中国抗癌协会：乳腺癌多基因精准检测指南

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

2019年版修订小组成员

（以汉语拼音字母为序）

• 步宏　｜四川大学华西医院

• 蔡莉　｜哈尔滨医科大学附属肿瘤医院

• 曹旭晨｜天津医科大学肿瘤医院

• 常才　｜复旦大学附属肿瘤医院

• 陈策实｜中国科学院昆明动物研究所

• 崔树德｜河南省肿瘤医院

• 范志民｜吉林大学白求恩第一医院

• 付丽　｜天津医科大学肿瘤医院

• 耿翠芝｜河北医科大学第四医院

• 顾林　｜天津医科大学肿瘤医院

• 顾雅佳｜复旦大学附属肿瘤医院

• 胡夕春｜复旦大学附属肿瘤医院

• 黄建　｜浙江大学医学院附属第二医院

• 江泽飞｜解放军总医院第五医学中心

• 姜军　｜陆军军医大学第一附属医院

• 解云涛｜北京大学肿瘤医院

• 金锋　｜中国医科大学附属第一医院

• 李惠平｜北京大学肿瘤医院

• 李金锋｜北京大学肿瘤医院

• 李志高｜哈尔滨医科大学附属肿瘤医院

• 厉红元｜重庆医科大学附属第一医院

• 廖宁　｜广东省人民医院

• 刘红　｜天津医科大学肿瘤医院

• 刘健　｜福建省肿瘤医院

• 刘冬耕｜中山大学肿瘤防治中心

• 刘晓安｜江苏省人民医院

• 柳光宇｜复旦大学附属肿瘤医院

• 马飞　｜中国医学科学院肿瘤医院

• 马力　｜河北医科大学第四医院

• 欧阳涛｜北京大学肿瘤医院

• 庞达　｜哈尔滨医科大学附属肿瘤医院

• 彭卫军｜复旦大学附属肿瘤医院

• 任国胜｜重庆医科大学附属第一医院

• 邵志敏｜复旦大学附属肿瘤医院

• 沈镇宙｜复旦大学附属肿瘤医院

• 盛湲　｜海军军医大学附属长海医院

• 宋传贵｜福建医科大学附属协和医院

• 宋尔卫｜中山大学孙逸仙纪念医院

• 孙强　｜北京协和医院

• 孙涛　｜辽宁省肿瘤医院

• 唐金海｜江苏省人民医院

• 唐利立｜中南大学湘雅医院

• 佟仲生｜天津医科大学肿瘤医院

• 王靖　｜中国医学科学院肿瘤医院

• 王颀　｜广东省妇幼保健院

• 王殊　｜北京大学人民医院

• 王水　｜江苏省人民医院

• 王曦　｜中山大学附属肿瘤医院

• 王翔　｜中国医学科学院肿瘤医院

• 王碧芸｜复旦大学附属肿瘤医院

• 王海波｜青岛大学附属医院

• 王树森｜中山大学肿瘤防治中心

• 王晓稼｜浙江省肿瘤医院

• 王永胜｜山东省肿瘤医院

• 王中华｜复旦大学附属肿瘤医院

• 吴炅　｜复旦大学附属肿瘤医院

• 吴新红｜湖北省肿瘤医院

• 徐兵河｜中国医学科学院肿瘤医院

• 徐莹莹｜中国医科大学附属第一医院

• 许玲辉｜复旦大学附属肿瘤医院

• 杨红健｜浙江省肿瘤医院

• 杨文涛｜复旦大学附属肿瘤医院

• 殷咏梅｜江苏省人民医院

• 余科达｜复旦大学附属肿瘤医院

• 俞晓立｜复旦大学附属肿瘤医院

• 袁芃　｜中国医学科学院肿瘤医院

• 张剑　｜复旦大学附属肿瘤医院

• 张频　｜中国医学科学院肿瘤医院

• 张斌　｜辽宁省肿瘤医院

• 张瑾　｜天津医科大学肿瘤医院

• 张宏伟｜复旦大学附属中山医院

• 张建国｜哈尔滨医科大学附属第二医院

• 张清媛｜哈尔滨医科大学附属肿瘤医院

• 张筱骅｜温州医科大学附属第一医院

• 赵文和｜浙江大学医学院附属邵逸夫医院

• 郑鸿　｜四川大学华西医院

• 郑莹　｜复旦大学附属肿瘤医院

• 邹强　｜复旦大学附属华山医院

• 左文述｜山东省肿瘤医院

编撰秘书处

• 余科达｜复旦大学附属肿瘤医院

• 李俊杰｜复旦大学附属肿瘤医院

• 李彬　｜复旦大学附属肿瘤医院

• 杨犇龙｜复旦大学附属肿瘤医院

目录

1. 乳腺原位癌治疗指南（附录Ⅸ）

2. HER2阳性乳腺癌临床诊疗专家共识

3. 乳腺癌局部和区域淋巴结复发诊治指南

4. 乳腺癌骨转移的临床诊疗指南

5. 乳腺癌患者BRCA1/2基因检测与临床应用

6. 乳腺癌多基因精准检测指南

   附录

原文参见：中国癌症杂志. 2019;29(8):609-680.

