Search

Your search keyword '"Bisagni, G"' showing total 27 results
Start Over Author "Bisagni, G" Database OpenAIRE

Refine your results

27 results on '"Bisagni, G"'

1. Nine weeks versus 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study

Author

Conte, P., Frassoldati, A., Bisagni, G., Brandes, A. A., Donadio, M., Garrone, O., Piacentini, F., Cavanna, L., Giotta, F., Aieta, M., Gebbia, V., Molino, A., Musolino, A., Ferro, A., Maltoni, R., Danese, S., Zamagni, C., Rimanti, A., Cagossi, K., Russo, A., Pronzato, P., Giovanardi, F., Moretti, G., Lombardo, L., Schirone, A., Beano, A., Amaducci, L., Bajardi, E. A., Vicini, R., Balduzzi, S., D'Amico, R., Guarneri, Falci C, V., Giarratano, T, Mcmahon, L, De Salvo GL, Dieci, Mv, Maiorana, A, Ficarra, G, Caggia, F, Grisolia, D, Bartolini, S, Lorusso, V, Ardito, R, Tartarone, A, Vanella, P, Taverniti, C, Porpiglia, M, Spanu, Pg, Biglia, N, Andreis, D, Piancastelli, A, Fedeli, A, Parra, Hs, Gambaro, Ar, Romito, S, Malossi, A, Gori, S, Miglietta, L, Del Mastro, L, Amoroso, D, Mansutti, M, Generali, D, Prati, G, Bertolini, A, Berardi, R, Zanni, A, Cottafavi, L, Bologna, A, Naso, G, Pancotti, A, Farci, D, Zoboli, A, Silva, R, Laudadio, L, Bordonaro, R, Marenco, D, Dongiovanni, V, Baldini, E, Saggia, C, Gorzegno, G, Cariello, A, Biganzoli, L, Rampello, E., Conte P., Frassoldati A., Bisagni G., Brandes A.A., Donadio M., Garrone O., Piacentini F., Cavanna L., Giotta F., Aieta M., Gebbia V., Molino A., Musolino A., Ferro A., Maltoni R., Danese S., Zamagni C., Rimanti A., Cagossi K., Russo A., Pronzato P., Giovanardi F., Moretti G., Lombardo L., Schirone A., Beano A., Amaducci L., Bajardi E.A., Vicini R., Balduzzi S., D'Amico R., and Guarneri V.

Subjects
Oncology, Time Factors, Adjuvant, Breast cancer, Cardiac safety, De-escalated treatment, Trastuzumab, Settore MED/06 - Oncologia Medica, Receptor, ErbB-2, medicine.medical_treatment, Anthracycline, 030204 cardiovascular system & hematology, Breast cancer, Antineoplastic Agents, Immunological, ErbB-2, 0302 clinical medicine, Trastuzumab, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Anthracyclines, skin and connective tissue diseases, Adjuvant, Mastectomy, Cardiac safety, De-escalated treatment, Hazard ratio, Hematology, Middle Aged, Chemotherapy regimen, Bridged-Ring Compound, Immunological, Local, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, Taxoids, Trastuzumab, adjuvant, breast cancer, cardiac safety, de-escalated treatment, Breast Neoplasm, Human, Receptor, medicine.drug, Adult, Bridged-Ring Compounds, medicine.medical_specialty, Time Factor, Socio-culturale, Breast Neoplasms, Antineoplastic Agents, Disease-Free Survival, Drug Administration Schedule, 03 medical and health sciences, Taxoid, Internal medicine, medicine, Humans, Chemotherapy, Risk factor, Aged, Neoplasm Staging, Antineoplastic Combined Chemotherapy Protocol, business.industry, medicine.disease, Cardiotoxicity, Neoplasm Recurrence, Neoplasm Recurrence, Local, business
Abstract

Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age 35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks trastuzumab (arm B, short). This study was designed as a non-inferiority trial with disease-free survival (DFS) as primary end point. A DFS hazard ratio (HR)

Published
2018
Full Text
View/download PDF

3. Erratum to: Tumor-infiltrating lymphocytes and molecular response after neoadjuvant therapy for HR+/HER2− breast cancer: results from two prospective trials (Breast Cancer Research and Treatment, (2017), 163, 2, (295-302), 10.1007/s10549-017-4191-y)

Author

Dieci, M. V., Frassoldati, A., Generali, D., Bisagni, G., Piacentini, F., Cavanna, L., Cagossi, K., Puglisi, F., Michelotti, A., Berardi, R., Banna, G., Goubar, A., Ficarra, G., Griguolo, G., Conte, Pierfranco, Guarneri, V., Dieci, M. V., Frassoldati, A., Generali, D., Bisagni, G., Piacentini, F., Cavanna, L., Cagossi, K., Puglisi, F., Michelotti, A., Berardi, R., Banna, G., Goubar, A., Ficarra, G., Griguolo, G., Conte, Pierfranco, and Guarneri, V.

Subjects
Cancer Research, Oncology
Abstract

N/A

Published
2017

4. 9 weeks vs 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study

Author

Conte, P, Frassoldati, A, Bisagni, G, Brandes, Aa, Donadio, M, Garrone, O, Piacentini, F, Cavanna, L, Giotta, F, Aieta, M, Gebbia, V, Molino, A, Musolino, A, Ferro, A, Maltoni, R, Danese, S, Zamagni, C, Rimanti, A, Cagossi, K, Russo, A, Pronzato, P, Giovanardi, F, Moretti, G, Lombardo, L, Schirone, A, Beano, A, Amaducci, L, Bajardi, Ea, Vicini, R, Balduzzi, Sara, D'Amico, R, and Guarneri, Valentina

Subjects
trastuzumab, breast cancer, trastuzumab, adjuvant, breast cancer, cardiac safety, de-escalated treatment, adjuvant, cardiac safety, de-escalated treatment
Published
2018

5. 3* Final analysis of the phase III multicentric Italian study Short-HER: 9 weeks vs 1 year adjuvant trastuzumab for HER2+ early breast cancer

Author

Conte, P, Bisagni, G, Frassoldati, A, Brandes, A, Cavanna, L, Giotta, F, Aieta, M, Gebbia, V, Musolino, A, Garrone, O, Donadio, M, Cavazzini, G, Turletti, A, Zamagni, C, Danese, S, Ferro, A, Piacentini, F, Balduzzi, S, D'Amico, R, and Guarneri, V

Subjects
trastuzumab, breast cancer, immunologic adjuvants, pharmaceutical adjuvants, trastuzumab, immunologic adjuvants, pharmaceutical adjuvants, breast cancer
Published
2017

7. Immunoglobulin g fragment c receptor polymorphisms and clinical outcome of EGFR-expressing metastatic colorectal cancer patients treated with Cetuximab-based therapy

Author

Negri F, Musolino A, Naldi N, Bortesi B, Boni C, Bisagni G, Camisa R, ARDIZZONI, ANDREA, Negri F, Musolino A, Naldi N, Bortesi B, Boni C, Bisagni G, Camisa R, and Ardizzoni A

Subjects
cetuximab, antibody-dependant cellular cytotoxicity, hemic and immune systems, neoplasms, FcgR polymorphism, digestive system diseases
Abstract

Antibody-dependent cellular cytotoxicity (ADCC), which is activated by effector cells via immunoglobulin G (IgG) fragment C receptors (FcRs), was proposed as a mechanism of cetuximab efficacy. Peripheral blood mononuclear cells (PBMCs) from 23 healthy donors and 13 patients with metastatic colorectal cancer (mCRC) treated with cetuximab were tested for FcγR polymorphisms and cetuximab-mediated ADCC. ADCC was measured by chromium-51 release on a epidermal growth factor receptor (EGFR)-positive human colon cancer cell line. Overall, 86 mCRC patients were genotyped for study purposes. PBMCs harbouring the FcγRIIIa 158 V/V genotype had a significantly higher cetuximab-mediated ADCC. No correlation was found between FcγR polymorphisms and response rate or time to progression after cetuximab-based therapy. Despite the in vitro analysis showing that the FcγRIIIa 158 V/V genotype is associated with higher ADCC, clinical data do not support a predictive role of FcγRIIIa polymorphisms in mCRC treated with cetuximab.

