P4-10-01: Tumor Markers Predicting Recurrence Type after a Primary Ductal Carcinoma In Situ.

Abstract

Abstract Background: The risk for recurrence after a primary ductal carcinoma in situ (DCIS) is approximately 8% after ten years. If a recurrence occurs, the risk of the recurrence being invasive is approximately 50%. However, the knowledge of determinants for type of recurrence is limited. The purpose of this study was to investigate the predictable effect of specific biologic markers on the type recurrence after a primary DCIS. Material and Methods: All women diagnosed with a primary DCIS between 1986 and 2004 in Uppsala and Västerås, Sweden were included (n=458). We also included all women from the SweDCIS Trial with a known recurrence (n= 166). TMA blocks were constructed and immunohistochemistry (IHC) was used to evaluate the status of estrogen receptor (ER), HER2, epidermal growth factor receptor (EGFR/HER1), cytokeratin 5/6 (CK 5/6), forkhead box A1 (FOXA1), forkhead box C1 (FOXC1), Ki 67, CD 10 and transacting T-cell-specific transcription factor GATA-3 (GATA-3) in the primary DCIS tumors. Logistic regression was employed to calculate the difference of expression status of biological markers between groups. Odds ratios (ORs) and 95% confidence interval (CI) were calculated, with adjustment for age, free margins, surgical type and molecular subtype by IHC. Results: Of the 624 patients, 358 without recurrence were grouped as controls. Of the 266 with recurrence, 130 developed an in situ recurrence, while the remaining 136 developed invasive recurrence. Mastectomy compared to breast conserving surgery (BCS) and free margins were associated with less recurrences (OR 0.07, 95% CI 0.03 — 0.15) and (OR 0.39, 95% CI 0.26 — 0.58). As compared with the most common molecular subtype Luminal A, the subtype Luminal B had statistically significant higher risk of recurrence (OR 2.01, 95% CI 1.12 — 3.59). Higher risk of all recurrences was also observed for FOXA1 (OR 3.16, 95% CI 1.48 — 4.74) and FOXC1 (OR 2.39, 95% CI 1.39 — 4.09). In the analyses of type of recurrence, ER-negative, HER2−positive and EGFR-positive tumors recurred more often as in situ; (OR 2.34, 95% CI 1.17 — 4.71), (OR 2.08, 95% CI 1.11 — 3.88) and (OR 2.20, 95% CI 1.11 — 4.36). The molecular subtype HER2+ was also associated with a lower risk of invasive recurrence (OR 0.27, 95% CI 0.11 — 0.67). Conclusion: As expected, mastectomy and free margins were associated with a lower risk of recurrence. Molecular subtype Luminal B and tumor markers FOXA1 and FOXC1 had a higher risk of recurrence. Recurrences after molecular subtype HER2+, ER-negative and EGFR-positive DCIS were more often of the in situ type. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-01.