　　18　乳腺癌多基因精准检测指南

　　肿瘤精准检测是指利用基因组学、表观遗传组学、转录组学、蛋白组学、代谢组学等多种组学检测技术，获取肿瘤相关的生物学信息，进一步分析组学检测结果对肿瘤筛查与诊疗的临床应用价值。其中，多基因突变检测指利用二代测序（NGS）技术，将多个基因对应的探针设计到同一张捕获芯片上以捕获目标肿瘤或者胚系DNA，并结合后续的测序分析检测肿瘤中的突变基因、突变类型与突变位点等相关信息。多基因突变检测应当由具备NGS与分析资质的机构提供精准的检测服务，并对乳腺癌发生、发展过程中的遗传易感性基因（BRCA1/2等）、高频突变基因、靶向用药相关基因和耐药相关基因等多类基因进行突变检测，检测结果应由专业人员结合患者具体情况进行合理解读。

　　多基因突变检测对于乳腺癌罹患风险预测、乳腺癌（尤其是三阴性乳腺癌）的分子分型和精准治疗方案选择具有重要参考意义。在临床实践中推荐对以下三类患者行多基因突变检测：①有肿瘤相关个人史或家族史，提示基因相关的肿瘤易感性；②能够充分解释精准检测结果；③检测结果有助于临床筛查、诊疗的应用。当前针对乳腺癌的多基因突变检测主要应用于晚期多线治疗方案失败的患者中（推荐结合临床试验进行），辅助临床医师发现这部分乳腺癌患者的相关基因突变信息，并对肿瘤患者进行精准分型与治疗靶点的精确定位，进而选择可能有效的治疗策略与治疗药物。结合三阴性乳腺癌的分子分型，多基因突变检测有望提示各亚型潜在治疗靶点和精准治疗策略，改善患者预后。

　　包括多基因突变检测在内的精准检测在乳腺癌诊断与治疗中有广阔的应用前景，也将随着各类组学检测技术的发展和相关证据的累积，在临床实践中发挥更加重要的作用。

参考文献

1. 杨文涛, 步宏. 乳腺癌新辅助化疗后的病理诊断专家共识. 中华病理学杂志. 2015;44(4):232-236.

2. 杨文涛, 步宏. 乳腺癌雌、孕激素受体免疫组织化学检测 指南. 中华病理学杂志. 2015;44(4):237-239.

3. 《乳腺癌HER2检测指南(2019版)》编写组. 乳腺癌HER2检测指南(2019版). 中华病理学杂志. 2019;48(3):169-175.

4. BUCHHOLZ T A, SOMERFIELD M R, GRIGGS J J, et al. Margins for breast-conserving surgery with whole-breast irradiation in stage I and II invasive breast cancer: American Society of Clinical Oncology endorsement of the Society of Surgical Oncology/American Society for Radiation Oncology consensus guideline. J Clin Oncol. 2014;32(14):1502-1506.

5. KUNKLER I H, WILLIAMS L J, JACK W J, et al. Breast conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial. Lancet Oncol. 2015;16(3):266-273.

6. GIULIANO A E, BALLMAN K, MCCALL L, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: long-term follow-up from the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 randomized trial. Ann Surg. 264(3):413-420.

7. DONKER M, VAN TIENHOVEN G, STRAVER M E, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised. multicentre. open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014;15(12):1303-1310.

8. 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 Clin Oncol. 2014;32(14):1507-1515.

9. 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. Lancet Oncol. 2018;19(1):27-39.

10. GIANNI L, PIENKOWSKI T, IM Y H, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab inpatients with locally advanced. inflammatory. or early-stage HER2-positive breast cancer (NeoSphere): a multicentre. open-label, phase 2 randomised trial. Lancet Oncol. 2016;17(6):791-800.

11. SIKOV W M, BERRY D A, PEROU C M, et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015;33(1):13-21.

12. ADAMS S, LOI S, TOPPMEYER D, et al. Pembrolizumab monotherapy for previously untreated. PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study. Ann Oncol. 2019;30(3):405-411.

13. ADAMS S, SCHMID P, RUGO H S, et al. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study. Ann Oncol. 2019;30(3):397-404.

14. GOETZ M P, TOI M, CAMPONE M, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35(32):3638-3646.

15. ROBSON M, IM S A, SENKUS E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017;377(17):523-533.

16. SLEDGE G W Jr, TOI M, NEVEN P, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2-advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017;35(25):2875-2884.

