeted drugs have been widely studied and applied in clinical practice.In order to further understand the clinical efficacy and safety of targeted therapy drugs and provide a theoretical basis for precise treatment of breast cancer patients,this article reviews the research on targeted therapy of HR+/HER2-type breast cancer.

参考文献/References:

［1］　SUNG H,FERLAY J S,SIEGEL R L,et al.Global cancer statistics 2020:globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］.CA Cancer J Clin,2021,71(3):209-249.
［2］　FINN R S,MARTIN M,RUGO H S,et al.Palbociclib and letrozole in advanced breast cancer［J］.N Engl J Med,2016,375(20):1925-1936.
［3］　RUGO H S,FINN R S,DIERAS V,et al.Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up［J］.Breast Cancer Res Treat,2019,174(3):719-729.
［4］　HORTOBAGYI G N,STEMMER S M,BURRIS H A,et al.Updated results from MONALEESA-2,a phase Ⅲ trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive,HER2-negative advanced breast cancer［J］.Ann Oncol,2018,29(7):1541-1547.
［5］　JOHNSTON S,MARTIN M,DI L A,et al.MONARCH 3 final PFS:a randomized study of abemaciclib as initial therapy for advanced breast cancer［J］.NPJ Breast Cancer,2019,5:5.
［6］　TRIPATHY D,IM S A,COLLEONI M,et al.Ribociclib plus endocrine therapy for premenopausal womenwith hormone-receptor-positive,advanced breast cancer (MONALEESA-7):a randomised phase 3 trial［J］.Lancet Oncol,2018,19(7):904-915.
［7］　IM S A,LU Y S,BARDIA A,et al.Overall survival with ribociclib plus endocrine therapy in breast cancer［J］.N Engl J Med,2019,381(4):307-316.
［8］　XU B H,ZHANG Q Y,ZHANG P,et al.Dalpiciclib or placebo plus fulvestrant in hormone receptor-positive and HER2-negative advanced breast cancer:a randomized,phase 3 trial［J］.Nat Med,2021,27(11):1904-1909.
［9］　PARK Y H,KIM T Y,KIM G M,et al.Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive,HER2-negative metastatic breast cancer(KCSG-BR15-10):a multicentre,open-label,randomised,phase 2 trial［J］.Lancet Oncol,2019,20(12):1750-1759.
［10］　COTTU P,D′HONDT V,DUREAU S,et al.Letrozole and palbociclib versus chemotherapy as neoadjuvant therapy of high-risk luminal breast cancer［J］.Ann Oncol,2018，29(12):2334-2340.
［11］　JOHNSTON S,PUHALLA S,WHEATLEYH D,et al.Randomized phase Ⅱ study evaluating palbociclib in addition to letrozole as neoadjuvant therapy in estrogen receptor-positive early breast cancer:PALLET trial［J］.J Clin Oncol,2019,37(3):178-189.
［12］　MA C X,GAO F,LUO J,et al.Neopalana:neoadjuvant palbociclib,a cyclin-dependent kinase4/6 inhibitor,and anastrozole for clinical stage 2 or 3 estrogen receptor positive breast cancer［J］.Clin Cancer Res,2017,23(15):4055-4065.
［13］　HURVITZ S A,MARTIN M,PRESS M F,et al.Potent cell-cycle inhibition and upregulation of immune response with abemaciclib and aanastrozole in neoMONARCH,Phase Ⅱ neoadjuvant study in HR/HER2 breast cancer［J］.Clin Cancer Res,2020,26(3):566-580.
［14］　KHAN Q J,O′DEA A,BARDIA A,et al.Letrozole+ribociclib versus letrozole+placebo as neoadjuvant therapy for ER+breast cancer (FELINEtrial)［J］.J Clin Oncol,2020，38（Suppl）:505.
［15］　PRAT A,SAURA C,PASCUAL T,et al.Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive,HER2-negative,luminal B breast cancer (CORALLEEN):an open-label,multicentre,randomised,phase 2 trial［J］.Lancet Oncol,2020,21(1):33-43.
