Sequencing of Chemotherapy and Radiation Therapy for Patients with Early Stage Breast Cancer: Updated Results of a Prospective Randomized Trial

Diana Stripp, MD
University of Pennsylvania Cancer Center
Last Modified: November 5, 2001

Presenter: Bellon, JR
Presenter's Affiliation: Harvard Medical School
Type of Session: Plenary


  • This study was designed to evaluate the optimal sequencing of radiation therapy and chemotherapy in early stage breast cancer patients treated initially with lumpectomy
  • The initial report with 5 yrs of follow-up showed for patients at substantial risk for systemic metastases, it is preferable to give a 12-week course of chemotherapy followed by radiation therapy, rather than radiation therapy followed by chemotherapy. Harris, JR et al, NEJM 1996
  • This presentation reports the long-term results of this prospective randomized trial with over 10 yrs of follow-up.

    Materials and Methods

  • This study included 244 patients with Stage I or II carcinoma of the breast presenting after lumpectomy.
  • Patients were randomized to receive a 12-week program of chemotherapy either before (CT-first arm) or following (RT-first arm) radiation therapy.
  • Median follow-up of surviving patients is now 135 months (range, 17-196). Ten patients were lost to follow-up at a median time of 76 months.


  • No statistically significant differences were seen between the CT-first and RT-first arms in time to failure, time to distant metastasis, or time to death.
  • The 25th percentile of distant failure was reached at 56 months in the CT-first arm compared with 37 months in the RT-first arm.
  • Treatment sequence was also not significant in proportional hazard models for either time to any failure (p=0.90) or time to distant failure (p=0.49).
  • Sites of first failure were also similar between the arms.
  • Both lower T stage and negative nodal status predict decreased local and distant recurrences.

    Author's Conclusions

  • At 10+ yrs of follow up, results of this randomized trial show no significant differences between the CT-first and RT-first arms in any endpoint studied.
  • This differs from the initial results which showed a higher percent of distant failure in the RT-first arm and a higher percent of local failure in the CT-first arm.
  • Local failure rates in the initial report may have been influenced by the high rate of close/positive margins in this study
  • While the time to distant failure may be delayed by giving chemotherapy first, the overall percent of patients with distant failure was almost identical between the two arms.
  • Recommend patients with negative margins be treated with CT first then followed by RT.
  • For patients with close or positive surgical margins, re-excision prior to proceeding to adjuvant treatment is recommended.

    Clinical/Scientific Implications

  • This update of the original report does not show any differences between the arms in relation to the sequencing of chemotherapy and radiation therapy.
  • This study clearly points out the need for long-term results when making recommendations regarding the treatment of breast cancer.
  • Studies reported with short follow-up (5 yrs) may have different results when the patients are followed long-term (>10 yrs).
  • The patients included in this study had a high rate of positive and close margins of resection and may have influenced the early report of this trial.
  • However, this study remains one of the few attempts to evaluate the role of sequencing of chemotherapy and radiation therapy in early stage breast cancer.