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

Background

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.

Results

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.

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