Neoadjuvant therapy refers to the systemic treatment of breast cancer before definitive surgery, it is also called preoperative therapy. Neoadjuvant therapy was initially used for patients with the advanced inoperable disease, however, it is now proved to be beneficial in different subsets of patients including those with early-stage operable breast cancer.
Several studies demonstrated comparable survival rate when compared to adjuvant therapy (postoperative therapy). Neoadjuvant therapy is commonly administered in the form of chemotherapy, however, endocrine therapy is also utilized in specific patient subsets.
Several randomized studies showed comparable survival between neoadjuvant therapy and adjuvant therapy
Response to neoadjuvant therapy has consistently shown to be a predictor of outcome in patients achieving complete pathologic response (pCR) will have improved survival compared to patients achieving less than pCR.
With the use of Her2 targeting agents, the use of Neoadjuvant therapy is now becoming the standard of care in a specific subset of Her2 positive patients.
Rationale, the main goal of neoadjuvant therapy is to downstage the tumor, and subsequently, the patient will be a candidate for less extensive surgery with better cosmetic results and even reducing postoperative complications such as lymphedema.
Indications, neoadjuvant chemotherapy (NAC) is primarily used in three main areas,
a. Locally advanced tumors such as clinical stage IIB T3 to stage IIIC this is regardless of tumor profile, i.e. even in ER positive tumors.
b. Select early breast cancer tumors, patient with early stage such as I or II can be good candidate for NAC in the following subsets,
- High tumor to breast size issue which may lead to poor cosmetic outcome
- Triple negative disease or HER2 positive disease.
- Patients with clinically positive lymph node disease, where NAC chemotherapy may downstage the lymph node status and may even obviate the need for axillary lymph node status.
The use of NAC in the category b. patients who are ER positive and HER2 negative is determined in a case by case basis.
c. When there is a temporary contraindication to surgery such as pregnancy.
d. In patient presenting with Inflammatory breast cancer.
Comparison of neoadjuvant to adjuvant chemotherapy This was originally investigated by National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 which randomized patients to either preoperative four cycles of AC followed by predetermined surgery vs. surgery followed by four cycles of AC. There was no difference in overall survival or disease-free survival between the two arms. However, the preoperative arm showed 79% objective clinical response ( 43% partial response, and 36% complete response) and 13% complete pathologic response. The B-18 study findings were also confirmed by large EORTC trial as well as a larger subsequent meta-analysis.