The prognostic significance of skin involvement in breast cancer patients with chest wall recurrence

Figures & data

Figure 1. A Flow chart outlining patients’ selection.

Table 1. Clinical-pathological characteristics of 476 patients with CWR.

Factor	Median (range)/number (frequency)
Age (year)	46 (24–83)
Primary site
Pathology subtype (IDC/others)	385 (80.9%)/91 (19.1%)
T stage (1–2/3–4/unknown)	252 (52.9%)/71 (14.9%)/153 (32.1%)
N stage (0/1/2/3/unknown)	158 (33.2%)/101 (21.2%)/60 (12.6%)/76 (16.0%)/81 (17.0%)
ER (<1%/≥1%/unknown)	163 (34.2%)/251 (52.7%)/62 (13.0%)
PR (<1%/≥1%/unknown)	186 (39.1%)/230 (48.3%)/60 (12.6%)
HER2 (positive/negative/unknown)	116 (24.4%)/258 (54.2%)/102 (21.4%)
Ki-67 (<15%/≥15%/unknown)	62 (13.0%)/236 (49.6%)/178 (37.4%)
Lymphovascular invasion (yes/no/unknown)	115 (24.2%)/172 (36.1%)/189 (39.7%)
Nerve invasion (yes/no/unknown)	31 (6.5%)/257 (54.0%)/188 (39.5%)
Systemic treatment (adjuvant/neoadjuvant/neither)	78 (16.4%)/402 (84.5%)/56 (11.8%)
Surgical intervention (lumpectomy/mastectomy)	26 (5.5%)/450 (94.5%)
Radiation (yes/no)	147 (30.9%)/329 (69.1%)
Chest wall
ER (<1%/≥1%/unknown)	170 (35.7%)/259 (54.4%)/47 (9.9%)
PR (<1%/≥1%/unknown)	233 (48.9%)/196 (41.2%)/47 (9.9%)
HER2 (positive/negative/unknown)	122 (25.6%)/277 (58.2%)/77 (16.2%)
Ki-67 (<15%/≥15%/unknown)	61 (12.8%)/314 (66.0%)/101 (21.2%)
Skin involvement (yes/no/unknown)	198 (41.6%)/147 (30.9%)/131 (27.5%)
Interval between primary tumour and CWR (months)	26.15 (1.87–285.07)
OS (months)	103.76 (0.6–255.9)

Figure 2. Representative images of non-skin involvement, tumours involving the dermis and tumours involving the epidermis. Representative images of non-skin involvement (A, 100× magnification; B, 400× magnification). Representative images of tumours involving the dermis (C, 100× magnification; D, 400× magnification). Representative images of tumours involving the epidermis (E, 100× magnification; F, 400× magnification).

Table 2. Pathological characteristics of primary tumour in 345 patients with/without skin involvement.

Factor	Skin involvement (n = 198)	Non-skin involvement (n = 147)	p
Pathology subtype			0.676
IDC	169 (85.4%)	88 (59.9%)
Others	29 (14.6%)	13 (8.8%)
T stage			0.003
T1–2	99 (50.0%)	88 (59.9%)
T3–4	40 (20.2%)	13 (8.8%)
N stage			<0.001
0	49 (24.7%)	66 (44.9%)
1	37 (18.7%)	40 (27.2%)
2	35 (17.7%)	10 (6.8%)
3	47 (23.7%)	9 (6.1%)
ER			0.726
<1%	75 (37.9%)	56 (38.1%)
≥1%	95 (48.0%)	77 (52.4%)
PR			0.694
<1%	78 (39.4%)	65 (44.2%)
≥1%	92 (46.5%)	70 (47.6%)
HER2			0.498
Positive	47 (23.7%)	34 (23.1%)
Negative	105 (53.0%)	91 (61.9%)
Ki-67			0.239
<15%	26 (13.1%)	25 (17.0%)
≥15%	106 (53.5%)	70 (47.6%)
Lymphovascular invasion			<0.001
Yes	71 (35.9%)	28 (19.0%)
No	52 (26.3%)	61 (41.5%)
Nerve invasion			0.669
Yes	13 (6.6%)	11 (7.5%)
No	111 (56.1%)	78 (53.1%)

The bold values represent p < 0.05.

Table 3. Clinical-pathological characteristics of chest wall lesions in 345 patients with/without skin involvement.

Factor	Skin involvement (n = 198)	Non-skin involvement (n = 147)	p
ER			0.659
<1%	71 (35.9%)	51 (34.7%)
≥1%	108 (54.5%)	86 (58.5%)
PR			0.226
<1%	87 (43.9%)	76 (51.7%)
≥1%	92 (46.5%)	61 (41.5%)
HER2			0.527
Positive	48 (24.2%)	43 (29.3%)
Negative	114 (57.6%)	87 (59.2%)
Ki-67			0.237
<15%	26 (13.1%)	25 (17.0%)
≥15%	138 (69.7%)	92 (62.6%)
Systemic treatment for CWR			0.519
Yes	183 (92.4%)	133 (90.5%)
No	15 (7.6%)	14 (9.5%)
Radiotherapy for CWR			0.360
Yes	66 (33.3%)	56 (38.1%)
No	132 (66.7%)	91 (61.9%)

Figure 3. Kaplan–Meier curve for DFS and OS of 200 patients treated with radical resection stratified by skin involvement. (A) Kaplan–Meier curve for DFS stratified by skin involvement in 200 patients treated with radical resection. (B) Kaplan–Meier curve for OS stratified by skin involvement in these patients.