［16］　HONG K,YAO L L,SHENG X N,et al.Neoadjuvant therapy of cyclin-dependent kinase 4/6 inhibitors combined with endocrine therapy in HR+/HER2- breast cancer:a systematic review and meta-analysis［J］.Oncol Res Treat,2021,44(10):557-567.
［17］　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.
［18］　MAYER E L,DUECK A C,MARTIN M,et al.Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS):interim analysis of a multicentre,open-label,randomised,phase3 study［J］.Lancet Oncol,2021,22(2):212-222.
［19］　LOIBL S,MARME 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.
［20］　TURNER S,CHIA S,KANAKAMEDALA H,et al.Effectiveness of alpelisib+fulvestrant compared with real-world standard treatment among patients with HR+,HER2-,PIK3CA-mutated breast cancer［J］.Oncologist,2021,26(7):e1133-e1142.
［21］　BASELGA J,IM S,IWATA H,et al.Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal,hormone receptor-positive,HER2-negative,advanced breast cancer (BELLE-2):a randomised,double-blind,placebo-controlled,phase 3 trial［J］.Lancet Oncol,2017,18(7):904-916.
［22］　ANDRE F,CIRUELOS E M,JURIC D,et al.Alpelisib plus fulvestrant for PIK3CA-mutated,hormone receptor-positive,human epidermal growth factor receptor-2-negative advanced breast cancer:final overall survival results from SOLAR-1［J］.Ann Oncol,2021,32(2):208-217.
［23］　DICKLER M N,SAURA C,RICHARDS D A,et al.Phase II study of Taselisib (GDC-0032) in combination with fulvestrant in patients with HER2-negative,hormone receptor-positive advanced breast cancer［J］.Clin Cancer Res,2018,24(18):4380-4387.
［24］　DI L A,JOHNSTON S,LEE K S,et al.Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive,HER2-negative,advanced breast cancer progressing on or after mTOR inhibition(BELLE-3):a randomised,double-blind,placebo-controlled,phase 3 trial［J］.Lancet Oncol,2018,19(1):87-100.
［25］　RUGO H S,LEREBOURS F,CIRUELOS E,et al.Alpelisib plus fulvestrant in PIK3CA-mutated,hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve):one cohort of a phase 2,multicentre,open-label,non-comparative study［J］.Lancet Oncol,2021,22(4):489-498.
［26］　XI J,MA C X.Sequencing endocrine therapy for metastatic breast cancer:what do we do after disease progression on a CDK4/6 inhibitor［J］.Curr Oncol Rep,2020,22(6):57.
［27］　HOWELL S J,CASBARD A,CARUCCI M,et al.Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic,oestrogen receptor-positive,HER2-negative breast cancer (FAKTION):over all survival,updated progression-free survival,and expanded biomarker analysis from a randomised,phase 2 trial［J］.Lancet Oncol,2022,23(7):851-864.
［28］　ELFGEN C,BJELIC-RADISIC V.Targeted therapy in HR+HER2- metastatic breast cancer:current clinical trials and their implications for CDK4/6 inhibitor therapy and beyond treatment options［J］.Cancers (Basel),2021,13(23):undefined.
［29］　GUARNERI V,GIORGI C A,CINIERI S,et al.Everolimus plus aromatase inhibitors as maintenance therapy after first-line chemotherapy:final results of the phase Ⅲ randomised MAIN-A (MAINtenance Afinitor) trial［J］.Eur J Cancer,2021,154:21-29.
［30］　BACHELOT T,BOURGIER C,CROPET C,et al.Randomized phase Ⅱ trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive,human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors:a GINECO study［J］.J Clin Oncol,2012,30(22):2718-2724.
［31］　KORNBLUM N,ZHAO F,MANOLA J,et al.Randomized phase Ⅱ trial of fulvestrant plus everolimus or placebo in postmenopausal women with hormone receptor-positive,human epidermal growth factor receptor 2-negative metastatic breast cancer resistant to aromatase inhibitor therapy:results of PrE0102［J］.J Clin Oncol,2018,36(16):1556-1563.