Published
2007

9. Preoperative chemotherapy plus trastuzumab, lapatinib or both in HER2 positive operable breast cancer: results of the randomized phase II CHER-LOB study

Author

Guarneri, Valentina, Frassoldati, A, Bottini, A, Cagossi, K, Bisagni, G, Sarti, S, Ravaioli, A, Cavanna, L, Giardina, G, Musolino, A, Untch, M, Orlando, L, Artioli, F, Boni, C, Generali, Dg, Serra, P, Bagnalasta, M, Marini, L, Piacentini, Federico, D'Amico, Roberto, and Conte, Pierfranco

Subjects
Trastuzumab, lapatinib, dual blockade, preoperative therapy, operable breast cancer, HER2
Published
2012

10. Trans-CHER-Lob: A Biomarker Analysis of the Randomized Phase II Study of Neoadjuvant Chemotherapy Plus Trastuzumab, Lapatinib or Combined Trastuzumab and Lapatinib in HER2 Positive Operable Breast Cancer

Author

Guarneri, V, Frassoldati, A, Ficarra, G, Maiorana, A, Bettelli, S, Bottini, A, Cagossi, K, Bisagni, G, Ravaioli, A, Amadori, D, Musolino, A, Cavanna, L, Orlando, L, Giardina, G, Piacentini, F, Bagnalasta, M, and Conte, Pierfranco

Subjects
pAKT, Ki67, dual HER2 blockade, lapatinib, trastuzumab
Published
2011

11. 9 Weeks vs 1 Year Adjuvant Trastuzumab in Combination with Chemotherapy: Preliminary Cardiac Safety Data of the Phase III Multicentric Italian Study Short-HER

Author

Guarneri, Valentina, Frassoldati, A, Gebbia, V, Bisagni, G, Cavanna, L, Donadio, M, Lelli, G, Musolino, A, Colucci, G, Banna, Gl, Degli Esposti, R, Ferro, A, Grasso, F, Zamagni, C, Amadori, D, Aieta, M, Molino, A, Garrone, O, Aitini, E, Fornari, G, Cascinu, Stefano, Rossi, G, D'Amico, Roberto, and Conte, Pierfranco

Subjects
trastuzumab, breast cancer, cardiac safety
Published
2010

12. Adjuvant chemotherapy in completely resected gastric cancer: A Randomized phase III trial conducted by GOIRC

Author

Di Costanzo, F., Gasperoni, S., Manzione, L., Bisagni, G., Labianca, R., Bravi, S., Cortesi, Enrico, Carlini, P., Bracci, R., Tomao, Silverio, Messerini, L., Arcangeli, A., Torri, V., Bilancia, D., Floriani, I., Tonato, M., Italian Oncology Group For Cancer Research, Dinota, A., Strafiuso, G., Corgna, E., Porrozzi, S., Boni, C., Rondini, E., Giunta, A., Monzio Compagnoni, B., Biagioni, F., Cesari, M., Fornarini, G., Nelli, F., Carboni, M., Cognetti, F., Enzo, Mr, Piga, A., Romiti, A., Olivetti, A., Masoni, Luigi, De Stefanis, M., Dalla Mola, A., Camera, S., Recchia, F., De Filippis, S., Scipioni, L., Zironi, S., Luppi, G., Italia, M., Banducci, S., Pisani Leretti, A., Massidda, B., Ionta, M. T., Nicolosi, A., Canaletti, R., Biscottini, B., Grigniani, F., Rovei, R., Croce, E., Carroccio, R., Gilli, G., Cavalli, C., Olgiati, A., Pandolfi, U., Rossetti, R., Natalini, G., Foa, P., Oldani, S., Bruno, L., Cascinu, S., Catalano, G., Catalano, V., Lungarotti, F., Farris, A., Sarobba, M. G., Trignano, M., Muscogiuri, A., Francavilla, F., Figoli, F., Leoni, M., Papiani, G., Orselli, G., Antimi, M., Bellini, V., Cabassi, A., Contu, A., Pazzola, A., Frignano, M., Lastraioli, E., Saggese, M., Bianchini, D., Antonuzzo, L., Mela, M., and Camisa, R.

Subjects
Male, Cancer Research, medicine.medical_treatment, Leucovorin, Kaplan-Meier Estimate, Gastroenterology, Antineoplastic Combined Chemotherapy Protocols, Medicine, Stomach cancer, Adult, Aged, Biomarkers, Tumor, Chemotherapy, Adjuvant, Cisplatin, Diarrhea, Disease-Free Survival, Epirubicin, Female, Fluorouracil, Hematologic Diseases, Humans, Immunohistochemistry, Italy, Lymph Node Excision, Lymphatic Metastasis, Middle Aged, Mucositis, Neoplasm Staging, Patient Compliance, Prognosis, Proportional Hazards Models, Stomach Neoplasms, Treatment Outcome, Vomiting, Gastrectomy, Hazard ratio, Chemotherapy regimen, Oncology, medicine.drug, medicine.medical_specialty, Internal medicine, Survival analysis, Chemotherapy, business.industry, Proportional hazards model, medicine.disease, Surgery, business
Abstract

Background Complete surgical resection of gastric cancer is potentially curative, but long-term survival is poor. Methods Patients with histologically proven adenocarcinoma of the stomach of stages IB, II, IIIA and B, or IV (T4N2M0) and treated with potentially curative surgery were randomly assigned to follow-up alone or to intravenous treatment with four cycles (repeated every 21 days) of PELF (cisplatin [40 mg/m 2 , on days 1 and 5], epirubicin [30 mg/m 2 , days 1 and 5], L-leucovorin [100 mg/m 2 , days 1-4], and 5-fluorouracil [300 mg/m 2 , days 1-4] in a hospital setting. Frequencies and severity of adverse events were determined. Overall survival (OS) and disease-free survival (DFS) were compared between the treatment arms using Kaplan-Meier analysis and a Cox proportional hazards regression model. All statistical tests were two-sided. Results From January 1995 through September 2000, 258 patients were randomly assigned to chemotherapy (n = 130) or surgery alone (n = 128). Patient characteristics were well balanced between the two arms. Among those who received chemotherapy, grade 3 or 4 toxic effects including vomiting, mucositis, and diarrhea were experienced by 21.1%, 8.4%, and 11.8% of patients, respectively. Leucopenia, anemia, and thrombocytopenia of grade 3 or 4 were experienced by 20.3%, 3.3%, and 4.2% of patients, respectively. After a median follow-up of 72.8 months, 128 patients (49.6%) experienced recurrence and 139 (53.9%) deaths were observed, one toxicity-related. Relative to treatment with surgery alone, adjuvant chemotherapy did not increase disease-free survival (hazard ratio [HR] of recurrence = 0.92; 95% confidence interval [Cl] = 0.66 to 1.27) or overall survival (HR of death = 0.90; 95% Cl = 0.64 to 1.26). Conclusions Our results failed to provide proof of an effect of adjuvant chemotherapy with PELF on overall survival or disease-free survival. The estimated effect of chemotherapy (10% reduction in the hazard of death or relapse) is modest and consistent with the results of meta-analyses of adjuvant chemotherapy without platinum agents.

Published
2008

14. 186O Tumor-infiltrating lymphocytes (TILs) as an independent prognostic factor for early HER2+ breast cancer patients treated with adjuvant chemotherapy and trastuzumab in the randomized shortHER trial

Author

MARIA VITTORIA DIECI, PIERFRANCO CONTE, Bisagni, G., A Brandes, A., Frassoldati, A., Cavanna, L., Musolino, A., Giotta, F., Rimanti, A., Garrone, O., Bertone, E., Cagossi, K., Sarti, S., Ferro, A., Omarini, C., Maiorana, A., Orvieto, E., Sanders, M., D Amico, R., and VALENTINA GUARNERI

18. Is There Still a Role for Endocrine Therapy Alone in HR+/HER2- Advanced Breast Cancer Patients? Results from the Analysis of Two Data Sets of Patients Treated with High-Dose Fulvestrant as First-Line Therapy in the Real-World Setting: The EVA and GIM-13 AMBRA Studies

Author

Michela Maur, A. Frassoldati, Alberto Zambelli, Antonio Febbraro, L. Livi, Raffaella Palumbo, Luca Clivio, Alessandra Fabi, D Sartori, Salvatore Artale, Ornella Garrone, A. Ferzi, N. La Verde, Marina Elena Cazzaniga, M. De Laurentiis, Lucia Mentuccia, Mariangela Ciccarese, M. Donadio, Piero Marchetti, Clara Natoli, A. Turletti, Mirco Pistelli, Claudio Scavelli, Luca Gianni, E. Romagnoli, Giancarlo Bisagni, G. Mustacchi, A. Schirone, Patrizia Vici, M. Porpiglia, M. Giordano, Daniele Generali, Livio Blasi, Andrea Michelotti, Valter Torri, Filippo Montemurro, Claudio Verusio, Giulia Bianchi, Paolo Pronzato, Corrado Ficorella, Laura Biganzoli, Ferdinando Riccardi, Francesco Atzori, L. Del Mastro, Daniele Santini, G. Moretti, A. Fumagalli, Vittorio Gebbia, Antonino Musolino, Maria Rosaria Valerio, Marta Airoldi, Cazzaniga, M. E., Verusio, C., Ciccarese, M., Fumagalli, A., Sartori, D., Valerio, M. R., Airoldi, M., Moretti, G., Ficorella, C., Gianni, L., Michelotti, A., Zambelli, A., Febbraro, A., Generali, D., Pistelli, M., Garrone, O., Musolino, A., Vici, P., Maur, M., Mentuccia, L., La Verde, N., Bianchi, G. V., Artale, S., Blasi, L., De Laurentiis, M., Atzori, F., Turletti, A., Porpiglia, M., Santini, D., Fabi, A., Gebbia, V., Schirone, A., Palumbo, R., Ferzi, A., Frassoldati, A., Scavelli, C., Clivio, L., Giordano, M., Donadio, M., Biganzoli, L., Del Mastro, L., Bisagni, G., Livi, L., Natoli, C., Montemurro, F., Riccardi, F., Romagnoli, E., Marchetti, P., Torri, V., Pronzato, P., Mustacchi, G., Cazzaniga M.E., Verusio C., Ciccarese M., Fumagalli A., Sartori D., Valerio M.R., Airoldi M., Moretti G., Ficorella C., Gianni L., Michelotti A., Zambelli A., Febbraro A., Generali D., Pistelli M., Garrone O., Musolino A., Vici P., Maur M., Mentuccia L., La Verde N., Bianchi G.V., Artale S., Blasi L., De Laurentiis M., Atzori F., Turletti A., Porpiglia M., Santini D., Fabi A., Gebbia V., Schirone A., Palumbo R., Ferzi A., Frassoldati A., Scavelli C., Clivio L., Giordano M., Donadio M., Biganzoli L., Del Mastro L., Bisagni G., Livi L., Natoli C., Montemurro F., Riccardi F., Romagnoli E., Marchetti P., Torri V., Pronzato P., Mustacchi G., Cazzaniga, M, Verusio, C, Ciccarese, M, Fumagalli, A, Sartori, D, Valerio, M, Airoldi, M, Moretti, G, Ficorella, C, Gianni, L, Michelotti, A, Zambelli, A, Febbraro, A, Generali, D, Pistelli, M, Garrone, O, Musolino, A, Vici, P, Maur, M, Mentuccia, L, La Verde, N, Bianchi, G, Artale, S, Blasi, L, De Laurentiis, M, Atzori, F, Turletti, A, Porpiglia, M, Santini, D, Fabi, A, Gebbia, V, Schirone, A, Palumbo, R, Ferzi, A, Frassoldati, A, Scavelli, C, Clivio, L, Giordano, M, Donadio, M, Biganzoli, L, Del Mastro, L, Bisagni, G, Livi, L, Natoli, C, Montemurro, F, Riccardi, F, Romagnoli, E, Marchetti, P, Torri, V, Pronzato, P, and Mustacchi, G

