Molecular Markers as Prognostic Factors in DCIS and Small Invasive Breast Cancers

 

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Abstract

Ductal carcinoma in situ (DCIS) accounts for up to half of screen-detected breast cancers and thus constitutes a major public health problem. Despite effective current treatment many patients with DCIS are either over- or undertreated because of the paucity of precise models to predict recurrence or progression. The combination of clinical and molecular factors as already applied for invasive disease may help to build such models also for DCIS. We compared 53 DCIS (36.6 %) and 92 (63.4 %) invasive breast cancer cases and found no significant differences in age, receptor status of ER, PR, and HER2, and the use of radiotherapy. Interestingly, the proportion of disseminated tumor cells (DTC) did also not significantly differ between DCIS and invasive cases (p = 0.57). A negative PR status was associated with the detection of DTCs (p = 0.026). We then compared relationships of clinical parameters and biomarkers with patientsʼ prognosis in 43 DCIS and 40 small invasive tumors ≤ 5 mm (T1a). ER negativity was associated with shorter relapse free survival in the complete cohort (p = 0.004) and showed a trend in both subgroups (p = 0.053 for DCIS and p = 0.046 for T1a, respectively). In conclusion, we found markedly similar properties of both DCIS and small invasive breast cancers with respect to the distribution of several parameters as well as to the prognostic value of biomarkers. DCIS with a luminal phenotype seem to be characterized by a favourable prognosis.

Zusammenfassung

Das duktale Carcinoma in situ (DCIS) ist aufgrund seiner durch das Mammografie-Screening stark angestiegenen Häufigkeit in den letzten Dekaden deutlicher ins Blickfeld von Forschung und Praxis gerückt. Trotz effektiver Behandlung stellt sich für viele Patientinnen die Frage einer Über- oder Untertherapie, da sich der Verlauf der Erkrankung individuell nicht vorhersagen lässt. Eine Kombination von klinischen und molekularen Parametern, wie sie bereits vielfach für das invasive Mammakarzinom angewandt wird, könnte hier möglicherweise helfen, entsprechende Prädiktoren zu entwickeln. Bei einem Vergleich von 53 DCIS (36,6 %) und 92 (63,4 %) invasiven Mammakarzinomen bezüglich klinischer und molekularer Parameter fanden wir keine signifikanten Unterschiede bez. Alter, Hormonrezepor- und HER2-Status sowie dem Einsatz adjuvanter Bestrahlung. Interessanterweise unterschied sich auch die Häufigkeit der Detektion disseminierter Tumorzellen (DTZ) nicht signifikant zwischen DCIS und invasiven Fällen (p = 0,57). Ein negativer Progesteronrezeptor-Status war mit dem DTZ-Nachweis assoziiert (p = 0,026). Untersucht wurde ebenfalls der Zusammenhang von klinischen Parametern und Biomarkern mit der Prognose bei 43 DCIS und 40 invasiven T1a-Karzinomen. Negativität für den Östrogenrezeptor zeigte hierbei einen signifikanten Zusammenhang zu einem kürzeren krankheitsfreien Intervall in der Gesamtkohorte (p = 0,004) und einen Trend in beiden Subgruppen (p = 0,053 bei DCIS bzw. p = 0,046 bei T1a). Zusammenfassend fanden wir sehr ähnliche Charakteristika bez. der Verteilung verschiedener Parameter und des prognostischen Werts von Biomarkern sowohl bei DCIS als auch invasiven Karzinomen. DCIS mit einem luminalen Phänotyp scheint durch eine günstigere Prognose gekennzeichnet zu sein.

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