Time-varying effect and long-term survival analysis in breast cancer patients treated with neoadjuvant chemotherapy

• Published in: British journal of cancer 2015-06, Vol.113 (1), p.30-36
• Main Authors: Baulies, S, Belin, L, Mallon, P, Senechal, C, Pierga, J-Y, Cottu, P, Sablin, M-P, Sastre, X, Asselain, B, Rouzier, R, Reyal, F
• Format: Article
• Language: English
• Subjects: 692/699/67/1059/99; 692/699/67/1347; 692/700/1750/1976; Adult; Aged; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - therapeutic use; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Breast Neoplasms - physiopathology; Cancer Research; Cancer therapies; Chemotherapy; Clinical Studies; clinical-study; Drug Resistance; Epidemiology; Female; Humans; Medical prognosis; Medical research; Medical screening; Middle Aged; Molecular Medicine; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Oncology; Prognosis; Survival Analysis; Tumors; Young Adult
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2015.174

Background: Recent studies have indicated the prognostic value of tumour subtype and pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). However these results were reported after a short follow-up and using a standard Cox model which could be unsatisfactory for time-dependent factors. In the present study, we identified the prognostic factors for long-term outcome after NAC, considering that they could have an inconstant impact over time. Methods: Prognostic factors from 956 consecutive breast cancer patients treated with NAC were identified and associated with long-term outcomes. We estimated survival by a time function multivariate Cox model regression and stratified by follow-up length. Results: The prognostic value of tumour histological grade and hormone receptors status varied as distant recurrence-free interval (DRFI) increased. The multivariate analysis identified the following significant prognostic factors: tumour size, N stage, clinical and pathological response to NAC, hormone receptors (HR) status and histological tumour grade. The ‘prognostic benefit’ of low-grade and positive-HR status decreased over the years. Thus, in the early years after cancer diagnosis, the hazard ratio of distant recurrences in patients with positive-HR status increased from 0.26 (95% CI 0.1–0.4) at 6 months to 2.2 (95% CI 1.3–3.7) at 120 months. The histological tumour grade followed a similar trend. The hazard ratio of grade III patients compared with grade I was 1.83 (95% CI 1.1–2.8) at 36 months and diminished over time to 0.70 (95% CI 0.4–1.3) at 120 months. This indicates that the risk of recurrence for positive-HR patients was 74% lower at 6 months compared with the negative-hormone receptor group, but 30% higher at 5 years and more than double at 10 years. High-grade tumours presented a risk of 83% in the earlier years decreasing to 30% at 10 years versus the low-grade group. Conclusion: From the present study, we conclude the importance of identifying time-dependent prognostic factors. Distant recurrence-free interval within women who receive NAC are influenced by achieving pCR and breast cancer subtype. Tumours with more aggressive biology have poorer survival during the first 5 years, but if they exceed this point their prognostic impact is no longer significant. Conversely, positive-HR patients remain at risk for distant recurrence for many years.