Are we ready to change clinical practice after the 'soft and text' results?

Luminal breast cancer is the most common subtype among molecular subgroups of breast cancer identified by gene profiling, and it accounts for more than half of all breast cancer cases around the world [1]. These cancers are characterized by hormonal receptors and low proliferative activity; in particular Luminal A (high rate of estrogen and progesterone receptors, low proliferative index, low grading) is the breast cancer type with the best prognosis, while Luminal B can be further subclassified into two phenotypes, depending of the expression of HER2 (Luminal B HER2 positive or Luminal B HER2 negative). Luminal B is characterized by low rate of estrogen and progesterone receptors and high proliferative index. The breast cancer incidence has increased in the last years, especially among younger women. The treatment of premenopausal women involves all the problems correlated to fertility preservation, an important issue for every woman affected by cancer [2]. The gold standard treatment for premenopausal women with hormone receptors positive early breast cancer is tamoxifen for 5 years, with or without ovarian suppression, which has demonstrated a significant effect on overall survival and in the reduction of relapses [3]. However, the association of ovarian suppression with aromatase inhibitors has emerged as a valid alternative in the adjuvant setting for premenopausal patients. The Phase III Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT) trials conducted by the International Breast Cancer Study Group (IBCSG) in collaboration with the Breast International Group (BIG) and the North American Breast Cancer Group (NABCG), involved 4690 patients in 27 countries across 6 continents [4]. These researches demonstrated, for the first time, the superiority of exemestane in combination with the gonadotropin-releasing hormone analogue (GnRH-A) triptorelin, over tamoxifen plus ovarian suppression in the prevention of recurrence in young premenopausal women with hormone-sensitive early-stage breast cancer [4]. Exemestane and triptorelin treatment determined a decrease of 28% in the relative risk of developing a recurrence, with a disease-free survival at 5 years of 91.1%, compared with 87.3% in the tamoxifen group [4]. Despite the significant improvement in disease-free survival (DFS), an improvement in overall survival (OS) has not been demonstrated in the exemestane arm at a median follow-up of 5.7 years (68 months). The BIG1.98, ATAC and IES trials had previously confirmed the efficacy of aromatase inhibitors compared with tamoxifen in the adjuvant treatment of postmenopausal women in terms of risk of recurrence (range 15-25%) and distant metastases (around 27%) [5-7] and increased DFS, although no significant change in the OS and a small increase in cardiovascular risk were evidenced [5].