Morphological types of breast cancer in family members and multiple primary tumours: is morphology genetically determined?

Abstract

We conducted the present study to determine whether breast cancer morphology is genetically determined. Using the nationwide Swedish Family Cancer Database, which includes data on 10.2 million individuals and over 25,000 morphology-specific breast cancers, we followed morphological types in familial cancers between mothers and daughters and between sisters. Additionally, we recorded morphological data in women who presented with two primary breast cancers and in those who presented with an invasive and in situ breast cancer. We used kappa statistics to examine the association between genetics and morphology. A kappa value of 0 indicates that the process is random and a value of 1 indicates that it is completely determined (i.e. genetic); values between 0.40 and 0.60 are considered to indicate a moderately determined process. The study sample included a total of 25,730 first and 3394 second invasive breast cancers, and 2990 in situ breast cancers. Ductal, lobular, tubuloductal and comedo were the most common invasive types. We identified 164 mother-daughter pairs with breast cancer of a defined morphology, yielding a low kappa value of 0.08. Among 100 sister pairs the kappa value was 0.002. In individuals with two primary breast cancers the kappa values were 0.22 and 0.01 for two invasive and in situ-invasive pairs, respectively. However, for a tumour with a subsequent tumour detected in the contralateral breast less than 1 year later the kappa value was 0.47. The data suggest that breast cancer morphology is not genetically determined. However, because of mixed morphologies and the overwhelming prevalence of ductal morphology, the results for rare morphologies should be interpreted with caution.