Targeting the subtypes of breast cancer: rethinking investigational drugs.
BACKGROUND
The choice of adjuvant treatments for women with breast cancer is based on several features that take into account the heterogeneity of the disease. Questions raised during the decision process include the following: i) What leads to the use of endocrine therapy? ii) What leads to the use of anti-HER2 therapy? iii) What justifies the use of chemotherapy?


METHODS
Choices of adjuvant treatment are based on parameters defined by molecular characterization of breast cancer subtypes or by approximations to this classification using traditional clinical-pathological features. Clinicians should consider cases within the various distinct subpopulation in order to properly select the most 'personalized' adjuvant therapeutic approach. Sensitivity to chemotherapy and/or targeted agents in subtypes of breast cancers are predictable based on gene pathway alterations and associated gene products. This review covers several clinical data on several investigational agents for early-stage breast cancer molecular subtypes. We selected from literature data prospective Phase I, II and III clinical trials of chemotherapy (weekly or daily schedules), including indicators of activity and toxicity and data on survival/mortality.


CONCLUSIONS
The future of many investigational therapeutics in breast cancer is linked to our ability to identify the most druggable target in each subtype.
Division of Medical Oncology, Istituto Europeo di Oncologia, Via Ripamonti 435, 20141 Milano, Italia. giuseppe.curigliano@ieo.it
Giuseppe
G
Curigliano
Marzia
M
Locatelli
Luca
L
Fumagalli
Janaina
J
Brollo
Elisabetta
E
Munzone
Franco
F
Nolé
Carmen
C
Criscitiello
Aron
A
Goldhirsch
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015507:Drugs, Investigational / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
D015507:Drugs, Investigational; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human