Risk of treatment related death (TRD) with adjuvant chemotherapy for breast cancer: A study in University Malaya Medical Centre (UMMC)

Background: The risk of TRD with adjuvant chemotherapy for early breast cancer is unknown in Malaysia despite its widespread usage. This study aims to determine this rate in a large cohort of patients treated in UMMC. Patients & Methods: Patients who were treated with neoadjuvant or adjuvant chemotherapy for early breast cancer stages I, II or III from 2000-2007 in UMMC were identified from our UMMC Breast Cancer Registry. The TRD rate and 5 years overall survival (OS) were determined. TRD is defined as death occurring during or within 30 days of completing chemotherapy as a consequence of the chemotherapy treatment. OS was defined as death from any cause from the date of diagnosis to the date of death. OS was determined using the Kaplan-Meier method and differences between AJCC stages were compared by log-rank test. Results: A total of 1317 were identified for analysis. The median age at diagnosis was 49 years with a range of 24 to 74 years. The rate of TRD was 0.1%. The 5 years OS rate was 77.3% with a median follow up of 62 months. The 5 years OS according to AJCC stage were 90.7% for stage I, 83.9% for stage II and 62.2% for stage III disease. The commonest chemotherapy regimen used was the FEC (5-Fluorouracil, Epirubicin, Cyclophosphamide) regimen accounting for approximately 90% of the cases. Conclusion: Adjuvant chemotherapy for early breast cancer with the FEC regimen is safe with a TRD rate of 0.1% in our centre. Background The role of chemotherapy in cancer treatment is highly misunderstood not just in the public domain but also amongst medical practitioners. The fact that chemotherapy only plays a minor role as a definitive modality of cancer treatment is not well understood and it is mainly limited to haematological malignancies and germ cell tumours. Chemotherapy's role in the treatment of solid tumours is mainly confined to neoadjuvant, adjuvant and palliative settings. As such, it is of utmost importance to be cognizant to the rate of TRDs with chemotherapy other than being aware of its potential benefits when used in these settings. Informing patients that this risk is negligible or less than one percent which is the figure often quoted by clinicians may be inadequate as this gives the impression that it is extremely rare. Moreover less than 1% can mean anywhere between 1 in 1001, 1 in 10000, 1 in 100000, 1 in 1000000 and so forth. Patients deserve to fully understand the real risk of TRDs and equally important is the need for clinicians to realize that TRDs are much commoner than perceived. There are various definitions of TRD used in the literature. For the purpose of this study the TRD was defined as deaths that occurred less than or equal to 30 days after the last cycle of chemotherapy, death of which was due to the chemotherapy itself. This definition was chosen as it was commonly used in many reported phase 3 trials and it is the least ambiguous amongst all definitions encountered in the literature. One major drawback is the fact that it does not take into account deaths that may be related to the long term side effects of chemotherapy for example deaths due to cardiac events which is especially relevant for anthracycline drugs commonly used for breast cancer treatment. Having said that, it is very difficult to prove that these deaths are directly due to the effect of chemotherapy alone as there are frequently many other confounding factors. Breast cancer is the commonest cancer treated with adjuvant chemotherapy in Malaysia. A commonly used regimen is the FAC regime (5 Fluorouracil, Adriamycin, Cyclophosphamide). In a trial involving 1491 patients in node positive breast cancer patients post definitive surgery, 745 patients received adjuvant TAC (Docetaxel, Adriamycin, Cyclophosphamide) and 746 patients received FAC. The TRDs for the TAC group and FAC group was similar at 0.3%. (1). The commonest regime used in our center is the FEC regime (5 Fluorouracil, Epirubicin, Cyclophosphamide). A pivotal phase 3 study, PACS 01 trial compared the FEC regime for 6 cycles with the FEC-D regime (FEC3-Docetaxel3) involving 996 patients in the FEC arm and 1003 patients in the FEC-D arm. Although significant high rates of febrile neutropaenia at 8.4% and 11.2% were reported in the FEC and FEC-D arms respectively, there were no early TRDs. However, there was one delayed cardiac death in each