Lack of the Tailored Use of Anthracycline in the Lobular Subtype of Breast Carcinoma: Evidence on the Topoisomerase-IIa Amplicon.
Eleonora Brunello, Matteo Brunelli, Erminia Manfrin, Alessia Nottegar, Samantha Bersani, Marco Vergine, Marco Chilosi, Guido Martignoni, Franco Bonetti. University of Verona, Italy
Background: In breast carcinoma, the topoisomerase-IIa gene amplification appears to be a good predictor bio-marker of response to anthracyclines. Interestingly, the lobular subtype usually do not respond to chemotherapies such as those including doxorubicin/anthracycline. Few data area available when matching topoisomerase-IIa gene and lobular breast carcinoma, thus we sought to assess the topoisomerase-IIa status in the lobular subtype.
Design: 46 infiltrative lobular carcinomas, 13 with available matched loco-regional lymph-nodal metastases were recruited. Tissue microarrays have been built by punching three neoplastic cores per case. Whole tumorous tissue sections were simultaneously evaluated. Topoisomerase-IIa gene amplification was evaluated by both chromogenic (Zytolight) (CISH) and fluorescent (Olympus) (FISH) in situ analyses. We also assessed the Her-2/neu status by CISH, FISH and SISH (Ventana). Amplification was assessed as recommanded criteria. HER-2 immunoexpression was assessed by using Hercept test.
Results: 44/46 (95%) of the cases did not reveal topoisomerase-IIa amplification whereas two of the 46 (5%) cases were amplified by using all three techniques. Eleven of the 13 metastatic sites did not reveal amplification neither in the primary neither in the matched metastases (85%); the two remaining were amplified (15%). All cases revealed an homogeneous status on all three neoplastic cores. The two cases showing Her-2/neu and topoisomerase-IIa amplification scored 3+ the remaining not-amplified cases scored 0 or 1+ in 40 and 2+ in 4 cases.
Conclusions: In conclusion, the infiltrative lobular subtype of breast carcinoma do not usually show topoisomerase-IIa gene amplification neither in the primary and matched lymph-nodal metastases. In the era of the personalised and tailored therapies, patients affected by the lobular subtype of breast carcinoma lack the biological rationale for receiving the common chemotherapy that include doxorubicin/anthracycline.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 31, Tuesday Afternoon