Her2 Status Following Neoadjuvant Trastuzumab Therapy for Primary Breast Cancer.
Mary Ann G Sanders, Andrea L Richardson, Amy Ly. Brigham and Women's Hospital, Boston, MA
Background: HER2 amplified breast cancer is associated with poor prognosis, but neoadjuvant anti-HER2 targeted therapy with trastuzumab in combination with traditional chemotherapy regimens improves outcome. HER2 status in residual and metastatic/recurrent disease (MRD) following neoadjuvant trastuzumab has not been independently reported in a large series.
Design: The surgical pathology archives at Brigham and Women's Hospital were searched for consecutive cases of HER2+ primary invasive breast cancer (BC) treated with neoadjuvant therapy that included trastuzumab from 2005 to 2010. Patient age, treatment modalities, and clinical follow-up data were recorded. HER2 status of BC was recorded for the initial biopsy, residual tumor at the time of definitive surgery, and subsequent MRD.
Results: A total of 121 cases were identified. Pre-treatment HER2 status was determined on core biopsies by 3+ immunohistochemistry (IHC) in 101 cases or by FISH amplification in 20 cases. After therapy, 86 received mastectomy and 35 received breast-conserving excision. Sentinel node was sampled in all cases, with 85 undergoing axillary dissection. Forty-one cases (41/121; 34%) showed complete pathologic response (pCR). Of the 80 cases with residual tumor, 47 cases (47/80, 59%) retained HER2 positivity, 3 were IHC 2+ but no FISH analysis was performed, and 12 cases (12/80, 15%) were HER2 negative. HER2 status of residual tumor was not reported in 18 cases; 6 of these were near-pCR (Miller-Payne grade 4).
Post-operative MRD was documented in 19 cases (19/121; 15%). The time from surgery to MRD ranged from 129 to 1494 days. The HER2 status of both residual tumor and MRD was known in 14 cases: in 13 cases both remained HER2+, and in 1 case both lost HER2 amplification. In 2 cases where residual tumor HER2 status was unknown and in 1 case showing pCR, subsequent MRD was HER2+.
Conclusions: In the setting of neoadjuvant therapy with trastuzumab, a significant proportion of cases with incomplete pathologic response showed loss of HER2 amplification. MRD that developed in a small percent of cases showed the same HER2 status as residual tumor. Although targeted neoadjuvant therapy with trastuzumab has improved outcome for HER2+ BC, our review has identified a subset that does not respond optimally. In addition, the loss of HER2 amplification in residual tumor persists in subsequent disease, arguing in favor of evaluating HER2 status in new disease sites as these may require a change in treatment regimen. Novel agents, such as those that target factors downstream of the HER2 receptor, may hold promise for this group of patients.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 12, Wednesday Morning