The Evolving Role of Neoadjuvant Therapy for Operable Breast Cancer

Authors: Laura M. Spring MD1,2, Yael Bar MD1, and Steven J. Isakoff MD, PhD1,2
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  • 1 Massachusetts General Hospital Cancer Center, and
  • | 2 Harvard Medical School, Boston, Massachusetts.

The role of neoadjuvant therapy (NAT) for localized breast cancer has evolved tremendously over the past several years. Currently, NAT is the preferred option for high-risk early triple-negative (TN) and HER2-positive (HER2+) breast cancers and is indicated for some estrogen receptor–positive (ER+) breast cancers. In addition to traditional absolute indications for NAT, relative indications such as the assessment of outcomes at the time of surgery and guidance of treatment escalation and de-escalation have greatly evolved in recent years. Pathologic complete response (pCR) and the Residual Cancer Burden (RCB) index are highly prognostic for disease recurrence and survival, mainly in patients with TN or HER2+ disease. Furthermore, post-NAT escalation strategies have been shown to improve long-term outcomes of patients who do not achieve pCR. Additionally, by allowing the direct assessment of drug effect on the tumor, the neoadjuvant setting has become an attractive setting for the exploration of novel agents and the identification of predictive biomarkers. Neoadjuvant trial design has also evolved, using adaptive treatment approaches that enable treatment de-escalation or escalation based on response. However, despite multiple practice-changing neoadjuvant trials and the addition of various new agents to the neoadjuvant setting for early breast cancer, many key questions remain. For example, patient selection for neoadjuvant immunotherapy in TN breast cancer, de-escalation methods in HER2+ breast cancer, and the use of gene expression profiles to guide NAT recommendations in ER+ breast cancer. This article reviews the current approach for NAT in localized breast cancer as well as evolving NAT strategies, the key remaining challenges, and the ongoing work in the field.

Submitted for publication February 2, 2022; accepted for publication March 28, 2022.

Disclosures: Dr. Spring has disclosed receiving consulting fees from Novartis and Puma Technology, and institutional research funding from Merck & Co., Inc. and Phillips. Dr. Isakoff has disclosed receiving consulting fees from Seagen, Novartis, Puma Technologies, and Paxman; and institutional research funding from Genentech, AbbVie, OncoPep, Inc., Merck & Co., Inc., and AstraZeneca. Dr. Bar has disclosed no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.

Funding: Research reported in this publication was supported by the NCI of the NIH under award number K12CA087723 (L.M. Spring) and a grant from NCCN (L.M. Spring).

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Correspondence: Steven J. Isakoff, MD, PhD, Massachusetts General Hospital Cancer Center, Harvard Medical School, 55 Fruit Street, BHX.231, Boston, MA 02114. Email: sisakoff@mgh.harvard.edu
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