HER2+ De Novo Metastatic Breast Cancer Case Report

Reshma L. Mahtani, DO:This is a 59-year-old postmenopausal woman who is poorly adherent with follow-up. She’s obese, has diabetes, and doesn’t really come to her physician very regularly. She did, however, actually present for her annual physical exam. At that point, she had reported some back pain, headaches, and occasional hip pain. She was referred for her annual mammography. She has never been pregnant. She has no family history of cancer. On exam, there was a palpable breast mass in her left breast with palpable lymph nodes.

On clinical workup, she had a laboratory analysis done that evaluated CBC and complete metabolic profile. All her labs were normal, except for an alkaline phosphatase that was elevated at 230 U/L, with the upper limit of normal in that lab being 140 U/L. The breast imaging did, indeed, reveal a suspicious irregular-appearing mass in the left breast with suspicious axillary nodes. And an ultrasound-guided core biopsy of the breast mass and lymph nodes unfortunately revealed invasive ductal carcinoma that was ER⁻, PR⁻, HER2 3+ by IHC.

Because she had reported headaches, a brain MRI was done, and it showed no suspicious lesions. A PET, CT and a bone scan were also done and, unfortunately, documented multiple suspicious lesions in her spine and pelvis, and several pulmonary nodules. She was not symptomatic at all with cough. A biopsy of 1 of these larger pulmonary nodules did confirm the diagnosis of metastatic breast cancer to lung and bone, ER⁻, HER2+. Her ECOG performance status was 1.

So in terms of her treatment and follow-up, she was started on paclitaxel, trastuzumab, and pertuzumab. She completed about 6 months of chemotherapy and then developed persistent neuropathy that started to interfere with her activities of daily living. The chemotherapy was dropped, and the trastuzumab and pertuzumab were continued. She had follow-up imaging several times that did show a good response to therapy. There were no FDG-avid lesions on her PET scan, and her bone pain actually resolved. Denosumab was also started to reduce the incidence of skeletal-related events.

Further follow-up imaging did show a response to therapy. At 18 months, she actually developed progressive disease. She reported a dry cough, and imaging showed progressive bone and multiple pulmonary nodules. So at this point, in the second line, she was started on trastuzumab emtansine [T-DM1] and tolerated this treatment very well. Follow-up imaging showed a response that lasted for about 9 months. At this point, she developed a headache and increasing bone pain. Imaging, including a brain MRI, was done and unfortunately did document multiple brain lesions. There were 3 lesions. They were all less than 2 cm without any edema. She was treated with stereotactic radiosurgery and then was initiated on neratinib at a dose of 240 mg, 6 tablets, and capecitabine. She was given prophylactic loperamide.

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