Updates in HER2-Positive and Triple-Negative Breast Cancers

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Melinda L. Telli
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William J. Gradishar
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The recent approval of 4 agents for the treatment of patients with metastatic HER2-positive breast cancer has led to expanded recommendations in the NCCN Guidelines for treatment of this disease. For triple-negative disease, immunotherapy continues to gain traction in this challenging subtype, both in the preoperative and metastatic settings, though not yet as adjuvant treatment. Sacituzumab govitecan is another new agent with strong utility in triple-negative disease, and PARP inhibitors are recommended options in BRCA-mutated disease.

Disclosures: Dr. Telli has disclosed serving as a scientific advisor for and receiving consulting fees from AbbVie, Inc., Celgene Corporation, Immunomedics, Inc., Merck & Co., Inc., Lilly Oncology, Natera, and Pfizer Inc. Dr. Gradishar has disclosed serving as a scientific advisor for AstraZeneca Pharmaceuticals LP, MacroGenics, Inc., Pfizer Inc., Roche Laboratories, Inc./Genentech, Inc., and Seattle Genetics, Inc.

Correspondence: Melinda L. Telli, MD, Stanford Cancer Institute, 875 Blake Wilbur Drive, CC 2241, Stanford, CA 94305-5826. Email: mtelli@stanford.edu; and William J. Gradishar, MD, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, 676 North St. Clair Street, Suite 850, Chicago, IL 60611. Email: w-gradishar@northwestern.edu
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  • 1.

    Gradishar W, Moran M, Abraham J, et al.. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Version 2.2021. Accessed March 12, 2021. To view the most recent version, visit NCCN.org

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Fehrenbacher L, Capra A, Quesenberry C Jr, et al.. Distant invasive breast cancer recurrence risk in human epidermal growth factor receptor 2–positive T1a and T1b node-negative localized breast cancer diagnosed from 2000 to 2006: a cohort from an integrated health care delivery system. J Clin Oncol 2014;32:21512158.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Tolaney S, Guo H, Pernas S, et al.. Seven-year follow-up analysis of adjuvant paclitaxel and trastuzumab trial for node-negative, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 2019;37:18681875.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Tolaney S, Trippa L, Barry W, et al.. TBCRC 033: a randomized phase II study of adjuvant trastuzumab emtansine (T-DM1) vs paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT) [abstract]. Presented at the 2019 San Antonio Breast Cancer Symposium; December 10–14, 2019; San Antonio, Texas. Abstract GS1-05.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Von Minckwitz G, Huang C, Mano M, et al.. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 2019;380:617628.

  • 6.

    Modi S, Saura C, Yamashita T. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med 2020;382:610621.

  • 7.

    Modi S, Saura C, Yamashita T, et al.. Updated results from DESTINY-breast01, a phase 2 trial of trastuzumab deruxtecan (T-DXd) in HER2 positive metastatic breast cancer [abstract]. Presented at the 2020 Virtual San Antonio Breast Cancer Symposium; December 8–11, 2020. Abstract PD3-06.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Murthy R, Loi S, Okines A, et al.. Tucatinib, trastuzumab, and capecitabine for HER-2 positive metastatic breast cancer. N Engl J Med 2020;382:597609.

  • 9.

    Lin N, Borges V, Anders C, et al.. Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial. J Clin Oncol 2020;38:26102619.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Rugo H, Im S, Cardoso F, et al.. Phase 3 SOPHIA study of margetuximab + chemotherapy vs trastuzumab + chemotherapy in patients with HER2+ metastatic breast cancer after prior anti-HER2 therapies: second interim overall survival analysis [abstract]. Presented at the 2019 San Antonio Breast Cancer Symposium; December 10–14, 2019; San Antonio, Texas. Abstract GS1-02.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Saura C, Oliveira M, Feng Y, et al.. Neratinib + capecitabine vs lapatinib + capecitabine in patients with HER2+ metastatic breast cancer previously treated with ≥2 HER2-directed regimens: findings from the multinational, randomized, phase III NALA trial [abstract]. Presented at the 2019 ASCO Annual Meeting; May 31–June 4, 2019; Chicago, Illinois. Abstract 1002.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Von Minckwitz G, Schneeweiss A, Loibl S, et al.. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomized phase 2 trial. Lancet Oncol 2014;15:747756.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Sikov W, Berry D, Perou C, 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;33:1321.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Poggio F, Bruzzone M, Ceppi M, et al.. Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis. Ann Oncol 2018;29:14971508.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Masuda N, Lee S, Ohtani S, et al.. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med 2017;376:2147159.

  • 16.

    Loibl S, Untch M, Burchardi N, et al.. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol 2019;30:12791288.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Schmid P, Cortes J, Pusztai L, et al.. Pembrolizumab for early triple-negative breast cancer. N Engl J Med 2020;382:810821.

  • 18.

    Mittendorf E, Zhang H, Barrios C, et al.. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomized, double-blind, phase 3 trial. Lancet 2020;396:10901100.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Gianni L, Huang C, Egle D, et al.. Pathologic complete response to neoadjuvant treatment with or without atezolizumab in triple-negative, early high-risk and locally advanced breast cancer. NeoTRIPaPDL1 Michelangelo randomized study [abstract]. Presented at the 2019 San Antonio Breast Cancer Symposium; December 10–14, 2019; San Antonio, Texas. Abstract GS3-04.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Schmid P, Rugo H, Adams S; IMpassion130 Investigators. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2020;21:4459.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Ermens L, Adams S, Barrios C, et al.. IMpassion130: final overall survival analysis from the pivotal phase III study of atezolizumab plus nab-paclitaxel vs placebo plus nab-paclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer [abstract]. Presented at the ESMO Virtual Congress 2020; September 19–21, 2020. Abstract LBA16.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Cortes J, Cescon D, Rugo H, et al.. Pembrolizumab plus chemotherapy versus placebo for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomized, placebo-controlled, double-blind, phase 3 clinical trial. Lancet 2020;396:18171828.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Miles D, Gilgorov J, Andre F, et al.. Primary results from IMpassion131, a double-blind placebo-controlled randomized phase 3 trial of first-line paclitaxel plus atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer [abstract]. Presented at the ESMO Virtual Congress 2020; September 19–21, 2020. Abstract LBA15.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Bardia A, Tolaney S, Loirat D, et al.. ASCENT: a randomized phase III study of sacituzumab govitecan vs treatment of physician’s choice in patients with previously treated metastatic triple-negative breast cancer [abstract]. Presented at the ESMO Virtual Congress 2020; September 19–21, 2020. Abstract LBA17.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Hurvitz S, Tolaney S, Punie K. Biomarker evaluation in the phase 2 ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer [abstract]. Presented at the 2020 Virtual San Antonio Breast Cancer Symposium; December 8–11, 2020. Abstract GS3-06.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Robson M, Im S, Senkus E. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 2017;377:523533.

  • 27.

    Litton J, Rugo H, Ettl J, et al.. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med 2018;379:753763.

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