Adjuvant radiotherapy trials in breast cancer

Abstract

Adjuvant radiotherapy in breast cancer according to stage of disease, present diagnostic and therapeutic advances, and the biology of the tumor is summarized: Stage I: The increasing number of small localized tumors occuring with earlier diagnosis motivates controlled clinical studies of irradiation of the breast with surgical axillary node status for exact biological classification. Encouraging results with local breast irradiation need confirmation in controlled studies. Improved survival by local interventions will most probably be due to selection of cases with earlier diagnosis rather than to variations in local therapies. Curative therapy saving the breast may be envisaged. Stage 11: Systemic therapies with effect also on local-regional soft tissue disease necessitate rethinking on the role of radiotherapy in Stage I1 Disease. Preoperative irradiation trials are biologically not logical in patients who are strictly operable and with a high risk of occult dissemination at time of irradiation. Adjuvant half body o r total body irradiation to very high risk Stage I1 patients may now b e logical to explore in a controlled study. Identification of the very limited subgroup(s) of patients who will benefit from radiotherapy in Stage I1 is open for trials. The routine use of postoperative irradiation in strictly operable patients is highly questionable. In spite of a demonstrated decrease of local and regional recurrence and the psychological trauma of discovering a local growth, the following four facts weigh heavily against the routine use of post-operative radiotherapy: 1) Overtreatment: (a) less than 10% have local-regional recurrence without distant metastases. (b) in the approximately 25% who get local recurrences, a watch policy with later radiotherapy gives complete local control in 70%. 2) Increased morbidity: besides a local-regional morbidity an increased mortality (+ 1 to 10%) can be correlated with the use of radiotherapy in 8/10 randomized trials (p > 0.04). 3) Systemic therapies: the logical way to improve survival. Multiple drug chemotherapy has been shown to be most effective against soft tissue metastases. It can not be excluded that radiotherapy diminishes the effect of systemic therapies (chemo-hormone or immunotherapy). 4) Social-economic aspects: The patient's time and money, doctor's time and society's resources may be better used. Priorities are necessary even in oncology. The interaction of radiotherpy with systemic therapies needs clarification. Stage 111: Radio-therapy has a clear therapeutic role in inoperable tumors limited to the breast. Its exact role in synergism with systemic therapies in a multiple modality approach still must be defined in controlled studies. An improved local therapeutic ratio ought to result from exploring advancements in radiotherapy using radiosensitizers, high energy particle radiation, interaction with chemotherapy, and hyperthermia. With increasingly efficient systemic therapies, local tumor control in Stage 111 may translate into increased survival. Stage...

Adjuvant Radiotherapy in Breast Cancer: The Treatment of Lymph Node Areas

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Meta-analysis as a manifestation of ‘bondförnuft’ (‘peasant sense’)

“…I was invited to a breast cancer conference later the same year, organized under the aegis of the White House, the National Cancer Institute and the American Cancer Society, and I presented all the then available results from the relevant trials. 9 In an attempt to explain the higher death rate in women treated with radiotherapy by a decrease in immuno-competent cells after irradiation, I had speculated that an increase of metastasis due to a decreased immuno-competence might explain the increased number of deaths observed in the irradiated groups. This speculation proved wrong, however.…”

“…Given our findings, engaging in discussion of statistical niceties seemed to us to be displacement activity. I was invited to a breast cancer conference later the same year, organized under the aegis of the White House, the National Cancer Institute and the American Cancer Society, and I presented all the then available results from the relevant trials 9 …”