Documentation of Complete Response in Metastatic Breast Cancer to Liver and Bone Achieved with Trastuzumab and Pegylated Liposomal Doxorubicin

We present a case report of a complete response to a combination of trastuzumab and pegylated liposomal doxorubicin in a female patient with recurrent metastatic HER-2 positive breast cancer after anthracy-cline-based adjuvant primary chemotherapy. To our knowledge this sequence of events has not previously been reported. In September 2003, after routine mammographic detection, this 59-year-old business executive mother of two underwent right mastectomy and axillary node dissection with immediate reconstruction. Pathologic diagnosis included a T1N0M0 poorly differentiated infi ltrating ductal carcinoma and further characterized by high proliferative fraction, negative hormone receptors, 3+ Her2 expression by immu-nohistochemistry, and 8-fold amplifi cation of Her2 by FISH. Entry into Intergroup Study N9831 (1) was precluded by presumed pressure related brachial paresis during her postoperative recovery. Her adjuvant chemotherapy consisted of four cycles of doxorubicin (60 mg/m 2) + cyclophosphamide (600 mg/m 2) on a dose-dense (biweekly) schedule with G-CSF, followed by 7 doses of paclitaxel (100 mg/m 2) every 10 to 11 days (without growth factors). She remained well for one and a half years, when lumbo-sacral and lower thoracic pain while exercising prompted a bone scan showing multiple lesions. PET/CT (Fig. 1a) confi rmed bone scan fi ndings and in addition showed liver involvement. Physical examination was unchanged, and cancer antigen (Ca 27.29) remained normal. Treatment with trastuzumab (loading dose 8 mg/kg and subsequently 6 mg/kg) every three weeks, combined with pegylated liposomal doxorubicin (Doxil) 30 mg/m2 every three weeks was instituted, based on causing the least disruption of her daily activities, and on our institutional study (2,3). A baseline left ventricular ejection fraction by MUGA was 70% and unchanged 9 and 18 weeks later. Zoledronate 4 mg IV was added and repeated every 6–9 weeks. With appearance of grade 2 hand-foot skin changes after the third dose, Doxil was then given at a 6-week interval. A follow-up PET/CT shows bone sclerosis, with no uptake of 18F-fl uoro-deoxyglucose (Fig. 1b). She will continued to receive trastuzumab 6 mg/kg every 3 weeks and Doxil 30 mg/m2 every 6 weeks in the absence of disease progression or adverse events. Human epidermal growth factor receptor 2(HER2) gene amplifi cation, found in 25% of primary breast tumors, is associated with an aggressive course and shortened overall survival (4) that has been known to improve with anthracycline-based therapy (5). Recently, this has been attributed to the frequent co-amplifi cation of the topoisomerase 2 gene that is located …