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Optimal Management for Residual Disease Following Neoadjuvant Systemic Therapy

  • Breast Cancer (WJ Gradishar, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion Statement

Treatment sequencing in early-stage breast cancer has significantly evolved in recent years, particularly in the triple negative (TNBC) and human epidermal growth factor receptor 2 (HER2)-positive subsets. Instead of surgery first followed by chemotherapy, several clinical trials showed benefits to administering systemic chemotherapy (and HER2-targeted therapies) prior to surgery. These benefits include more accurate prognostic estimates based on the extent of residual cancer that can also guide adjuvant treatment, and frequent tumor downstaging that can lead to smaller surgeries in patients with large tumors at diagnosis. Patients with extensive invasive residual cancer after neoadjuvant therapy are at high risk for disease recurrence, and two pivotal clinical trials, CREATE-X and KATHERINE, demonstrated improved recurrence free survival with adjuvant capecitabine and ado-trastuzumab-emtansine (T-DM1) in TNBC and HER2-positive residual cancers, respectively. Patients who achieve pathologic complete response (pCR) have excellent long-term disease-free survival regardless of what chemotherapy regimen induced this favorable response. This allows escalation or de-escalation of adjuvant therapy: patients who achieved pCR could be spared further chemotherapy, while those with residual cancer could receive additional chemotherapy postoperatively. Ongoing clinical trials are testing this strategy (CompassHER2-pCR: NCT04266249). pCR also provides an opportunity to assess de-escalation of locoregional therapies. Currently, for patients with residual disease in the lymph nodes (ypN+), radiation therapy entails coverage of the undissected axilla, and may include supra/infraclavicular/internal mammary nodes in addition to the whole breast or chest wall, depending on the type of surgery. Ongoing trials are testing the safety of omitting post-mastectomy breast and post-lumpectomy nodal irradiation (NCT01872975) as well as omitting axillary lymph node dissection (NCT01901094) in the setting of pCR. Additionally, evolving technologies such as minimal residual disease (MRD) monitoring in the blood during follow-up may allow early intervention with “second-line systemic adjuvant therapy” for patients with molecular relapse which might prevent impending clinical relapse.

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Authors and Affiliations

  1. Section of Medical Oncology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA

    Julia Foldi MD PhD, Mariya Rozenblit MD & Lajos Pusztai MD DPhil

  2. Department of Surgery, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA

    Tristen S. Park MD & Mehra Golshan MD

  3. Department of Therapeutic Radiation, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA

    Christin A. Knowlton MD & Meena Moran MD

  4. Breast Medical Oncology, Yale Cancer Center, Yale School of Medicine, 300 George St, Suite 120, Rm 133, New Haven, CT, 06520, USA

    Lajos Pusztai MD DPhil

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Lajos Pusztai has received consulting fees and honoraria from Seagen, Pfizer, Astra Zeneca, Merck, Novartis, Bristol Myers Squibb, Pfizer, Genentech, Eisai, Pieris, Immunomedics, Clovis, Syndax, H3Bio, Radius Health, and Daiichi, and institutional research funding from Seagen, AstraZeneca, Merck, Pfizer and Bristol Myers Squibb. The rest of the authors have no conflicts of interest to disclose.

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Foldi, J., Rozenblit, M., Park, T.S. et al. Optimal Management for Residual Disease Following Neoadjuvant Systemic Therapy. Curr. Treat. Options in Oncol. 22, 79 (2021). https://doi.org/10.1007/s11864-021-00879-4

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