HER2+ Inflammatory Breast Cancer: Neoadjuvant Approaches

Debu Tripathy, MD:This patient does go on to receive doxorubicin and cyclophosphamide followed by docetaxel, trastuzumab, and pertuzumab and does have a clinical response at the time of surgery. In fact, she does have a complete pathologic response, which is defined by no invasive disease in either the breast or the lymph nodes.

Neoadjuvant therapy is typically used for patients with larger tumors or node-positive tumors or if there is an interest in breast-conserving surgery. The ability to use breast-conserving surgery is much greater in patients who have a significant response, and that’s been shown very clearly in HER2-positive breast cancer.

Now, in this particular case, there’s an additional important factor, and that is that the patient has inflammatory breast cancer. Historically, the outcome with surgery up front has been very poor. The recurrence rates are extremely high. For many, many years now, even before the advent of HER2-targeted therapies, we have been using preoperative chemotherapy for these patients because of the involvement of the dermal lymphatics. It’s very difficult to know where the borders of the dermal lymphatics are—if they are just involved right over the tumor or if they go further out—because the clinical changes are quite subtle, the redness and the swelling. So, it is very typical now for us to use neoadjuvant chemotherapy for these cases. Obviously, in the case of HER2-positive breast cancer, we would now add both antibodies, trastuzumab and pertuzumab.

The use of anthracyclines in the initial setting for HER2-positive breast cancer remains somewhat controversial. The data so far actually project equivalent outcomes from anthracycline or nonanthracycline therapy. If you look at the most important outcomes, which are disease-free survival and overall survival data from the older trials where anthracycline and nonanthracycline therapies were tested side by side, they show equivalent results. BCIRG-006 is the study that compared doxorubicin and cyclophosphamide followed by docetaxel along with trastuzumab to the nonanthracycline regimen of docetaxel, carboplatin, and trastuzumab. This was in the pre-pertuzumab era, but very clearly, the outcomes there were equivalent. At this point in time, there are some favorites. Some people like to use anthracyclines or feel that they might be more important for younger patients and for higher-stage disease. We don’t really have clear, definitive proof that there’s a right or wrong way to go when it comes to choosing anthracyclines or not.

Transcript edited for clarity.

60-year-old Woman WithHER2+ Inflammatory Breast Cancer

• A 60-year-old woman presented to her gynecologist with redness, tenderness, and swelling of her right breast over the last 2 weeks
  • PMH: HTN managed with HCTZ/triamterene
  • FH: unremarkable
  • PE: palpable mass in the right inferior breast with skin thickening; no palpable lymphadenopathy
  • ROS: clear, no fever
• Breast ultrasound revealed a solid right-sided 3.8-cm mass at the 10:00 position with no posterior acoustic shadowing; abnormal enlargement of 2 right axillary lymph nodes
• Core needle biopsy of the breast mass revealed high grade infiltrating ductal carcinoma;HER2+
• Fine needle biopsy of a right axillary node confirmed carcinoma
• Punch biopsy of the skin showed dermal lymphatic invasion with carcinoma cells
• PET/CT staging showed increased uptake over right breast, diffusely, and with at least 2 nodes seen in the right axillary basin; no evidence of distant metastases
• Clinical staging: T4dN1M0
• She received neoadjuvant therapy consisting of dose-dense AC X 4-THP X 4; physical exam was consistent with a complete clinical response
• She then underwent right modified radical mastectomy; pathology showed a complete pathologic response
• Following surgery, she was treated with adjuvant trastuzumab + pertuzumab to complete one year of monoclonal antibody therapy
• The patient completed radiation therapy to the right chest wall and regional nodes
• She was placed on letrozole