Pathobiological characteristics of the 1st primary and risk of metachronous contralateral invasive breast-carcinoma - clinical implications

The study was undertaken to determine the clinico-pathobiological characteristics in a series of 49 patients who developed metachronous breast carcinoma. Possible differences between the two tumours of conventional clinico-pathological features and of some biological markers such as DNA ploidy, c-erbB-2 oncoprotein overexpression and tumour angiogenesis were evaluated. The McNemar's test for independence showed that all the characteristics analyzed between the two tumours, in the same case, were not significantly different. After a median follow-up time of 69 months the overall survival of the series was 87.5% and the only significant prognostic factor for clinical outcome was peritumoural lymphatic vessel invasion (PLVI). The median second tumour-free interval was of 32 months ( 13 to 160 months) and none of the variables analyzed on the first primary was predictive of the timing of appearance of the second tumour. To assess the association between the characteristics of the first tumour and the odds of developing a metachronous carcinoma a case-control analysis was conducted. For each woman of the present series who developed bilateral cancer (case) a woman who had unilateral breast cancer (control) was matched for the length of the follow-up. A log-logistic regression model for matched sets was also performed to assess the risk of developing the second tumour. Applying multivariate analysis we found that progesterone receptor (PgR) status was the most important prognostic factor for the odds of bilateral tumour (odds ratio 0.22, p=0.013) followed by histological grade (odds ratio 0.20, p=0.063) and presence of PLVI (odds ratio 3.13, p=0.067). These findings suggest that the knowledge on the initial primary of PgR, grading and PLVI could be important to assess the individual risk of developing metachronous breast cancer. The determination of these factors could improve our ability to identify subsets of patients operated for breast cancer with different risks for bilateral tumour, allowing for a better selection of those patients who need intensive surveillance of their contralateral breast, and eligible for chemoprevention.