Post mastectomy radiotherapy (PMRT) improves both locoregional control and overall survival in patients with locally advanced breast cancer. This has been demonstrated in both pre and postmenopausal women.
The evidence supporting this protocol is provided by a meta-analysis of 8135 women with early breast cancer enrolled in 22 trials of post-mastectomy chest wall and regional nodal irradiation.r There were 1314 women with 1-3 positive axillary nodes in the analysis. PMRT reduced the locoregional recurrence rate (2p<0.00001), overall recurrence rate (RR 0.68, 2p<0.00006), breast cancer mortality (RR 0.80, 2p=0.01). Of those 1314 women, 1133 also had systemic therapy with CMF chemotherapy or tamoxifen.
There were 1772 women with 4 or more nodes positive in the analysis. PMRT reduced the locoregional recurrence rate (2p<0.00001), overall recurrence rate (RR 0.79, 2p=0.0003), breast cancer mortality (RR=0.87, 2p=0.04). Any death 20 year gain=7.6% (RR=0.89, 2p=0.05). Median follow up time for the group was 9.4 years. For every 1.5 recurrences (either locoregional or distant) prevented during the first 10 years, 1 breast cancer death was prevented at 20 years.
Figure 1. Effect of radiotherapy (RT) after mastectomy and axillary dissection (Mast+AD) on 10-year risks of locoregional and overall recurrence and on 20-year risk of breast cancer mortality in 1314 women with one to three pathologically positive nodes (pN1–3) and in 1772 women with four or more pathologically positive nodes (pN4+).
PMRT in patients with T1-2 tumours and 1-3 positive axillary nodes
While the available evidence shows that PMRT reduces the risk of locoregional failure (LRF), any recurrence and breast cancer mortality for patients with T1-2 tumours and 1-3 positive nodes, the routine use of PMRT in these patients remains controversial, especially in the era of modern systemic therapy. Zeidan et al. retrospectively analysed the data from the BIG 02-98 trial which randomised 684 patients with T1-2 N1 breast cancer to receive adjuvant anthracycline with or without taxane chemotherapy.r 337 (49%) of these patients received PMRT. At 10 years, the LRR remained low in both groups at 2.5% (PMRT) and 6.5% (no-PMRT) (HR 0.29, 95% CI 0.12-0.73; p=0.05). No significant differences between the groups were observed in breast cancer specific survival (84.3% vs 83.9%) and or overall survival (81.7% vs 78.3%). There may be some subgroups of patients who may have an acceptably low risk of LRF such that the potential harms of PMRT may outweigh its absolute benefit. These subgroups are not well defined, and the acceptable ratio of benefits versus harms varies among physicians and patients. Results are pending from the MRC-SUPREMO trial to better inform decision making regarding the absolute benefit of PMRT in patients deemed at intermediate risk of LRF (defined as pT1-2N1, pT3N0 or pT2N0 if also grade 3 or with LVI).r The decision to use PMRT in these patients should ideally be made with a multidisciplinary team and with full involvement of the patient. Additional factors predicting a higher risk of LRF in these patients and therefore greater benefit with PMRT, may include younger age (<45), presence of LVI, high grade, ER-negativity, and large size of involved nodal metastases or presence of extra nodal extension.
PMRT in “triple negative” receptor breast cancer patients
For women with triple-negative (ER, PR and HER2) early stage breast cancer, the use of adjuvant radiation therapy has been found to be favourable.rr
Wang et al. 2011 r randomised 681 patients with triple negative, stage I-II breast cancer after mastectomy to receive adjuvant chemotherapy +/- adjuvant radiotherapy. After a median follow up of 86.5 months, five-year recurrence free survival rates were 88.3% for adjuvant chemotherapy plus radiation and 74.6% for adjuvant chemotherapy alone with a significant difference between the two groups (HR 0.77 [95% CI 0.72, 0.98]; P = 0.02). Five year overall survival significantly improved in adjuvant chemotherapy plus radiation group compared with chemotherapy alone (90.4% and 78.7%) (HR 0.79 [95% CI 0.74, 0.97]; P = 0.03) with no significant toxicity reported.
Hypofractionation for PMRT
The START trials were two randomized controlled trials of hypofractionation compared with standard fractionation following complete excision of primary invasive pT1-3a pN0-1 breast cancer, and while most patients were treated with breast conservation these studies also included patients who received PMRT.r 2236 patients in START-A were randomly assigned to either 50Gy/25 fractions (control) or 41.6Gy/13 fractions or 39Gy/13 fractions over 3 weeks, and approximately 15% of these patients were treated with PMRT. In START-B, 2215 patients were randomly assigned to either 50Gy/25 fractions (control) over 5 weeks or 40Gy/15 fractions over 3 weeks, and approximately 8% of these patients were treated with PMRT. In both trials, there was no significant difference in 10 year locoregional control between the conventional and hypofractionated regimens. Both trials also showed a significant reduction in late normal tissue effects in the hypofractionated groups.
Wang et al. 2019 randomised 820 patients with stage pT3-4 or at least 4 positive axillary nodes who had undergone mastectomy to receive PMRT with conventional fractionation (50Gy/25 fractions) or 43.5Gy/15 fractions to the chest wall, supraclavicular fossa and level III axillary nodal region.r Hypofractionation was found to be non-inferior to conventional fractionation at median follow-up of 58.5 month in terms of locoregional recurrences (8.3% vs. 8.1%, p < 0.0001). There were no significant differences between groups in acute and late toxicities, except that fewer patients in the hypofractionated group had grade 3 acute skin toxicities (3% vs. 8%, p<0.0001).
PMRT in the setting of neoadjuvant chemotherapy
Prospective data are lacking to inform PMRT decision making following neoadjuvant systemic therapy (NST), and at present clinical decision making should consider both pre and post chemotherapy risk factors. Consider radiotherapy in patients with clinical stage III disease regardless of pathological response. Consider omission of radiotherapy in patients with clinical stage II disease with complete response depending on other risk factors (trials are currently ongoing).