［32］　PRAT A,BRASE J C,CHENG Y,et al.Everolimus plus exemestane for hormone receptor-positive advanced breast cancer:a PAM50 intrinsic subtype analysis of BOLERO-2［J］.Oncologist,2019,24(7):893-900.
［33］　MO H,RENNA C E,MOORE H C F,et al.Real-world outcomes of everolimus and exemestane for the treatment of metastatic hormone receptor-positive breast cancer in patients previously treated with CDK4/6 inhibitors［J］.Clin Breast Cancer,2022,22(2):143-148.
［34］　COOK M M,AL R L,KAEMPF A J,et al.Everolimus plus exe-mestane treatment in patients with metastatic hormone receptor-positive breast cancer previously treated with CDK4/6 inhibitor therapy［J］.Oncologist,2021,26(2):101-106.
［35］　YARDLEY D A,ISMAIL-KHAN R R,MELICHAR B,et al.Randomized phase Ⅱ,double-blind,placebo-controlled study of exe-mestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on treatment with a nonsteroidal aromatase inhibitor［J］.J Clin Oncol,2013,31(17):2128-2135.
［36］　CONNOLLY R M,ZHAO F,MILLER K D,et al.E2112:randomized phase Ⅲ trial of endocrine therapy plus Entinostat or placebo in hormone receptor-positive advanced breast cancer.a trial of the ECOG-ACRIN cancer research group［J］.J Clin Oncol,2021,39(28):3171-3181.
［37］　ROBSON M E,TUNG N,CONTE P,et al.OlympiAD final overall survival and tolerability results:olaparib versus chemotherapy treatment of physician′s choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer［J］.Ann Oncol,2019,30(4):558-566.
［38］　LITTON J K,HURVITZ S A,MINA L A,et al.Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer:final overall survival results from the EMBRACA trial［J］.Ann Oncol,2020,31(11):1526-1535.
［39］　ELMELIEGY M,YU Y,LITTON J K,et al.Exposure-safety analyses of talazoparib in patients with advanced breast cancer and germline BRCA1/2 mutations in the EMBRACA and ABRAZO trials［J］.J Clin Pharmacol,2020,60(10):1334-1343.
［40］　DIERAS V,HAN H S,KAUFMAN B,et al.Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3):a randomised,double-blind,placebo-controlled,phase 3 trial［J］.Lancet Oncol,2020,21(10):1269-1282.
［41］　FASCHING P A,LINK T,HAUKE J,et al.Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatinum in patients with HER2-negative breast cancer and homologous recombination deficiency (GeparOLA study)［J］.Ann Oncol,2021,32(1):49-57.
［42］　TUTT A N J,GARBER J E,KAUFMAN B,et al.BRCA1adjuvant olaparib for patients with - or -mutated breast cancer［J］.N Engl J Med,2021,384(25):2394-2405.
［43］　MODI S,JACOT W,YAMASHITA T,et al.Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer［J］.N Engl J Med,2022,387(1):9-20.
［44］　RUGO H S,BARDIA A,MARME F,et al.Sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer［J］.J Clin Oncol,2022,40(29):3365-3376.
［45］　RUGO H S,DELORD J P,IM S,et al.Safety and antitumor activity of pembrolizumab in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer［J］.Clin Cancer Res,2018,24(12):2804-2811.
［46］　DIRIX L Y,TAKACS I,JERUSALEM G,et al.Avelumab,an anti-PD-L1 antibody,in patients with locally advanced or metastatic breast cancer:a phase 1b JAVELIN solid tumor study［J］.Breast Cancer Res Treat,2018,167(3):671-686.
［47］　NANDA R,LIU M C,YAU C,et al.Effect of pembrolizumab plus neoadjuvant chemotherapy on pathologic complete response in women with early-stage breast cancer:an analysis of the ongoing phase 2 adaptively randomized I-SPY2 trial［J］.JAMA Oncol,2020,6(5):676-684.
