Complete pathologic response of HER2-positive breast cancer liver metastasis with dual Anti-HER2 antagonism

Background Although breast cancer frequently metastasizes to the bones and brain, rarely breast cancer patients may develop isolated liver metastasis. There is increasing data that anti-HER2 targeted therapy in conjunction with systemic chemotherapy may lead to increased rates of pathologic complete response in the primary breast cancer. However, little is known about its effects on metastatic liver disease. Case presentation We report the treatment of a 54-year-old female who was diagnosed with HER2-positive invasive ductal carcinoma and synchronous breast cancer liver metastasis (BCLM). The patient underwent eight cycles of standard docetaxel with two anti-HER2 targeted agents, trastuzumab and pertuzumab. Subsequent radiographic imaging demonstrated complete radiographic response in the primary lesion with an approximate 75% decrease in the liver metastasis. After informed consent the patient underwent modified radical mastectomy that revealed pathologic complete response. Re-staging demonstrated no new disease outside the liver and a left hepatectomy was performed for resection of BCLM. Final pathologic examination revealed no residual malignant cells in the liver specimen, indicating pathologic complete response. Herein, we discuss the anti-HER2 targeted agents trastuzumab and pertuzumab and review the data on dual HER2 antagonism for HER2-positive breast cancer and the role of surgical resection of BCLM. Conclusions The role of targeted agents for metastatic HER2-positive breast cancer is under active clinical trial investigation and we await the maturation of trial results and long-term survival data. Our results suggest that these agents may also be effective for producing considerable pathologic response in patients with BCLM.

history or co-morbidities presented to an outside institu-  1). Ultrasound-guided biopsy 55 of this ill-defined hypoechoic mass demonstrated poorly-56 differentiated, grade 3 of 3, ER-negative, PR-negative, 57 HER2-positive infiltrating ductal carcinoma. Biopsy of an 58 enlarged 1.4 cm left axillary lymph node revealed meta-59 static adenocarcinoma. Human epidermal growth factor 60 receptor-2 (HER2) protein expression was 3+ by immuno-61 histochemistry and HER2 gene was amplified with a ratio 62 of 6.7 by fluorescence in situ hybridization; Ki-67 was 63 markedly elevated at 50%. High-grade comedo and solid 64 ductal carcinoma in situ (DCIS) was also identified. Meta-65 static workup with computed tomographic scans of the 66 chest, abdomen, and pelvis revealed an 8.2 × 6.8 cm mass 67 in the left lobe of the liver ( Figure   F2 2), but no evidence of 68 metastatic disease elsewhere. The liver lesion was biopsied 69 and showed adenocarcinoma that was ER/PR-negative and 70 HER2-positive ( Figure   F3 3a and 3b), consistent with meta-71 static breast cancer.   105 to resection of the primary breast cancer following the 8th 106 treatment cycle. As such, the patient underwent left modi-107 fied radical mastectomy with tissue-expander reconstruc-108 tion seven months after the diagnosis of stage IV breast 109 cancer was made. Final pathologic examination revealed 110 residual high-grade DCIS with necrosis (2.7 cm); however 111 no residual invasive carcinoma was identified. Therefore, 112 pathologic complete response (i.e., ypTisN0M1) of the 113 invasive tumor was observed. Due to the original size of 114 the primary lesion, the patient received standard post-115 mastectomy radiation therapy to the left chest wall and 116 nodal basin. After the breast operation the patient was 117 continued on trastuzumab 6 mg/kg and pertuzumab 118 420 mg given every three weeks.

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The patient subsequently transferred her care to our 120 institution and was evaluated for resection of the liver 121 metastasis. Triple-phase CT scan at our institution taken 122 12 months after her initial presentation revealed the left

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The first anti-HER2 targeted agent was the monoclonal 163 antibody trastuzumab, which initially was approved for 164 the treatment of HER2-overexpressing breast cancer with 165 standard chemotherapy in the metastatic setting. Trastu-166 zumab inhibits ligand-independent HER2 activity and re-167 lated downstream signaling by binding to its extracellular   222 patients with HER2-positive BCLM, we expect that out-223 comes in the future will be even further improved given 224 the high rates of tumor response to HER2 targeted ther-225 apy and the possibility of achieving a complete pathologic 226 response.
227 Conclusion 228 The role of HER2 targeted agents such as pertuzumab will 229 continue to evolve in the treatment of patients with 230 BCLM, and may lead to curative therapeutic plans. There 231 is no data on pathologic complete response from this new 232 treatment option and we anticipate that our experience 233 may prove in the future to be a common and frequent 234 outcome. Targeted agents in combination with chemo-235 therapy will undoubtedly increase the resectability of liver 236 metastasis. Continued multi-disciplinary treatment strat-237 egies will be essential in the future to coordinate the roles 238 of targeted therapy and liver resection, ultimately with the 239 goal of providing patients improved survival benefit.
240 Consent 241 Written informed consent was obtained from the patient 242 for publication of this Case Report and any accompanying 243 images. A copy of the written consent is available for re-244 view by the Editor of this journal.