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LIAO Xingyu, LIU Huimin, SUN Jie, HU Li, ZHANG Juan, YAO Lu, XU Ye, XIE Yuntao. Clinicopathological Characteristics of HER2-Positive Breast Cancer Patients with BRCA1/2 Pathogenic Variants and Their Response to Neoadjuvant Targeted Therapy[J]. Cancer Research on Prevention and Treatment, 2025, 52(6): 491-495. DOI: 10.3971/j.issn.1000-8578.2025.25.0101
Citation: LIAO Xingyu, LIU Huimin, SUN Jie, HU Li, ZHANG Juan, YAO Lu, XU Ye, XIE Yuntao. Clinicopathological Characteristics of HER2-Positive Breast Cancer Patients with BRCA1/2 Pathogenic Variants and Their Response to Neoadjuvant Targeted Therapy[J]. Cancer Research on Prevention and Treatment, 2025, 52(6): 491-495. DOI: 10.3971/j.issn.1000-8578.2025.25.0101

Clinicopathological Characteristics of HER2-Positive Breast Cancer Patients with BRCA1/2 Pathogenic Variants and Their Response to Neoadjuvant Targeted Therapy

Funding: 

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Key Supported Project of the Major Research Program of the National Natural Science Foundation of China (No. 92359201); National Natural Science Foundation of China General Program (No. 82272932, 82473481)

More Information
  • Corresponding author:

    XIE Yuntao, E-mail: zlxyt2@bjmu.edu.cn

  • Received Date: February 16, 2025
  • Revised Date: April 08, 2025
  • Accepted Date: April 09, 2025
  • Available Online: April 22, 2025
  • Objective 

    To analyze the proportion and clinicopathological characteristics of HER2-positive breast cancer patients with BRCA1/2 pathogenic variants, and their response to neoadjuvant anti-HER2 targeted therapy.

    Methods 

    The clinicopathological data of 531 breast cancer patients with germline BRCA1/2 pathogenic variants (201 with BRCA1 variants and 330 with BRCA2 variants) were analyzed.

    Results 

    Among the 201 BRCA1 and 330 BRCA2 variants, 17 (8.5%) and 42 (12.7%) HER2-positive breast cancer cases were identified, respectively, accounting for 11.1% of all BRCA1/2-mutated breast cancers. Compared with BRCA1/2-mutated HR-positive/HER2-negative patients, HER2-positive patients did not present any significant differences in clinicopathological features; however, compared with triple-negative breast cancer patients, HER2-positive patients had a later onset age and lower tumor grade. Among the 17 patients who received neoadjuvant anti-HER2 targeted therapy, 10 cases achieved pCR (58.8%), whereas 7 cases did not (41.2%).

    Conclusion 

    HER2-positive breast cancer accounts for more than 10% of BRCA1/2-mutated patients. Approximately 40% of these patients fail to achieve pCR after neoadjuvant targeted therapy. This phenomenon highlights the possibility of combining anti-HER2 targeted agents with poly (adenosine diphosphate-ribose) polymerase inhibitors.

  • Competing interests: The authors declare that they have no competing interests.

