Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer

Publication Date: April 13, 2022


New Recommendation from 2022 Guideline Rapid Recommendation Update

For patients with T1cN1-2 or T2-4N0 (stage II or III), early-stage triple negative breast cancer, the Panel recommends use of pembrolizumab (200 mg every 3 weeks or 400 mg every 6 weeks) in combination with neoadjuvant chemotherapy, followed by adjuvant pembrolizumab after surgery. Adjuvant pembrolizumab may be given either concurrent with or after completion of radiation therapy. Given that immune-related adverse events (irAEs) associated with pembrolizumab therapy can be severe and permanent, careful screening for and management of common toxicities are required. The ASCO guideline for management of irAEs in patients treated with immune checkpoint inhibitor therapy offers detailed practice recommendations and should be consulted by clinicians who prescribe pembrolizumab for patients with early-stage TNBC, ( EB , I , B , M )
Qualifying Statements: Results from KEYNOTE-522 are based on continued pembrolizumab in the adjuvant setting. There is uncertainty concerning the optimal adjuvant treatment given independent benefits of capecitabine in TNBC and olaparib in patients with germline BRCA mutations without pembrolizumab. There are no data to support the use of pembrolizumab in combination with either capecitabine or olaparib.


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. ( IC , L , , S )
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. ( IC , Ins , , M )
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. ( EB , H , B , S )
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. ( EB , I , B , M )
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. ( IC , L , B , M )

Measuring Response

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. ( IC , Ins , , M )

Blood- and tissue-based biomarkers should not be used for monitoring patients receiving neoadjuvant therapy. ( IC , Ins , , S )

pCR, defined as absence of invasive disease in breast and lymph nodes, should be used to measure response to guide clinical decision making. ( IC , Ins , , M )

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. ( EB , H , B , S )

Patients with cT1a or cT1bN0 TNBC should not routinely be offered neoadjuvant therapy outside of a clinical trial. ( EB , H , B , S )

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. ( EB , I , B , M )

There is insufficient evidence to recommend routinely adding the immune checkpoint inhibitors to neoadjuvant chemotherapy in patients with early-stage TNBC. ( IC , I , , M )

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. ( IC , L , , M )

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. ( EB , I , B , M )

For premenopausal patients with HR+, HER2-negative early-stage disease, neoadjuvant endocrine therapy should not be routinely offered outside of a clinical trial. ( EB , I , B , M )

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. ( EB , H , B , S )

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. ( IC , I , , M )

Recommendation Grading




Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer

Authoring Organization

Publication Month/Year

April 13, 2022

Document Type


Country of Publication


Target Patient Population

Patients with nonmetastatic breast cancer

Target Provider Population

Medical oncologists, surgical oncologists, radiologists, pathologists, oncology nurses, patients or caregivers or advocates

Inclusion Criteria

Female, Adult, Older adult

Health Care Settings

Ambulatory, Outpatient, Radiology services

Intended Users

Nurse, nurse practitioner, physician, physician assistant


Treatment, Management

Diseases/Conditions (MeSH)

D001943 - Breast Neoplasms, D017024 - Chemotherapy, Adjuvant


breast cancer, chemotherapy, endocrine therapy, HER2-targeted therapy, Targeted Therapy

Source Citation

Korde LA, Somerfield MR, Hershman DL, et al. Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer Guideline Expert Panel. Use of Immune Checkpoint Inhibitor Pembrolizumab in the Treatment of High-risk, Early-stage Triple Negative Breast Cancer: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2022 April 13. doi: 10.1200/JCO.22.00503

Korde LA, Somerfield MR, Carey LA, et al. Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline. J Clin Oncol. 2021 May 1;39(13):1485-1505

Supplemental Methodology Resources

Data Supplement, Evidence Tables,


Number of Source Documents
Literature Search Start Date
January 1, 2000
Literature Search End Date
August 31, 2020