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Background:
Rates of post-mastectomy radiotherapy for locally advanced breast cancer have been steadily rising. Although the risk of increased surgical morbidity from radiation to breast reconstruction has been well established, the effect of radiation on health-related quality of life (HR-QOL) in patients undergoing breast reconstruction has not been extensively studied. The purpose of this study was to determine the effect of post-mastectomy radiotherapy on HR-QOL throughout the breast reconstruction process.
Methods:
After obtaining IRB approval, we prospectively consented and followed all patients undergoing breast reconstruction between November 2010 and June 2013. Patient-reported outcomes, using Breast-Q^©, were tracked at the following time points: preoperatively, after tissue expanders, 6 months after final reconstruction, and 12 months after final reconstruction. Clinical outcomes were retrospectively collected. Paired t-test, Wilcoxon rank sum test, and multiple linear regression analysis were used to determine the effect of post-mastectomy radiation on change in patient-reported QOL during the reconstruction process.
Results:
Two hundred patients completed 12-month follow-up and were included in the study, of which 51 (25.5%) patients received post-mastectomy radiotherapy and 149 (74.5%) patients did not. Implant based reconstruction was performed in 75 patients (37.5%), autologous in 118 (59.%), and pure fat grafting in 7 (3.5%). Reconstructive modality was not significantly different between irradiated and non-irradiated patients. At long-term follow-up, non-irradiated patients reported significantly higher Breast-Q^© scores compared to irradiated patients in the following domains: satisfaction with breasts (p=0.003), psychosocial wellbeing (p=0.003), sexual wellbeing (p<0.001), physical wellbeing of chest (p=0.024), and satisfaction with outcome (p=0.03). There was no significant difference between the groups at preoperative baseline or after tissue expanders, and only psychosocial wellbeing (p=0.038) was significantly lower in irradiated patients at 6 months after reconstruction. When accounting for baseline QOL by examining Delta Breast-Q^© (Long-term Breast-Q^© - preoperative Breast-Q^©), there was no significant difference between irradiated and non-irradiated patients in satisfaction with breasts and physical wellbeing of chest. Non-irradiated patients did have significantly higher Delta Breast-Q^© in psychosocial wellbeing (p=0.001) and sexual well being (p=0.001) than irradiated patients. After adjusting for confounders, only psychosocial wellbeing (p= 0.002) remained significantly differen.
Conculsions:
Radiotherapy seems to have a negative effect on HR-QOL and satisfaction with breasts and outcome in patients undergoing breast reconstruction, when examining a single time-point. However, when patient-reported outcomes are tracked throughout the reconstruction process, accounting for baseline values and confounders, the detrimental effects of radiotherapy to HR-QOL do not significantly dissipate the benefits from breast reconstruction and patient's satisfaction with their breasts. Radiotherapy does seem to specifically take a toll on psychosocial wellbeing than other aspects of HR-QOL.

Table 6. Difference in Breast-Q from preoperative baseline to long-term follow-up by receipt of post-mastectomy radiotherapy*
No Radiotherapy (n=137 patients)	Radiotherapy (n=42 patients)	Comparison between groups
Unadjusted	Adjusted
Median1 Pre-operative Breast-Q (IQR)	Median1 Long-term Breast-Q (IQR)	Mean Delta Breast-Q 2	Median1 Pre-operative Breast-Q (IQR)	Median1 Long-term Breast-Q (IQR)	Mean Delta Breast-Q 2	Δ Mean Difference3	95% CI	p-value	Adjusted Δ Mean Difference4	95% CI	p-value
58 (36)	69 (26)	7.43	53 (25)	56 (17)	4.19	-3.24	-13.52 to 7.04	0.535	-4.02	-17.44 to 9.4	0.555
70 (29)	82 (35)	6.9	70 (37)	67 (37)	-6.31	-13.21	-21.07 to -5.34	0.001	-12.95	-20.96 to -4.94	0.002
58.5 (18)	60 (27)	4.04	57 (24)	47 (22)	-10.68	-14.72	-23.62 to -5.83	0.001	-8.4	-20.91 to 4.11	0.186
81 (20)	81 (23)	-0.72	81 (34)	75.5 (31)	-5.14	-4.42	-9.8 to 0.95	0.106	-2.52	-4.95 to 9.99	0.505
*- Delayed Reconstruction Patients were excluded from this analysis because a preoperative baseline prior to mastectomy was unobtainable for these patients as they presented for reconstructive consultation after prior mastectomy 1. Individual Breast-Q Scores at preoperative and long term time points are reported with median Breast-Q score (interquartile range) because of a skewed distribution
2. Delta Breast-Q (Long-term Breast-Q - Preoperative Breast-Q) scores are reported with mean because of their normal distribution 3. Δ Mean Difference= Mean Delta Breast-Q (Radiotherapy) - Mean Delta Breast-Q (No Radiotherapy) 4. Adjusted Δ Mean Difference: Beta Coefficient from Multiple Linear Regression Analysis with Radiotherapy group compared to No Radiotherapy group as reference