Case Presentation: Treating Patients With HER2-Positive Breast Cancer Case Presentation

Gina, a healthy 59-year-old, post-menopausal woman with no underlying medical problems, palpated a right breast mass when she was in the shower. Her most recent screening mammogram was >2 years ago. She was seen by her primary care provider and breast imaging was ordered. Right breast diagnostic mammogram revealed 3 cm hypoechoic solid mass in the right breast. Right breast axillary ultrasound revealed enlarged axillary lymph nodes.

Gina was referred to a breast surgeon for further evaluation. Ultrasound-guided biopsy of the mass and axillary lymph node revealed invasive ductal carcinoma, grade 2. Estrogen receptor (ER)-positive (100%); progesterone receptor (PR) positive (100%); HER2-positive by immunohistochemistry (IHC; 3+).

Given a diagnosis of locally advanced disease, she was referred to medical oncology to discuss neoadjuvant therapy. Gina was overwhelmed by her diagnosis and her upcoming treatment plans, but she had a supportive family to help her with the diagnosis and treatment journey.

After extensive discussions with Gina and her family, the decision was made to treat with a non-anthracycline-based regimen of docetaxel, carboplatin in combination with dual anti-HER2 blockade (trastuzumab and pertuzumab), based on the data from NeoSphere and TRYPHAENA trials. These studies showed improvement in pathologic complete response (pCR) with dual anti-HER2 blockade.

Given the risk of cardiotoxicity associated with trastuzumab and pertuzumab, baseline echocardiogram was done, which was normal. A mediport was placed for systemic therapy, and Gina was referred to the early breast cancer support group. Nurse educators provided additional chemotherapy teaching prior to the start of therapy.

Gina tolerated 6 cycles of systemic therapy without any dose reductions. She had grade 2 nausea, grade 2 mucositis, grade 1 diarrhea, grade 2 alopecia, and grade 1 fatigue. Over the course of the therapy, she was noted to have clinical response in the palpable breast mass. She developed grade 1 taxane-related neuropathy in her fingertips. Post-therapy mammogram revealed an irregular persistent mass in the right breast, which was smaller. The previously biopsied lymph node was smaller with a thinner cortex.

While waiting on surgery, Gina continued to receive trastuzumab and pertuzumab every 3 weeks. Gina had partial mastectomy of the right breast with sentinel lymph node biopsy. Final pathology revealed 8 mm residual disease in the right breast. Three sentinel axillary lymph nodes were negative for malignancy. pT1bN0. Biomarkers were repeated on the residual disease: ER-positive (100%); PR-positive (80%); HER2-positive by IHC (3+).

Given residual disease, the benefit of switching HER2-targeted therapy to trastuzumab emtansine (T-DM1), an antibody–drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, was discussed with Gina.

The KATHERINE study randomized patients who had residual disease to adjuvant T-DM1 or trastuzumab for 14 cycles. Invasive disease–free survival, which was the primary end point, was significantly higher among patients who received T-DM1 than among those who received trastuzumab.

Gina was referred to radiation oncology for adjuvant radiation to the breast and regional lymph nodes. She continued on T-DM1 every 3 weeks, during adjuvant radiation. After completion of radiation, endocrine therapy was recommended since the tumor had ER/PR expression.

Given post-menopausal status, she was started on aromatase inhibitors. Baseline DEXA scan revealed osteopenia. Adjuvant bisphosphonates were recommended given its benefit in reducing bone recurrence and improving survival in postmenopausal patients. She completed 14 cycles of T-DM1.

Gina is tolerating aromatase inhibitors with grade 1 arthralgia and grade 1 hot flashes. The neuropathy related to taxane chemotherapy has resolved. She continues to follow up with the breast clinic and is uptodate on mammograms.

She was advised to follow up with primary care provider for routine health exams and to be uptodate on all age-appropriate screening recommendations.

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