Table 3.

Ultrasound skin toxicity findings of the irradiated breast compared with the nonirradiated or pre-RT breast.

Author(s), Year	Measured Parameters and Locations	Ultrasound Skin Findings	Main Findings
(Borm et al. 2021) [39]	Skin thickness Locations: at 12:00, 3:00, 6:00, and 9:00 around the mamilla	Healthy breast: 1.7–1.8 mm at all timepoints for both groups Treated breast: HF: 2.3 mm before RT, 2.4 mm at the end of RT, and 2.5 mm post RT CF: 2.3 mm before RT, 2.3 mm at the end of RT, and 2.5 mm post RT	-↑ skin thickness compared to the HB before and after RT -Skin thickness ↑ after RT in both groups -No significant difference between HF-WBI and CF-WBI both at the end and following RT
(Landoni et al. 2013) [40]	Skin thickness Locations: the irradiated breast, boost region, and corresponding positions on the untreated breast	Mean skin thickness: Irradiated breast: 2.13 ± 0.72 mm Contralateral site: 1.61 ± 0.29 mm Boost region: 2.25 ± 0.79 mm. Contralateral site: 1.63 ± 0.33 mm	-Significant difference in both examined regions -No significant difference between the boosted area and the irradiated breast
(Garnier et al. 2017) [41]	Dermal thickness Locations: the irradiated breast, boost region, and corresponding positions on the untreated breast	Median dermal thickness (mm): Irradiated skin: 1.7 [1.4–2.1] Contralateral site: 1.3 [1.0–1.5] Boost region: 1.7 [1.4–2.1] Contralateral site: 1.2 [1.0–1.4]	-↑ dermal thickness compared to the HB -↑ breast volume, young age, and dark skin phototype were associated with more severe skin toxicity
(Wang et al. 2020) [33]	Mean epidermal thickness STRA Locations: the four quadrants of both breasts	Mean STRA: Baseline CF: 1.3, HF: 1.3 During RT CF: 1.5, HF: 1.4 12 weeks post RT CF: 1.6, HF: 1.5 1 year post RT CF: 1.5, HF: 1.5	-STRA was ↑ before RT -Mean STRA was ↑ post RT compared to baseline -Breast volume and supraclavicular irradiation were associated with the most significant changes in breast asymmetry
(Torres et al. 2016) [32]	Mean epidermal thickness and STRA Locations: the four quadrants and boost region in both breasts	STRA: Baseline: 1.27 (SD 0.29). During RT: 1.52 (SD 0.46) 6 weeks post RT: 1.6 (SD 0.46).	-Mean ↑: Before RT: 27% During RT: 25% Post RT: 33% -Mean STRA 6 weeks after RT was significantly larger than baseline -↑ breast volume is a consistent patient-related factor associated with ↑ epidermal thickening secondary to RT
(Lin et al. 2019) [9]	Epidermal thickness STRA Locations: the four quadrants of both breasts	Mean STRA: Baseline: 1.28 ± 0.31. At week 6: 1.55 6 weeks post RT: 1.62 6 months post RT: 1.65 ± 0.41 1 year post RT: 1.44 ± 0.38	-↑ STRA post RT compared to baseline -Significant increase at 6 months (absolute mean ↑ of 65%, SD 0.054) -1 year post RT (absolute mean ↑ of 44%, SD 0.048) -In MVA, ALND, longer interval between surgery and RT, ↑ baseline STRA, and Caucasian race predicted more severe changes in STRA at one year compared to baseline (all p < 0.05)
(Yoshida et al. 2012) [34]	Ultrasound RF data: skin thickness PCC of the hypodermis Locations: 12:00, 3:00, 6:00, 9:00, and tumour bed of both breasts	Dermal toxicity: 28.5% ± 26.6% for RTOG = 0 and 69.7% ± 39.7% for RTOG = 1 or 2 Hypodermal toxicity: 5.4% ± 35.8% for RTOG = 0 and 19.2% ± 26.2% for RTOG = 1 or 2	-Significant dermal toxicity changes in the acute and late toxicity groups -Significant hypodermal toxicity changes in the early but not in the late group
(Yoshida et al. 2011) [35]	Ultrasound RF data: skin thickness and PCC Locations: 12:00, 3:00, 6:00, and 9:00 positions of both breasts	The average skin thickness: Treated breast: 2.61 mm (1.53–3.65 mm) Untreated breast: 2.05 mm (1.66–2.41 mm) Average PCC: Treated breast: 0.28 (range: 0.21–0.41) Untreated breast: 0.41 (range: 0.03–0.52)	-Significant differences -27.3% mean ↑ in skin thickness, 34.1% mean ↓ in PCC
(Liu et al. 2010) [31]	Ultrasound RF signals: skin thickness and PCC Locations: 12:00, 3:00, 6:00, and 9:00 of both breasts	Skin thickness range: Untreated breasts: 1.66–2.41 mm Treated breasts: 1.53–3.65 mm PCC range: Untreated hypodermis: 0.03 to 0.52 Treated hypodermis: 0.21 to 0.41	-Significant changes in both parameters -Average skin thickness ↑ by 27.3%, and the PCC ↓ by 31.7%