Subjects
Oncology, medicine.medical_specialty, medicine.drug_class, Population, Anastrozole, NO, Internal medicine, Fulvestrant · First-line setting · Hormone receptor positive, Advanced breast cancer, medicine, Adjuvant therapy, Progression-free survival, education, Fulvestrant, First-Line setting, education.field_of_study, Hormone receptor positive, Aromatase inhibitor, EVA, business.industry, trials, Cancer, Endocrine Therapy, GIM-13, medicine.disease, Endocrine Therapy, HR+/HER2–, Advanced Breast Cancer, High-Dose, Fulvestrant, First-Line setting, EVA, GIM-13, AMBRA, trials, Advanced breast cancer, First-line setting, HR+/HER2–, Advanced Breast Cancer, Surgery, AMBRA, business, High-Dose, Tamoxifen, Research Article, medicine.drug
Abstract

Background: Different studies suggest that fulvestrant 500 mg every 28 days (HD-FUL) could be an active treatment in HR+ advanced breast cancer (ABC) patients even treated with aromatase inhibitors in the adjuvant setting. The aim of this analysis is to describe the outcome of ABC patients treated with HD-FUL as first-line treatment in terms of median duration of treatment and the overall response rate in a real-world setting. Methods: For the purpose of the present analysis, we considered two data sets of HR+ ABC patients collected in Italy between 2012 and 2015 (EVA and GIM-13 AMBRA studies). Results: Eighty-one and 91 patients have been identified from the two data sets. The median age was 63 years (range 35–82) for the EVA and 57.8 years (range 35.0–82.3) for the AMBRA patients. ORRs were 23.5 and 24.3% in the whole population, 26.9% in the patients with bone only, and 21.8 and 21.4% in those with visceral metastases. The median duration of HD-FUL was 11.6 months (range 1–48) and 12.4 months (range 2.9–70.0) in the two data sets, respectively. Conclusion: These data suggest that HD-FUL should still continue to play a significant role as first-line therapy in HR+ ABC patients.

