Online Tumor Board
With each issue of eOncology Report, Providence Cancer Center will present a brief case and discussion of relevant clinical issues from one of our local physicians. This month Dr. Stacy Lewis, medical director, Providence Cancer Center and medical oncologist, Pacific Oncology, begins the case series.
Case Presentation
A 45-year-old postmenopausal patient was diagnosed with a T2N1 breast cancer of the right breast in 2004. The tumor did not express estrogen or progesterone receptors, but did overexpress HER2. She received chemotherapy with doxorubicin and cyclophosphamide for four cycles followed by four cycles of paclitaxel. Local therapy consisted of a lumpectomy, axillary node dissection, and local radiation therapy. In September 2005 she presented with a recurrent right breast mass and skin nodules. The nodules were biopsied and were found to be recurrent breast cancer with a similar receptor profile. She received neoadjuavnt cisplatin, docetaxel, and trastuzumab for sixteen weeks followed by bilateral mastectomies. At the time of mastectomy, she had significant residual disease with a 4.2 cm right breast cancer. Postoperatively, she received trastuzumab every three weeks. This continued for nine months until she presented with recurrent skin nodules. A biopsy demonstrated recurrent breast cancer. Further staging showed no evidence of distant metastases. She was referred to us and was placed on an expanded access trial of capecitabine along with lapatinib. She had resolution of her skin nodules. Her toxicities to date have included fatigue, diarrhea, and mild palmar erythema. Her capecitabine dose has been decreased and she remains in a clinical remission.
This patient’s breast cancer exhibited many features at diagnosis which suggested a higher risk of recurrence – larger size, involvement of axillary lymph nodes, absence of hormone receptors, and overexpression of HER2. (1) And, in fact, despite aggressive local and systemic therapy the patient developed locally recurrent disease which was resistant to further systemic therapy, including trastuzumab. The management of “trastuzumab resistance” has been unclear. (2) The mainstay for most oncologists has often been to continue trastuzumab and switch chemotherapy agents.
Lapatinib is an oral tyrosine kinase inhibitor that blocks both epidermal growth factor receptor type 1 (EGFR) and HER2. In a recent randomized trial, women with locally recurrent or metastatic breast cancer who had progressive disease following treatment that included trastuzumab, a taxane, and an anthracycline were randomized to receive capecitabine alone or capecitabine and lapatinib. (3) Over 300 women were enrolled. Treatment with the two-drug combination was associated with a significant prolongation of progression-free survival. The toxicity was mild with the most frequent side effects being diarrhea, hand-foot syndrome, fatigue, nausea, vomiting, and a skin rash. Cardiac function was also monitored, and there was no significant cardiac toxicity.
This trial demonstrates that lapatinib, an oral medication, is an active agent in the management of HER2-positive breast cancer that has progressed on trastuzumab. At present this drug is available on an expanded access trial through the Providence Cancer Center. For more information, call the cancer program at 503-215-6588.
Contact Stacy Lewis, M.D.
References:
1. J. Chang and S. Hilsenbeck, in Diseases of the Breast, J. Harris, M. Lippman,
M. Morrow, C.K. Osborne, Eds. (Philadelphia, PA: Lippincott Williams & Wilkins,
2004), pp. 675-696.
2. Tripathy D, Slamon DJ, Cobleigh M, et al. Safety of treatment of metastatic
breast cancer with trastuzumab beyond disease progression. J Clinical Oncology
2004; 22: 1063-1070.
3. Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for
HER2-positive advanced breast cancer. New England Journal of Medicine 2006;355:
2733-2743.