No Difference in Recurrence After 5 Years With or Without Radiotherapy Following Sector Resection in Stage I Breast Cancer
The 20-year follow-up of the Swedish Uppsala/Örebro trial, reported by Wickberg et al in the Journal of Clinical Oncology, shows that improved control of recurrence over 5 years with radiotherapy after sector resection in patients with stage I breast cancer is followed by similar recurrence rates with or without radiotherapy. The findings indicate that the late recurrences are new tumors. No significant differences in overall mortality, breast cancer mortality, or mortality from causes other than breast cancer were observed between the radiotherapy and no radiotherapy groups.
In the trial, 381 women with pT1N0 breast cancer were randomly assigned to receive sector resection (more extensive than lumpectomy but less extensive than quadrantectomy) with (n = 184) or without (n = 197) postoperative radiotherapy. Cumulative proportions of recurrence, breast cancer death, and all-cause mortality were estimated over follow-up through 2010.
Protective Effect in First 5 Years
The cumulative probability of a first breast cancer event of any type after 20 years was significantly lower in the radiotherapy group (30.9% vs 45.1%, hazard ratio [HR] = 0.58, P = .002). The difference was almost completely captured by the difference in risk of local recurrence as a first event (11.5% vs 25.8%).
Regression analysis adjusting for study center, mode of detection, and tumor size at mammography showed that the benefit of radiotherapy was confined to the first 5 years after diagnosis (HR = 0.35, P < .001), with no difference between the radiotherapy and no radiotherapy groups after 5 years (HR = 0.99, P = .965).
No Differences in Overall or Breast Cancer Mortality
After 20 years, there were no significant differences between the radiotherapy and no radiotherapy groups in rates of overall mortality (50.4% vs 54.0%, adjusted HR = 0.92, P = .521), contralateral cancer or death as a result of cancer other than breast cancer (27.1% vs 24.9%, HR = 1.17, P = .453), mortality from generalized breast cancer (HR 1.11, P = .654), or mortality from causes other than breast cancer (HR = 0.84, P = .254).
In an anticipated low-risk group, consisting of 96 radiotherapy group patients and 103 no radiotherapy group patients aged > 55 years without comedo-type or lobular carcinomas, the cumulative incidence of first breast cancer of any type was 24.8% vs 36.1% (adjusted HR = 0.61, P = .084).
The investigators concluded: “In our trial, radiotherapy protects effectively against breast cancer events that are prone to develop during the first 5 years of follow-up. Hereafter, the yearly rate of recurrences is similar in the [radiotherapy] and non-[radiotherapy] groups. Thus, the protective effect of [radiotherapy] seems mainly to eradicate subclinical, multifocal cancers that are undetectable by mammography and are present at the time of primary treatment.”
They further noted that sterilizing the breast parenchyma results in a limited long-term protective effect on local recurrences, with a similar rate of recurrences after 5 years occurring in the two groups. The investigators wrote: “The long-term occurrence of new tumors that may be curable has implications for follow-up. Our findings also imply that there is a possibility to find subgroups with clinically relevant differences in risk. Although we cannot reliably define a group with little benefit of [radiotherapy], the data implicate that searching for a group with modern biomarkers for either radiosensitivity or further risk stratification is of high priority.”
Åsa Wickberg, MD, of University Hospital Örebro, Sweden, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by grants from the Swedish Cancer Society, Local Research Committé, University Hospital, Örebro, and Regional Research Foundation, Uppsala/Örebro, Sweden. The study authors reported no potential conflicts of interest.
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