［48］　RUGO H S,KABOS P,BECK J T,et al.Abemaciclib in combination with pembrolizumab for HR +,HER2- metastatic breast cancer:phase 1b study［J］.NPJ Breast Cancer,2022,8(1):118.
［49］　DICKLER M N,BARRY W T,CIRRINCIONE C T,et al.Phase III trial evaluating letrozole as first-line endocrine therapy with or without bevacizumab for the treatment of postmenopausal women with hormone receptor-positive advanced-stage breast cancer:CALGB 40503 (Alliance)［J］.J Clin Oncol,2016,34(22):2602-2609.
［50］　MARTIN M,LOIBL S,VON M G,et al.Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer:the letrozole/fulvestrant and avastin (LEA) study［J］.J Clin Oncol,2015,33(9):1045-1052.
［51］　LI C,LI X.Advances in therapy for hormone receptor (HR)-positive,human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer patients who have experienced progression after treatment with CDK4/6 inhibitors［J］. Onco Targets Ther,2021,14:2929-2939.
［52］　MUSOLINO A,CAMPONE M,NEVEN P,et al.Phase II,randomized,placebo-controlled study of dovitinib in combination with fulvestrant in postmenopausal patients with HR,HER2 breast cancer that had progressed during or after prior endocrine therapy［J］.Breast Cancer Res,2017,19(1):18.

相似文献/References:

[1]张光谋,吴俊琢,徐振平,等.抗细胞凋亡基因bcl一2在乳腺癌中的表达[J].新乡医学院学报,2001,18(03):160.
[2]刘玉生 ． 万里,李森恺.乳腺癌切除即期乳房再造[J].新乡医学院学报,2001,18(01):023.
[3]王承正,张锦瑜,邱树升,等.C—erbB一2与ER、PS一2在乳腺癌中的表达及其临床相关性[J].新乡医学院学报,2003,20(05):324.
[4]王承正,张锦瑜,邱树升,等.C2erbB22 与ER、PS22 在乳腺癌中的表达及其临床相关性[J].新乡医学院学报,2003,20(05):324.
[5]王志民,段西华,祁天义,等.多点皮瓣固定法预防乳腺癌术后皮下积液效果观察 [J].新乡医学院学报,2007,24(03):287.
[6]郭兰青.乳腺癌患者生活质量影响因素[J].新乡医学院学报,2008,25(06):637.
[7]曹兴玥,赵庆伟,靳艳,等.CD44和nm23在乳腺浸润性导管癌中的表达及其与淋巴结转移的关系[J].新乡医学院学报,2011,28(01):042.
[8]靳艳,曹兴玥,赵庆伟,等.CD62P在人乳腺癌组织中的表达及其与淋巴结转移的关系[J].新乡医学院学报,2011,28(01):045.
[9]王　乐,王静萱,张清媛.乳腺癌骨转移靶向治疗进展[J].新乡医学院学报,2015,32(09):887.
[10]杨绍英,刘朝荣,张志刚,等.乳腺癌新辅助化学治疗前后雌激素受体、乳激素受体、Ki-67抗原和人类表皮生长因子受体-2的表达[J].新乡医学院学报,2017,34(2):125.[doi:10.7683/xxyxyxb.2017.02.012]
　YANG Shao-ying,LIU Chao-rong,ZHANG Zhi-gang,et al.Expressions of estrogen receptor，progestin recetor，Ki-67 antigen，and human epidermal growth factor receptor 2 before and after neoadjuvant chemotherapy in patients with breast cancer[J].Journal of Xinxiang Medical University,2017,34(5):125.[doi:10.7683/xxyxyxb.2017.02.012]
[11]刘德总,杨颖涛.乳腺癌辅助治疗现状与展望[J].新乡医学院学报,2021,38(8):781.[doi:10.7683/xxyxyxb.2021.08.017]

更新日期/Last Update: 2023-05-05