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Radiotherapy is utilized as a part of breast-conserving therapy (lumpectomy followed by radiation therapy) or as an adjuvant therapy to mastectomy. This chapter focuses on recommendations for the use of adjuvant radiation therapy in the treatment of lymph node positive and high-risk lymph node negative breast cancer. Lower-risk disease will be covered in other chapters. Adjuvant radiation therapy recommendations for patients with node-positive disease are equally applicable in both mastectomy and breast-conserving therapy patients in most cases. Thus, the following recommendations for postmastectomy radiation therapy can be used interchangeably with patients treated with breast-conserving therapy. Controversial management decisions in the setting of one to three positive nodes, neoadjuvant chemotherapy, positive/close mastectomy margins, and T3N0 primary tumors will be covered in this chapter.
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ONE TO THREE NODE-POSITIVE BREAST CANCER
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Early randomized prospective trials in oncology addressed the role of radiation for breast cancer in the postmastectomy setting. Oslo I, Oslo II, and the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-02 are examples of early trials in which women with nonmetastatic breast cancer were randomized to adjuvant radiation or no radiation after mastectomy.1-3 Although the specifics of fields irradiated, dose delivered, and systemic therapy administered differed markedly in these trials, a statistically significant local control benefit was consistently associated with postmastectomy radiation therapy (PMRT). However, radiation therapy was associated with improved local control, an overall survival benefit was not identified. In fact, there was a suggestion of survival detriment in B-02. The negative impact on survival from PMRT was further substantiated by a meta-analysis by Cuzick and colleagues.2 In this meta-analysis, which included PMRT trials from 1949 to 1974, there was a significant decrease in 10-year OS in patients treated with PMRT (57% vs. 54%; p < 0.05).2
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Seven years following the initial publication, the difference was no longer statistically significant.3 The difference in OS was attributed to excess “cardiac deaths” in the irradiated patients.
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This and other meta-analyses were widely criticized. The trials studied spanned three decades and consequently, the radiation techniques were not uniform. Many would consider them inadequate or outdated today. Additionally and importantly, there was no uniform use of systemic therapy in the trials analyzed in the meta-analyses.3 Despite the valid criticisms of these meta-analyses, PMRT was generally reserved for only the most advanced cases (e.g., Haagensen’s 5-grave characteristics)4 and mainly viewed as a means to improve local control, not survival. However, with modern radiation techniques, the local control benefit associated with PMRT would be strengthened into a survival benefit.
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Between 1997 and 1999, three randomized prospective trials of PMRT were published, the Danish Premenopausal and Postmenopausal trials (82b and 82c, respectively) and the British Columbia trial.5-7 The Danish trials (1982 to 1989), with approximately 1400 patients each, and the smaller Canadian trial (1978 to 1985), with 318 patients, ...