Published
2019

19. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial

Author

Sabino De Placido, Ciro Gallo, Michelino De Laurentiis, Giancarlo Bisagni, Grazia Arpino, Maria Giuseppa Sarobba, Ferdinando Riccardi, Antonio Russo, Lucia Del Mastro, Alessio Aligi Cogoni, Francesco Cognetti, Stefania Gori, Jennifer Foglietta, Antonio Frassoldati, Domenico Amoroso, Lucio Laudadio, Luca Moscetti, Filippo Montemurro, Claudio Verusio, Antonio Bernardo, Vito Lorusso, Adriano Gravina, Gabriella Moretti, Rossella Lauria, Antonella Lai, Carmela Mocerino, Sergio Rizzo, Francesco Nuzzo, Paolo Carlini, Francesco Perrone, Antonello Accurso, Biagio Agostara, Michele Aieta, Oscar Alabiso, Maria Grazia Alicicco, Dino Amadori, Laura Amaducci, Gianna Amiconi, Giustino Antuzzi, Mara Ardine, Antonio Ardizzoia, Caterina Aversa, Giuseppe Badalamenti, Sandro Barni, Carlo Basurto, Rossana Berardi, Cinzia Bergamasco, Paolo Bidoli, Claudia Bighin, Edoardo Biondi, Corrado Boni, Karen Borgonovo, Mario Botta, Stefano Bravi, Paolo Bruzzi, Giuseppe Buono, Alfredo Butera, Alessia Caldara, Giampiero Candeloro, Claudia Cappelletti, Cinzia Cardalesi, Elisabetta Carfora, Anna Cariello, Francesco Carrozza, Giacomo Cartenì, Michele Caruso, Virginia Casadei, Claudia Casanova, Luigi Castori, Luigi Cavanna, Giovanna Cavazzini, Marina Cazzaniga, Mario Chilelli, Paolo Chiodini, Silvia Chiorrini, Fortunato Ciardiello, Mariangela Ciccarese, Saverio Cinieri, Mario Clerico, Mariarosa Coccaro, Mario Comande, Claudia Corbo, Giuseppina Cortino, Stefania Cusenza, Gennaro Daniele, Alfonso Maria D'arco, Giuliana D'auria, Claudio Dazzi, Carmine De Angelis, Filippo de Braud, Gianfranco De Feo, Andrea De Matteis, Michele De Tursi, Anna Di Blasio, Giuseppe di Lucca, Liberato Di Lullo, Francesca Di Rella, Gianfranco Di Renzo, Pia Di Stefano, Aida Di Stefano, Anna Diana, Sara Donati, Agnese Fabbri, Alessandra Fabi, Marina Faedi, Gabriella Farina, Antonio Farris, Antonio Febbraro, Palma Fedele, Piera Federico, Francesco Ferraù, Gianluigi Ferretti, Antonella Ferro, Irene Floriani, Rosachiara Forcignanò, Samantha Forciniti, Valeria Forestieri, Gianni Fornari, Michela Frisinghelli, Vittorio Fusco, Giulia Gallizzi, Antonio Galvano, Antonio Gambardella, Angelo Gambi, Vittorio Gebbia, Erika Gervasi, Mara Ghilardi, Alice Giacobino, Giovanni Giardina, Francesco Giotta, Sara Giraudi, Mario Giuliano, Antonino Grassadonia, Donatella Grasso, Federica Grosso, Lorenzo Guizzaro, Pasquale Incoronato, Lorena Incorvaia, Giovanni Iodice, Nicla La Verde, Vincenzo Labonia, Gabriella Landi, Agnese Latorre, Vita Leonardi, Alessia Levaggi, Gennaro Limite, Linda Lina Bascialla, Lorenzo Livi, Evaristo Maiello, Daniela Mandelli, Ilaria Marcon, Daniela Menon, Michele Montedoro, Lucia Moraca, Anna Moretti, Maria Grazia Morritti, Patrizia Morselli, Antonella Mura, Silvia Mura, Michela Musacchio, Alberto Muzio, Donato Natale, Clara Natoli, Cinzia Nigro, Cecilia Nisticò, Antonio Nuzzo, Michele Orditura, Laura Orlando, Carmen Pacilio, Giuliano Palumbo, Raffaella Palumbo, Felice Pasini, Emanuela Paterno, Antonio Pazzola, Silvia Pelliccioni, Matilde Pensabene, Davide Perroni, Angela Pesenti Gritti, Fausto Petrelli, Maria Carmela Piccirillo, Graziella Pinotti, Claudia Pogliani, Davide Poli, Sonia Prader, Francesco Recchia, Daniele Rizzi, Carmen Romano, Rosalba Rossello, Chiara Rossini, Giuseppina Salvucci, Valeria Sanna, Alessandra Santini, Silvana Saracchini, Clementina Savastano, Giovanni Scambia, Francesco Schettini, Paola Schiavone, Alessio Schirone, Elena Seles, Simona Signoriello, Giuseppe Signoriello, Rosa Rita Silva, Antonia Silvestri, Vittorio Simeon, Ilaria Spagnoletti, Stefano Tamberi, Cristina Teragni, Verena Thalmann, Renato Thomas, Guglielmo Thomas, Amelia Tienghi, Nicola Tinari, Vincenza Tinessa, Federica Tomei, Giuseppe Tonini, Valter Torri, Divina Traficante, Marianna Tudini, Monica Turazza, Roberto Vignoli, Maria Giuseppa Vitale, Alessandra Zacchia, Pasquale Zagarese, Alda Zanni, Laura Zavallone, Maria Zavettieri, Alessandra Zoboli, De Placido, S., Gallo, C., De Laurentiis, M., Bisagni, G., Arpino, G., Sarobba, M. G., Riccardi, F., Russo, A., Del Mastro, L., Cogoni, A. A., Cognetti, F., Gori, S., Foglietta, J., Frassoldati, A., Amoroso, D., Laudadio, L., Moscetti, L., Montemurro, F., Verusio, C., Bernardo, A., Lorusso, V., Gravina, A., Moretti, G., Lauria, R., Lai, A., Mocerino, C., Rizzo, S., Nuzzo, F., Carlini, P., Perrone, F., Accurso, A., Agostara, B., Aieta, M., Alabiso, O., Alicicco, M. G., Amadori, D., Amaducci, L., Amiconi, G., Antuzzi, G., Ardine, M., Ardizzoia, A., Aversa, C., Badalamenti, G., Barni, S., Basurto, C., Berardi, R., Bergamasco, C., Bidoli, P., Bighin, C., Biondi, E., Boni, C., Borgonovo, K., Botta, M., Bravi, S., Bruzzi, P., Buono, G., Butera, A., Caldara, A., Candeloro, G., Cappelletti, C., Cardalesi, C., Carfora, E., Cariello, A., Carrozza, F., Carteni, G., Caruso, M., Casadei, V., Casanova, C., Castori, L., Cavanna, L., Cavazzini, G., Cazzaniga, M., Chilelli, M., Chiodini, P., Chiorrini, S., Ciardiello, F., Ciccarese, M., Cinieri, S., Clerico, M., Coccaro, M., Comande, M., Corbo, C., Cortino, G., Cusenza, S., Daniele, G., D'Arco, A. M., D'Auria, G., Dazzi, C., De Angelis, C., de Braud, F., De Feo, G., De Matteis, Ma., De Tursi, M., Di Blasio, A., di Lucca, G., Di Lullo, L., Di Rella, F., Di Renzo, G., Di Stefano, P., Di Stefano, A., Diana, A., Donati, S., Fabbri, A., Fabi, A., Faedi, M., Farina, G., Farris, A., Febbraro, A., Fedele, P., Federico, P., Ferrau, F., Ferretti, G., Ferro, A., Floriani, I., Forcignano, R., Forciniti, S., Forestieri, V., Fornari, G., Frisinghelli, M., Fusco, V., Gallizzi, G., Galvano, A., Gambardella, A., Gambi, A., Gebbia, V., Gervasi, E., Ghilardi, M., Giacobino, A., Giardina, G., Giotta, F., Giraudi, S., Giuliano, M., Grassadonia, A., Grasso, D., Grosso, F., Guizzaro, L., Incoronato, P., Incorvaia, L., Iodice, G., La Verde, N., Labonia, V., Landi, G., Latorre, A., Leonardi, V., Levaggi, A., Limite, G., Lina Bascialla, L., Livi, L., Maiello, E., Mandelli, D., Marcon, I., Menon, D., Montedoro, M., Moraca, L., Moretti, A., Morritti, M. G., Morselli, P., Mura, A., Mura, S., Musacchio, M., Muzio, A., Natale, D., Natoli, C., Nigro, C., Nistico, C., Nuzzo, A., Orditura, M., Orlando, L., Pacilio, C., Palumbo, G., Palumbo, R., Pasini, F., Paterno, E., Pazzola, A., Pelliccioni, S., Pensabene, M., Perroni, D., Pesenti Gritti, A., Petrelli, F., Piccirillo, M. C., Pinotti, G., Pogliani, C., Poli, D., Prader, S., Recchia, F., Rizzi, D., Romano, C., Rossello, R., Rossini, C., Salvucci, G., Sanna, V., Santini, A., Saracchini, S., Savastano, C., Scambia, G., Schettini, F., Schiavone, P., Schirone, A., Seles, E., Signoriello, S., Signoriello, G., Silva, R. R., Silvestri, A., Simeon, V., Spagnoletti, I., Tamberi, S., Teragni, C., Thalmann, V., Thomas, R., Thomas, G., Tienghi, A., Tinari, N., Tinessa, V., Tomei, F., Tonini, G., Torri, V., Traficante, D., Tudini, M., Turazza, M., Vignoli, R., Vitale, M. G., Zacchia, A., Zagarese, P., Zanni, A., Zavallone, L., Zavettieri, M., Zoboli, A., De Placido, Sabino, Gallo, Ciro, De Laurentiis, Michelino, Bisagni, Giancarlo, Arpino, Grazia, Sarobba, Maria Giuseppa, Riccardi, Ferdinando, Russo, Antonio, Del Mastro, Lucia, Cogoni, Alessio Aligi, Cognetti, Francesco, Gori, Stefania, Foglietta, Jennifer, Frassoldati, Antonio, Amoroso, Domenico, Laudadio, Lucio, Moscetti, Luca, Montemurro, Filippo, Verusio, Claudio, Bernardo, Antonio, Lorusso, Vito, Gravina, Adriano, Moretti, Gabriella, Lauria, Rossella, Lai, Antonella, Mocerino, Carmen, Rizzo, Sergio, Nuzzo, Francesco, Carlini, Paolo, Perrone, Francesco, Accurso, Antonello, Agostara, Biagio, Aieta, Michele, Alabiso, Oscar, Alicicco, Maria Grazia, Amadori, Dino, Amaducci, Laura, Amiconi, Gianna, Antuzzi, Giustino, Ardine, Mara, Ardizzoia, Antonio, Aversa, Caterina, Badalamenti, Giuseppe, Barni, Sandro, Basurto, Carlo, Berardi, Rossana, Bergamasco, Cinzia, Bidoli, Paolo, Bighin, Claudia, Biondi, Edoardo, Boni, Corrado, Borgonovo, Karen, Botta, Mario, Bravi, Stefano, Bruzzi, Paolo, Buono, Giuseppe, Butera, Alfredo, Caldara, Alessia, Candeloro, Giampiero, Cappelletti, Claudia, Cardalesi, Cinzia, Carfora, Elisabetta, Cariello, Anna, Carrozza, Francesco, Cartenì, Giacomo, Caruso, Michele, Casadei, Virginia, Casanova, Claudia, Castori, Luigi, Cavanna, Luigi, Cavazzini, Giovanna, Cazzaniga, Marina, Chilelli, Mario, Chiodini, Paolo, Chiorrini, Silvia, Ciardiello, Fortunato, Ciccarese, Mariangela, Cinieri, Saverio, Clerico, Mario, Coccaro, Mariarosa, Comande, Mario, Corbo, Claudia, Cortino, Giuseppina, Cusenza, Stefania, Daniele, Gennaro, D'arco, Alfonso Maria, D'auria, Giuliana, Dazzi, Claudio, De Angelis, Carmine, de Braud, Filippo, De Feo, Gianfranco, De Matteis, Andrea, De Tursi, Michele, Di Blasio, Anna, di Lucca, Giuseppe, Di Lullo, Liberato, Di Rella, Francesca, Di Renzo, Gianfranco, Di Stefano, Pia, Di Stefano, Aida, Diana, Anna, Donati, Sara, Fabbri, Agnese, Fabi, Alessandra, Faedi, Marina, Farina, Gabriella, Farris, Antonio, Febbraro, Antonio, Fedele, Palma, Federico, Piera, Ferraù, Francesco, Ferretti, Gianluigi, Ferro, Antonella, Floriani, Irene, Forcignanò, Rosachiara, Forciniti, Samantha, Forestieri, Valeria, Fornari, Gianni, Frisinghelli, Michela, Fusco, Vittorio, Gallizzi, Giulia, Galvano, Antonio, Gambardella, Antonio, Gambi, Angelo, Gebbia, Vittorio, Gervasi, Erika, Ghilardi, Mara, Giacobino, Alice, Giardina, Giovanni, Giotta, Francesco, Giraudi, Sara, Giuliano, Mario, Grassadonia, Antonino, Grasso, Donatella, Grosso, Federica, Guizzaro, Lorenzo, Incoronato, Pasquale, Incorvaia, Lorena, Iodice, Giovanni, La Verde, Nicla, Labonia, Vincenzo, Landi, Gabriella, Latorre, Agnese, Leonardi, Vita, Levaggi, Alessia, Limite, Gennaro, Lina Bascialla, Linda, Livi, Lorenzo, Maiello, Evaristo, Mandelli, Daniela, Marcon, Ilaria, Menon, Daniela, Montedoro, Michele, Moraca, Lucia, Moretti, Anna, Morritti, Maria Grazia, Morselli, Patrizia, Mura, Antonella, Mura, Silvia, Musacchio, Michela, Muzio, Alberto, Natale, Donato, Natoli, Clara, Nigro, Cinzia, Nisticò, Cecilia, Nuzzo, Antonio, Orditura, Michele, Orlando, Laura, Pacilio, Carmen, Palumbo, Giuliano, Palumbo, Raffaella, Pasini, Felice, Paterno, Emanuela, Pazzola, Antonio, Pelliccioni, Silvia, Pensabene, Matilde, Perroni, Davide, Pesenti Gritti, Angela, Petrelli, Fausto, Piccirillo, Maria Carmela, Pinotti, Graziella, Pogliani, Claudia, Poli, Davide, Prader, Sonia, Recchia, Francesco, Rizzi, Daniele, Romano, Carmen, Rossello, Rosalba, Rossini, Chiara, Salvucci, Giuseppina, Sanna, Valeria, Santini, Alessandra, Saracchini, Silvana, Savastano, Clementina, Scambia, Giovanni, Schettini, Francesco, Schiavone, Paola, Schirone, Alessio, Seles, Elena, Signoriello, Simona, Signoriello, Giuseppe, Silva, Rosa Rita, Silvestri, Antonia, Simeon, Vittorio, Spagnoletti, Ilaria, Tamberi, Stefano, Teragni, Cristina, Thalmann, Verena, Thomas, Renato, Thomas, Guglielmo, Tienghi, Amelia, Tinari, Nicola, Tinessa, Vincenza, Tomei, Federica, Tonini, Giuseppe, Torri, Valter, Traficante, Divina, Tudini, Marianna, Turazza, Monica, Vignoli, Roberto, Vitale, Maria Giuseppa, Zacchia, Alessandra, Zagarese, Pasquale, Zanni, Alda, Zavallone, Laura, Zavettieri, Maria, Zoboli, Alessandra, Mocerino, Carmela, D'Arco, Alfonso Maria, D'Auria, Giuliana, De Placido, S, Gallo, C, De Laurentiis, M, Bisagni, G, Arpino, G, Sarobba, M, Riccardi, F, Russo, A, Del Mastro, L, Cogoni, A, Cognetti, F, Gori, S, Foglietta, J, Frassoldati, A, Amoroso, D, Laudadio, L, Moscetti, L, Montemurro, F, Verusio, C, Bernardo, A, Lorusso, V, Gravina, A, Moretti, G, Lauria, R, Lai, A, Mocerino, C, Rizzo, S, Nuzzo, F, Carlini, P, Perrone, F, Accurso, A, Agostara, B, Aieta, M, Alabiso, O, Alicicco, M, Amadori, D, Amaducci, L, Amiconi, G, Antuzzi, G, Ardine, M, Ardizzoia, A, Aversa, C, Badalamenti, G, Barni, S, Basurto, C, Berardi, R, Bergamasco, C, Bidoli, P, Bighin, C, Biondi, E, Boni, C, Borgonovo, K, Botta, M, Bravi, S, Bruzzi, P, Buono, G, Butera, A, Caldara, A, Candeloro, G, Cappelletti, C, Cardalesi, C, Carfora, E, Cariello, A, Carrozza, F, Carteni, G, Caruso, M, Casadei, V, Casanova, C, Castori, L, Cavanna, L, Cavazzini, G, Cazzaniga, M, Chilelli, M, Chiodini, P, Chiorrini, S, Ciardiello, F, Ciccarese, M, Cinieri, S, Clerico, M, Coccaro, M, Comande, M, Corbo, C, Cortino, G, Cusenza, S, Daniele, G, D'Arco, A, D'Auria, G, Dazzi, C, De Angelis, C, de Braud, F, De Feo, G, De Matteis, A, De Tursi, M, Di Blasio, A, di Lucca, G, Di Lullo, L, Di Rella, F, Di Renzo, G, Di Stefano, P, Di Stefano, A, Diana, A, Donati, S, Fabbri, A, Fabi, A, Faedi, M, Farina, G, Farris, A, Febbraro, A, Fedele, P, Federico, P, Ferrau, F, Ferretti, G, Ferro, A, Floriani, I, Forcignano, R, Forciniti, S, Forestieri, V, Fornari, G, Frisinghelli, M, Fusco, V, Gallizzi, G, Galvano, A, Gambardella, A, Gambi, A, Gebbia, V, Gervasi, E, Ghilardi, M, Giacobino, A, Giardina, G, Giotta, F, Giraudi, S, Giuliano, M, Grassadonia, A, Grasso, D, Grosso, F, Guizzaro, L, Incoronato, P, Incorvaia, L, Iodice, G, La Verde, N, Labonia, V, Landi, G, Latorre, A, Leonardi, V, Levaggi, A, Limite, G, Lina Bascialla, L, Livi, L, Maiello, E, Mandelli, D, Marcon, I, Menon, D, Montedoro, M, Moraca, L, Moretti, A, Morritti, M, Morselli, P, Mura, A, Mura, S, Musacchio, M, Muzio, A, Natale, D, Natoli, C, Nigro, C, Nistico, C, Nuzzo, A, Orditura, M, Orlando, L, Pacilio, C, Palumbo, G, Palumbo, R, Pasini, F, Paterno, E, Pazzola, A, Pelliccioni, S, Pensabene, M, Perroni, D, Pesenti Gritti, A, Petrelli, F, Piccirillo, M, Pinotti, G, Pogliani, C, Poli, D, Prader, S, Recchia, F, Rizzi, D, Romano, C, Rossello, R, Rossini, C, Salvucci, G, Sanna, V, Santini, A, Saracchini, S, Savastano, C, Scambia, G, Schettini, F, Schiavone, P, Schirone, A, Seles, E, Signoriello, S, Signoriello, G, Silva, R, Silvestri, A, Simeon, V, Spagnoletti, I, Tamberi, S, Teragni, C, Thalmann, V, Thomas, R, Thomas, G, Tienghi, A, Tinari, N, Tinessa, V, Tomei, F, Tonini, G, Torri, V, Traficante, D, Tudini, M, Turazza, M, Vignoli, R, Vitale, M, Zacchia, A, Zagarese, P, Zanni, A, Zavallone, L, Zavettieri, M, and Zoboli, A

