Adjuvant Approaches to Treating HER2+ Breast Cancer

Denise A. Yardley, MD:The surgical outcomes for this patient are what we would have expected. When we see a patient receive neoadjuvant therapy with chemotherapy and the dual HER2-targeted agent, the expectation of a PCR [pathologic complete response] is upwards of 50%. Looking at this patient at the time of surgery, she had only a small residual burden of above 4 mm, but her lymph nodes were all negative and that certainly plays into the highest outcomes and prognostic features for the patient—having lymph node-negative disease.

We’re trying to incorporate how to make risk predictions for patients in terms of recurrence based on the presence or absence of residual disease after neoadjuvant therapy. If we look at this patient’s 4-mm burden, she would likely fall into a residual cancer burden of 1 that has an excellent prognosis and really patterns after those patients who have a pathologic CR. I think that’s an excellent finding for the patient, who has cleared her lymph nodes that were not only abnormal by imaging but also documented to have metastatic disease. I still think her prognosis is excellent based on the fact that we were able to eradicate the metastatic disease in the lymph nodes and have only this microscopic burden left in the breast.

Regarding the recommended adjuvant therapy for a HER2-positive patient who has undergone neoadjuvant therapy, the standard guidelines really look at Herceptin [trastuzumab], and that’s where the data have been. When we look at the neoadjuvant trials, they gave a dual HER2-targeted therapy upfront, but at that time the trials completed the adjuvant component of their therapy post surgery with single-agent Herceptin. In looking at pertuzumab and the indications for pertuzumab in a high-risk patient in the adjuvant setting from the APHINITY data, I clearly think that this patient is a high-risk patient who had documented lymph node-positive disease, and I would recommend the addition of Perjeta, pertuzumab, to Herceptin in the adjuvant setting. That would typically be what I would talk to the patient about in the absence of any prohibitive toxicity.

When I look at the patient and try to figure out my adjuvant treatment strategies, I would say for anyone who I’ve treated neoadjuvantly and who tolerated the dual HER2-targeted therapy, I have a tendency to continue that in the adjuvant setting. I do think if they had a lower risk cancer—maybe just 2 cm nodes were noted to be negative—you could continue, and this would definitely be within the guidelines as well, just a Herceptin-based regimen. But for the most part, I think in patients who I treat with neoadjuvant dual HER2-targeted therapy and who are not facing an intolerance, I would continue that after surgery in the adjuvant fashion for the patient.

The dual HER2-targeted therapies have offered patients the best overall disease-free survival and overall survival, and we can look at both the neoadjuvant trials and really extrapolate that. In the case of the APHINITY trial as well, the addition of pertuzumab to HER2-targeted therapy was tested in the adjuvant setting, which I think is for a year of therapy. If I look at my practice preference of treating the patient both in the neoadjuvant and adjuvant setting, I think I’m giving that patient the best chance for curability.

When we look at HER2-targeted therapy as a whole, we know that it’s decreased the risk of recurrence in disease-free survival by 40%. And so, I would really want to offer that for patients. In the adjuvant trial, APHINITY, we know it had an absolute disease-free benefit for those patients and put their disease-free survival in the 90% or higher range. I really roll out all these treatment options for the patient to ensure that they’re getting their best chance for curability.

Transcript edited for clarity.

A 56-Year-Old Woman Receiving Adjuvant Therapy forHER2+ Breast Cancer

• A 56-year-old postmenopausal woman was referred for evaluation of a left-sided spiculated mass (2.4-cm) with scattered microcalcifications, found incidentally on screening mammography. Mammogram 12 months earlier was normal.
• Ultrasound confirmed a hypoechoic mass of approximately 2.4 cm X 2,3 cm by 1.8 cm at the 2 o’clock position in the left breast, 4 cm from the nipple. Axillary ultrasound demonstrated 3 enlarged lymph nodes with cortex thickening.
• Core biopsy of the breast mass revealed poorly differentiated invasive ductal carcinoma, ER/PR-negative, HER2 IHC 3+; lymph node sampling revealed the presence of breast cancer.
• Staging: T2N1M0
• She received neoadjuvant docetaxel and carboplatin with concurrent trastuzumab and pertuzumab.
• Surgical resection scattered microscopic foci of residual disease spanning 4 mm; no involved lymph nodes
  • Re-staging, ypT1aypN0M0