Table 1 Immunostain assay results, based on two independent TMAs 1 and 2, for 30 randomly selected breast cancer tumor specimens (5 per decade; all FFPE) for: CK cocktail, ER, PR, HER2, CK 5/6, EGFR, Ki67, and molecular phenotype (Kaiser Permanente, Northern California, USA, 1947–2009)

From: Analyzing historical trends in breast cancer biomarker expression: a feasibility study (1947–2009)

Year range

ID

Year of diagnosis

Histologic diagnosis

Histologic grade

CK cocktail

ER

PR

HER2

CK 5/6

EGFR

Ki67

Molecular phenotype

     

TMA1

TMA2

TMA1

TMA2

TMA1

TMA2

TMA1

TMA2

TMA1

TMA2

TMA1

TMA2

TMA1

TMA2

TMA1

TMA2

1947–1959

1–1

1955

Invasive carcinoma with ductal and lobular features

2

+

+

+

+

1.3%

0.3%

Luminal A

Luminal A

 

1–2

1957

IDC

2

+

+

+

+

+

+

3+

3+

9.0%

4.7%

Luminal B

Luminal B

 

1–3

1959

IDC

3

+

+

+

+

+

+

2.7%

5.3%

Luminal A

Luminal A

 

1–4

1956

Invasive lobular carcinoma

2

+

+

+

+

+

+

1.3%

2.0%

Luminal A

Luminal A

 

1–5

1956

IDC

3

12.3%

12.7%

Unclassifiable

Unclassifiable

1960–1969

2–6

1968

Solid papillary carcinoma

2

+

+

+

+

+

+

3.0%

3.3%

Luminal A

Luminal A

 

2–7

1969

IDC

3

+

+

2+

2+

+

23.0%

18.0%

Basal-like

Unclassifiable

 

2–8

1969

IDC

2

+

+

+

+

+

+

3+

3+

9.0%

5.7%

Luminal B

Luminal B

 

2–9

1968

Invasive mucinous carcinoma

2

+

+

+

+

2.7%

4.0%

Luminal A

Luminal A

 

2–10

1965

IDC with medullary features

3

+

+

+

+

+

7.0%

5.0%

Basal-like

Basal-like

1970–1979

3–11

1973

IDC

1

+

+

+

+

+

+

6.0%

4.7%

Luminal A

Luminal A

 

3–12

1974

IDC

3

+

+

+

+

+

+

6.0%

7.3%

Luminal A

Luminal A

 

3–13

1977

IDC

3

a

+

a

+

a

+

a

a

a

a

16.3%

a

Luminal B

 

3–14

1979

Solid papillary carcinoma

2

+

+

+

+

+

+

+

+

1.7%

2.5%

Luminal A

Luminal A

 

3–15

1974

IDC

3

+

+

3+

3+

+

8.7%

8.0%

HER2

HER2

1980–1989

4–16

1988

IDC

3

+

+

+

+

+

+

2.0%

2.0%

Luminal A

Luminal A

 

4–17

1980

IDC

3

+

+

9.7%

7.3%

Unclassifiable

Unclassifiable

 

4–18

1985

IDC

3

+

+

+

+

+

10.0%

3.5%

Luminal A

Luminal A

 

4–19

1986

Tubular carcinoma

1

+

+

+

+

b

1.3%

1.0%

Luminal A

Unknown

 

4–20

1985

IDC

1

+

+

+

+

+

1.0%

0.5%

Luminal A

Luminal A

1990–1999

5–21

1999

IDC

3

+

+

3+

3+

12.7%

13.3%

HER 2

HER 2

 

5–22

1994

Mixed IDC and mucinous carcinoma

3

+

+

+

+

+

+

9.3%

11.0%

Luminal A

Luminal A

 

5–23

1996

Invasive carcinoma with ductal and lobular features

2

+

+

+

+

+

+

1.7%

3.5%

Luminal A

Luminal A

 

5–24

1995

Invasive carcinoma with ductal and lobular features

2

+

+

+

+

+

+

16.0%

8.0%

Luminal B

Luminal A

 

5–25

1998

Invasive carcinoma with ductal and lobular features

2

+

+

+

+

5.7%

7.7%

Luminal A

Luminal A

2000–2009

6–26

2006

IDC

3

+

+

+

+

+

+

3+

3+

17.7%

12.0%

Luminal B

Luminal B

 

6–27

2002

IDC

3

+

+

3+

3+

13.3%

14.0%

HER 2

HER 2

 

6–28

2000

Invasive carcinoma with ductal and lobular features

2

+

+

+

+

+

+

b

5.7%

8.3%

Luminal A

Luminal A or Luminal B

 

6–29

2002

IDC with medullary features

3

+

+

2+

+

+

+

+

6.3%

7.7%

Basal-like

Basal-like

 

6–30

2000

IDC

3

+

+

+

+

+

+

6.3%

6.7%

Luminal A

Luminal A

Percent concordance

100%

100%

93%

97%

93%

97%

90%

90%

Kappa (95% confidence interval)

1.000 (1.000, 1.000)

1.000 (1.000, 1.000)

0.926 (0.705, 1.000)

0.908 (0.731, 1.000)

0.628 (0.155, 1.000)

0.782 (0.372, 1.000)

0.346 c (−0.225, 0.916)

0.724 (0.591, 0.976)

  1. Abbreviations: CK, cytokeratin; ER, estrogen receptor; EGFR, epidermal growth factor receptor; FFPE, formalin-fixed paraffin-embedded; HER2, human epidermal growth factor receptor 2; ID, case identification; IDC, invasive ductal carcinoma; PR, progesterone receptor; TMA, tissue microarray.
  2. Molecular phenotype algorithm13,1921:
  3. Luminal A—ER+ and/or PR+, HER2, Ki67<14%.
  4. Luminal B—ER+ and/or PR+ and HER2+ OR ER+ and/or PR+, HER2, and Ki6714%.
  5. HER2—ER and PR, and HER2+.
  6. Basal-like—ER, PR, HER2, CK 5/6+ and/or EGFR+.
  7. aResults for case 3–13 were missing for TMA1.
  8. bResults unknown owing to no tissue being present in all 3 cores obtained for the TMA.
  9. cKappa for Ki67 for dichotomous categorization as <14% vs. 14%.