17. SCHMID P, ADAMS S, RUGO H S, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379(22):2108-2121.

18. TRIPATHY D, IM S A, COLLEONI M, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19(7):904-915.

19. TURNER N C, SLAMON D J, RO J, et al. Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med. 2018;379(20):1926-1936.

20. BLOK E J, KROEP J R, MEERSHOEK-KLEIN KRANENBARG E, et al. Optimal duration of extended adjuvant endocrine therapy for early breast cancer;Results of the IDEAL trial (BOOG 2006-05). J Natl Cancer Inst. 2018;110(1).

21. BURSTEIN H J, LACCHETTI C, ANDERSON H, et al. Adjuvant endocrine therapy for women with hormone receptorpositive breast cancer: ASCO clinical practice guideline focused update. J Clin Oncol. 2019;37(5):423-438.

22. FRANCIS P A, PAGANI O, FLEMING G F, et al. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379(2):122-137.

23. GNANT M, MLINERITSCH B, STOEGER H, et al. Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group trial 12. Ann Oncol. 2015;26(2):313-320.

24. MAMOUNAS E P, BANDOS H, LEMBERSKY B C, et al. Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG Oncology/NSABP B-42): a randomised. double-blind, placebo-controlled. phase 3 trial. Lancet Oncol. 2019;20(1):88-99.

25. METZGER FILHO O, GIOBBIE-HURDER A, MALLON E, et al. Relative effectiveness of letrozole compared with tamoxifen for patients with lobular carcinoma in the BIG 1-98 trial. J Clin Oncol. 2015;33(25):2772-2779.

26. PAN H, GRAY R, BRAYBROOKE J, et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836-1846.

27. BLUM J L, FLYNN P J, YOTHERS G, et al. Anthracyclines in early breast cancer: the ABC trials-USOR 06-090;NSABP B-46-I/USOR 07132;and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017;35(23):2647-2655.

28. CARDOSO F, VAN'T VEER L J, BOGAERTS J, et al. 70-gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016;375(8):717-729.

29. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015;386(10001):1353-1361.

30. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level metaanalysis of 37 298 women with early breast cancer in 26 randomised trial. Lancet. 2019;393(10179):1440-1452.

31. LOIBL S, WEBER K E, TIMMS K M, et al. Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response-final results from GeparSixto. Ann Oncol. 2018;29(12):2341-2347.

32. MASUDA N, LEE S J, OHTANI S, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017;376(22):2147-2159.

33. MOORE H C, UNGER J M, PHILLIPS K A, et al. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med. 2015;372(10):923-932.

34. NITZ U, GLUZ O, CLEMENS M, et al. West German planB trial: adjuvant four cycles of epirubicin and cyclophosphamide plus docetaxel versus six cycles of docetaxel and cyclophosphamide in HER2 negative early breast cancer. J Clin Oncol. 2019;37(10):799-808.

35. SPARANO J A, GRAY R J, MAKOWER D F, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379(2):111-121.

36. PROWELL T M, BEAVER J A, PAZDUR P. Residual disease after neoadjuvant therapy-developing drugs for high-risk early breast cancer. N Engl J Med. 2019;380(7):612-615.

37. SPARANO J A, GRAY R J, RAVDIN P M, et al. Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer. N Engl J Med. 2019;380(25):2395-2405.

38. EARL H M, HILLER L, VALLIER A L, et al. 6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial. Lancet. 2019;393(10191):2599-2612.

39. MARTIN M, HOLMES F A, EJLERTSEN B, et al. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised. double-blind, placebo-controlled. phase 3 trial. Lancet Oncol. 2017;18(12):1688-1700.

40. VON MINCKWITZ G, HUANG C S, MANO M S, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380(7):617-628.

41. VON MINCKWITZ G, PROCTER M, DE AZAMBUJA E, et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017;377(2):122-131.

42. GIANNI L, PIENKOWSKI T, IM Y H, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced. inflammatory. or early HER2-positive breast cancer (NeoSphere): a randomised multicentre. open-label, phase 2 trial. Lancet Oncol. 2016;13(1):25-32.

43. MA F, LI Q, CHEN S, et al. Phase I study and biomarker analysis of pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2017;35(27):3105-3112.

44. LANG G T, SHI J X, HU X, et al. The spectrum of BRCA mutations and characteristics of BRCA-associated breast cancers in China: screening of 2 991 patients and 1 043 controls by next-generation sequencing. Int J Cancer. 2017;141(1):129-142.

45. JIANG Y Z, MA D, SUO C, et al. Genomic and transcriptomic landscape of triple-negative breast cancers: subtypes and treatment strategies. Cancer Cell. 2019;35(3):428-440. e5.

46. ZUO W J, JIANG Y Z, WANG Y J, et al. Dual characteristics of novel HER2 kinase domain mutations in response to HER2-targeted therapies in human breast cancer. Clin Cancer Res. 2016;22(19):4859-4869.

以下广告内容与本微信公众号无关