4. Discussion
toxicity, tumors, neutropenia, breast cancer
NEUTROPENIA, BREAST CANCER, DISEASE, SAID, BREAST TUMOR, TUMORS
Both TC-H (4 cycles of 3-weekly docetaxel (T) and cyclophosphamide (C) with 1 year of 3-weekly trastuzumab (H)), and P-H (12 weeks of weekly paclitaxel (P) and 1 year of 3-weekly trastuzumab (H)) are widely used in patients with lower-risk HER2-positive EBC [The primary objective of this study was to evaluate whether performing a future confirmatory trial with DFS or OS as the primary outcome would be feasible. The study confirmed the feasibility of doing such a trial, with 65% of oncologists approaching patients and 95% of patients received their treatment as per the arm of the study to which they were randomized. Unfortunately, to detect even a modest effect (e.g., hazard ratio of 0.80), assuming a 2-year DFS of 95% would require in excess of 5000 patients accrued and a study duration of at least 7 years. Hence, even though the majority of feasibility endpoints were met, this does not remove the barriers to performing such a trial. Use of other endpoints, such as toxicity or QOL, could allow a smaller and shorter study to be performed. Based on the data observed in this study, TC-H was associated with detrimental scores on FACT-T, FACT-G and FACT-F questionnaires, while early discontinuation of chemotherapy was more common in the P-H arm.The limitations of this study are recognized and include a small sample size, open-label design, and participation of patients from a single country. Patients had to complete multiple questionnaires during the study, which was arduous and time-consuming. It also restricts the study sample size to modest number of participants to keep the study feasible. It is also important to mention that the patient population did include some high-risk characteristics, such as node-positive disease and larger tumors. Overall, 16.8% of patients had node-positive disease and 1 patient had a 7 cm breast tumor. The increased rate of FN observed in the TC arm could also reflect the lower use of primary neutropenia prophylaxis than one would normally expect. It is, therefore, possible that great use of prophylaxis could have reduced the QOL differences between the two arms. Finally, as this was a feasibility trial, there will be a bias in accrual towards those physicians who truly believe in the study. That being said, 65% of medical oncologists among the three study sites who treat breast cancer, agreed to study participation, therefore, it reflects a high acceptance of the study proposal.In conclusion, the importance of comparing chemotherapy regimens in a real-world population with either lower-risk breast cancer or increased frailty, assessing the relative benefits and toxicity of a chosen chemotherapy regimen is essential, particularly in patients with low-risk HER2-positive disease, which are underrepresented in the pivotal randomized adjuvant trials [