Radiotherapy in the curative setting for breast cancer has evolved over the past 15 years, from a one size fits all approach to a personalized, risk-adapted treatment within a multidisciplinary environment, taking more and more patient factors, the biology of the tumor, and the extent of disease in the lymph nodes into account. Before the year 2000, the picture was straightforward, with no radiotherapy following mastectomy (postmastectomy radiotherapy, PMRT), and whole breast radiotherapy (WBRT) with 50 Gy over 5 weeks after breast-conserving surgery in all patients. The picture is more complex today (see Fig. 1).

Fig. 1
figure 1

Adjuvant radiotherapy for breast cancer; a before 2000, b in 2017. PMRT postmastectomy radiotherapy, WBRT whole breast radiotherapy, RNI regional nodal irradiation, APBI accelerated partial breast irradiation, IORT intraoperative radiation therapy, brachy brachytherapy, EBRT external beam radiotherapy, Int integrated, RF risk factors

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Postmastectomy radiotherapy

The Danish and British Columbia trials [1,2,3] identified pre- and postmenopausal patients with locally advanced tumors (T3-4Nx or TxN+) for whom an overall survival benefit was achieved by postmastectomy radiotherapy (PMRT) of 50 Gy. The initial consensus was that patients with four and more positive nodes benefitted the most in terms of overall survival; however, a recent analysis by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) [4] underlined that patients with one to three positive nodes also showed a consistent benefit, particularly when chemotherapy was given. This benefit is substantial in high-risk patients (G3, triple negative, lymph vascular invasion, Her2 positive, or age <40 years) [5]. One should keep in mind that all patients included in the EBCTCG analysis received PMRT to the chest wall and regional nodal irradiation (RNI; medial supraclavicular and mostly mammary internal). On the other hand, there was a lack of consistent benefit for all T3N0 patients. Meta-analyses have identified subgroups of the T3N0 category with risk factors, e. g., large tumor, young age, high grading, lymph vessel invasion, and triple negative, which may still show a benefit based on the individual risk assessment, particularly when two or more risk factors are positive [6, 7].

Concerning the situation after neoadjuvant chemotherapy, there is still a paucity of data regarding the indication for PMRT. Therefore, the initial clinical staging before neoadjuvant chemotherapy is used until ongoing prospective studies have reported results (e. g., NSABP B 51).

In summary, PMRT is currently recommended in patients with T4 or N+ disease, or following R+ resection. PMRT can be avoided following R0 mastectomy in T1–2N0 patients and in T3N0 patients without risk factors. Typically, PMRT should include the chest wall and the regional nodal areas [7].

Radiotherapy and breast-conserving surgery

Radiotherapy is an integral part of the breast-conserving therapy approach. If at all, no radiotherapy following breast conserving surgery (BCS) may be an option for patients whose life expectancy is shorter than 10 years, with hormone receptor-positive T1N0 tumors without Her2neu overexpression. Patients have to be counselled that even with rigorous antihormonal therapy, there is a considerably increased risk for local recurrence (CALBG, BASO2, PRIME II trials: 4–6% local recurrence without radiotherapy after 5 years for patients above 70/65/65 years of age with receptor-positive T1N0 tumors; non-grade III; for a summary see [8, 9]).

Based on long-term results from three randomized studies, (accelerated) partial breast irradiation ((A)PBI) using intraoperative radiotherapy or postoperative multicatheter brachytherapy or external beam radiotherapy is an option for postmenopausal patients with low-risk tumors (T1N0, R0 resection, hormone receptor positive, non-lobular histology). Participation in a clinical study is recommended for patients between 50 and 70 years of age [10,11,12].

Fractionated WBRT is the standard of care for the overwhelming majority of patients following BCS. Hypofractionated WBRT, i. e., the application of single doses larger than 2 Gy up to reduced total doses, e. g., 15–16 fractions of 2.66 Gy, has been shown in large randomized trials with sufficient follow-up to be at least as effective in terms of local tumor control as conventionally fractionated radiotherapy and results in significantly less acute and late effects [13,14,15]. Consequently, hypofractionated radiotherapy is the preferred radiation schedule in patients who do not need radiotherapy of regional lymph nodes. In younger and high-risk patients, a sequential boost of 10–16 Gy to the tumor bed is recommended, although the improvement in local control is modest and there was no overall survival benefit in long-term follow-up [16, 17].

Based on the PMRT data, two recent randomized trials (MA20, EORTC), and a Danish cohort study [18,19,20], the indication for RNI was expanded following BCS [21,22,23]. Depending on the number of positive nodes (>3, 1–3, 0 but high risk), the strength of the recommendation to include the supraclavicular/medial axillary region decreases in AGO (++, +, +/−) and in S3 (have to/should/can). In most of the cases where RNI is indicated, irradiation of the internal mammary nodes should be considered (for a detailed analysis see [23]). Typically, conventional fractionation is used when RNI is given following BCS. Based on the AMOROS trial, it is obvious that RNI yields lower rates of side effects following sentinel node biopsy compared to radical axillary dissection [24].

Conclusion

This short overview summarizes the current developments in risk-adapted radiotherapy for breast cancer. One has to keep in mind that the different guideline committees come to slightly different conclusions depending on the composition of their membership and the process of literature collection and interpretation [25,26,27].