Subjects
Oncology, Receptor, ErbB-2, Settore MED/06 - Oncologia Medica, letrozole, law.invention, Adjuvant anastrozole, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, Exemestane, law, exemestane, tamoxifen, breast cancer, Antineoplastic Combined Chemotherapy Protocols, 030212 general & internal medicine, Aromatase Inhibitors, Letrozole, Hazard ratio, Middle Aged, Receptors, Estrogen, Tolerability, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, Receptors, Progesterone, Breast Neoplasm, Human, medicine.drug, medicine.medical_specialty, Socio-culturale, Anastrozole, Breast Neoplasms, Disease-Free Survival, Drug Administration Schedule, 03 medical and health sciences, Breast cancer, Internal medicine, medicine, Aromatase Inhibitor, Humans, Aged, Antineoplastic Combined Chemotherapy Protocol, Androstadiene, business.industry, medicine.disease, Androstadienes, chemistry, business, Tamoxifen
Abstract

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is registered with the European Clinical Trials Database, number 2006-004018-42, and ClinicalTrials.gov, number NCT00541086. Findings: Between March 9, 2007, and July 31, 2012, 3697 patients were enrolled into the study. After a median follow-up of 60 months (IQR 46–72), 401 disease-free survival events were reported, including 211 (11%) of 1850 patients allocated to the switch strategy and 190 (10%) of 1847 patients allocated to upfront treatment. 5-year disease-free survival was 88·5% (95% CI 86·7–90·0) with the switch strategy and 89·8% (88·2–91·2) with upfront treatment (hazard ratio 0·89, 95% CI 0·73–1·08; p=0·23). 5-year disease-free survival was 90·0% (95% CI 87·9–91·7) with anastrozole (124 events), 88·0% (85·8–89·9) with exemestane (148 events), and 89·4% (87·3 to 91·1) with letrozole (129 events; p=0·24). No unexpected serious adverse reactions or treatment-related deaths occurred. Musculoskeletal side-effects were the most frequent grade 3–4 events, reported in 130 (7%) of 1761 patients who received the switch strategy and 128 (7%) of 1766 patients who received upfront treatment. Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule (924 [52%] of 1766 patients vs 745 [42%] of 1761 patients). All other grade 3–4 adverse events occurred in less than 2% of patients in either group. Interpretation: 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors. None of the three aromatase inhibitors was superior to the others in terms of efficacy. Therefore, patient preference, tolerability, and financial constraints should be considered when deciding the optimal treatment approach in this setting. Funding: Italian Drug Agency.

Published
2018

20. Composite risk and benefit from adjuvant dose-dense chemotherapy in hormone receptor-positive breast cancer

Author

Lorenzo Gerratana, Matteo Lambertini, Filippo Montemurro, Mario Giuliano, Sabino De Placido, Lucia Del Mastro, Fabio Puglisi, Luca Boni, G. Colantuoni, Teresa Gamucci, A. Turletti, Andrea Ardizzoni, Giancarlo Bisagni, Antonio Durando, Adriano Gravina, Ornella Garrone, Michelino De Laurentiis, Stefania Russo, Francesco Cognetti, Marcello Ceppi, Claudia Bighin, Puglisi F., Gerratana L., Lambertini M., Ceppi M., Boni L., Montemurro F., Russo S., Bighin C., De Laurentiis M., Giuliano M., Bisagni G., Durando A., Turletti A., Garrone O., Ardizzoni A., Gamucci T., Colantuoni G., Gravina A., De Placido S., Cognetti F., Del Mastro L., Puglisi, Fabio, Gerratana, Lorenzo, Lambertini, Matteo, Ceppi, Marcello, Boni, Luca, Montemurro, Filippo, Russo, Stefania, Bighin, Claudia, De Laurentiis, Michelino, Giuliano, Mario, Bisagni, Giancarlo, Durando, Antonio, Turletti, Anna, Garrone, Ornella, Ardizzoni, Andrea, Gamucci, Teresa, Colantuoni, Giuseppe, Gravina, Adriano, De Placido, Sabino, Cognetti, Francesco, and Del Mastro, Lucia

