The Pathological Response of Her2+ Breast Cancer with Neoadjuvant Chemotherapy and Radiation Therapy

Abstract

The use of neoadjuvant chemotherapy (NACT) followed by neoadjuvant radiotherapy (NART) in locally advanced breast cancers prior to definitive oncological surgery allows for a mastectomy to be performed with an immediate autologous breast reconstruction (ABR) in a single operation. The aim of this study is to review the pathological outcomes of 40 Her2+ patients who underwent NART. This is a multi-institutional prospective review of 40 pts with clinically staged Her2+ breast cancers who underwent NART with 41 evaluable breasts (clinical stages 2A-3C). All pts had initial chemotherapy with anti Her2 directed therapy, followed by NART (median dose 50.4 Gy in 28 fractions) to the breast, supraclavicular fossa and level 3 axilla. Approximately 6 weeks after completing NART, pts underwent definitive surgery with mastectomy, axillary dissection and ABR. The clinical T stages were T1 2%, T2 46%, T3 39% and T4 12%. The majority of T1-2 lesions were multifocal. The clinical N stages were N1 63%, N2 29% and N3 7%. The clinical TNM stages were 2 (34%) and 3 (66%). Fifty one percent of tumors were Her2+/ER- and 49% were Her2+/ER+. All patients completed their NART and proceed to mastectomy and ABR. Of the 41 Her2+ breasts, 95.1% achieved Miller-Payne (MP) downstaging of 4-5/5 despite their locally advanced disease. Her2+/ER- patients were more likely to achieve a MP score of 5/5 compared to Her2+/ER- patients (85.7% vs 75%). Even when a MP score of 5/5 was not obtained, the majority with a MP score of 4/5 only had residual microscopic or small volume invasive disease. All tumors achieved significant pre NART clinical to post NART pathological T and N downstaging. In addition, Her2+/ER– patients were more likely to achieve a Chevalier score of 1 (no residual invasive or in situ disease in breast or lymph nodes) compared to Her2+/ER+ patients (71.4% vs 35%). No Her2+/ER- patients had residual in situ disease (Chevalier score of 2) compared to 40% of the Her2+/ER+ patients. An additional 3 Her2+/ER- patients had residual disease in level 1 and 2 axilla which were not specifically targeted by radiation therapy. The combination of NACT and NART results in a significant pathological complete response rate in patients with Her2+ breast cancer. In the adjuvant setting, this will aid with downstaging, increasing the chances of an R0 resection and perhaps local control. In patients with metastatic disease, the use of high dose palliative breast with or without nodal radiotherapy may be considered as an alternative to surgery to achieve local and regional control.Abstract 2038; Table 1Downstaging by Miller Payne (MP) ScoreHer2+ SubtypeMP 1-2/5MP 3/5MP 4/5MP 5/5Her2+/ER-04.8%9.5%85.7%Her2+/ER+05%20%75%Total04.9%14.6%80.5% Open table in a new tab Abstract 2038; Table 2Downstaging by Chevalier Score (CS)Her2+ SubtypeCS 1CS 2CS 3CS 4Her2+/ER-71.4%0%28.6%0%Her2+/ER+35%40%25%0%Total53.7%19.5%26.8%0% Open table in a new tab