The “Tipping Point” for Breast Cancer Mortality Decline Has Resulted from Size Reductions Due to Mammographic Screening

Abstract

Considering the declining breast cancer mortality in the United States, it is apparent that a ‘‘tipping point’’ was reached between 1986 and 1991, most apparent after 1990. For the first time since 1930, the previously unyielding ageadjusted breast cancer mortality rate began a continuous decline, starting about 5 years after the upsurge in use of mammographic screening in the 1980s (Fig. 1). This mortality decline had reached 30% in the entire United States by 2007 (Fig. 2; http://www.seer.cancer.gov) and had reached as much as 48% in Delaware, 41% in Rhode Island, and 40% in Massachusetts (http://statecancerprofiles.cancer.gov), the three highest states in mammography use recorded by the 2006 Behavioral Risk Factor Surveillance System (BRFSS) telephone surveys (http://cdc.gov/brfss/). The BRFSS estimates mammography use at least every 2 years by women over the age of 40. In contrast, mortality decline has been only 11% in Utah, 12% in Mississippi, and 14% in Oklahoma, three of the four lowest states in BRFSS reports of screening incidence (Fig. 3; http://statecancerprofiles. cancer.gov). Although the BRFSS rates may be somewhat exaggerated because they are based on women’s recall, the resultant relative ranking is undoubtedly correct because survey techniques are similar across the country. States with the greatest decline in mortality are also states with high initial incidence and mortality from breast cancer due to well-established demographic features such as older age, higher socioeconomic status, and higher education level. Because mammographic screening reduces mortality by earlier detection of a cancer with a biologically progressive disease course in most situations, a reduced rate of advanced breast cancers in a population is a surrogate for the success of screening. Here, we analyze the role of the steady change in tumor size as a result of breast cancer screening and attempt to demonstrate a temporal and possible causal relationship between changes in tumor size and the beginning of the decrease in breast cancer mortality (that is, the tipping point). The mean maximum diameter of all breast cancers was about 3.5 cm before 1950, about 3.0 cm in 1968 (just before the introduction of mammography), reached about 2.5 cm by 1987, and had a progressive further decline to less than 2.0 cm by 2006. The median maximum diameter of breast cancer, a better description of the usual presentation because it eliminates the bias of the extended ‘‘tail’’ of very large cancers, was 2.5 cm in 1968, 2.0 cm by 1987, and 1.5 cm after 2002. Accompanying this overall size decrease, the axillary lymph node metastatic rate, which was over 60% in the 1950s, usually with multiple node metastases, decreased to about 50% by 1968, and thereafter progressively declined to less than 30% by 2006. Equally important was the progressive decline in the number of lymph node metastases involved in women with invasive breast cancer through the years, so that now only one node metastasis is found in about 50% of patients who have regional nodal metastases, and all nodal metastases are limited to the excised sentinel nodes in up to two-thirds of patients. With the adoption of limited axillary node sampling by sentinel node biopsy, smaller volumes of nodal involvement have been recorded as pathologists more rigorously section and examine the few sentinel nodes submitted (median # 2), which in turn technically increases the rate of nodal metastases by up to 20%, a good example of the Society of Surgical Oncology 2011