Recommendations for HER2 Testing in Metastatic Breast Cancer

Reshma L. Mahtani, DO:As we review this case, my initial observation is this type of presentation is becoming increasingly rare. Only about 5% of patients present with de novo metastatic breast cancer in the United States, and this is largely due to progress we’ve made in getting the word out about the importance of breast self-exams and screening with mammography. So patients tend to receive a diagnosis at an earlier stage.

In this case, the patient has HER2+ breast cancer, which we know accounts for about 1 in 5—or 20% of all—cases of breast cancer, and can be very effectively targeted with anti-HER2 therapies. These treatments have changed the natural history of this disease.

In terms of prognosis, this patient is likely to respond very well to therapy given that she’s treatment naïve in the early stage setting without the opportunity for resistance to have emerged.

I would say it’s standard to do HER2 testing at the time of diagnosis. The site of biopsy is important here. Oftentimes, there are difficulties associated with bone biopsies, especially with false-negative results on bone biopsies due to the process of bone decalcification. Here, the patient had a pulmonary nodule that was biopsied, and I would say this would be considered fairly reliable.

One may consider repeating a biopsy at some point in the clinical course, such as when the patient is not responding for the duration of time one would expect, based on pivotal trials, with the therapies that are being offered. In this case, she certainly did respond as average based on what we saw in the CLEOPATRA and EMILIA trials, in terms of her responses to first- and second-line therapies. So, I don’t know that I would stop to repeat a biopsy at this point. But there can be instances for which there is tumor heterogeneity or a change in HER2 status. Also, another reason I’d say to repeat a biopsy may be to perform NGS [next-generation sequencing] testing, which may guide participation on a clinical trial.

Transcript edited for clarity.

Case: A 59-Year-Old Woman WithHER2+ De Novo Metastatic Breast Cancer

Initial presentation

• A 59-year-old, postmenopausal woman presented to her PCP for an annual physical exam, she was referred to undergo screening mammography; she reported back and hip pain along with occasional headaches
• PMHx: diabetes, medically controlled
• OB/GYNHx: nulliparous
• FHx: no family history of cancer
• PE: obese, palpable left breast mass with axillary adenopathy

Clinical workup

• Labs: alkaline phosphatase 230 IU/L (normal range 20-140 IU/L); otherwise WNL
• Breast imaging revealed a 2.1 cm irregular appearing mass in the left breast with suspicious axillary adenopathy
• Ultrasound-guided core biopsy of the left breast mass and axillary node confirmed high-grade infiltrative ductal carcinoma; ER-, PR-,HER2,3+ by IHC
• Brain MRI was negative
• PET/CT and bone scan revealed multiple lesions in the spine and pelvis; and several pulmonary nodules; pulmonary nodule biopsy revealed invasive ductal carcinoma; ER-,HER2+
• ECOG PS 1

Treatment and Follow-Up

• She was started on paclitaxel + trastuzumab + pertuzumab and completed 6 months of chemotherapy at which point paclitaxel was discontinued due to worsening neuropathy; trastuzumab and pertuzumab were continued
• Follow-up imaging at 3 months showed no FDG activity in the bones or lungs; bone pain resolved
  • Denosumab was started to reduce skeletal related events
• Further follow-up imaging showed stable disease until 18 months when she developed worsening cough; imaging showed progressive bone disease and multiple new pulmonary nodules
  • Trastuzumab emtansine (T-DM1) was started
• Follow-up imaging showed response to treatment which lasted for ~ 9 months
  • She developed headaches, and increasing bone pain
• Brain MRI at that time showed 3 lesions, all < 2-cm; she was treated with SRS (stereotactic radio surgery)
  • Bone scan showed progressive bone metastases
• Initiated neratinib 240 mg (6 tablets) PO QD + capecitabine
  • She was started on prophylactic loperamide