Neoadjuvant Chemotherapy Plus HER2-Targeted Therapy for Early Stage HER2-Positive Breast Cancer

Sara Hurvitz, MD, David Geffen School of Medicine – UCLA, Los Angeles, CA, outlines a treatment plan for a patient with early stage HER2-positive breast cancer.

Transcript:

Hi there. I'm Dr. Sara Hurvitz, professor of medicine at the David Geffen School of Medicine at UCLA Johnson Comprehensive Cancer Center, and it's my pleasure to go over a case with you of early stage HER2-positive breast cancer.

My patient is a 38-year-old woman who presents to the oncology clinic for treatment recommendations for a newly diagnosed left breast cancer. Her cancer history began about 3 months ago when she self-detected a painless breast lump in the left breast while showering. She initially thought this was due to menstrual changes, but when it persisted, she presented to her gynecologist who did an exam. At the gynecologist visit, she reported she had never had a mammogram previously. She has no family history of breast or ovarian cancers or other cancers. She does have a personal history of gestational diabetes that resolved when she was postpartum. She is overweight with a BMI of 28 and has hypertension, which is managed by a diuretic. She is G1P1 and is interested in preserving fertility as she'd like to have another child potentially in the future. She works as an editor at a publishing firm, and she is married.

On examination a firm left breast mass is found with a mobile, slightly enlarged lymph node in the left axilla. Her gynecologist referred her for imaging, and a mammogram found a 2.8-centimeter left breast mass in the upper outer quadrant. The ultrasound confirmed it was solid and was about 3 centimeters, and there was a slightly enlarged lymph node in the left axilla with a thickened cortex. There were no other abnormalities. She had a biopsy of the left breast mass, which revealed a grade 3 invasive ductal carcinoma. Estrogen receptor (ER) and progesterone receptor (PR) were both negative, and HER2 was positive by both immunohistochemical analysis (IHC) and fluorescence in situ hybridization (FISH).

A lymph node biopsy confirmed metastatic cancer in the lymph node. Blood work was completed and was unremarkable for complete blood count (CBC) and metabolic panel. An echocardiogram was within normal limits. She is presented to the oncology clinic for treatment recommendations.

In general, my approach for a patient like this is to recommend neoadjuvant chemotherapy plus HER2-targeted therapy. This is because we know the response to neoadjuvant treatment for HER2-positive breast cancer is both prognostic and predictive. In terms of being prognostic, patients who achieve a pathologic complete response to neoadjuvant chemotherapy and trastuzumab based therapy have a very good clinical outcome in terms of disease recurrence afterwards. In terms of predictive nature of the response to neoadjuvant therapy, we now know that those patients who have residual disease after standard chemotherapy and HER2-targeted therapy in the neoadjuvant setting have a poor prognosis, but that prognosis can be improved by utilizing adjuvant trastuzumab emtansine based on the KATHERINE clinical trial.

I would recommend this patient does proceed with neoadjuvant chemotherapy and HER2-targeted therapy, but before starting chemotherapy I would certainly refer her for fertility discussion. The options include having fertility preservation through in vitro fertilization and embryo harvest, oocyte preservation, or use of drugs such as leuprorelin. Once that's been accomplished, I would initiate therapy with docetaxel, carboplatin, trastuzumab, and pertuzumab, or the neoadjuvant TCHP regimen.

This regimen is my preference due to its improved safety profile in terms of cardiac safety compared to anthracycline based options, as well as its similar efficacy profile. The rate of pathologic complete response (pCR) in the breast and lymph nodes with TCHP is over 60% for an ER/PR-negative, HER2 positive breast cancer. I would recommend the patient have 6 cycles, given every 3 weeks of this regimen. Her tumor should be measured by clinical exam after each cycle at her return follow-up visits to confirm that it is responding and not progressing, and imaging can be done midway through the treatment around cycle 3 or 4 to confirm the patient is having a response.

At the time of surgery, if there is residual disease, I would recommend T-DM1, trastuzumab emtansine, every 3 weeks for 14 cycles, based on the KATHERINE trial. I would not recommend, in general, the use of neratinib after T-DM1 In this patient whose tumor does not co-express ER or PR, as the ExteNET trial did appear to indicate that benefit with neratinib is restricted to those patients with ER or PR co-expression. If she has complete pathologic response at the time of surgery in the breast and lymph nodes, I would utilize trastuzumab and pertuzumab in the adjuvant setting to complete the full year. I would use the pertuzumab in combination with trastuzumab for this patient given that her lymph node was positive, and the APHINITY adjuvant study indicated the benefit of full year of adjuvant pertuzumab in patients with node positive disease. Although APHINITY wasn't a study looking at the use of pertuzumab in the adjuvant setting in patients who'd had a pCR, I'm extrapolating from that trial and making my treatment recommendation.

The patient should certainly also be referred to radiation oncology for treatment recommendations. Radiation would be certainly recommended for a patient if she had breast-conserving surgery and maybe considered post-mastectomy, depending on the response of a lymph node and the number of lymph nodes taken at the time of surgery.

One final note about this patient's particular history is that I would consider referral to cardio-oncology. This patient is overweight and has hypertension being treated with a diuretic, and had gestational diabetes, so she may be at higher risk of the development of cardiomyopathy with HER2-targeted therapy. I think it would be worthwhile for her to see a cardio-oncologist to make sure her cardiac health is optimized prior to and during treatment with HER2-targeted therapy. Thank you very much.

Source:

von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380(7):617-628. doi:10.1056/NEJMoa1814017

Chan A, Delaloge S, Holmes FA, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016;17(3):367-377. doi: 10.1016/S1470-2045(15)00551-3

von Minckwitz G, Procter M, de Azambuja E, et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017;377(2):122-131. doi: 10.1056/NEJMoa1703643