The natural history of locally advanced primary breast carcinoma and metastatic disease

Breast cancer is considered a chronic disease in most women. This belief is based on natural history data that suggest that some patients with untreated, advanced disease may survive for up to and beyond 20 years after diagnosis. These data are corroborated by studies of treated patients in whom breast cancer recurred up to 15 to 20 years postmastectomy. Conversely, there are also patients who die rapidly after presentation. These divergent observations suggest that there are at least two subpopulations of patients with breast cancer-one that co-exists with the disease and one that rapidly succumbs to it. This heterogeneous biologic behavior is likely related to divergent tumor cell growth rates that have been documented as well as to other unidentified factors. These two subsets of patients, unfortunately, are quite difficult to distinguish. With the promise of the ongoing genetic revolution, the hope is that genes associated with rapidly progressing disease states can be identified. It is important to be cognizant of the prolonged natural history of this disease whenever we attempt to draw conclusions regarding a promising new treatment and we must make every attempt to ensure that patients are improving because of, rather than despite, a therapeutic intervention. Patients entered into trials examining survival as an endpoint should make every attempt to follow patients for 20 to 30 years after treatment. These considerations will ensure that patients requiring therapy are treated to derive benefit, whereas those who would normally not benefit or fare just as well without treatment are not exposed to unnecessary morbidity and mortality. Finally, it must be concluded as Bloom et al have stated that "the value of treatment of primary breast cancer cannot be measured entirely by survival statistics." The quality of a patient's remaining life once the diagnosis of breast cancer has been made should be considered. From untreated natural history data, we know that patients may suffer a painful death without intervention, and we are aware as well that overtreatment may impart untoward symptomatic consequences in the final stages of life when quality is of paramount importance to both the patient and the family.