Clinicopathological characteristics and treatment outcomes of occult breast cancer: a SEER population-based study

Figures & data

Table 1 Multivariable analysis of BCSS and OS in all patients

Variables	BCSS			OS
	n	HR (95% CI)	P-value	n	HR (95% CI)	P-value
Group			<0.001			<0.001
OBC	51	0.37 (0.27–0.50)	<0.001	68	0.41 (0.31–0.52)	<0.001
non-OBC	12,847	Reference	–	18,644	Reference	–
Year of diagnosis			0.402			0.831
2004–2009	10,260	Reference	–	15,020	Reference	–
2010–2014	2,638	0.93 (0.77–1.11)	0.402	3,692	1.02 (0.88–1.17)	0.831
Age at diagnosis (years)			<0.001			<0.001
18–49	3,877	Reference	–	4,340	Reference	–
≥50	9,021	1.25 (1.20–1.30)	<0.001	14,372	1.72 (1.66–1.78)	<0.001
Race			<0.001			<0.001
White	9,730	Reference	–	14,356	Reference	–
Black	2,294	1.31 (1.25–1.37)	<0.001	3,153	1.25 (1.20–1.30)	<0.001
Othersa	848	0.79 (0.73–0.84)	<0.001	1,167	0.77 (0.72–0.82)	<0.001
Unknown	26	0.48 (0.33–0.70)	<0.001	36	0.43 (0.31–0.61)	<0.001
Marital status			<0.001			<0.001
Married	6,592	Reference	–	8,663	Reference	–
Not marriedb	5,875	1.32 (1.27–1.36)	<0.001	9,407	1.58 (1.54–1.63)	<0.001
Unknown	431	1.13 (1.02–1.25)	0.014	642	1.26 (1.16–1.36)	<0.001
Grade			<0.001			<0.001
1 and 2	4,211	Reference	–	7,482	Reference	–
3 and UD	8,220	1.78 (1.71–1.85)	<0.001	1,0529	1.45 (1.40–1.50)	<0.001
Unknown	467	1.13 (1.03–1.25)	0.012	701	1.18 (1.09–1.27)	<0.001
ER status			<0.001			<0.001
Positive	7,308	Reference	–	11,691	Reference	–
Negative	5,057	1.52 (1.44–1.60)	<0.001	6,181	1.40 (1.34–1.46)	<0.001
Unknownc	533	1.25 (1.06–1.47)	0.009	840	1.23 (1.07–1.40)	0.004
PR status			<0.001			<0.001
Positive	5,530	Reference	–	9,086	Reference	–
Negative	6,708	1.63 (1.55–1.72)	<0.001	8,582	1.44 (1.38–1.50)	<0.001
Unknownc	660	1.29 (1.11–1.51)	<0.001	1,044	1.21 (1.07–1.37)	<0.001
HER2 status			<0.001			<0.001
Positive	395	Reference	–	523	Reference	–
Negative	2,119	1.76 (1.58–1.96)	<0.001	2,962	1.63 (1.49–1.79)	<0.001
Unknownd	10,384	1.48 (1.21–1.82)	<0.001	15,227	1.60 (1.36–1.88)	<0.001
Breast surgery type			<0.001			<0.001
Mastectomy	8,803	Reference	–	5,892	Reference	–
BCS	3,894	0.72 (0.69–0.75)	<0.001	12,563	0.74 (0.72–0.77)	<0.001
No surgery	201	2.17 (0.69–1.36)	<0.001.	257	1.80 (1.58–2.06)	<0.001
RT			<0.001			<0.001
Yes	6,486	Reference	–	8,604	Reference	–
No	6,412	1.23 (1.19–1.27)	<0.001	10,108	1.39 (1.35–1.43)	<0.001
No. of positive LNs			<0.001			<0.001
1–3	6,254	Reference	–	10,244	Reference	–
4–9	3,802	2.13 (2.04–2.22)	<0.001	5,054	1.79 (1.73–1.86)	<0.001
≥10	2,808	3.79 (3.62–3.97)	<0.001	3,376	2.92 (2.81–3.04)	<0.001
Unknown	34	0.97 (0.69–1.36)	0.843	38	0.80 (0.58–1.11)	0.179

Notes:

a Including American Indian/Alaskan native and Asian/Pacific Islander.

b Including divorced, separated, single (never married), and widowed.

c Including borderline and unknown.

d HER2+ unknown includes borderline, unknown, and before 2010 breast cancer. Reference indicates the control population.

Abbreviations: BCS, breast-conserving surgery; BCSS, breast cancer-specific survival; ER, estrogen receptor; LNs, lymph nodes; n, the number of deaths; OBC, occult breast cancer; OS, overall survival; PR, progesterone receptor; RT, radiotherapy; UD, undifferentiated.

Table 2 Multivariable analysis of BCSS and OS in OBC patients

Variables	BCSS			OS
	n	HR (95% CI)	P-value	n	HR (95% CI)	P-value
ER status
Positive	15	Reference	–	21	Reference	–
Negative	21	1.45 (0.61–3.47)	0.403	30	1.48 (0.72–3.05)	0.292
Unknowna	5	2.83 (0.32–31.28)	0.524	6	3.19 (0.36–28.31)	0.297
PR status
Positive	10	Reference	–	14	Reference	–
Negative	26	1.62 (0.63–4.16)	0.317	36	1.53 (0.69–3.38)	0.296
Unknowna	5	0.74 (0.29–6.27)	0.795	7	0.63 (0.08–5.00)	0.660
Treatment strategy
Mastectomy group	17	Reference	–	24	Reference	–
BCS group	12	0.81 (0.38–1.72)	0.588	14	0.64 (0.33–1.25)	0.331
ALND-only group	4	1.17 (0.38–3.61)	0.785	7	1.33 (0.55–3.17)	0.527
SLND-only group	8	10.12 (3.09–33.18)	<0.001	12	7.95 (3.13–20.17)	<0.001
No. of positive LNs
1–3	11	Reference	–	18	Reference	–
4–9	9	4.73 (1.55–14.41)	0.006	15	4.30 (1.85–10.00)	0.001
≥10	19	11.91 (4.30–32.97)	<0.001	21	7.19 (3.21–16.12)	<0.001
Unknown	2	6.49 (1.37–30.69)	0.018	3	6.97 (1.96–24.81)	0.003

Note:

a Including borderline and unknown.

