The sick lobe hypothesis, field cancerisation and the new era of precision breast surgery

Mona P. Tan, Tibor Tot


Understanding the ductal anatomy of the breast provides insights into tumorigenesis, which in turn offers guidance on therapeutic decisions. In this regard, the sick lobe hypothesis, which states that cancer arises from genetically unstable cells through mutations acquired in utero, forms the basis of malignant transformation. These ‘at risk’ cells line the mammary ductal-lobular system of a single ‘sick’ lobe and when exposed to noxious events in the surrounding microenvironment, further genetic changes occur which completes conversion to malignancy, in certain defined patterns. This review explores how anatomy, pathology and genomics can merge, not only to guide optimum surgery, but also to provide a more comprehensive portal for precision medicine.