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Dose-dense chemotherapy, GIM2, medicine.drug_class, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, Progesterone receptor, medicine, Pharmacology (medical), Radiology, Nuclear Medicine and imaging, RC254-282, Proportional hazards model, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 030104 developmental biology, Quartile, Estrogen, Hormone receptor, Outcomes research, 030220 oncology & carcinogenesis, Number needed to treat, business
Abstract

The GIM2 phase III trial demonstrated the benefit of dose-dense chemotherapy in node-positive early breast cancer (eBC). To better define the dose-dense effect in the hormone receptor-positive subgroup, we evaluated its benefit through a composite measure of recurrence risk. We conducted an ancillary analysis of the GIM2 trial evaluating the absolute treatment effect through a composite measure of recurrence risk (CPRS) in patients with hormone receptor-positive HER2-negative eBC. CPRS was estimated through Cox proportional hazards models applied to the different clinicopathological features. The treatment effect was compared to the values of CPRS by using the Sub-population Treatment Effect Pattern Plot (STEPP) process. The Disease-Free Survival (DFS)-oriented STEPP analysis showed distinct patterns of relative treatment effect with respect to CPRS. Overall, 5-year DFS differed across CPRS quartiles ranging from 95.2 to 66.4%. Each CPRS quartile was characterized by a different patients’ composition, especially for age, lymph node involvement, tumor size, estrogen and progesterone receptor expression, and Ki-67. A number needed to treat of 154 and 6 was associated with the lowest and the highest CPRS quartile, respectively. Dose-dense adjuvant chemotherapy showed a consistent benefit in node-positive eBC patients with hormone receptor-positive HER2-negative disease, but its effect varied according to CPRS.

Published
2021

21. Extended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: a multicentre, open-label, randomised, phase 3 trial

Author

Francesco Cognetti, Riccardo Ponzone, Mauro Mansutti, Giovanni Sanna, Matteo Lambertini, Lucia Del Mastro, Gruppo Italiano Mammella investigators, Antonio Durando, Silvia Mura, Fabio Puglisi, Stefano Tamberi, Alberto Ballestrero, Francesca Poggio, Grazia Arpino, Paolo Bruzzi, Giancarlo Bisagni, Ornella Garrone, Enrico Campadelli, Sabino De Placido, Andrea Michelotti, Ylenia Urracci, Claudia Bighin, Stefania Gori, Filippo Montemurro, Laura Amaducci, Carla Barone, Alessandra Fabi, Antonio Frassoldati, G. Moretti, Del Mastro, L., Mansutti, M., Bisagni, G., Ponzone, R., Durando, A., Amaducci, L., Campadelli, E., Cognetti, F., Frassoldati, A., Michelotti, A., Mura, S., Urracci, Y., Sanna, G., Gori, S., De Placido, S., Garrone, O., Fabi, A., Barone, C., Tamberi, S., Bighin, C., Puglisi, F., Moretti, G., Arpino, G., Ballestrero, A., Poggio, F., Lambertini, M., Montemurro, F., and Bruzzi, P.

Subjects
Selective Estrogen Receptor Modulators, medicine.medical_specialty, Time Factors, Time Factor, medicine.drug_class, Population, Selective Estrogen Receptor Modulator, Context (language use), Antineoplastic Agents, Breast Neoplasms, Disease-Free Survival, Drug Administration Schedule, Antineoplastic Agent, Breast cancer, Internal medicine, Clinical endpoint, Aromatase Inhibitor, Medicine, Humans, education, Mastectomy, Aged, Neoplasm Staging, education.field_of_study, Aromatase inhibitor, business.industry, Aromatase Inhibitors, Letrozole, Hazard ratio, Middle Aged, medicine.disease, Postmenopause, Tamoxifen, Oncology, Italy, Female, business, Breast Neoplasm, Human, medicine.drug
Abstract

Summary Background The benefit of extending aromatase inhibitor therapy beyond 5 years in the context of previous aromatase inhibitors remains controversial. We aimed to compare extended therapy with letrozole for 5 years versus the standard duration of 2–3 years of letrozole in postmenopausal patients with breast cancer who have already received 2–3 years of tamoxifen. Methods This multicentre, open-label, randomised, phase 3 trial was done at 69 hospitals in Italy. Women were eligible if they were postmenopausal at the time of study entry, had stage I–III histologically proven and operable invasive hormone receptor-positive breast cancer, had received adjuvant tamoxifen therapy for at least 2 years but no longer than 3 years and 3 months, had no signs of disease recurrence, and had an Eastern Cooperative Oncology Group performance status of 2 or lower. Patients were randomly assigned (1:1) to receive 2–3 years (control group) or 5 years (extended group) of letrozole (2·5 mg orally once a day). Randomisation, with stratification by centre, with permuted blocks of size 12, was done with a centralised, interactive, internet-based system that randomly generated the treatment allocation. Participants and investigators were not masked to treatment assignment. The primary endpoint was invasive disease-free survival in the intention-to-treat population. Safety analysis was done for patients who received at least 1 month of study treatment. This trial was registered with EudraCT, 2005-001212-44, and ClinicalTrials.gov, NCT01064635. Findings Between Aug 1, 2005, and Oct 24, 2010, 2056 patients were enrolled and randomly assigned to receive letrozole for 2–3 years (n=1030; control group) or for 5 years (n=1026; extended group). After a median follow-up of 11·7 years (IQR 9·5–13·1), disease-free survival events occurred in 262 (25·4%) of 1030 patients in the control group and 212 (20·7%) of 1026 in the extended group. 12-year disease-free survival was 62% (95% CI 57–66) in the control group and 67% (62–71) in the extended group (hazard ratio 0·78, 95% CI 0·65–0·93; p=0·0064). The most common grade 3 and 4 adverse events were arthralgia (22 [2·2%] of 983 patients in the control group vs 29 [3·0%] of 977 in the extended group) and myalgia (seven [0·7%] vs nine [0·9%]). There were three (0·3%) serious treatment-related adverse events in the control group and eight (0·8%) in the extended group. No deaths related to toxic effects were observed. Interpretation In postmenopausal patients with breast cancer who received 2–3 years of tamoxifen, extended treatment with 5 years of letrozole resulted in a significant improvement in disease-free survival compared with the standard 2–3 years of letrozole. Sequential endocrine therapy with tamoxifen for 2–3 years followed by letrozole for 5 years should be considered as one of the optimal standard endocrine treatments for postmenopausal patients with hormone receptor-positive breast cancer. Funding Novartis and the Italian Ministry of Health. Translation For the Italian translation of the abstract see Supplementary Materials section.

Published
2021

22. Tumor-infiltrating lymphocytes and molecular response after neoadjuvant therapy for HR+/HER2− breast cancer: results from two prospective trials

Author

Maria Vittoria Dieci, Aicha Goubar, Giancarlo Bisagni, Gaia Griguolo, Daniele Generali, Valentina Guarneri, A. Michelotti, Antonio Frassoldati, Rossana Berardi, Fabio Puglisi, Guido Ficarra, Katia Cagossi, Federico Piacentini, Giuseppe Luigi Banna, Pierfranco Conte, Luigi Cavanna, Dieci, M. V., Frassoldati, A., Generali, D., Bisagni, G., Piacentini, F., Cavanna, L., Cagossi, K., Puglisi, F., Michelotti, A., Berardi, R., Banna, G., Goubar, A., Ficarra, G., Griguolo, G., Conte, P., and Guarneri, V.

Subjects
0301 basic medicine, Oncology, Cancer Research, Receptor, ErbB-2, medicine.medical_treatment, Tumor-infiltrating lymphocytes, law.invention, ErbB-2, 0302 clinical medicine, Randomized controlled trial, law, Chemotherapy, Endocrine therapy, Ki67, Neoadjuvant, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Breast Neoplasms, Chemotherapy, Adjuvant, Female, Humans, Lymphocytes, Tumor-Infiltrating, Middle Aged, Neoadjuvant Therapy, Nitriles, Prospective Studies, Quinazolines, Receptors, Cell Surface, Treatment Outcome, Triazoles, Receptors, 80 and over, Lymphocytes, Prospective cohort study, Adjuvant, Neoadjuvant therapy, Tumor, 030220 oncology & carcinogenesis, Letrozole, Cell Surface, Cohort, Nitrile, Breast Neoplasm, Human, Receptor, medicine.drug, medicine.medical_specialty, Socio-culturale, Tumor-infiltrating lymphocyte, Lapatinib, 03 medical and health sciences, Breast cancer, Internal medicine, medicine, Tumor-Infiltrating, Antineoplastic Combined Chemotherapy Protocol, business.industry, Quinazoline, medicine.disease, Prospective Studie, 030104 developmental biology, Triazole, business, Biomarkers
Abstract

