Triple Positive Breast Carcinomas: Is OncoType Dx™ Test Justified?
E Marchetti, R Bhargava, DJ Dabbs. Magee-Womens Hospital of UPMC, Pittsburgh, PA
Background: As part of our laboratory program of continuous quality assurance (QA) for monitoring predictive and prognostic marker results for breast tumors, we review our metrics for hormone receptors (HR), HER-2/neu testing and correlate them with results of send-out tests, specifically, the oncotype Dx™ Recurrence Score (RS). This data affords an opportunity to assess metrics for breast cancer subclasses.
Design: Our QA coordinator collects all estrogen/progesterone receptors (ER and PR) and HER2 results, from breast cancer pathology reports. HR are reported according to the Histologic Score (H Score), with a range of 0 (negative results) to 300 (maximum positive result, 100% cells stain 3+). HER2 testing is reported according to recent CAP-ASCO guidelines using immunohistochemistry (IHC) and FISH for IHC 2+ cases. The results of the oncotype Dx™ test are also collected. These results are used to compare pathologist's performance with tumor grading and interpretation of HR and HER2 results. This was a focused study on ER+/PR+/HER2+ breast carcinomas termed as “Triple Positive” (TP) tumors.
Results: Of the 76 TP tumors available in QA files from 2004-09, 40 tumors were HER2 IHC 3+(73% of these had high, 15% intermediate, 12% low RS); 17 tumors were IHC 2+/FISH amplified (41% of these had high, 12% intermediate, 47% low RS); 19 tumors were 2+/equivocal FISH (11% had high, 63% intermediate, 26% low RS). The mean ER/PR H Scores for these groups were 195/77, 277/87, 261/167 respectively, with a significant difference in ER H scores between the HER2 IHC3+ versus IHC2+ groups. The PR scores were significantly different between the HER2 IHC 3+ and amplified groups versus FISH equivocal group. There was a preponderance of high RS scores in high grade tumors compared to lower grade tumors, probably reflecting lower mitotic activity in lower grade tumors, and higher ER/PR content for HER2 IHC 2+/FISH equivocal tumors.
Conclusions: (1) TP tumors show heterogeneity in hormone receptor content and degree of HER2 amplification. (2) IHC 3+ tumors have the lowest ER & PR content, while IHC 2+/FISH equivocal cases have highest ER & PR content. (3) Predictably, RS are highest with highest HER2 content/lowest ER & PR content and lowest with lowest HER2 content and higher ER & PR content. (4) Dual endocrine & anti-HER2 therapy (which is often used in combination with chemotherapy) is a mainstay for these patients making it unlikely that oncotype Dx™ test will add value to therapeutic decisions.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 26, Monday Morning