Method of detection of DCIS to predict HER2 overexpression.

Abstract

1557 Background: Overdiagnosis of DCIS has become a major concern. Overexpression of the human epidermal growth factor receptor-2 (HER2) has been introduced as a prognostic marker that correlates with a higher biologic aggressiveness of breast cancer. We investigated the rate of HER2 overexpression of DCIS diagnosed by breast MRI compared to the DCIS diagnosed by mammography. Aim was to find out whether the additional DCIS diagnosed by MRI represents prognostically relevant disease or whether it will lead to additional overdiagnosis. Methods: During a 5-year period 7,319 women underwent breast MRI in addition to mammography for screening or for diagnostic assessment. A total of 167 women received the final surgical pathology diagnosis of pure DCIS. HER2 receptor status was established by standardized methods and dichotomized as positive (DAKO score 3+ or c-erbB2-amplifikation at FISH) or negative (DAKO score < 3+ or FISH negative). It was available in 127/137 women. We investigated the detection rate of breast MRI and of mammography for DCIS. We compared the HER2 receptor status of all MRI-detected versus all mammography-detected DCIS. Furthermore we compared the HER2 receptor status off only mammography-detected versus only MRI-detected DCIS. Results: Of the 127 DCIS, 95 (75%) were categorized as HER2 negative, and 32 (25%) as HER2 positive. Of the 32 HER2 positive DCIS, 13 (41%) were diagnosed through mammography, and 31 (97%) through MRI. Of the 10 DCIS which were only mammography-detected, one (10%) was HER2 positive. Of the 52 DCIS which were only MRI detected, 21 (40%) were HER2 positive. In the entire cohort, two-thirds of HER2-positive DCIS (66%, 21/32) were only detected by MRI (p < 0.005). Conclusions: DCIS not visible at MRI is virtually always HER2 negative. Two-thirds of HER2 positive DCIS are not visible on mammography, but only diagnosed by MRI. The method of detection of a DCIS correlates with its biologic aggressiveness: Detectability by mammography is correlated with a lower aggressiveness compared with detectability by MRI. MRI-detected additional DCIS are associated with a higher biologic aggressiveness. We conclude that MRI-detected DCIS do not add to mammography-induced overdiagnosis, but represent prognostically relevant disease. No significant financial relationships to disclose.