Abbreviations: ALND, axillary LN dissection; BCS, breast-conserving surgery; BCSS, breast cancer-specific survival; ER, estrogen receptor; LNs, lymph nodes; n, the number of deaths; OBC, occult breast cancer; OS, overall survival; PR, progesterone receptor; SLND, sentinel LN dissection.

Table 3 Clinicopathological characteristics of patients with OBC and non-OBC

Variables	OBC (N=479), (%)	non-OBC (N=115,739), (%)	P-valuea
Year of diagnosis			0.787
2004–2009	258 (53.86)	61,624 (53.24)
2010–2014	221 (46.14)	54,115 (46.76)
Age at diagnosis (years)			<0.001
18–49	113 (23.59)	37,141 (32.09)
≥50	366 (76.41)	78,598 (67.91)
Race			0.400
White	388 (81.00)	90,859 (78.51)
Black	56 (11.69)	14,110 (12.19)
Othersb	34 (7.10)	10,152 (8.77)
Unknown	1 (0.21)	61,8 (0.53)
Marital status			0.260
Married	276 (57.62)	66,767 (57.69)
Not marriedc	191 (39.87)	44,443 (38.40)
Unknown	12 (2.51)	4,529 (3.91)
Laterality			0.001
Left	246 (51.36)	58,563 (50.60)
Right	232 (48.43)	57,161 (49.39)
Only one side, NOS	1 (0.21)	15 (0.01)
Grade			<0.001
1 and 2	29 (6.06)	63,146 (54.56)
3 and UD	113 (23.59)	48,818 (42.18)
Unknown	337 (70.35)	3,775 (3.26)
AJCC stage			0.002
II	288 (60.13)	77,385 (66.86)
III	191 (39.87)	38,354 (33.14)
AJCC N stage			<0.001
N1	288 (60.13)	84,314 (72.85)
N2	97 (20.25)	20,940 (18.09)
N3	94 (19.62)	10,485 (9.06)
ER status			<0.001
Positive	265 (55.32)	90,126 (77.87)
Negative	175 (36.54)	22,415 (19.37)
Othersd	39 (8.14)	3,198 (2.76)
PR status			<0.001
Positive	179 (37.37)	77,211 (66.71)
Negative	250 (52.19)	34,421 (29.74)
Othersd	50 (10.44)	4,107 (3.55)
HER2 status			<0.001
Positive	58 (12.11)	9,113 (7.87)
Negative	136 (28.39)	4,2601 (36.81)
Otherse	285 (59.50)	6,4025 (55.32)
Breast subtype			<0.001
HoR+/Her2+	38 (7.93)	6,408 (5.54)
HoR+/Her2–	92 (19.21)	36,839 (31.83)
HoR–/Her2+	18 (3.76)	2,691 (2.33)
Triple negative	44 (9.19)	5,708 (4.93)
Unknown	287 (59.91)	64,093 (55.37)
Breast surgery type			<0.001
BCS	66 (13.78)	48,245 (41.68)
Mastectomy	179 (37.37)	66,487 (57.45)
No surgery	234 (48.85)	1,007 (0.87)
RT			0.294
Yes	269 (59.16)	62,225 (53.76)
No	210 (43.84)	53,514 (46.24)
No. of examined LNs			0.001
1–3	78 (16.28)	17,408 (15.04)
4–9	75 (15.66)	26,421 (22.83)
≥10	326 (68.06)	71,910 (62.13)
No. of positive LNs			<0.001
1–3	292 (60.96)	82,638 (71.40)
4–9	94 (19.62)	22,557 (19.49)
≥10	76 (15.87)	9,686 (8.37)
Unknown	17 (3.55)	858 (0.74)

Notes:

a P-value was assessed using Pearson’s chi-squared test or Fisher’s exact test.

b Including American Indian/Alaskan native and Asian/Pacific Islander.

c Including divorced, separated, single (never married), and widowed.

d Including borderline and unknown.

e HER2+ unknown includes borderline, unknown, and before 2010 breast cancer.

Abbreviations: AJCC, American Joint Committee on Cancer; BCS, breast-conserving surgery; ER, estrogen receptor; HoR, hormone receptor; LNs, lymph nodes; NOS, not otherwise specified; OBC, occult breast cancer; PR, progesterone receptor; RT, radiotherapy; UD, undifferentiated.

Figure 1 Kaplan–Meier survival curves according to the two groups of 1:1 matched patients.

Notes: (A) BCSS. (B) OS. Stratified log-rank tests were compared between OBC and non-OBC patients.

Abbreviations: BCSS, breast cancer-specific survival; OBC, occult breast cancer; OS, overall survival.

Figure 2 Kaplan–Meier survival curves according to the four groups based on different treatment strategies in OBC patients.

Notes: (A) BCSS. (B) OS. Log-rank tests were compared between groups.

Abbreviations: ALND, axillary lymph node dissection; BCS, breast-conserving surgery; BCSS, breast cancer-specific survival; OBC, occult breast cancer; OS, overall survival; SLND, sentinel lymph node dissection.