Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, oestrogen receptor-positive breast cancer patients. Very late results of the ‘gruppo di ricerca per la chemio-ormonoterapia adiuvante (GROCTA)’ 01-Trial in early breast cancer

First, to evaluate whether the benefits of combined chemotherapy (CT) and Tamoxifen (T), previously documented in the GROCTA-01 Trial, were long-lasting and, second, to show whether ER or PgR levels could allow the identification of the patients who could benefit from T alone. 504 node-positive, ER-positive, women were randomly assigned to ten CT courses or to 5 years of T or to the combination of the two (CTT). Disease-free (DFS) and overall survival (OS) were the primary trial-endpoints. DFS data were updated in 75% of the patients and S data in 95% of them. Cox regression models were used to check for prognostic features to estimate hazard ratios for treatment comparisons and to test for possible interaction between variables and treatment effects. Interactions between treatments and ER or PgR median levels were studied with the sub-population treatment effect pattern plot (STEPP) methodology. After a median follow-up time of 21 years, the DFS and OS benefits, previously favouring T over CT, continued to be observed, even though they were more evident in the first 6–7 years. The CTT advantages of DFS and OS over T alone were also confirmed. However, the additional benefit was limited to the first 10–12 years as S curves crossed over afterwards. After STEPP analysis, neither ER nor PgR concentrations fully discriminated the patients who could benefit from T alone. Even after such a long follow-up time, we have demonstrated that T is an effective alternative to CT for node-positive, ER-positive, breast cancer patients, regardless of their actual menopausal status, and that the additional benefit, especially on late survival, provided by the addition of CT to this anti-oestrogen, was minimal.