HER2+ Early-Stage Breast Cancer: Neoadjuvant Strategies

Denise A. Yardley, MD:The treatment options for a patient who presents with a HER2-positive breast cancer really focus on the timing of surgery and the timing of adjuvant therapy. The guidelines really support an approach of chemotherapy given with HER2-targeted therapy, both in the adjuvant and the neoadjuvant setting. Those are all going to be features of her disease. I think the key component is really looking at the timing and the sequencing. For this patient, who as a 2-cm tumor and lymph node-positive disease, the best recommendation would be to approach neoadjuvant chemotherapy with dual HER2-targeted therapy followed by surgery.

Now, discussing the specific parameters of chemotherapy gives some options for patients. There can be an anthracycline-based regimen followed by a taxane, at which time the standard of using dual HER2-targeted therapy is concurrently with a weekly taxane.

I’m much more of a fan of the taxane/platinum programs, so docetaxel/carboplatin/Herceptin [trastuzumab]/Perjeta [pertuzumab]. I think it’s really well tolerated. The issue of cardiotoxicity is a little different between the regimens. They’re very effective regimens, both of them. But I do think the risk of cardiotoxicity and symptomatic congestive heart failure is slightly higher in the anthracycline-based regimen. I also look at whether the patient has left-sided breast cancer or whether there’s going to be a role of radiation therapy, and that certainly would dissuade me from the consideration of an anthracycline-based regimen. But largely I practice with a docetaxel/carboplatin, dual HER2-targeted neoadjuvant regimen.

When I talk to patients about treatment options, I do talk about how the standard was just single-agent HER2-targeted therapy with chemotherapy, and then we looked at the data that have evolved regarding the addition of pertuzumab to Herceptin in neoadjuvant therapy and what the advantages of that are to the patient.

We have a long discussion because the therapy can come with a few more adverse effects, but the advantages increase the chance that there’s no disease at the time of surgery. We know from our meta-analysis that patients who have no disease at the time of surgery have the best disease-free and overall survival. For those patients, I really talk about Perjeta. It does have an increased risk of diarrhea for patients, and we talk about what that looks like currently with chemotherapy since some of the chemotherapy agents can also result in diarrhea and it’s sometimes hard to distinguish. We talk about the prophylactic medications that we are going to try to get onboard if the patient does experience that toxicity. But I think with the advantages of the dual HER2-targeted therapy that has now become a standard of care for our HER2-positive patients in the neoadjuvant setting, we’re going to really try hard to commit to that program. I have occasionally had to drop pertuzumab in a patient after dose modifying the chemotherapy. And then, I do revisit with that patient with pertuzumab in the adjuvant setting in the absence of chemotherapy.

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