Classical lobular breast carcinoma consistently lacks topoisomerase-IIa gene amplification: implications for the tailored use of anthracycline-based chemotherapies

Aims: There is consistent lack of data focusing the topoisomerase-IIa gene status in lobular breast carcinoma, a subtype that usually shows poor responsiveness to chemotherapies including those using anthracycline drugs. Methods and results: Forty-six infiltrative lobular carcinomas, 13 with matched metastases, were used. Topoisomerase-IIa gene amplification was evaluated by chromogenic in situ hybridization (CISH) and fluorescence in situ hybridization (FISH). We also assessed Her2/neu status by CISH, FISH and silver in situ hybridization (SISH). HER2 immunoexpression was assessed by the HercepTest. Forty-four of 46 (95%) cases revealed no topoisomerase-II alpha amplification, whereas two of 46 (5%) cases were amplified by all three techniques. Eleven of the 13 metastatic sites showed no amplification either in the primary or in the metastases (85%); the remaining two were amplified (15%). Her2/neu was not amplified in 44 of 46 (95%) cases nor was it amplified in 11 of 13 (95%) metastatic tissues. The two cases showing Her2/neu and topoisomerase-IIa amplification scored 3+; the remaining non-amplified cases scored 0 or 1+ in 40 and 2+ in four cases. Conclusions: In the era of personalized and tailored therapies, we suggest that patients affected by the classical lobular subtype of breast carcinoma constantly lack the ad hoc predictive rationale for receiving common chemotherapy that includes anthracyclines.