SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. Approximately 266,120 new cases of invasive breast cancer will be diagnosed in 2018 and about 40,920 women will die of the disease. Approximately 15-20% of invasive breast cancers overexpress HER2/neu oncogene, which is a negative predictor of outcomes without systemic therapy. HERCEPTIN® (Trastuzumab) is a humanized monoclonal antibody targeting HER2, and adjuvant and neoadjuvant chemotherapy given along with HERCEPTIN® reduces the risk of disease recurrence and death, among patients with HER2-positive, early stage as well as advanced metastatic breast cancer.
ASCO published an adaptation of the Cancer Care Ontario guideline, on optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for HER2 (Human Epidermal Growth Factor receptor 2) positive breast cancers, in 2016. The recent publication of phase III studies relevant to the clinical care of breast cancer patients prompted the ASCO Update Steering Group of the original Expert Panel, to provide a focused update of the 2016 guideline. With the exception of this focused update, the remaining recommendations from the 2016 ASCO guideline are unchanged.
Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Clinical Practice Guideline Focused Update
Questions Addressed in Focused Update
1) Should adjuvant Capecitabine be given following completion of standard preoperative Anthracycline- and Taxane-based combination chemotherapy in patients with early-stage HER2-negative breast cancer with residual invasive disease at surgery?
2) Should 1 year of adjuvant Pertuzumab be added to Trastuzumab-based combination chemotherapy in patients with early stage HER2-positive breast cancer?
3) Should Neratinib be offered as extended adjuvant therapy for patients after combination chemotherapy and Trastuzumab-based adjuvant therapy with early-stage, HER2-positive breast cancer?
Target Population
Patients who are being considered for, or who are receiving, systemic therapy following definitive surgery for early-stage invasive breast cancer, defined largely as invasive cancer anatomic Stages I to IIIC
Target Audience
Medical oncologists, Pathologists, Surgeons, Oncology nurses, Patients, and Caregivers.
Focused Update Recommendations
Patients with early-stage HER2-negative breast cancer with pathologic invasive residual disease at surgery following standard Anthracycline and Taxane-based preoperative therapy may be offered up to six to eight cycles of adjuvant Capecitabine (XELODA®).
Qualifying statements: If clinicians decide to use Capecitabine, then the Expert Panel preferentially supports the use of adjuvant Capecitabine in the subgroup of patients with Hormone Receptor negative, HER2-negative disease. The Capecitabine dosage used in the CREATE-X study (1,250 mg/m2 PO twice daily) is associated with higher toxicity in patients 65 years or older.
Clinicians may add 1 year of adjuvant Pertuzumab (PERJETA® ) to Trastuzumab (HERCEPTIN®)-based combination chemotherapy in patients with high-risk, early-stage, HER2-positive breast cancer.
Qualifying statements: The Expert Panel preferentially supports Pertuzumab in patients with node-positive, HER2-positive breast cancer in view of the clinically insignificant absolute benefit observed among node-negative patients. After a median follow up of 3.8 years, Pertuzumab offered a modest Disease Free Survival (DFS) benefit. The first planned interim analysis did not show an Overall Survival (OS) benefit in the trial population. There are no data to guide the duration of Pertuzumab in patients who received neoadjuvant Pertuzumab and achieved a pathologic Complete Response.
Clinicians may use extended adjuvant therapy with Neratinib (NERLYNX®) to follow Trastuzumab in patients with early stage, HER2-positive breast cancer. Neratinib causes substantial diarrhea and diarrhea prophylaxis must be used.
Qualifying statements: The Expert Panel preferentially favors use of Neratinib in patients with HER2-positive, Hormone Receptor positive, and node-positive disease. At a median follow-up of 5.2 years, no OS benefit has been observed. Patients who began Neratinib within 1 year of Trastuzumab completion appeared to derive the greatest benefit. There are no data on the added benefit of Neratinib in patients who also received Pertuzumab in the neoadjuvant or adjuvant setting.
Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Clinical Practice Guideline Focused Update. Denduluri N, Chavez-MacGregor M, Telli ML, et al. J Clin Oncol. 2018;36:2433-2443.