(Liu et al. 2008) [42]	Ultrasound RF signals: skin thickness and PCC Locations: irradiated breast and nonirradiated breast	Average skin thickness: Irradiated skin: 3.3 ± 1.4 mm (2.01 to 5.82 mm) Nonirradiated skin: 2.2 ± 0.4 mm (1.93 to 2.75 mm) Average PCC: Irradiated hypodermis: 0.18 ± 0.08 (0.01 to 0.36) Nonirradiated hypodermis: 0.27 ± 0.10 (0.10 to 0.42)	-Significant changes in both parameters -The average skin thickness ↑ by 40%, and the average PCC↓ by 35%
(Keskikuru et al. 2004) [43]	Skin thickness of induced suction blisters Location: in the upper medial quadrant of both breasts	The mean skin thickness of the Irradiated breast: Before RT: 1.9 mm, 4 months: 2.1 mm 7 months: 2.00 mm 1 year: 1.9 mm 2 years: 1.7 mm Nonirradiated breast: <1.8 mm at all timepoints	-Significant changes from 2.5 weeks of RT, peaked at around 4 months, then declined until 2 years -9% ↑ in skin thickness in the operated breast before RT
(Wratten et al. 2002) [37]	Skin thickness Locations: 4 cm medial and lateral to the nipple in both breasts	Mean skin thickness of: Medial treated breast 2.23 mm Lateral treated breast 1.91 Medial untreated breast 1.38 mm Lateral untreated breast 1.16 mm	-The treated breast skin is overall thicker than the untreated breast -Thickening is evident before RT -The medial aspect is thicker than the outer aspect in both breasts
(Wratten et al. 2000) [38]	Total cutaneous thickness Locations: 4 cm medial and lateral to the nipple in both breasts	The mean total cutaneous thickness: Treated breast: 2.71 mm (range 1.42–4.66 mm, SD 0.83 mm) Untreated breast: 1.35 mm (range 0.84–1.82 mm, SD 0.21 mm)	-Significant changes -The medial aspect of the breast was thicker than the lateral aspect in both breasts -↑cutaneous thickness before RT in those patients with axillary dissection
(Warszawski et al. 1998) [44]	Entry echo of the skin Corium (dermal) thickness The echogenicity of the upper and lower corium Structure of the border between the corium and subcutis Locations: at the edge between the upper quadrants 2–3 cm above the mammilla in both breasts	Mean corium thickness (µm): Nonirradiated skin: 1683 ± 308 Early reactions: 2683 ± 721 Late reactions: 2307 ± 934 The mean echogenicity of the upper and lower corium: Nonirradiated skin: 3.63 ± 1.58 to 5.04 ± 1.56 Early reactions: 1.90 ± 1.37 to 1.93 ± 0.76 Late reactions: 2.32 ± 0.88 to 3.33 ± 1.41 Unsharp dermis-subcutaneous border: Nonirradiated skin: 5/31, 16.1% Early reactions: 15/44, 34.1% Late reactions: 8/21, 38.1%	-Significant changes in the early and late reactions for the thickness and echogenicity of the dermis -Nonsignificant changes for the entry echo and poor visibility of the dermis-subcutaneous border -No significant difference between early and late reactions except for the echogenicity of the lower corium
(Schack et al. 2016) [45]	Dermis thickness Locations: 3 cm from the areola in all four quadrants of both breasts	The mean dermis thickness: Untreated breast: 1.26 mm (95% CI 1.08–1.44) Irradiated breast: 2.22 mm (95% CI 1.78–2.66) The mean difference: 0.96 mm (95% CI 0.50–1.42)	-Statistically significant changes
(Wong et al. 2011) [46]	Skin thickness Locations: 9 points within the medial, central, and lateral areas of both breasts	Mean skin thickness (mm): Irradiated Rt chest wall: 0.1712 Nonirradiated Rt side: 0.1845 Irradiated Lt chest wall: 0.1764 Nonirradiated Lt side: 0.1835	-A significant difference in ↓ skin thickness of the irradiated chest wall compared to the non-irradiated chest -The findings indicated chronic skin reactions -The medial aspect was consistently thicker than the lateral aspect
(Wratten et al. 2007) [36]	Mean epidermal thickness Locations: 4 cm medial and lateral to the nipple in both breasts	Treated breast: Baseline: 1.9–2.3 mm During RT: 1.9–2.5 mm 4–6 months: 2.3–3 mm 1–2 years: 1.5–2.5 mm Untreated breast: 1.3–1.5 mm at all timepoints	-Peaked at 4–6 months post RT and mostly returned to baseline levels by 12 months post-RT -↑ epidermal thickness before RT in patients with ALND -The thickness of the epidermis was greater medially in both breasts -Irradiation of the breast causes little cutaneous oedema in the absence of axillary dissection or nodal irradiation

Abbreviations: RT = radiotherapy, HB = healthy breast, RF = radiofrequency, CF-WBI = conventional fractionated whole-breast irradiation, HF-WBI = hypofractionated whole-breast irradiation, ALND = axillary lymph node dissection, PCC = Pearson correlation coefficient, MVA = multivariate analysis, STRA = skin thickness ratio.