title: Molecular oncology and the neoadjuvant setting: the perfect blend for treatment personalization and clinical trial design.
abstract: Breast cancer is a heterogeneous disease. Predictive molecular markers are crucial in patient management, but the only recommended predictive biomarkers are estrogen and progesterone receptors and HER2. There are many new targeted therapies, and although the target pathway expression is readily analyzed on conventional pathology, the dynamic response cannot be assessed and pathway expression is no guarantee it has a major driver role, even if mutated. Selecting therapies requires considering the patient, the molecular characteristics of the tumor, and the microenvironment of the tumor. Thus, the integration of molecular pathology, imaging, and early tumor biological response to therapy may provide evidence of drug activity and allow more rapid changes of therapy. The adaptive response of the tumor is a key resistance mechanism that can be assessed readily in the neoadjuvant setting. Although there are no markers that meet all surrogacy criteria, their use could provide crucial information on mechanisms of drug sensitivity/resistance. Validation of such markers requires a major emphasis on neoadjuvant trials to relate early-biomarker response to outcome.
authors: Unità Sperimentale di Patologia Mammaria, Centro di Medicina Molecolare, Istituti Ospitalieri di Cremona, Cremona 26100, Italy. daniele.generali@gmail.com
authors: Daniele
authors: D
authors: Generali
authors: Alfredo
authors: A
authors: Berruti
authors: Chiara
authors: C
authors: Foroni
authors: Letizia
authors: L
authors: Bazzola
authors: Daniele
authors: D
authors: Andreis
authors: Giovanni
authors: G
authors: Allevi
authors: Alessandra
authors: A
authors: Bersiga
authors: Luigi
authors: L
authors: Dogliotti
authors: Stephen B
authors: SB
authors: Fox
authors: Adrian L
authors: AL
authors: Harris
authors: Alberto
authors: A
authors: Bottini
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020360:Neoadjuvant Therapy / Q000379:methods*; D009360:Neoplastic Cells, Circulating; D057285:Precision Medicine / Q000379:methods / Q000639:trends; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015203:Reproducibility of Results; D012107:Research Design / Q000592:standards / Q000639:trends; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone