The natural history of breast carcinoma: what have we learned from screening?

BACKGROUND: The availability of breast carcinoma data from trials of mammographic screening provides an opportunity to study the natural history of breast carcinoma. METHODS: The Swedish Two-County study is a randomized, controlled trial of mammographic screening for breast carcinoma in which 77,080 women were randomized to receive an invitation to mammographic screening and 55,985 were randomized to receive no invitation. During the trial, a total of 2468 breast carcinoma cases were diagnosed. The authors examined the effect of screening on the pathologic attributes of the tumors diagnosed, mortality and survival from breast carcinoma, and the consequences of arresting tumor development by screening. RESULTS: Screening reduces mortality from breast carcinoma largely through its effect in detecting tumors at a smaller size, decreasing the probability of lymph node metastases, and reducing the opportunity for worsening of the grade of malignancy of the tumor. CONCLUSIONS: Breast carcinoma is not a systemic disease at its inception, but is a progressive disease and its development can be arrested by screening. The point at which the tumor's progression is arrested is crucial. Detection of small (<15 mm) and lymph node negative invasive tumors will save lives and confer an opportunity for less radical treatment. Tumor progression in the preclinical phase occurs more rapidly in women age <50 years, suggesting the need for a shorter screening interval for this group.     

Does surgery unfavourably perturb the “natural history” of early breast cancer by accelerating the appearance of distant metastases?

This historical perspective on breast cancer tells us how and why certain therapeutic eras have reached ascendancy and then declined. Therapeutic revolutions occur after a crisis develops when there is a general recognition that clinical interventions are not producing positive results predicted by the prevailing paradigm. The attitude of pre-modern surgeons was influenced by the very real possibility of doing more harm than good by operating upon women with breast cancer. Up until Halsted, the general consensus was clearly that, unless forced by the circumstances, surgical resection should be avoided for disease much more advanced than very early stage tumours (the cacoethesis of Celsus). Twentieth century progress in antisepsis, anaesthesia, and surgery changed this point of view. The first three quarters of that century saw more and more aggressive operations performed while the last quarter century reversed this trend, with reduction of the size of breast cancer operations based largely on the teachings of Fisher. A new crisis is upon us now in that trials of early detection have resulted in unexpected disadvantages to certain subgroups and there is previously unreported structure in early hazard of relapse, clinical data that suggests the act of surgery might accelerate the appearance of distant metastases. The explanation we propose that agrees with these results, as well as physicians of antiquity, is that surgery can induce angiogenesis and proliferation of distant dormant micrometastases, especially in young patients with positive nodes.