Background: Since the advent of screening, breast cancer incidence has significantly increased in the United States as well as other countries. SEER data from the US shows that the increase is largely in localized disease without a concomitant or significant decrease in regionalized disease. In addition, the increase has occurred essentially in women over 50. We asked whether molecular characterization of tumors would shed light on the types of tumors detected in screening and in locally advanced breast cancers (LABC). 

Methods:We identified two groups of patients from European studies before and after the introduction of population based screened (in 1995) where the 70-gene prognosis test (MammaPrint) results were available. The first source is the European Validation Study (EVS) (Buyse et al, J Natl Cancer Inst. 2006). The second was a prospective implementation trial of MammaPrint in the Netherlands (RASTER study) (Bueno de Mesquita et al, Lancet Oncol. 2007). The source of LABC patients comes from the multicenter I-SPY TRIAL (CALGB 150007/150012) who underwent routine screening (prior mammogram within 2 years of diagnosis). 

Results: In women age 50–60, the fraction of cancers that were MammaPrint good prognosis were 40% and 60% prior to and after the introduction of screening, respectively. For women 50–60 who were actually undergoing screening, the fraction of tumors that were MammaPrint good prognosis was 67%. For patients aged 30–40 with stage I and II lymph node-negative disease, who did not undergo screening in either period, the fraction of MammaPrint good prognosis tumors did not change (29% and 31%, for EVS and Raster, respectively). For patients with LABC, from the I-SPY TRIAL, the fraction of tumors that are MammaPrint good prognosis is 7% and 29% for women aged 30–40 and 50–60, respectively. Of the LABC patients undergoing screening, 80% presented clinically during the interval between routine mammograms. 

Conclusions: Current screening programs are increasing the burden of low-risk cancers. Screening programs should consider including molecular profiles at the time of diagnosis to reduce overtreatment. The majority of LABCs have high-risk molecular profiles and do not present as screen detected cancers. New strategies are needed for early detection of LABC.