title: Neoadjuvant Treatment Approach: The Rosetta Stone for Breast Cancer?
abstract: Breast cancer represents a heterogeneous group of diseases with varied biological features, behavior, and response to therapy; thus, management of breast cancer relies on the availability of robust predictive and prognostic factors to support therapy decision-making. Traditionally, neoadjuvant treatment for breast cancer was preserved for locally advanced, converting an inoperable to a surgical resectable cancer. Neoadjuvant trials, additionally, offer: 1) the opportunity to evaluate new treatment options in a faster way and with fewer patients than large adjuvant trials; 2) to identify and validate the prognostic and predictive value of a marker with its association with clinical outcome in relation to the administered treatment. In this setting, thanks to new, affordable technologies which help to detail the molecular profiles of tumors, new trial designs based on new target therapies, like window-of-opportunity, are also suggested, as they represent the chance to identify tumor sensitivity or to overcome tumor resistance to the treatment used, based on its interaction with tumor biology in early tumor stages. However, clinicians and researchers should pay particular attention: In this setting, the safety of patients is paramount, given the exposure of potentially curable patients to investigational agents with limited safety experience, the definition of the study population and the study design, such as adaptive strategies, should limit patient exposure to ineffective agents, and intensify safety monitoring in the course of the treatment. Here, issues related to outcome determination in breast cancer, including some critical points of view, are presented.
authors.affiliation: U.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy (DG, MA, CS, MMi, MRC, LZ, MF, FB, MMa, ABo); U.O. Oncologia Medica, Spedali Civili si Brescia, Brescia, Italy (VA, ES, ABe); Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy (FB, SS). d.generali@ospedale.cremona.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Generali
authors.affiliation: U.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy (DG, MA, CS, MMi, MRC, LZ, MF, FB, MMa, ABo); U.O. Oncologia Medica, Spedali Civili si Brescia, Brescia, Italy (VA, ES, ABe); Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy (FB, SS).
authors.forename: Mara
authors.initials: M
authors.lastname: Ardine
authors.affiliation: U.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy (DG, MA, CS, MMi, MRC, LZ, MF, FB, MMa, ABo); U.O. Oncologia Medica, Spedali Civili si Brescia, Brescia, Italy (VA, ES, ABe); Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy (FB, SS).
authors.forename: Carla
authors.initials: C
authors.lastname: Strina
authors.affiliation: U.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy (DG, MA, CS, MMi, MRC, LZ, MF, FB, MMa, ABo); U.O. Oncologia Medica, Spedali Civili si Brescia, Brescia, Italy (VA, ES, ABe); Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy (FB, SS).
authors.forename: Manuela
authors.initials: M
authors.lastname: Milani
authors.affiliation: U.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy (DG, MA, CS, MMi, MRC, LZ, MF, FB, MMa, ABo); U.O. Oncologia Medica, Spedali Civili si Brescia, Brescia, Italy (VA, ES, ABe); Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy (FB, SS).
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Cappelletti
authors.affiliation: U.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy (DG, MA, CS, MMi, MRC, LZ, MF, FB, MMa, ABo); U.O. Oncologia Medica, Spedali Civili si Brescia, Brescia, Italy (VA, ES, ABe); Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy (FB, SS).
authors.forename: Laura
authors.initials: L
authors.lastname: Zanotti
authors.affiliation: U.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy (DG, MA, CS, MMi, MRC, LZ, MF, FB, MMa, ABo); U.O. Oncologia Medica, Spedali Civili si Brescia, Brescia, Italy (VA, ES, ABe); Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy (FB, SS).
authors.forename: Michela
authors.initials: M
authors.lastname: Forti
authors.affiliation: U.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy (DG, MA, CS, MMi, MRC, LZ, MF, FB, MMa, ABo); U.O. Oncologia Medica, Spedali Civili si Brescia, Brescia, Italy (VA, ES, ABe); Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy (FB, SS).
authors.forename: Francesca
authors.initials: F
authors.lastname: Bedussi
authors.affiliation: U.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy (DG, MA, CS, MMi, MRC, LZ, MF, FB, MMa, ABo); U.O. Oncologia Medica, Spedali Civili si Brescia, Brescia, Italy (VA, ES, ABe); Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy (FB, SS).
authors.forename: Mario
authors.initials: M
authors.lastname: Martinotti
authors.affiliation: U.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy (DG, MA, CS, MMi, MRC, LZ, MF, FB, MMa, ABo); U.O. Oncologia Medica, Spedali Civili si Brescia, Brescia, Italy (VA, ES, ABe); Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy (FB, SS).
authors.forename: Vito
authors.initials: V
authors.lastname: Amoroso
authors.affiliation: U.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy (DG, MA, CS, MMi, MRC, LZ, MF, FB, MMa, ABo); U.O. Oncologia Medica, Spedali Civili si Brescia, Brescia, Italy (VA, ES, ABe); Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy (FB, SS).
authors.forename: Sandra
authors.initials: S
authors.lastname: Sigala
authors.affiliation: U.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy (DG, MA, CS, MMi, MRC, LZ, MF, FB, MMa, ABo); U.O. Oncologia Medica, Spedali Civili si Brescia, Brescia, Italy (VA, ES, ABe); Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy (FB, SS).
authors.forename: Edda
authors.initials: E
authors.lastname: Simoncini
authors.affiliation: U.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy (DG, MA, CS, MMi, MRC, LZ, MF, FB, MMa, ABo); U.O. Oncologia Medica, Spedali Civili si Brescia, Brescia, Italy (VA, ES, ABe); Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy (FB, SS).
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berruti
authors.affiliation: U.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy (DG, MA, CS, MMi, MRC, LZ, MF, FB, MMa, ABo); U.O. Oncologia Medica, Spedali Civili si Brescia, Brescia, Italy (VA, ES, ABe); Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy (FB, SS).
authors.forename: Alberto
authors.initials: A
authors.lastname: Bottini
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D017024:Chemotherapy, Adjuvant / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D020360:Neoadjuvant Therapy / Q000379:methods*; D017063:Outcome Assessment, Health Care / Q000379:methods*; D011379:Prognosis; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen