In vivo magnetic resonance imaging of the progression of murine ductal carcinoma in situ : finding timescales and predictors of future invasion

• Published in: Cancer research (Chicago, Ill.) Ill.), 2009-01, Vol.69 (2_Supplement), p.6011
• Main Authors: Jansen, SA, Conzen, SD, Newstead, GM, Markiewicz, EJ, Karczmar, GS
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.SABCS-6011

Abstract #6011 Background: Understanding the natural history of breast cancer is important for effective patient management and treatment. For example, some evidence suggests that preinvasive ductal carcinoma in situ (DCIS) may be over-treated, since not all will progress to invasive cancer. Unfortunately, due to obligate surgical excision of newly diagnosed breast cancers, the natural history of disease is difficult to study in women. However, mouse models of breast cancer can serve as an alternative; the purpose of this study was to use magnetic resonance imaging (MRI) to investigate the progression of DCIS into invasive cancer in a transgenic model.
 Methods:12 SV40 Tag mice were imaged every 2-3 weeks (wks) starting at 10 wks of age. SV40 mice develop mammary cancer similar to DCIS and IDC, and usually live to 22 wks when they succumb to breast cancer. T1-weighted gradient echo images of inguinal mammary glands were obtained. DCIS lesions and invasive tumors were identified and volumes were measured over time. For each lesion we measured: the time at initial development (TDCIS and Ttumor), the growth rate of DCIS and invasive tumors (calculated from 'V=V0exp(αt)'), and for DCIS lesions that progressed to invasive tumors the progression time Tprog was measured.
 Results:DCIS (n=21) and invasive (n=16) tumors developed, at an average initial age of TDCIS =12.7±2.6 wks and Ttumor =16.3±3.1 wks, and at an initial volume of 0.3±0.2 mm3 and 1.7 mm3, respectively. The average growth rate for DCIS lesions was αDCIS= 0.08±0.23 wk-1, significantly smaller than that of invasive tumors (αtumor= 0.55±0.35 wk-1, p =0.001). 9/21 DCIS lesions progressed to invasive cancers in an average time of Tprog=4.56 ± 1.9 wks(Figure 1a). 11/21 DCIS did not progress within the study window and 5/21 were stable for over 8 wks (Figure 1b).
 
 The volume of DCIS was not a predictor of progression, but there was a trend for DCIS growth rate to be related to eventual development of invasiveness.
 Discussion:To our knowledge, the results reported here are the first direct measurements of the timescales and characteristics of progression from in situ to invasive carcinoma. Surprisingly, even in transgenic mice that are strongly pre-disposed to develop cancer, some DCIS lesions did not progress to invasive cancer. Interestingly, DCIS volume did not predict future progression to invasive tumors, but growth rate may have been a predictor. The methods and data here provide a foundation for