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

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. 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. Zusammenfassung

Is invasion a necessary step for metastases in breast cancer?

“…Support for the notion that breast cancer dissemination can occur in pre-invasive stages of tumour progression comes from the consistent finding of circulating tumour cells in the peripheral blood (or in the bone marrow) of patients with DCIS. In six studies (range 19–404 patients), between 13 and 25% of DCIS patients were found to have circulating tumour cells [ 29 – 34 ]. It has been proposed that such cells derive from an occult (micro)-invasive lesion within DCIS.…”

A Case of Noninvasive Her2-positive DCIS with Multiple Recurrences Involving the Liver, Bone and Lung 3 Years after Surgery

“…術後 ３ 年で多発肝骨肺転移を認めた非浸潤部 Her2 強陽性 DCIS の １ 例 聖隷佐倉市民病院乳腺外科 1) ，同 病理科 2) 黒 野 健 司 1) 川 島 太 一 1) 河 上 牧 夫 2) 症例は56歳，女性．健診にて DCIS ( Departments of Breast Surgery 1) and Pathology 2) , Seirei Sakura Citizen Hospital The case involved a 56-year-old woman who was diagnosed as having ductal carcinoma in situ (DCIS) at a medical check-up and underwent mastectomy + sentinel lymph node biopsy. Adjuvant chemotherapy was not selected.…”

Local Treatment of Breast Cancer

“…5 Much controversy exists over the extent of treatment or if DCIS is a high-risk condition that only requires close follow-up despite potential future development of an invasive cancer. 12 Nomograms using breast cancer molecular markers 13 and multigene expression 14,15 as prognostic indicators show promise to predict the invasive component. [13][14][15] At the current time and until research yields decisive data, high-grade DCIS is surgically treated and, in the case of a lumpectomy, followed by radiation therapy to further reduce the risk that the lesion will recur either as DCIS or invasive disease.…”

“…12 Nomograms using breast cancer molecular markers 13 and multigene expression 14,15 as prognostic indicators show promise to predict the invasive component. [13][14][15] At the current time and until research yields decisive data, high-grade DCIS is surgically treated and, in the case of a lumpectomy, followed by radiation therapy to further reduce the risk that the lesion will recur either as DCIS or invasive disease. [12][13][14] Total or simple mastectomy provides for 90% risk reduction 16 without follow-up radiation therapy.…”

“…[12][13][14][15] Therefore, SLNB will often be performed at the same time as the surgical intervention as a means to examine the axillary nodes. For low-and medium-grade DCIS, SLNB is often not performed.…”