INTRODUCTION
Neoadjuvant therapy refers to the systemic treatment of breast cancer prior to definitive surgical therapy (ie, preoperative therapy). In the past, this almost always consisted of neoadjuvant chemotherapy (NACT), but, more recently, there has been increasing interest in assessing the role of neoadjuvant endocrine therapy, as well as targeted therapies, sometimes administered concurrent with, and sometimes in lieu of, chemotherapy, in certain subsets of patients.This topic will review patient selection, pretreatment assessment, treatment options, and evaluation of response to and treatment after neoadjuvant therapy. Where clinical guidance is provided in this topic, the anatomic staging system set forth in the eighth edition of the American Joint Committee on Cancer (AJCC) Staging Manual is used (table 1). Clinicians may also find it useful to refer to the clinical prognostic staging system set forth in the eighth edition AJCC manual, which incorporates prognostic features such as tumor grade and hormone and human epidermal growth factor receptor 2 (HER2) receptor status, and thus provides more refined prognostic information prior to surgery (table 2). Of note, the AJCC eighth edition does not have a pathologic staging system for patients treated with neoadjuvant therapy. Additionally, the studies cited in this topic typically used previous editions of the staging system to define and describe their patient populations, which is a limitation of available data. Further discussion of existing staging systems, including the clinical and pathologic prognostic staging systems, are found elsewhere (table 2 and table 3). (See "Tumor, node, metastasis (TNM) staging classification for breast cancer".)
Specific issues related to deciding between NACT versus neoadjuvant endocrine therapy in hormone receptor-positive/HER2-negative cancers, the role of HER2-directed therapies in HER2-positive cancers, selecting a NACT regimen, and the impact of response to neoadjuvant therapy on choice of postoperative therapy are discussed elsewhere. (See "Neoadjuvant management of newly diagnosed hormone-positive breast cancer" and "Neoadjuvant therapy for patients with HER2-positive breast cancer" and "Adjuvant endocrine and targeted therapy for postmenopausal women with hormone receptor-positive breast cancer" and "Selection and administration of adjuvant chemotherapy for HER2-negative breast cancer" and "Adjuvant systemic therapy for HER2-positive breast cancer" and "ER/PR negative, HER2-negative (triple-negative) breast cancer" and "Choice of neoadjuvant chemotherapy for triple-negative breast cancer".)
GOALS
While all systemic therapy given for non-metastatic, invasive breast cancer is intended to reduce the risk of distant recurrence, the purpose of administering it prior to surgery is to downstage the extent of disease in the breast and/or regional lymph nodes and provide information regarding treatment response to direct adjuvant therapies. Downstaging may allow less extensive surgery on the breast and/or axilla, including avoiding the risks associated with breast reconstruction in patients able to undergo breast-conserving surgery in place of mastectomy, improving cosmetic outcomes, and reducing postoperative complications such as lymphedema [1-6]. Neoadjuvant therapy also permits evaluation of the effectiveness of systemic therapy, which is increasingly used to guide adjuvant treatment recommendations. The presence and extent or absence of residual invasive cancer after neoadjuvant therapy is a strong prognostic factor for risk of recurrence, especially in triple-negative breast cancer and human epidermal growth factor receptor 2-positive breast cancer. (See 'Poor response to or progression on neoadjuvant therapy' below.)In addition to these clinical objectives, neoadjuvant therapy gives researchers the opportunity to obtain imaging studies, tumor specimens, and blood samples prior to, during, and, in patients with sufficient residual disease at surgery, after the preoperative treatment, which may assist in the identification of tumor- or patient-specific biomarkers of response or resistance.
