Oncology Abstracts

The establishment of mammographic screening programs has resulted in a striking increase in the incidence of ductal carcinoma in situ (DCIS), with DCIS accounting for approximately 20% of all new screen-detected breast cancers. An estimated 40% to 70% of DCIS lesions may progress to invasive disease if left untreated. This number is considerably reduced by treatment: surgical excision followed by radiation therapy is curative in over 95% of cases. However, of the DCIS cases that do recur, 50% recur as invasive breast cancer. The key distinguishing feature for DCIS is the presence of myoepithelial cells, which harbour tumour suppressor functions and confine the tumour cells within the duct. However, malignancy-associated changes to the myoepithelial cells lead to progressive loss of the myoepithelial layer, permitting microinvasion and metastasis of the tumour cells resulting in invasive cancer. Currently, the likelihood of recurrence or malignant progression of each DCIS case is unpredictable, thus surgery plus radiotherapy, is the current standard of care, resulting in substantial overtreatment. Emerging evidence has revealed that the levels and distribution of myoepithelial markers become progressively altered in DCIS compared to normal myoepithelium, and that these changes are correlated with recurrence or progression to invasive disease. To explore this, we assembled a cohort of low and high grade DCIS (with or without association with invasive breast cancer) with extensive clinical follow-up in which to characterise expression of a panel of markers by immunohistochemistry. The markers p63, CD10, smooth muscle myosin heavy chain and calponin, were universally strongly positive in myoepithelium of normal breast. Marker expression was significantly reduced in DCIS-associated myoepithelium, compared to normal breast tissue. Moreover, marker loss was associated with disease progression, with early data suggesting that marker loss predicts long-term outcome. Our study suggests utility of myoepithelial markers in clinical management and reducing over-treatment of DCIS.