  • [1]
    Loibl S, Poortmans P, Morrow M, et al. Breast cancer[J]. Lancet, 2021, 397(10286): 1750-1769. doi: 10.1016/S0140-6736(20)32381-3
    [2]
    Marra A, Chandarlapaty S, Modi S. Management of patients with advanced-stage HER2-positive breast cancer: current evidence and future perspectives[J]. Nat Rev Clin Oncol, 2024, 21(3): 185-202. doi: 10.1038/s41571-023-00849-9
    [3]
    Swain SM, Shastry M, Hamilton E. Targeting HER2-positive breast cancer: advances and future directions[J]. Nat Rev Drug Discov, 2023, 22(2): 101-126. doi: 10.1038/s41573-022-00579-0
    [4]
    Gianni L, Pienkowski T, Im YH, 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
    [5]
    Diéras V, Miles D, Verma S, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial[J]. Lancet. Oncol, 2017, 18(6): 732-742. doi: 10.1016/S1470-2045(17)30312-1
    [6]
    Murthy RK, Loi S, Okines A, et al. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer[J]. N Engl J Med, 2020, 382(7): 597-609. doi: 10.1056/NEJMoa1914609
    [7]
    Saura C, Oliveira M, Feng YH, et al. Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase Ⅲ NALA Trial[J]. J Clin Oncol, 2020, 38(27): 3138-3149. doi: 10.1200/JCO.20.00147
    [8]
    Swain SM, Miles D, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study[J]. Lancet Oncol, 2020, 21(4): 519-530. doi: 10.1016/S1470-2045(19)30863-0
    [9]
    Xu B, Yan M, Ma F, et al. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial[J]. Lancet Oncol, 2021, 22(3): 351-360. doi: 10.1016/S1470-2045(20)30702-6
    [10]
    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. doi: 10.1056/NEJMoa2203690
    [11]
    Cortés J, Kim SB, Chung WP, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer[J]. N Engl J Med, 2022, 386(12): 1143-1154. doi: 10.1056/NEJMoa2115022
    [12]
    Harbeck N. Neoadjuvant and adjuvant treatment of patients with HER2-positive early breast cancer[J]. Breast, 2022, 62 Suppl 1(Suppl 1): S12-S16.
    [13]
    Cortazar P, Zhang L, 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
    [14]
    Sun J, Meng H, Yao L, et al. Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients[J]. Clin Cancer Res, 2017, 23(20): 6113-6119. doi: 10.1158/1078-0432.CCR-16-3227
    [15]
    Zang F, Ding X, Chen J, et al. Prevalence of BRCA1 and BRCA2 pathogenic variants in 8627 unselected patients with breast cancer: stratification of age at diagnosis, family history and molecular subtype[J]. Breast Cancer Res Treat, 2022, 195(3): 431-439. doi: 10.1007/s10549-022-06702-4
    [16]
    Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers[J]. JAMA, 2017, 317(23): 2402-2416. doi: 10.1001/jama.2017.7112
    [17]
    Sun J, Chu F, Pan J, et al. BRCA-CRisk: A Contralateral Breast Cancer Risk Prediction Model for BRCA Carriers[J]. J Clin Oncol, 2023, 41(5): 991-999. doi: 10.1200/JCO.22.00833
    [18]
    Turner NC, Reis-Filho JS. Basal-like breast cancer and the BRCA1 phenotype[J]. Oncogene, 2006, 25(43): 5846-5853. doi: 10.1038/sj.onc.1209876
    [19]
    Atchley DP, Albarracin CT, Lopez A, et al. Clinical and Pathologic Characteristics of Patients With BRCA-Positive and BRCA-Negative Breast Cancer[J]. J Clin Oncol, 2008, 26(26): 4282-4288. doi: 10.1200/JCO.2008.16.6231
    [20]
    Robson ME, 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. doi: 10.1093/annonc/mdz012
    [21]
    Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer[J]. N Engl J Med, 2021, 384(25): 2394-2405. doi: 10.1056/NEJMoa2105215
    [22]
    Geyer CE, Garber JE, Gelber RD, 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. doi: 10.1016/j.annonc.2022.09.159
    [23]
    Tomasello G, Gambini D, Petrelli F, et al. Characterization of the HER2 status in BRCA-mutated breast cancer: a single institutional series and systematic review with pooled analysis[J]. ESMO Open, 2022, 7(4): 100531. doi: 10.1016/j.esmoop.2022.100531
    [24]
    Viansone A, Pellegrino B, Omarini C, et al. Prognostic significance of germline BRCA mutations in patients with HER2-POSITIVE breast cancer[J]. Breast, 2022, 65: 145-150. doi: 10.1016/j.breast.2022.07.012
    [25]
    Akkoc Mustafayev FN, Shukla MA, Lanier A, et al. Survival outcomes of patients with HER2/neu-positive breast cancer with germline BRCA mutations[J]. Cancer, 2024, 130(9): 1600-1608. doi: 10.1002/cncr.35159
    [26]
    Evans DG, Lalloo F, Howell S, et al. Low prevalence of HER2 positivity amongst BRCA1 and BRCA2 mutation carriers and in primary BRCA screens[J]. Breast Cancer Res Treat, 2016, 155(3): 597-601. doi: 10.1007/s10549-016-3697-z
    [27]
    García-Parra J, Dalmases A, Morancho B, et al. Poly (ADP-ribose) polymerase inhibition enhances trastuzumab antitumour activity in HER2 overexpressing breast cancer[J]. Eur J Cancer, 2014, 50(15): 2725-2734. doi: 10.1016/j.ejca.2014.07.004
    [28]
    Alés-Martínez JE, Balmaña J, Sánchez-Rovira P, et al. Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study[J]. Breast, 2024, 77: 103780. doi: 10.1016/j.breast.2024.103780
    [29]
    von Minckwitz G, Procter M, de Azambuja E, et al. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer[J]. N Engl J Med, 2017, 377(2): 122-131. doi: 10.1056/NEJMoa1703643
    [30]
    Martin M, Holmes FA, 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[J]. Lancet Oncol, 2017, 18(12): 1688-1700. doi: 10.1016/S1470-2045(17)30717-9
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