Maria Di Vita¹, Massimiliano Berretta ², Antonio Zanghi¹, Bruno Cacopardo³, Andrea Cavallaro⁴, Davide Lombardi ⁵, Emanuele Lo Menzo⁶, Alessandro Cappellani¹

1Department of Surgery , General Surgery and Breast Unit, University of Catania, Italy, ²Department of Medical Oncology, National Cancer Institute, I.R.C.C.S. Aviano (PN), ³Department of Internal Medicine and Medical Specialties, Section of Infectious Diseases, University of Catania, Italy, ⁴Department of Surgery, University of Catania, Italy, ⁵Breast Unit, National Cancer Institute,I.R.C.C.S. Aviano (PN), ⁶Division of Laparoscopic and Bariatric Surgery, University of Maryland, Baltimore, MD USA

TABLE OF CONTENTS

1. Abstract

2. Introduction

3. SCREENING

3.1. Genetic Markers

3.2. Estrogens

3.3. Cytokines

4. Pathological classification and biomarkers

5. The prognosis

5.1. St. Gallen's Classification

5.2. The Rotterdam 76-Gene set

5.3. Invasive Gene Signature

5.4. The wound response indicator

5.5. Oncotype DXTM

5.6. Mammaprint

5.7. The HER family

5.8. The BCL 2 family

5.9. uPA /PAI-1

5.10. TIMP

5.11. Chemokines

5.12. NHERF1/EBP50

5.13. p 27 and Skp2

5.14. p 27 and Skp2

5.15. Proliferative activity

6. Breast cancer and therapy

6.1. ER and PR

6.2. HER 2

6.2.1. HER 2 and endocrine therapies

6.2.2. Her 2 and chemotherapy

6.2.3. HER2 as a target for specific therapies

6.3. VEGF

6.4. Triple negative or basal-like breast cancer

6.5. Generic markers of treatment response

6.5.1. Circulating tumor cells

6.5.2. TOP 2A (Topoisomerase 2 Alpha)

6.5.3. Class III beta-tubulin isotype

6.5.4.Thymidine phosphorylase (TP)

6.5.5. HIF-1 (hypoxia-inducible factor-1)

6.5.6. betaIII-tubulin isoform

6.5.7. Other

7. Follow up and detection of recurrence

8. Conclusions

9. Acknowledgement

10. References

1. ABSTRACT

Molecular studies have definitely changed our knowledge of the biology of cancers, and breast cancer's tremendous social impact has stimulated a large mass of research. Classic markers have opened a road, but their usefulness appears limited to prognosis or follow up, while several new markers, both genetic and molecular, are assuming different, yet still controversial, importance: they may play a major role in the surveillance of subjects at risk, in detecting primary or recurrent cancers, and in predicting the need of adjuvant therapy, or the response to therapy.