- Multiple studies of both chemotherapy and endocrine therapy have shown that neoadjuvant treatment can increase the likelihood of breast-conserving surgery.
- The CTNeoBC pooled analysis of neoadjuvant breast cancer clinical trials published in 2014 confirmed that achievement of a pathologic complete response (pCR) with neoadjuvant treatment was prognostic.
- It also showed that the association between pCR and outcomes was strongest in patients with triple negative and human epidermal growth factor receptor 2 (HER2)-positive disease.
- Optimal therapy for breast cancer is driven by subtype.
- Neoadjuvant chemotherapy is the treatment of choice for patients with inflammatory breast cancer (IBC) or those with unresectable/locally advanced disease at presentation whose disease may be rendered resectable with neoadjuvant treatment. (Strong recommendation; IC-L)
- Tumor histology, grade, stage and estrogen, progesterone, and HER2 expression should routinely be used to guide clinical decisions as to whether or not to pursue neoadjuvant chemotherapy. There is insufficient evidence to support the use of other immunochemical markers, morphological markers (e.g., tumor infiltrating lymphocytes or TILs) or genomic profiles to guide a clinical decision as to whether or not to pursue neoadjuvant chemotherapy. (Moderate recommendation; IC-Ins)
- Neoadjuvant systemic therapy should be offered to patients with high-risk HER2+ or triple negative breast cancer (TNBC) in whom the finding of residual disease would guide recommendations related to adjuvant therapy. (Strong recommendation; EB-B-H)
- Neoadjuvant systemic therapy may be offered to reduce the extent of surgery (breast conserving surgery [BCS]; axillary lymph node dissection, ALND). Chemotherapy with or without targeted therapy, or endocrine therapy (if HR+) may be offered. (Moderate recommendation; EB-B-I)
- In patients for whom a delay in surgery is preferable (e.g., for genetic testing required for surgical treatment decision making, to allow time to consider reconstructive options) or unavoidable, neoadjuvant systemic therapy may be offered. (Moderate recommendation; IC-B-L)
- Patients receiving neoadjuvant therapy should be monitored for response with clinical examination at regular intervals. Breast imaging may be used to confirm clinical suspicion of progression and for surgical planning. When imaging is used, the modality that was most informative at baseline — mammography, ultrasound, or magnetic resonance imaging — should be used at follow up. (Moderate recommendation; IC-Ins)
- Blood- and tissue-based biomarkers should not be used for monitoring patients receiving neoadjuvant therapy. (Strong recommendation; IC-Ins)
- pCR, defined as absence of invasive disease in breast and lymph nodes, should be used to measure response to guide clinical decision making. (Moderate recommendation; IC-Ins)
Recommended Regimens for Patients with TNBC
- Patients with TNBC who have clinically node positive and/or at least T1c disease should be offered an anthracycline- and taxane-containing regimen in the neoadjuvant setting. (Strong recommendation; EB-B-H)
- Patients with cT1a or cT1bN0 TNBC should not routinely be offered neoadjuvant therapy outside of a clinical trial. (Strong recommendation; EB-B-H)
- Carboplatin may be offered as part of a neoadjuvant regimen in patients with TNBC to increase likelihood of pCR. The decision to offer carboplatin should take into account the balance of potential benefits and harms. (Moderate recommendation; EB-B-I)
- There is insufficient evidence to recommend routinely adding the immune checkpoint inhibitors to neoadjuvant chemotherapy in patients with early-stage TNBC. (Moderate recommendation; IC-I)
Recommended Neoadjuvant Treatment for Patients with HER2-negative/HR-positive Breast Cancer
- Neoadjuvant chemotherapy can be used instead of adjuvant chemotherapy in any patient with HR+, HER2-negative breast cancer in whom the chemotherapy decision can be made without surgical pathology data and/or tumor specific genomic testing. (Moderate Recommendation; IC-L)
- For postmenopausal patients with HR+, HER2-negative disease, neoadjuvant endocrine therapy with an aromatase inhibitor may be offered to increase locoregional treatment options. If there is no intent for surgery, endocrine therapy may be used for disease control.(Moderate Recommendation; EB-B-I)
- For premenopausal patients with HR+, HER2-negative early-stage disease, neoadjuvant endocrine therapy should not be routinely offered outside of a clinical trial. (Moderate Recommendation; EB-B-I)
Recommended Neoadjuvant Treatment for Patients with HER2-Positive Disease
- Patients with node-positive or high-risk node-negative, HER2-positive disease should be offered neoadjuvant therapy with an anthracycline and taxane or non-anthracycline-based regimen in combination with trastuzumab. Pertuzumab may be used with trastuzumab in the neoadjuvant setting. (Strong Recommendation; EB-B-H)
- Patients with T1a N0 and T1b N0, HER2+ disease should not be routinely offered neoadjuvant chemotherapy or anti-HER2 agents outside of a clinical trial. (Moderate Recommendation; IC-I)