Benefit from anthracyclines in relation to biological profiles in early breast cancer

Abstract

There are no validated predictors of benefit from anthracyclines. We compared cyclophosphamide, methotrexate, 5-fluorouracil (CMF), and epirubicin in different sequences with CMF alone in a phase III trial on operable breast cancers. Outcomes were analyzed in relation to tumor biological profiles to identify potential predictors of the efficacy of different treatments/drug combinations. Patients with N- or 1-3N+ tumors, were randomized to receive (a) epirubicin (4 cycles) followed by CMF (4 cycles); (b) CMF (4 cycles) followed by epirubicin (4 cycles), or (c) CMF (6 cycles) alone. Immunohistochemical assessments of estrogen (ER) and progesterone (PgR) receptors, HER2 and Ki67 were available for 705 patients (arm A/B/C: 276/269/160). Prognostic and predictive relevance was analyzed by log-rank tests and Cox models. Ki67 > 20 % and absent/low expression of ER and PgR were associated with worsen disease-free (DFS) and overall survival (OS). In patients with triple negative tumors (ER-, PgR-, HER2-), epirubicin-containing regimens yielded better DFS (HR 0.33, 95 % CI 0.17-0.62, P = 0.0007) and OS (HR 0.24, 95 % CI 0.10-0.57, P = 0.001) compared with CMF alone, whereas no differences were found in patients with HER2-positive (HER2+, ER-, PgR-) subtype. Treatment by subtype interaction (HER2-positive vs. others) was significant for DFS (χ (2) = 6.72, P = 0.009). In triple unfavorable (ER-, PgR-, Ki67 > 20 %) tumors, the use of epirubicin yielded better DFS (HR 0.45,95 % CI 0.26-0.78, P = 0.005) and OS (HR 0.30, 95 % CI 0.15-0.63, P = 0.001). Epirubicin-containing regimens seem to be superior to CMF alone in patients with highly proliferating, triple negative or triple unfavorable tumors.

Time to initiation of adjuvant chemotherapy in patients with rapidly proliferating early breast cancer

“…Finally, because of the potentially confounding effects of inter-and intracenter sources of variation in the data, a final check was performed on 200 cases. More than 90% agreement was observed between the results of two independent IRST observers, as previously reported [10].…”

“…This study was a secondary analysis of a prospective, randomised, multicentre, open label phase III trial comparing the efficacy of three treatment arms in patients with rapidly proliferating EBC, that had previously been reported [9,10]. The study was approved by the institutional review boards of each participating centre and has been registered as a National Cancer Institute trial (NCT01031030).…”

The impact of progesterone receptor expression on prognosis of patients with rapidly proliferating, hormone receptor-positive early breast cancer: apost hocanalysis of the IBIS 3 trial

“…Biomarker determination ER and PgR receptors were assessed at each participating center by IHC with different platforms and antibody clones, as previously reported, 10,13 and semiquantitatively quantified as the percentage of immunopositive tumor cells out of the total number of tumor cells. Tumors with ⩾10% immunopositive cells were considered positive, as in most studies published in the period when the present study was carried out.…”

Androgen and oestrogen receptors as potential prognostic markers for patients with ductal carcinoma in situ treated with surgery and radiotherapy

“…) has helped to better define disease aggressiveness and to identify tumours responding differently to conventional treatments (Rocca et al . ).…”

“…The discovery of biological subgroups of lesions such as triple negative (oestrogen receptor [ER]‐, progesterone receptor [PgR]‐, human epidermal growth factor receptor 2 [HER2]‐) or triple unfavourable (ER‐, PgR‐, Ki67 > 20%) (Rocca et al . ; Amadori et al . ) has helped to better define disease aggressiveness and to identify tumours responding differently to conventional treatments (Rocca et al .…”