Intrinsic Breast Tumor Subtypes, Race, and Long-Term Survival in the Carolina Breast Cancer Study

Katie M. O'Brien; Stephen R. Cole; Chiu-Kit Tse; Charles M. Perou; Lisa A. Carey; William D. Foulkes; Lynn G. Dressler; Joseph Geradts; Robert C. Millikan

doi:10.1158/1078-0432.CCR-10-1533

DOI: 10.1158/1078-0432.CCR-10-1533 Published December 2010

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Fig. 1.
Race-stratified Kaplan–Meier plots and race effect estimates for breast cancer–specific mortality by immunohistochemical subtype in the Carolina Breast Cancer Study, 1993–2006. AA, African Americans.

Table 1.

Hazard ratios for breast cancer–specific mortality, stratified by race

	White (n = 631)		African American (n = 518)
	HR adjusted for age at diagnosis and date of diagnosis (95% CI)	HR adjusted for age at diagnosis, date of diagnosis, and stage at diagnosis (95% CI)	HR adjusted for age at diagnosis and date of diagnosis (95% CI)	HR adjusted for age at diagnosis, date of diagnosis, and stage at diagnosis (95% CI)
Menopausal status
Premenopausal	1.00	1.00	1.00	1.00
Postmenopausal	0.6 (0.3–1.0)	0.6 (0.3–1.0)	0.8 (0.5–1.3)	0.8 (0.5–1.3)
Subtype
Luminal A	1.00	1.00	1.00	1.00
Luminal B	1.6 (0.9–2.9)	1.5 (0.8–2.7)	1.3 (0.6–2.4)	1.2 (0.6–2.2)
Basal-like	2.0 (1.2–3.4)	1.7 (1.0–2.9)	1.5 (1.0–2.4)	1.4 (0.9–2.1)
HER2⁺/ER⁻	2.4 (1.2–4.7)	1.4 (0.7–2.9)	2.3 (1.3–4.0)	1.8 (1.0–3.1)
Unclassified	1.6 (0.9–3.1)	1.6 (0.9–3.1)	1.3 (0.8–2.3)	1.2 (0.7–2.0)
Subtype combined
Luminal A or B	1.00	1.00	1.00	1.00
Basal-like	1.8 (1.1–3.0)	1.6 (0.9–2.6)	1.5 (1.0–2.2)	1.3 (0.9–2.0)
HER2⁺/ER⁻	2.1 (1.1–4.2)	1.3 (0.6–2.6)	2.2 (1.3–3.7)	1.7 (1.0–2.9)
ER status
ER⁺	1.00	1.00	1.00	1.00
ER⁻	1.5 (1.0–2.2)	1.3 (0.9–1.9)	1.7 (1.2–2.5)	1.5 (1.0–2.2)
PR status
PR⁺	1.00	1.00	1.00	1.00
PR⁻	1.8 (1.2–2.7)	1.6 (1.1–2.4)	1.6 (1.1–2.3)	1.4 (0.9–2.0)
HER2 status
HER2⁻	1.00	1.00	1.00	1.00
HER2⁺	1.5 (0.9–2.3)	1.2 (0.7–1.9)	1.4 (0.9–2.2)	1.3 (0.8–1.9)

Table 2.

Hazard ratios for breast cancer–specific mortality, stratified by race and menopausal status and adjusted for age at diagnosis and date of diagnosis

	White		African American
	Premenopausal (n = 323)	Postmenopausal (n = 308)	Premenopausal (n = 238)	Postmenopausal (n = 280)
Subtype
Luminal A	1.00	1.00	1.00	1.00
Luminal B	1.2 (0.6–2.5)	2.9 (1.0–8.4)	1.2 (0.5–2.9)	1.3 (0.5–3.6)
Basal-like	1.8 (1.0–3.4)	3.9 (1.5–10.0)	1.3 (0.8–2.3)	1.9 (0.9–3.8)
HER2⁺/ER⁻	2.1 (0.9–5.0)	4.3 (1.4–13.6)	1.9 (0.9–4.2)	3.1 (1.3–7.2)
Unclassified	1.4 (0.7–3.0)	2.1 (0.6–7.4)	1.0 (0.5–2.0)	1.9 (0.8–4.3)
Subtype combined
Luminal A or B	1.00	1.00	1.00	1.00
Basal-like	1.8 (1.0–3.2)	3.0 (1.2–7.4)	1.3 (0.8–2.2)	1.8 (0.9–3.6)
HER2⁺/ER⁻	2.0 (0.9–4.8)	3.4 (1.1–10.3)	1.9 (0.9–4.0)	3.0 (1.3–6.9)
ER status
ER⁺	1.00	1.00	1.00	1.00
ER⁻	1.4 (0.9–2.2)	2.1 (1.0–4.2)	1.3 (0.8–2.2)	2.3 (1.3–3.9)
PR status
PR⁺	1.00	1.00	1.00	1.00
PR⁻	1.9 (1.2–3.0)	2.1 (1.0–4.2)	1.4 (0.9–2.3)	1.9 (1.1–3.4)
HER2 status
HER2⁻	1.00	1.00	1.00	1.00
HER2⁺	1.2 (0.7–2.1)	2.3 (1.1–5.1)	1.4 (0.8–2.5)	1.5 (0.8–2.9)

Table 3.