Figure 4. Kaplan–Meier curve for PFS and OS of 145 patients with locally unresectable CWR stratified by skin involvement. (A) Kaplan–Meier curve for PFS stratified by skin involvement in 145 patients with locally unresectable CWR. (B) Kaplan–Meier curve for OS stratified by skin involvement in these patients.

Table 4. Cox proportional hazard regression analysis of DFS in 200 patients treated with radical resection.

Faction	Univariable		Multivariable
	HR (95% CI)	p	HR (95% CI)	p
Age (<46 vs. ≥46)	0.940 (0.626–1.410)	0.765
Pathology subtype (IDC vs. others)	0.585 (0.337–1.016)	0.057	1.090 (0.446–2.662)	0.850
T (1–2 vs. 3–4)	1.610 (0.853–3.039)	0.142
N (<1 vs. ≥1)	1.544 (0.984–2.424)	0.059	1.481 (0.844–2.597)	0.171
ER (<1% vs. ≥1%)	0.844 (0.546–1.306)	0.447
PR (<1% vs. ≥1%)	0.849 (0.552–1.305)	0.455
HER2 (negative vs. positive)	0.700 (0.397–1.233)	0.217
Ki-67 (<15% vs. ≥15%)	1.763 (0.972–3.200)	0.062	1.595 (0.845–3.009)	0.149
Skin involvement (no vs. yes)	2.211 (1.443–3.388)	<0.001	1.809 (1.018–3.215)	0.043

Note: ER, PR, HER2 and Ki-67 are all from pathology of chest wall.

The bold values represent p < 0.05.

Figure 5. Kaplan–Meier curve for local and distant disease progression of 200 patients treated with radical resection stratified by skin involvement. (A) Kaplan–Meier curve for local disease progression stratified by skin involvement in 200 patients treated with radical resection. (B) Kaplan–Meier curve for distant disease progression stratified by skin involvement in these patients.

Figure 6. Kaplan–Meier curve for local and distant disease progression of 145 patients with locally unresectable CWR stratified by skin involvement. (A) Kaplan–Meier curve for local disease progression stratified by skin involvement in 145 patients with locally unresectable CWR. (B) Kaplan–Meier curve for distant disease progression stratified by skin involvement in these patients.

Table 5. Comparison of pathological characteristics of primary tumour in patients with/without persistent chest wall progression.

Factor	Persistent chest wall progression (n = 40)	Non-persistent chest wall progression (n = 191)	p
Pathology			0.431
IDC	34 (85.0%)	152 (79.6%)
Others	6 (15.0%)	39 (20.4%)
T stage			0.403
1–2	20 (50.0%)	104 (54.5%)
3–4	7 (17.5%)	21 (11.0%)
N stage			0.002
0	10 (25.0%)	70 (36.6%)
1	5 (12.5%)	43 (22.5%)
2	9 (22.5%)	19 (9.9%)
3	12 (30.0%)	20 (10.5%)
ER			0.061
<1%	19 (47.5%)	59 (30.9%)
≥1%	17 (42.5%)	105 (55.0%)
PR			0.001
<1%	24 (60.0%)	59 (30.9%)
≥1%	13 (32.5%)	106 (55.5%)
HER2			0.046
Positive	15 (37.5%)	41 (21.5%)
Negative	18 (45.0%)	107 (56.0%)
Ki-67			0.052
<15%	4 (10.0%)	34 (17.8%)
≥15%	25 (62.5%)	72 (37.7%)

Note: Persistent CWR is defined as three consecutive chest wall progressions without new distant organ involvement.

The bold values represent p < 0.05.

Table 6. Comparison of clinical-pathological characteristics of chest wall lesions in patients with/without persistent chest wall progression.

Factor	Persistent chest wall progression (n = 40)	Non-persistent chest wall progression (n = 191)	p
ER			0.027
<1%	19 (47.5%)	57 (49.5%)
≥1%	18 (45.0%)	120 (49.5%)
PR			0.013
<1%	24 (60.0%)	75 (29.8%)
≥1%	13 (32.5%)	102 (53.4%)
HER2			0.586
Positive	14 (35.0%)	53 (27.7%)
Negative	23 (57.5%)	107 (56.0%)
Ki-67			0.817
<15%	7 (17.5%)	32 (16.8%)
≥15%	29 (72.5%)	119 (62.3%)
Skin involvement			0.020
Yes	29 (72.5%)	100 (52.4%)
No	11 (27.5%)	91 (47.6%)

Note: Persistent CWR is defined as three consecutive chest wall progressions without new distant organ involvement.

The bold values represent p < 0.05.

Data availability statement

The data presented in this study are available on request from the corresponding author.