Table 1.

Natural history of DCIS in the CISNET models.

Model	in situ or DCIS?*	Do all tumors start as in situ?	Progression/regression	Model structure
D	DCIS only	Yes, but some DCIS is not screen detectable and assumed to progress to invasive directly	DCIS progress to clinical DCIS or invasive breast cancer at exponential rates with mean sojourn time of 1.5-3 years; DCIS may also go back to a state in which it is undetectable [19]	Figure 1A
E	All in situ	Yes	DCIS progress to clinical or invasive breast cancer at an exponential rate with age and calendar year dependent sojourn times; DCIS may also regress [22]	Figure 1B
GE	DCIS only	Yes	DCIS progress to clinical or invasive breast cancer at an exponential rate with mean sojourn time of 2.97 years; DCIS may also regress [21]	Figure 1C
M	Model M is not a natural history model. It does not specify how tumors grow. It is an empirical model to describe screening, incidence, treatment and mortality. Under different screening scenarios, different stage distribution tables obtained from observed data [28] are used to assign tumor stages: DCIS, stages I, II, III or IV. DCIS patients are assumed to have the same survival as normal population, given age and birth year, no matter what treatments they receive.[18]
W	All in situ. Model W also separated in situ into DCIS and non-DCIS in situ	Yes	All tumors, including DCIS, progress according to a Gompertz-type growth function, where the growth parameter is a random variable distributed with Gamma. Small size defines in situ. All tumors grow until they reach a maximum size. All tumors progress although a subset with “limited malignant potential” (LMP) stop at early invasive. LMPs comprise approximately 30-50% of all onset tumors [17]	Figure 1D

Model D: Dana-Farber Cancer Institute, Boston, Massachusetts. Model E: Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. Model GE: Georgetown University Medical Center, Washington, DC, and Albert Einstein College of Medicine, Bronx, New York. Model M: MD Anderson Cancer Center, Houston, Texas. Model W: University of Wisconsin, Madison, Wisconsin, and Harvard Medical School, Boston, Massachusetts.

^*in situ: DCIS and lobular carcinoma in situ (LCIS)