HER2+ Inflammatory Breast Cancer: Adjuvant Strategies

Debu Tripathy, MD:The risk of recurrence in patients who have surgery up front is dictated mostly by their clinical stage, as well as other factors such as the grade of the tumor. In patients who receive neoadjuvant therapy, however, one of the strongest predictors is whether or not the patient achieves a complete pathologic response. Patients who achieve a complete pathologic response have a short-term 5-to-10-year outcome that’s quite good. Maybe 10% to 15% of patients recur, so the disease-free survival typically tends to be about 90%.

In the case of inflammatory breast cancer, however, our experience is more limited given the rarity of this type of cancer. The data seem to show that the long-term outcomes, even in patients who achieve a complete pathologic response, may not be as favorable. Maybe 20% or 25% of these patients may still recur. The pathologic complete response rate is also lower in inflammatory breast cancer to start with.

Although pathologic complete response rate does predict a better outcome, and patients who do not have a complete pathologic response do have a worse outcome, the outcome is serially worse depending on how much residual disease there is. Especially if there are multiple nodes involved, these patients may have as high as a 30%, 40%, or 50% long-term risk of metastatic recurrence.

Following surgery and the determination of pathologic response, this patient who presented with inflammatory breast cancer that’s stage T4d, as well as node-positive, would clearly have an indication for chest-wall radiotherapy to include the regional nodes, which is what the patient receives. Following that, because the tumor was hormone receptor—positive, the patient would have gone on endocrine therapy. The typical endocrine therapy for a postmenopausal patient would be an aromatase inhibitor.

In addition to hormonal therapy following radiation and even during radiation, the continuation of a maintenance antibody would be given. The optimal therapy is to continue both antibodies, trastuzumab and pertuzumab, for completion of a full year, including what was given with the chemotherapy.

Typically, a patient who receives neoadjuvant therapy does not receive additional cytotoxic therapy. They obviously do get maintenance therapy with antibodies. We don’t have much experience in how to handle these patients. Many times, if a patient receives nonanthracycline therapy, they may then be given additional anthracycline therapy if they have significant residual disease. That’s the case, at least with chemotherapy. Now, with biological therapy, as I mentioned, we always give maintenance therapy with trastuzumab alone in lower-risk cases. But in higher-risk cases, pertuzumab and trastuzumab are now indicated, and they’re given in the maintenance setting.

Recently, there has also been a demonstration that the tyrosine kinase inhibitor neratinib can add a further reduction in the risk of recurrence when it’s given after the completion of maintenance trastuzumab. This is from the ExteNET study, which compared neratinib to placebo and found that there was a reduction in the risk of recurrence in higher risk patients who were given neratinib. That is another adjuvant option, especially for higher-risk patients.

Certainly, in the adjuvant setting for this patient, the maintenance antibody should definitely be continued. That’s a standard part of care. After the completion of antibody, the patient would then probably be on hormonal therapy because the patient’s tumor is ER—positive. That, after the completion of antibody therapy, is when one would also consider the use of neratinib along with, in this case, hormonal therapy. That would typically start as soon as the antibody is over. The clinical trial that looked at neratinib, the ExteNET trial, initially enrolled within the first 2 years, but then the protocol was amended, and patients had to go on therapy within a year of completing adjuvant antibody therapy.

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