HER2+ Inflammatory Breast Cancer: Addressing Unmet Needs

Debu Tripathy, MD:Neratinib is also used in the setting of higher-risk disease. Like other therapies, we try to project, what is this patient’s risk of recurrence? And then, based on the hazard rate reduction that we project with that drug based on the clinical trials, we calculate what their absolute benefit would be. In this patient, I believe they have a high enough residual risk—even with all the therapy they’re receiving—such that the addition of neratinib may add a few more percentage points in lowering the risk of recurrence.

There are several different directions that are being taken to improve outcomes in HER2-positive breast cancer. Metastatic recurrences remain incurable, so our goal really needs to be to keep that number as low as possible—with an acceptable risk profile, of course. The addition of other therapies that may complement these drugs is always going to be important. But then, we also have to realize that these drugs have side effects, there are costs, and there are convenience issues.

We don’t want to just keep piling on more and more drugs. We would like to be at a point where we can personalize therapy and know which patients do or do not need drugs. That falls into 2 general areas. One is understanding and discovering biomarkers that may predict who will respond to specific drugs. One example of a biomarker is PI3 kinase mutations, which seem to indicate some degree of resistance to trastuzumab and maybe to pertuzumab. They’re not really clinically used right now, but we need more biomarkers like that, and they need to be validated. Of course, we also need to look at other factors that predict who might be at higher risk of recurrence, whether it’s the stage or other clinical features, and this will help us be more precise.

The other movement that’s going on in this area is, are there patients in whom you can deescalate therapy? Someone who looks like they’re going to have an absolutely good outcome might not need the full year of antibody therapy. At this point, we don’t know that, but there are some discussions about identifying patients—not with inflammatory cancers, but maybe who start off with node-negative cancers—who have a complete pathologic response and maybe don’t need to complete the full year of maintenance antibodies. Those kinds of studies are being discussed, as well.

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