New ASCO Guideline Offers Recommendations for Neoadjuvant Breast Cancer Treatment

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ASCO has released a new guideline regarding the use of neoadjuvant chemotherapy, endocrine therapy, and targeted therapy in breast cancer.1 “This is the first time ASCO has embarked on a guideline for neoadjuvant therapy,” said Larissa A. Korde, MD, of the National Cancer Institute, and guideline
Co-Chair. “It is a broad and complex topic, and one that clinicians face quite frequently in the care of patients with breast cancer.”

Guideline Co-Chair Dawn L. Hershman, MD, FASCO, of the Herbert Irving Comprehensive Cancer Center at Columbia University, noted that the guideline committee developed its recommendations based on emerging evidence in the literature. In total, the guideline was based on data from 41 clinical trials that reported pathologic complete response and survival endpoints associated with neoadjuvant therapy in breast cancer.

Neoadjuvant Breast Cancer Therapy: ASCO Recommendations

The new guideline focuses on how clinicians can determine whether a patient should receive neoadjuvant treatment and also provides an overview of what regimens have been extensively studied. “I think the most important issue stressed in the guideline is that response to neoadjuvant therapy can be used in particular situations, such as in high-risk triple-negative and HER2-positive breast cancer, to guide further treatment,” Dr. Korde said.


Larissa A. Korde, MD

Larissa A. Korde, MD


Dawn L. Hershman, MD, FASCO

Dawn L. Hershman, MD, FASCO

Data from the phase III, open-label -KATHERINE trial, for instance, showed that women with HER2-positive breast cancer and residual disease after neoadjuvant HER2-directed therapy benefit from switching to adjuvant ado-trastuzumab emtansine. Switching to this option led to a substantial reduction in the risk of a distant recurrence in the trial. In addition, the CREATE-X trial showed that patients with triple-negative breast cancer and residual disease derive a survival benefit from adjuvant capecitabine.

“While there are multiple indications for neoadjuvant therapy, it has become particularly important as we have learned that patients who have residual disease have worse outcomes, and those patients may benefit from a change in therapy plan as a result,” Dr. Hershman said. “Simultaneously, we have found that patients without residual disease may be able to reduce the extent of local treatment.”

Based on the data, the ASCO guideline suggests the absence or presence of residual disease following neoadjuvant treatment can help guide treatment recommendations. The guideline committee also recommends clinicians routinely use tumor histology; grade; stage; and estrogen, progesterone, and HER2 expression to guide decision-making regarding whether or not to move forward with neoadjuvant chemotherapy.

Additionally, the ASCO guideline recommends offering neoadjuvant systemic therapy in patients with high-risk, HER2-positive or triple-negative breast cancer “in whom the finding of residual disease would guide recommendations related to adjuvant therapy.”

For patients with hormone receptor–positive, HER2-negative breast cancer, ASCO recommends the use of neoadjuvant chemotherapy instead of adjuvant chemotherapy but only in patients where a chemotherapy decision can be made without tumor-specific genomic testing and/or surgical pathology data. Neoadjuvant endocrine therapy is recommended in conjunction with an aromatase inhibitor in postmenopausal patients with hormone receptor–positive, HER2-negative breast cancer.

The ASCO guideline also recommends an anthracycline- and taxane-containing regimen in the neoadjuvant setting of patients with triple-negative breast cancer and clinically node-positive and/or at least T1c disease. In contrast, neoadjuvant therapy should not be offered to patients with cT1a or cT1bN0 triple-negative breast cancer outside the context of a clinical trial.

Role of Immunotherapy

Immunotherapy was also briefly discussed in the guideline. “There is a lot of excitement about the addition of immune checkpoint inhibitor therapy to neoadjuvant chemotherapy in patients with triple-negative [breast] cancer,” Dr. Hershman said. The guideline cites increasing interest in pembrolizumab and atezolizumab in the metastatic setting, with some data suggesting atezolizumab can increase pathologic complete response rates.

Other randomized studies, like KEYNOTE-522, have examined the use of carboplatin plus paclitaxel with or without pembrolizumab followed by neoadjuvant chemotherapy with or without pembrolizumab in stage II/III triple-negative breast cancer. However, due to the insufficient and conclusive evidence supporting the addition of immunotherapy to neoadjuvant chemotherapy, Dr. Hershman added, further data are needed for future immunotherapy recommendations.

Future Directions of the Guideline

“We are excited to see ongoing trials that have used neoadjuvant therapy both to escalate therapy in those who have high-risk disease and to de-escalate therapy in patients with complete and rapid responses,” Dr. Hershman said.

Dr. Korde stated that the current outstanding issue is whether there is a role for immunotherapy in neoadjuvant treatment of breast cancer. “The studies that have looked at this show an increase in pathologic complete response, but longer-term data on outcomes, such as invasive disease–free survival and overall survival, are not mature,” she added. “This is definitely something that we will be hearing more about in the months and years to come.” 


1. Korde LA, Somerfield MR, Carey LA, et al: Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO guideline. J Clin Oncol. January 28, 2021 (early release online).

Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, January 29, 2021. All rights reserved.