Retrospective analysis of the impact of anthracycline dose reduction and chemotherapy delays on the outcomes of early breast cancer molecular subtypes.

BACKGROUND: The objective of study was to determine the effect of anthracycline dose reduction and chemotherapy delays on 5-year overall survival in patients with stage I-III breast cancer, to establish the impact of molecular subtypes on the anthracycline modification effects and to analyze reasons for such chemotherapy scheme modifications.

METHODS: Medical records of patients with stage I-III breast cancer were reviewed. Inclusion criteria involved stage I- III breast carcinoma; radical surgery performed and 4 courses of AC regimen (doxorubicin and cyclophosphamide), or at least 6 courses of FAC regimen (fluorouracil, doxorubicin and cyclophosphamide) completed; no neoadjuvant chemotherapy applied; no taxane group medications administered; medical records maintain comprehensive data on treatment and follow-up. 5- year overall survival were analyzed using Kaplan-Meier and Cox proportional hazards models.

RESULTS: Significant 3.17 times higher death risk at 5 year period in patients who experienced anthracycline dose reduction compared with patients who did not experience any modifications was established (HR = 3.17, 95% CI 1.7-5.9, p < 0.001). Increased death risk in patients who experienced both chemotherapy dose reduction and treatment delays compared with patients who did not experience any modifications was also established (HR = 2.76, 95% CI 1.3-5.6, p < 0.05). 5- year overall survival was affected by anthracycline dose reduction by more than 15% in ER-HER2- group (80% v. 55.6%, p = 0.015), ER + HER2- group (90.7% v. 64.9%, p < 0.01) and ER+/-HER2+ group (100% v. 84.4%, p = 0.019). 5-year overall survival was affected by chemotherapy delays more than 2 cycles in ER-HER2- group (79.2% v. 51.4%, p = 0.002), ER + HER2- group (86.3% v. 58.8%, p = 0.014) and there was no difference in ER+/-HER2+ group. Main reasons for chemotherapy scheme modifications (in decreasing order) were the following: neutropenia, modifications with no objective medical reasons, thrombocytopenia, anaemia, fatigue, infection.

CONCLUSIONS: Anthracycline dose reduction in patients with stage I- III breast cancer were associated with higher mortality risk and significantly decreased 5- year absolute survival in all molecular subtypes. Chemotherapy delays alone were not associated with decreased survival only in HER2 positive subtype. The most common reason for dose reduction or chemotherapy delays was neutropenia.