PURPOSE: The aim was to evaluate the role of tumor-infiltrating lymphocytes (TIL) in predicting molecular response after preoperative endocrine or cytotoxic treatment for HR+/HER2- patients who do not achieve a pathological complete response. METHODS: Stromal (Str) TIL were centrally evaluated on samples from diagnostic core-biopsies of HR+/HER2- patients included in two prospective randomized trials: the LETLOB trial (neoadjuvant endocrine-based treatment) and the GIOB trial (neoadjuvant chemotherapy-based treatment). Pre- and post-treatment Ki67 was centrally assessed. RESULTS: StrTIL were evaluable in 111 cases (n = 73 from the LETLOB trial and n = 38 from the GIOB trial). Median StrTIL was 2%. Patients with high StrTIL (StrTIL ≥10%, n = 28) had more frequently breast cancer of ductal histology (p = 0.02), high grade (p = 0.049), and high Ki67 (p = 0.02). After neoadjuvant endocrine treatment (LETLOB cohort), a significant Ki67 suppression (p < 0.01) from pre- to post-treatment was observed in both the low and high StrTIL groups. High StrTIL patients achieve more frequently a relative Ki67 suppression ≥50% from baseline as compared to low StrTIL patients (55 vs. 35%, p non significant). After neoadjuvant chemotherapy (GIOB cohort), a significant Ki67 suppression was observed only for low StrTIL patients (Wilcoxon p = 0.001) and not in the high StrTIL group (p = 0.612). In this cohort, the rate of patients achieving a relative Ki67 suppression ≥50% from baseline was significantly higher in the low vs high StrTIL group (64% vs 10%, p = 0.003). Geometric mean Ki67 suppression was evaluated in each cohort according to StrTIL: the lowest value (-41%) was observed for high StrTIL cases treated with chemotherapy. CONCLUSIONS: This hypothesis-generating study suggests that in HR+/HER2- breast cancer StrTIL at baseline may influence the achievement of a molecular response after neoadjuvant treatment. Further evaluation in large studies is needed, and interaction with the type of treatment warrants to be explored.

Published
2017
Full Text
View/download PDF

23. Validation of the AJCC prognostic stage for HER2-positive breast cancer in the ShortHER trial

Author

Gaia Griguolo, Maria Vittoria Dieci, Roberto D'Amico, Samanta Sarti, R. Vicini, Luigi Cavanna, Claudio Zamagni, Anita Rimanti, Ornella Garrone, Alessandra Beano, S. Danese, Antonio Frassoldati, Alba A. Brandes, Francesco Giotta, Viviana Bazan, Michele Aieta, Katia Cagossi, Maria Pia Foschini, L. Amaducci, Antonella Ferro, Federico Piacentini, Sante Romito, Michela Donadio, Vittorio Gebbia, Valentina Guarneri, Pierfranco Conte, Anna Rita Gambaro, Sara Balduzzi, G. Moretti, Giancarlo Bisagni, Hector Soto Parra, Antonino Musolino, Dieci M.V., Bisagni G., Brandes A.A., Frassoldati A., Cavanna L., Giotta F., Aieta M., Gebbia V., Musolino A., Garrone O., Donadio M., Rimanti A., Beano A., Zamagni C., Soto Parra H., Piacentini F., Danese S., Ferro A., Cagossi K., Sarti S., Gambaro A.R., Romito S., Bazan V., Amaducci L., Moretti G., Foschini M.P., Balduzzi S., Vicini R., D'Amico R., Griguolo G., Guarneri V., and Conte P.F.

Subjects
Oncology, Settore MED/06 - Oncologia Medica, medicine.medical_treatment, lcsh:Medicine, Antineoplastic Agents, Immunological, 0302 clinical medicine, Breast cancer, Trastuzumab, Antineoplastic Combined Chemotherapy Protocols, 8th AJCC, 030212 general & internal medicine, Stage (cooking), HER2-positive, Prognostic stage, General Medicine, Middle Aged, Prognosis, Immunological, Local, 030220 oncology & carcinogenesis, Female, Research Article, medicine.drug, Adult, medicine.medical_specialty, Randomization, Socio-culturale, Antineoplastic Agents, Breast Neoplasms, Disease-Free Survival, 03 medical and health sciences, Internal medicine, medicine, Adjuvant therapy, Humans, erbB-2, Aged, Neoplasm Staging, Cancer staging, Chemotherapy, business.industry, lcsh:R, Cancer, Genes, erbB-2, medicine.disease, HER2-positive, Breast cancer, Trastuzumab, Prognostic stage, 8th AJCC, Neoplasm Recurrence, Genes, Neoplasm Recurrence, Local, business
Abstract

Background The 8th edition of the American Joint Committee on Cancer (AJCC) staging has introduced prognostic stage based on anatomic stage combined with biologic factors. We aimed to validate the prognostic stage in HER2-positive breast cancer patients enrolled in the ShortHER trial. Methods The ShortHER trial randomized 1253 HER2-positive patients to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. Patients were classified according to the anatomic and the prognostic stage. Distant disease-free survival (DDFS) was calculated from randomization to distant relapse or death. Results A total of 1244 patients were included. Compared to anatomic stage, the prognostic stage downstaged 41.6% (n = 517) of patients to a more favorable stage category. Five-year DDFS based on anatomic stage was as follows: IA 96.6%, IB 94.1%, IIA 92.4%, IIB 87.3%, IIIA 81.3%, IIIC 70.5% (P P P = 0.975). Within anatomic stage I, the outcome was similar for patients treated with 9 weeks or 1 year trastuzumab (5-year DDFS 96.2% and 96.6%, P = 0.856). Within prognostic stage I, the outcome was numerically worse for patients treated with 9 weeks trastuzumab (5-year DDFS 93.7% and 96.3%, P = 0.080). Conclusions The prognostic stage downstaged 41.6% of patients, while maintaining a similar prognostic performance as the anatomic stage. The prognostic stage is valuable in counseling patients and may serve as reference for a clinical trial design. Our data do not support prognostic stage as guidance to de-escalate treatment. Trial registration EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.

Published
2019

24. Role of immunoglobulin G fragment C receptor polymorphism-mediated antibody-dependant cellular cytotoxicity in colorectal cancer treated with cetuximab therapy

Author

Nadia Naldi, Tauro Maria Neri, A. Zerbini, Diletta Laccabue, Roberta Camisa, Fotios Loupakis, N. Chernyschova, Gabriele Missale, Beatrice Bortesi, Francesca Negri, Annamaria Ruzzo, Antonino Musolino, Andrea Ardizzoni, Giancarlo Bisagni, Negri, F.V, Musolino, A., Naldi, N., Bortesi, B., Missale, G., Laccabue, D., Zerbini, A., Camisa, R., Chernyschova, N., Bisagni, G., Loupakis, F., Ruzzo, A., Neri, T.M., and Ardizzoni, A.

Subjects
Male, Colorectal cancer, Cetuximab, Predictive Value of Test, Colorectal Neoplasm, Immunoglobulin G, Antineoplastic Agent, Antineoplastic Combined Chemotherapy Protocols, Genotype, Medicine, Epidermal growth factor receptor, Aged, 80 and over, Antibody-dependent cell-mediated cytotoxicity, biology, hemic and immune systems, Middle Aged, Treatment Outcome, Monoclonal, Molecular Medicine, Female, Antibody, Colorectal Neoplasms, Human, medicine.drug, Adult, Antineoplastic Agents, Antibodies, Monoclonal, Humanized, Disease-Free Survival, FcγR polymorphism, Genetic, Predictive Value of Tests, Genetics, Humans, neoplasms, Aged, Pharmacology, Antineoplastic Combined Chemotherapy Protocol, Polymorphism, Genetic, business.industry, Receptors, IgG, Antibody-Dependent Cell Cytotoxicity, medicine.disease, digestive system diseases, Immunology, Leukocytes, Mononuclear, biology.protein, antibody-dependant cellular cytotoxicity, business
Abstract

Antibody-dependent cellular cytotoxicity (ADCC), which is activated by effector cells via immunoglobulin G (IgG) fragment C receptors (FcRs), was proposed as a mechanism of cetuximab efficacy. Peripheral blood mononuclear cells (PBMCs) from 23 healthy donors and 13 patients with metastatic colorectal cancer (mCRC) treated with cetuximab were tested for FcγR polymorphisms and cetuximab-mediated ADCC. ADCC was measured by chromium-51 release on a epidermal growth factor receptor (EGFR)-positive human colon cancer cell line. Overall, 86 mCRC patients were genotyped for study purposes. PBMCs harbouring the FcγRIIIa 158 V/V genotype had a significantly higher cetuximab-mediated ADCC. No correlation was found between FcγR polymorphisms and response rate or time to progression after cetuximab-based therapy. Despite the in vitro analysis showing that the FcγRIIIa 158 V/V genotype is associated with higher ADCC, clinical data do not support a predictive role of FcγRIIIa polymorphisms in mCRC treated with cetuximab. © 2014 Macmillan Publishers Limited All rights reserved.

