Molecular phenotypes of DCIS predict invasive and DCIS recurrence

Introduction: Molecular phenotypes of invasive breast cancer predict early recurrence and survival. DCIS exhibits similar phenotypes but their frequency and clinical significance remain uncertain. To determine whether molecular phenotypes of DCIS predict recurrence, 273 women (median age 57 years) with primary DCIS who were screened for or entered DCIS trials (Iressa/Lapatinib/ERISAC) in one unit from 1990-2010 were studied. Methods: HER2, oestrogen receptor (ER) and progesterone receptor (PR) expression within primary DCIS were established using immunohistochemistry within the trial protocols. HER2 was scored 0 (absent) to 3 (maximum). Scores 2 were taken as positive if amplified on FISH testing. ER and PR scored positive if 5% of cells stained. 64.2% patients were ER positive, 43.3% were HER2 positive and 31.8% were high-grade lesions. 94 underwent mastectomy whilst 185 had BCS. Results: There was an overall recurrence rate of 20.14% after a median follow-up period of 74 months (range 12-240). Of these recurrences, 36.4% were invasive. Conservation surgery (BCS) was used in 185 women who suffered 47 recurrences. Molecular phenotype predicted local recurrence by Log Rank analysis (P < 0.01) and invasive recurrences (P < 0.016) overall and in the BCS group remained predictive of invasive recurrence (p <0.005) and overall recurrence (p < 0.001). (Figure Presented) ER negative DCIS had higher invasive recurrence (p < 0.01: Chi-squared). Grade 3 was a weak predictor of overall (p < 0.02) but not invasive recurrence. HER2 positive DCIS had poorer cumulative 5-year disease-free survival than HER2 negative cases (p = <0.001, Kaplan-Meier), irrespective of ER status. On multivariate COX regression analysis, HER2 positivity was an independent predictor of increased recurrence risk (p = 0.01) H.R. 7.39, 95% CI 1.61-33.8) Discussion: Determination of molecular phenotypes of DCIS aids identification of women at high-risk of recurrence. ER-HER2+ patients need maximal adjuvant treatment to avoid invasive recurrence whereas lower-risk ER+HER2- patients might avoid adjuvant radiotherapy.