Patterns of Recurrence by Sequence of Chemotherapy and Radiotherapy in Early Stage Breast Cancer

Reviewer: S. Jack Wei, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 20, 2003

Presenter: Lori Pierce, M.D.
Presenter's Affiliation: University of Michigan
Type of Session: Scientific


    The impact of sequencing of chemotherapy and radiation therapy (RT) for breast conservation therapy (BCT) is unclear. A previous large randomized trial of the sequencing of chemotherapy and RT following surgery showed no difference in local, regional, or distant recurrence rates with sequencing, although these results were closely tied to margin status. Patients with positive margins were more likely to have local recurrence when RT was delayed for the administration of chemotherapy. The lack of difference in recurrence based on sequencing has also been supported by several other smaller studies. However, the length of recent chemotherapy regimens has increased the interval between surgery and radiation, and it is unclear if this will affect recurrence patterns in patients undergoing BCT.

Materials and Methods

  • A retrospective analysis of patients undergoing BCT was performed using 1230 patients previously enrolled in 4 multi-institutional trials.
  • Microscopic negative margins were required for entry into each of these trials
  • Patients were separated into two groups: 1) Early radiation, consisting of patients receiving RT prior to chemotherapy following surgery 2) Delayed radiation, consisting of patients receiving RT after chemotherapy
  • The sequencing of chemotherapy and RT was left up to the discretion of the physician in all four trials
  • Overall, 236 patients received early radiation while 967 patients received delayed radiation
  • Endpoints were in-breast, regional, and distant recurrence by timing of RT.


  • Median follow-up was 10.1 yrs.
  • Median surgery-to-radiation interval was 6.5 weeks for the early radiation group, 29 weeks for the delayed radiation group.
  • The delayed radiation group had a higher rate of node-positive patients; otherwise, the two groups were well balanced with regard to prognostic factors.
  • There was no difference in the rate of local recurrence (8% for both groups) or regional recurrence (0.7%, for both groups)
  • There was no difference for pattern of failure for each group when separated by nodal status.
  • 10-year DFS and OS when adjusted for nodal status (74% and 83%, respectively for both groups).

Author's Conclusions

  • These 10-year results show no difference in local, reginal, or distant recurrence with regards to sequencing of chemotherapy and RT, supporting the findings of previous trials.
  • These patients almost universally had microscopically negative margins which likely played an important role in these results
  • Future investigations of chemotherapy and RT sequencing should be performed as treatments continue to change.

Clinical/Scientific Implications

    This study confirms previously presented studies showing the lack of impact of the sequencing of chemotherapy and RT after surgery for BCT. Importantly, this study has significantly longer follow-up than other studies that are available regarding this topic, and continues to show no difference between the two groups. The current practice of allowing physician discretion to determine the sequencing of adjuvant therapy remains appropriate for patients with microscopically negative margins.

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