Abstract

Abstract BACKGROUND Decision criteria about systemic adjuvant treatment of patients affected by breast cancer include estrogen receptor (ER), progesterone receptor (PgR), HER2 status, histologic grading, and proliferative index. In case of multifocal or multicentric breast cancer, the College of American Pathologists (CAP) recommends to provide features for the largest invasive carcinoma. We evaluated the discordance of ER, PgR, HER2, grading, and proliferative index among all nodules with the same histotype of patients with multifocal or multicentric breast cancer and the impact on the choice of adjuvant treatment. METHODS We retrospectively analyzed 113 consecutive patients operated for breast cancer between 2004 and 2009 in Forli (Italy). We performed histological examination of all nodules of each patient after surgery, at the same time. Immunohistochemical methods were used to detect ER/PgR status, and proliferative index (Ki67), whereas fluorescent in situ hybridization was used to determine HER2 status. ER/PgR < 10% was considered negative. Ki67 was considered high if ≥20%. Grading was determined according to Nottingham's score system. HER2 amplification was defined according to CAP guidelines or as the presence of a focal HER2 amplified clone ≥30% of tumor cells. We considered as “discordance” a difference in at least one nodule for any of the biologic features considered. In order to determine whether discordance among nodules affects systemic treatment approaches, we asked ten independent oncologists whether and how they would modify their prescribed adjuvant treatment. RESULTS Discordance in ER or PgR status among different nodules was detected in 5 (4.4%) and 16 patients (14.1%), respectively. The majority of the oncologists (7 out of 10) decided to modify their prescribed systemic treatment in 3 patients (2.6%), in favor of a combined treatment (endocrine plus chemotherapy), instead of endocrine-or chemotherapy alone as if their decision was based on the receptor status only of the largest nodule. Discordance in HER2 status was detected in 10 (8.8%) patients. In 4 patients (3.5%), all clinicians found indication to an anti-HER2 treatment. Discordance in proliferative index occurred in 17 (15.0%) patients and discordance in grading was detected in 18 (17.8% over 101) patients. Five of ten oncologists decided to modify their prescribed systemic treatment by adding chemotherapy to endocrine-therapy alone in 5 patients (4.4%) based on Ki67 value, whereas there was no change based on grade. DISCUSSION This study shows a discordance for all analyzed histological features among different nodules with the same histotype in multifocal and multicentric tumors. In a total of 8 patients (about 7%) this discordance affected the therapeutic decisions of oncologists, resulting in changes of the prescribed adjuvant systemic treatment, with respect to the prescriptions based on the clinicopathologic features only of the largest nodule. Therefore, we conclude that the analysis of all nodules in case of multifocality/multicentricity should be taken into consideration, in order to identify the best adjuvant treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-05-02.

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