How the 70-gene tumour expression profile “MammaPrint” can assist in St Gallen 2009 treatment recommendations in 12 Italian hospitals

Background: The 70-gene tumor expression profile ‘‘MammaPrint’’ was established as a powerful predictor of disease outcome in breast cancer. The St Gallen 2009 recommendations include gene-expression signatures as an indicator for adjuvant therapy. Here we determined in an Italian cohort how the 70-gene profile could assist in patient management. Methods: Fresh tumor samples (n=584) from breast cancer patients (clinical T1-4N0- 3M0) aged 26 to 98 years (median age 63 years), were collected in 12 Italian hospitals IN 2008 and 2009 by core needle biopsy or from a surgical specimen (study protocol MP 090). We assessed agreement between the treatment advice as recommended by the 2009 St Gallen Highlights and classification according to the 70-gene MammaPrint profile. Results: According to the St Gallen 2009 treatment recommendations, 4 patients could forego any adjuvant treatment (<1cm, LN0, PVI 0). Of these patients, 3 were classified to be poor prognosis signature by MammaPrint. Another 17 patients with tumors <1cm, LN0, PVI- are ER+ and are recommended endocrine treatment, of whom 9 are MammaPrint high risk. The 126 Her2+ patients would be recommended anti-HER2 treatment as well as adjuvant chemotherapy according to the 2009 recommendations. Of these patients, 19 (15%) were classified as good prognosis signature by MammaPrint. All 47 (ER-) patients who are recommended chemotherapy alone are classified as poor prognosis by MammaPrint. For the 389 ER+, HER2- patients, 17 would be recommended no adjuvant chemotherapy (Grade I and LN0 and £2cm and ER >50%) and 198 would be recommended adjuvant chemotherapy being either Grade III, or 34LN, or >5cm, or ER <50%. Of these 215 patients, 73 (34%) are classified as low risk by MammaPrint. The remaining 174 ER+, HER2- patients fall in the subgroup for which St Gallen 2009 states that they have characteristics that are not useful for decision making; MammaPrint classified 101 (58%) as poor prognosis and 73 (42%) as good prognosis. Conclusion: For the majority (93%) of these 584 breast cancer patients from 12 Italian community hospitals, the St Gallen 2009 either recommends or suggests considering treatment with cytotoxic adjuvant therapy for whom MammaPrint indicates a low risk of recurrence in 30% of cases