Time-stratified hazard ratios, breast cancer–specific mortality adjusted for race, age at diagnosis, and date of diagnosis

	Breast cancer–specific, time-stratified HR (95% CI)
	Years 0–5	Years > 5
Race
White	1.00	1.00
African American	1.6 (1.2–2.3)	1.9 (1.2–3.0)
Menopause
Premenopausal	1.00
Postmenopausal	0.8 (0.6–1.1)^a
Subtypes
Luminal A	1.00	1.00
Luminal B	1.3 (0.7–2.5)	1.5 (0.8–2.8)
Basal	2.7 (1.8–4.0)	0.6 (0.3–1.3)
HER2⁺/ER⁻	2.9 (1.7–5.0)	1.6 (0.8–3.5)
Unclassified	1.9 (1.2–3.2)	0.8 (0.3–1.8)
Combined subtypes
Luminal A and B	1.00	1.00
Basal	2.5 (1.7–3.7)	0.6 (0.3–1.1)
HER2⁺/ER⁻	2.8 (1.6–4.6)	1.5 (0.7–3.2)
ER status
ER⁺	1.00	1.00
ER⁻	2.5 (1.8–3.5)	0.7 (0.4–1.1)
PR status
PR⁺	1.00	1.00
PR⁻	2.2 (1.6–3.1)	1.0 (0.6–1.6)
HER2 status
HER2⁻	1.00
HER2⁺	1.4 (1.0–1.8)^a

↵^aSingle estimate given because proportional hazards assumption was not violated.

Table 4.

Hazard ratios for clinical characteristics according to tumor subtype, breast cancer–specific mortality, adjusted for race, age at diagnosis, and date of diagnosis

	All	Basal-like	Luminal A	Luminal B	HER2⁺/ER⁻	Unclassified
	(n = 1,149)	(n = 205)	(n = 625)	(n = 112)	(n = 73)	(n = 134)
Stage
Stage I	1.00	1.00	1.00	1.00	1.00	1.00
Stage II or III	2.9 (2.0–4.1)	3.6 (1.4–9.1)	3.0 (1.8–5.0)	2.6 (0.9–7.6)	3.6 (0.8–15.8)	1.3 (0.6–2.9)
Stage IV	12.7 (7.4–21.7)	6.4 (1.5–27.0)	18.9 (7.8–46.0)	11.0 (1.8–68.6)	14.0 (2.5–77.5)	13.1 (3.8–45.8)
Tumor size
≤2 cm	1.00	1.00	1.00	1.00	1.00	1.00
>2–5 cm	2.2 (1.7–3.1)	1.5 (0.8–2.9)	2.5 (1.6–4.0)	2.0 (0.8–4.9)	2.7 (0.8–9.6)	1.8 (0.8–4.1)
>5 cm	3.9 (2.7–5.9)	3.2 (1.5–7.1)	5.3 (2.9–9.8)	3.3 (1.0–11.5)	9.4 (2.2–40.1)	1.0 (0.3–3.7)
Number of lymph nodes positive for malignancy
None	1.00	1.00	1.00	1.00	1.00	1.00
1—2	2.0 (1.4–3.8)	2.7 (1.4–5.4)	2.2 (1.2–3.9)	1.6 (0.5–5.6)	2.0 (0.5–7.3)	1.0 (0.3–3.6)
3—5	3.7 (2.5–5.4)	6.4 (2.6–15.5)	4.9 (2.7–8.7)	2.4 (0.7–8.3)	2.5 (0.9–7.3)	1.8 (0.6–5.7)
≥6	5.4 (3.9–7.5)	7.2 (3.7–14.2)	7.7 (4.5–13.0)	5.4 (1.9–14.7)	4.7 (1.6–14.4)	1.9 (0.7–4.9)
Metastasis
No	1.00	1.00	1.00	1.00	1.00	1.00
Yes	5.8 (3.7–9.2)	2.2 (0.7–7.2)	8.9 (4.0–19.4)	5.2 (1.1–25.3)	4.5 (1.6–12.7)	11.3 (3.7–34.9)

Table 5.

Axillary lymph node variables stratified by tumor size, according to breast tumor subtype

	Basal-like	Luminal A	Luminal B	HER2⁺/ER⁻	Unclassified
	(n = 199)	(n = 608)	(n = 111)	(n = 69)	(n = 132)
Lymph node status, % positive tumors (n)
≤2 cm	30 (70)	19 (329)	35 (57)	23 (22)	21 (63)
>2–5 cm	41 (106)	54 (228)	61 (44)	59 (37)	47 (51)
>5 cm	57 (21)	79 (48)	86 (7)	100 (10)	56 (18)
P value^a	0.07	<0.0001	0.004	0.0002	0.002
Number of positive lymph nodes, mean (median)
≤2 cm	1.4 (0)	0.7 (0)	1.4 (0)	0.5 (0)	1.3 (0)
>2–5 cm	1.8 (0)	2.2 (1.0)	3.1 (1.0)	3.2 (1.0)	2.5 (0)
>5 cm	4.0 (1.0)	5.4 (2.0)	7.6 (4.0)	6.3 (6.0)	4.1 (1.0)
P value^b	0.04	<0.0001	0.001	<0.0001	0.002
% positive lymph nodes, mean (median)
≤2 cm	13% (0)	5% (0)	13% (0)	5% (0)	10% (0)
>2–5 cm	14% (0)	19% (7%)	19% (10%)	19% (11%)	22% (4%)
>5 cm	24% (8%)	34% (18%)	46% (54%)	47% (42%)	29% (7%)
P value^b	0.17	<0.0001	0.005	<0.0001	0.007