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Nodal Positivity in Early-Stage Triple-Negative Breast Cancer: Implications for Preoperative Immunotherapy

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Adding pembrolizumab to preoperative chemotherapy improves event-free survival in patients with early-stage triple-negative breast cancer (TNBC). However, owing to potential toxicities, the risk–benefit ratio of pembrolizumab must be considered. There is consensus that the addition of immunotherapy should be recommended in node-positive patients. This study is undertaken to determine nodal positivity rates in patients with TNBC presenting with cT1–2N0 disease undergoing upfront surgery and to evaluate the utility of axillary ultrasound and biopsy in the setting of a negative clinical examination.

Patients and Methods

Patients with cT1–2N0 TNBC undergoing upfront surgery were identified from our institutional database (January 2016–February 2021; n = 343) and from the National Cancer Database (NCDB) (n = 46,015). Pathologic nodal status was determined. A second cohort of patients with cT1–T2 TNBC with a negative clinical examination was defined in our institutional database (n = 499), and utilization of axillary ultrasound was examined.

Results

For patients undergoing upfront surgery, pathologically positive nodes were found in 14.6% patients of our institutional cohort: 9.4% cT1a/b, 14.9% cT1c, and 20.8% cT2 tumors. In the NCDB cohort, 13.7% patients were node positive: 4.9% cT1a/b, 11.4% cT1c, and 19.7% cT2 tumors. For patients with a normal clinical examination undergoing axillary ultrasound, 7.5% of cT1c and 8.7% of cT2 had suspicious nodes biopsied and confirmed positive for metastasis.

Conclusions

Pathologic node-positive disease is found in > 10 and 20% patients with cT1cN0 and cT2N0 TNBC, respectively. Axillary ultrasound can be used to identify patients presenting with a normal clinical examination for whom preoperative pembrolizumab should be considered.

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Acknowledgements

E.A.M. acknowledges support as the Rob and Karen Hale Distinguished Chair in Surgical Oncology. The authors also acknowledge Tonia Parker and Julie Vincuilla for their oversight of the Dana-Farber Brigham Cancer Center prospectively maintained breast clinical oncology quality database.

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Author notes

  1. Ian E. Krop MD, PhD & Eric P. Winer MD

    Present address: Yale Medical School, New Haven, CT, USA

Authors and Affiliations

  1. Division of Breast Surgery, Department of Surgery, Brigham and Women’s Hospital, Boston, MA, USA

    Elizabeth A. Mittendorf MD, PhD, Olga Kantor MD, Anna Weiss MD & Tari A. King MD

  2. Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA

    Elizabeth A. Mittendorf MD, PhD, Olga Kantor MD, Anna Weiss MD, Edward Richardson MD, PhD, Ana Garrido-Castro MD, Leah H. Portnow MD, Ian E. Krop MD, PhD, Nancy U. Lin MD, Eric P. Winer MD, Sara M. Tolaney MD & Tari A. King MD

  3. Harvard Medical School, Boston, MA, USA

    Elizabeth A. Mittendorf MD, PhD, Olga Kantor MD, Anna Weiss MD, Edward Richardson MD, PhD, Ana Garrido-Castro MD, Leah H. Portnow MD, Ian E. Krop MD, PhD, Nancy U. Lin MD, Eric P. Winer MD, Sara M. Tolaney MD & Tari A. King MD

  4. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA

    Edward Richardson MD, PhD

  5. Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Ana Garrido-Castro MD, Ian E. Krop MD, PhD, Nancy U. Lin MD, Eric P. Winer MD & Sara M. Tolaney MD

  6. Department of Radiology, Brigham and Women’s Hospital, Boston, MA, USA

    Leah H. Portnow MD

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  1. Elizabeth A. Mittendorf MD, PhD
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Corresponding author

Correspondence to Elizabeth A. Mittendorf MD, PhD.

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Disclosure

E.A.M. reports compensated service on scientific advisory boards for AstraZeneca, Exact Sciences (formerly Genomic Health), Merck, Roche/Genentech; uncompensated service on steering committees for Bristol Myers Squibb, Lilly, and Roche/Genentech; and institutional research support from Roche/Genentech (via SU2C grant) and Gilead. A.W. reports institutional research support from Myriad. E.R. reports institutional research support from AstraZeneca. A.G.C. reports institutional research support from AstraZeneca, Gilead, and Merck. I.E.K. reports employment from AMAG Pharmaceuticals and Freeline Therapeutics; stock and other ownership interests from AMAG Pharmaceuticals, Freeline Therapeutics, and Vertex; honoraria from AstraZeneca, Roche/Genentech, and Celltrion; consulting or advisory role for AstraZeneca, Bristol Myers Squibb, Context Therapeutics, Daiichi Sankyo, Macrogenics, Merck, Novartis, Roche/Genentech, Seattle Genetics, and Taiho Pharmaceutical; and institutional research support from Roche/Genentech and Pfizer. N.U.L. reports stock and other ownership interests from Artera Inc.; consulting or advisory role for Affinia Therapeutics, Aleta Biopharma, AstraZeneca, Daichii-Sankyo, Denali Therapeutics, Olema Pharmaceuticals, Prelude Therapeutics, Puma, and Voyager Therapeutics; and institutional research support from AstraZeneca, Merck, Olema Pharmaceuticals, Roche/Genentech, Seattle Genetics, and Pfizer. E.P.W. reports honoraria from Exact Sciences (formerly Genomic Health) and Roche/Genentech; consulting or advisory role for Athenex, Carrick Therapeutics, G1 Therapeutics, GlaxoSmithKline, Gilead, Jounce Therapeutics, Leap Therapeutics, Lilly, Roche/Genentech, Syros Pharmaceuticals, and Zymeworks; and institutional research support from Roche/Genentech. S.M.T. reports consulting or advisory role for 4D Pharma, ARC Therapeutics, AstraZeneca, Athenex, BeyondSpring Pharmaceuticals, Blueprint Medicine, Bristol Myers Squibb, Certara, CytomX Therapeutics, Daiichi Sankyo, Eisai, Ellipses Pharma, G1 Therapeutics, Gillead, Kyowa Hakko Kirin, Lilly, Merck, Mersana, Nanostring Technologies, Nektar, Novartis, Odonate, OncoPep, OncoSec Medical, OncXerna, Paxman, Pfizer, Puma Biotechnology, Reveal Genomics, Roche/Genentech, Samsung Bioepis, Sanofi, Seattle Genetics, Silverback Therapeutics, Zentalis, and Zymeworks; and institutional research support from AstraZeneca, Bristol Myers Squibb, Cyclacel, Eisai, Exelixis, Gilead, Lily, Merck, Nanostring, Nektar, Novartis, Odonate Therapeutics, Roche/Genentech, Sanofi, Seattle Genetics, and Pfizer. T.A.K. reports speakers honoraria and compensated service on scientific Advisory Board of Exact Sciences (formerly Genomic Health); compensated service as faculty, PrecisCa cancer information service; and compensated service for a Global Advisory Board of Berins Healthcare.

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Mittendorf, E.A., Kantor, O., Weiss, A. et al. Nodal Positivity in Early-Stage Triple-Negative Breast Cancer: Implications for Preoperative Immunotherapy. Ann Surg Oncol 30, 100–106 (2023). https://doi.org/10.1245/s10434-022-12357-8

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