Published
2013
Full Text
View/download PDF

25. Immunoglobulin G fragment C receptor polymorphisms and efficacy of preoperative chemotherapy plus trastuzumab and lapatinib in HER2-positive breast cancer

Author

Nadia Naldi, Katia Cagossi, Federico Piacentini, Daniela Boggiani, Antonino Musolino, Daniele Zanoni, Luca Gianni, Daniele Generali, Anita Rimanti, Pierfranco Conte, P. Sgargi, Maria Vittoria Dieci, Valentina Guarneri, Massimo Ambroggi, Samanta Sarti, Giancarlo Bisagni, Andrea Ardizzoni, Musolino, GIUSEPPE ANTONIO, Naldi, N., Dieci, M. V., Zanoni, D., Rimanti, A., Boggiani, D., Sgargi, P., Generali, Daniele, Piacentini, F., Ambroggi, M., Cagossi, K., Gianni, L., Sarti, S., Bisagni, G., Ardizzoni, A., Conte, P. F., Guarneri, V., Musolino, A, Generali, D. G., and Ardizzoni, Andrea

Subjects
0301 basic medicine, Oncology, Time Factors, Pharmacogenomic Variants, Receptor, ErbB-2, Pharmacology, Immunoglobulin G, 0302 clinical medicine, Gene Frequency, Trastuzumab, HER2 Positive Breast Cancer, Antineoplastic Combined Chemotherapy Protocols, Preoperative chemotherapy, skin and connective tissue diseases, Receptor, Mastectomy, Randomized Controlled Trials as Topic, biology, Middle Aged, Neoadjuvant Therapy, Phenotype, Treatment Outcome, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Molecular Medicine, Female, medicine.drug, Adult, medicine.medical_specialty, Genotype, Genetics, Breast Neoplasms, Lapatinib, Polymorphism, Single Nucleotide, Disease-Free Survival, 03 medical and health sciences, Breast cancer, Clinical Trials, Phase II as Topic, Genetic, Internal medicine, mental disorders, medicine, Biomarkers, Tumor, Humans, neoplasms, Protein Kinase Inhibitors, Aged, Retrospective Studies, business.industry, Receptors, IgG, medicine.disease, Molecular medicine, Pharmacogenomic Testing, 030104 developmental biology, Pharmacogenetics, biology.protein, Quinazolines, business
Abstract

Lapatinib enhances antibody-dependent cell-mediated cytotoxicity (ADCC) activity of trastuzumab. FcγR polymorphisms have been associated with both ADCC and clinical activity of trastuzumab in HER2+ breast cancer (BC) patients (pts). We analyzed FcγRIIa-H131R and FcγRIIIa-V158F polymorphisms in the CHER-LOB trial population of HER2+ BCs treated with preoperative chemotherapy plus trastuzumab (arm A), lapatinib (arm B) or both (arm C). Genotyping was successfully performed in 73/121 (60%) pts. A significant improvement in pathological complete response (pCR) rate was observed for the combination arm C, but only in FcγRIIIa V allele carriers (C vs A, 67 vs 27%, P=0.043; C vs B, 67 vs 22%, P=0.012). An independent interaction between arm C and FcγRIIIa V allele was found for pCR (odds ratio=9.4; 95% confidence interval, 2.3-39.6; P=0.003). No significant associations were observed between pCR and FcγRIIa polymorphism, and between pre-treatment tumor-infiltrating lymphocytes and FcγR polymorphisms. Our study provides evidence for a FcγRIIIa V allele-restricted pCR benefit from neoadjuvant trastuzumab plus lapatinib in HER2+ BC.

Published
2016

26. The Breast Avastin Trial: Phase II study of bevacizumab maintenance therapy after induction chemotherapy with docetaxel and capecitabine for the first-line treatment of patients with locally recurrent or metastatic breast cancer

Author

Giancarlo Bisagni, A. De Matteis, Antonino Musolino, Teresa Gamucci, Rodolfo Passalacqua, Michele Panebianco, G. Moretti, Andrea Ardizzoni, Francesco Nuzzo, R. Gnoni, Stefania Gori, Corrado Boni, Bisagni, G, Musolino, A., Panebianco, M., De Matteis, A., Nuzzo, F., Ardizzoni, A., Gori, S., Gamucci, T., Passalacqua, R., Gnoni, R., Moretti, G., and Boni, C.

Subjects
Oncology, Cancer Research, genetic structures, Docetaxel, Toxicology, Deoxycytidine, Maintenance therapy, Antineoplastic Combined Chemotherapy Protocols, polycyclic compounds, Pharmacology (medical), Neoplasm Metastasis, skin and connective tissue diseases, First-line chemotherapy, Trial Phase, Middle Aged, Metastatic breast cancer, Bevacizumab, Neoplasm Metastasi, Angiogenesi, Taxoids, Female, Fluorouracil, Breast Neoplasm, medicine.drug, Human, Adult, medicine.medical_specialty, Breast Neoplasms, Antibodies, Monoclonal, Humanized, Capecitabine, Therapeutic approach, Internal medicine, Taxoid, medicine, Humans, neoplasms, Aged, Pharmacology, Antineoplastic Combined Chemotherapy Protocol, business.industry, Induction chemotherapy, medicine.disease, eye diseases, Patient Compliance, Neoplasm Recurrence, Local, business
Abstract

Background: Therapeutic approach for patients with metastatic breast cancer (MBC) is still controversial. This study was conducted to assess the efficacy and safety of bevacizumab in combination with docetaxel plus capecitabine as first-line treatment for MBC. The feasibility of bevacizumab maintenance therapy in this setting was also evaluated. Patients and methods: In this single-arm, multicenter phase II study, patients received bevacizumab 15 mg/kg and docetaxel 60 mg/m2 on day 1, plus capecitabine 900 mg/m2 twice daily on days 1-14 every 21 days. Treatment was administered for up to 6 cycles, then bevacizumab continued until progressive disease. The primary end point was progression-free survival (PFS); secondary end points were tumor response rate, overall survival, and toxicity. Results: Seventy-nine eligible patients were treated with bevacizumab in combination with docetaxel plus capecitabine. The overall response rate was 61 %, with a complete response rate of 8 % and a median duration of response of 10 months. At a median follow-up of 28 months, the median PFS was 11 months. Fifty-two (65 %) patients received bevacizumab maintenance therapy for a median duration of 7 months (range 1 to 33+). Neutropenia was the most common grade 3-4 toxicity (28.1 % of patients), and two fatal adverse events occurred (septic shock and gastrointestinal perforation). Conclusions: Bevacizumab in combination with docetaxel and capecitabine demonstrates significant activity and quite acceptable toxicity profile as first-line treatment of MBC. Subsequent maintenance therapy with bevacizumab is feasible for a long period of stable disease. Results deserve confirmation. © 2013 Springer-Verlag Berlin Heidelberg.

Published
2013

27. Evaluation of HER-2/neu amplification and other biological markers as predictors of response to neoadjuvant anthracycline-based chemotherapy in primary breast cancer: the role of anthracycline dose intensity

Author

Eugenia Martella, Cecilia Bozzetti, Rita Nizzoli, Cristina Bassano, Costanza Lagrasta, Roberta Camisa, Marcella Flora, Giancarlo Bisagni, Antonino Musolino, Francesco Leonardi, Andrea Ardizzoni, Giorgio Cocconi, Nicola Personeni, Bozzetti C, Musolino A, Camisa R, Bisagni G, Flora M, Bassano C, Martella E, Lagrasta C, Nizzoli R, Personeni N, Leonardi F, Cocconi G, and Ardizzoni A

Subjects
Oncology, Adult, Cancer Research, medicine.medical_specialty, Anthracycline, medicine.medical_treatment, Breast Neoplasms, Breast cancer, Predictive Value of Tests, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Medicine, Humans, Doxorubicin, Anthracyclines, Aged, Retrospective Studies, Biologic marker, Aged, 80 and over, Univariate analysis, Chemotherapy, medicine.diagnostic_test, Dose-Response Relationship, Drug, business.industry, Gene Amplification, Genes, erbB-2, Middle Aged, medicine.disease, Prognosis, Neoadjuvant Therapy, anthracyclines, breast cancer, HER2/neu, neoadjuvant chemotherapy, Ki-67 Antigen, Treatment Outcome, Multivariate Analysis, Female, business, medicine.drug, Epirubicin, Fluorescence in situ hybridization
Abstract

OBJECTIVES The value of HER-2/neu status as a predictor of response to anthracycline-based chemotherapy is still a matter of debate. We evaluated the contribution of HER-2/neu gene amplification and other biologic markers in predicting response to different doses of neoadjuvant anthracycline-based chemotherapy. METHODS Clinical and pathologic records of 115 primary breast cancer patients were reviewed. Forty-eight and 67 patients received high (doxorubicin > or =20 mg/m2/wk; epirubicin > or =30 mg/m2/wk) and moderate-low anthracycline dose intensity regimens, respectively. Pathologic diagnosis, hormonal receptor status (HR), Ki67, and HER-2/neu status were assessed on tumor samples before neoadjuvant chemotherapy. HER-2/neu was determined by fluorescence in situ hybridization (FISH). RESULTS HER-2/neu amplification was observed in 29/115 (25%) tumors, 18 from moderate-low-dose and 11 from high-dose group. In the univariate analysis, a high Ki67 index (> or =20%) and positive clinical axillary nodes were predictive of an objective tumor response (P = 0.033 and 0.001, respectively). In the multivariate analysis, Ki67 was the only factor predictive of response (OR = 3.08, 95% CI = 1.1-8.5, P = 0.03). HER-2/neu status was not a factor in predicting objective response to different anthracycline dose intensities. The same finding was observed with regards to HR and Ki67. CONCLUSIONS In our series, no significant dose-response relationship was found according to HER-2/neu status.

Published
2006

Catalog

Books, media, physical & digital resources
See catalog results