A Stage II HER2+ Breast Cancer Patient

Joyce O'Shaughnessy, MD: This patient is a 54-year-old postmenopausal woman who noted a mass in the upper outer quadrant of her right breast. There was no skin involvement, but it was persistent, and she sought medical attention, where she was noted on physical examination to have about a 4 cm mass. It was quite indistinct on physical exam, clinically node negative. Breast imaging with mammogram and ultrasound showed a little bit over 4 cm, about a 4.2 cm breast cancer. On the ultrasound of her axilla she was found to have 2 positive axillary lymph nodes, and 1 of them was biopsied and clipped, so we know it was a positive lymph node.

The biopsy of the breast mass showed estrogen receptor-positive about 80%, progesterone receptor-negative, and HER2 [human epidermal growth factor receptor 2] 3+ score by IHC [immunohistochemistry]. It was a grade 3 breast cancer, so a highly proliferative breast cancer. No LVI [lymphovascular invasion] was seen. She did undergo PET [positron emission tomography] scanning and CT [computed tomography] scanning, and there was no evidence of metastatic disease. But the axilla was positive with FDG [fluorodeoxyglucose]-avid lymph nodes, and her breast was positive as well.

She is otherwise healthy—no particular comorbidities—and she received preoperative therapy with docetaxel, carboplatin, trastuzumab, and pertuzumab, the TCHP regimen quite standard, along with pegfilgrastim for immune support, and that’s every 3 weeks for 6 cycles. It’s very important to give preoperative therapy so we really know if someone has developed a pathologic complete response because the therapy in the adjuvant setting is very different, depending on if somebody achieves a pathologic complete response or not.

She had an excellent clinical response. She had a clinical complete response, so it was quite encouraging that the therapy was benefitting her. She finished her 6 cycles and then she went to right mastectomy. She did have residual disease in her breast, about 1 cm residual disease in her breast and 1 positive axillary lymph node. Approximately 4 sentinel lymph nodes were removed and only 1 was positive, so she did have residual disease.

With that, she’s had an excellent response but she still has residual disease. We know from the KATHERINE trial that she will have improvement in her invasive disease-free survival if instead of continuing on the trastuzumab and pertuzumab, she switches over to T-DM1 [trastuzumab emtansine], the antibody drug conjugate. So she did. She received 14 cycles, which is standard, of the T-DM1 [trastuzumab emtansine] every 3 weeks in the adjuvant setting, along with an aromatase inhibitor. She received letrozole daily for a planned 10 years, along with post-mastectomy radiation therapy to her chest wall and all the regional lymphatics. So she had that standard of care.

She finished up the now full year of the anti-HER2-based therapy with the trastuzumab. She’s doing well on her aromatase inhibitor. We have another decision point there, and that is whether to consider the addition of the oral pan-HER tyrosine kinase inhibitor neratinib for 1 year, per the ExteNET trial. It’s FDA approved in that context, particularly beneficial in patients with estrogen receptor-positive breast cancer. I did recommend that to her because of the substantial impact on invasive disease-free survival in the high-risk population. We did go ahead with the year of neratinib, continuing her aromatase inhibitor. She also received IV [intravenous] zoledronic acid, per the NCCN [National Comprehensive Cancer Network] guidelines, every 6 months, planned 3 to 5 years. It’s a lot of therapy, but again, it’s a high-risk cancer. We have a number of very good therapies for her, so we did use them.

Transcript edited for clarity.

Case: A 54-Year-Old Woman With Stage 2HER2+ Breast Cancer

Initial presentation

• A 54-year-old, postmenopausal woman presented with a painless palpable mass on the right upper outer quadrant of her right breast
• PMH/SH: unremarkable, no family history of cancer
• PE: ~ 4-cm palpable right breast mass, clinically node negative, no visible sink involvement

Clinical workup

• Labs: WNL
• Ultrasound showed a right breast mass, and two axillary lymph nodes
• Mammogram confirmed a right—sided, poorly defined speculated 4.2-cm mass
• PET/CT showed increased uptake in the right breast diffusely, with 2 FDG—avid axillary lymph node involvement; no evidence of distant metastases
• Ultrasound—guided FNA biopsy of the breast mass confirmed grade 3 infiltrative ductal carcinoma
  • Hormone receptor/HER2 Status:HER2+:3+ by IHC,80%ER+, PR-
• Stage T2N1M0; ECOG PS 0

Treatment and Follow-Up

• The patient was started on preoperative docetaxel + carboplatin + trastuzumab + pertuzumab (TCHP), and pegfilgrastim every 3 weeks for 6 cycles;
  • Achieved clinical complete response
• She underwent right mastectomy; residual disease: 1 positive axillary lymph node, and 1-cm RD in the right breast; 4 sentinel lymph nodes removed, 1 positive for disease; she also received post mastectomy radiation therapy of her chest wall and regional lymphatics
• She was started on trastuzumab emtansine every 3 weeks for 14 cycles + aromatase inhibitor PMRT + letrozole planned for 10 years
• Extended adjuvant neratinib was initiated
  • Week 1: 160 mg (4 tablets) PO qDay; week 2: 200 mg (5 tablets) PO qDay; week 3: 240 mg (6 tablets) PO qDay for 1 year
  • IV zoledronic acid every 6 months was added to her regimen for 3-5 years