Co-expression of estrogen receptor α and Apolipoprotein D in node positive operable breast cancer – possible relevance for survival and effects of adjuvant tamoxifen in postmenopausal patients

Figures & data

Figure 1.  Flowsheet over patients included in the present paper. The 1^st sub-analysis was done to evaluate a possible role of ApoD_CN co-expression with ERα in the elderly patients ≥ 70 years. The 2^nd sub-analysis evaluated the potential influence of ApoD_CN status on the predictive effect of tamoxifen in the ERα positive postmenopausal patients with node positive disease included in the NBCG-1 trial [13]. DCIS, ductal carcinoma in situ; y, years; ERα, estrogen receptor alfa; ApoD_CN, Combined cytoplasmic and nuclear ApoD staining; pN+, node positive; NBCG-1, Norwegian Breast Cancer Group adjuvant study # 1 [13].

Table I.  Comparison of features between subgroups of ERα /ApoD_CN status (n = 290).

	ERα + /ApoDCN−	ERα + /ApoDCN+	p	ERα − /ApoDCN−	ERα − /ApoDCN+	p
	165	62		40	23
Age (median)	63(21–88)	65 (34–83)	0.49	53(25–82)	71(27–89)	<0.0001
<55 y*	44	18	0.93	23	4	<0.0001
55–69 y	76	27		13	5
≥70 y	45	17		4	14
pT1†	84	24	0.10	13	8	0.66
pT2	79	73		25	12
Unknown	2	1		2	3
pN0†	86	27	0.25	24	10	0.21
pN+	79	35		16	13
WHO Grade 1††	17	13	0.01	1	1	0.18
WHO Grade 2	105	34		9	10
WHO Grade 3	43	15		30	12
Tumor morphology††
IDC	144	56	0.54	34	22	0.38
ILC	18	6		4	1
Other	3	0		2	0
PR ≥10%§	138	7	0.65	19	14	0.31
PR <10%	22	54		21	9
Missing	5	1
Stage I†	58	17	0.30	9	9	0.16
Stage IIa	107	44		31	14
Unknown		1
Pre-menopausal∣∣	40	12	0.46	15	4	0.09
Postmenopausal	123	48		25	19
Unknown	2	2

*Age distribution according to the Norwegian Breast Cancer Group [18].

†pT, pN according to UICC criteria [15].

††Histological grading and tumor morphology according to WHO criteria [14]. IDC, infiltrating ductal carcinoma; ILC, infiltrating lobular carcinoma.

§PR, progesterone receptor; immunohistochemistry determination in TMA, cutoff 10%.

∣∣Clinical status.

Figure 2.  A. Relapse free survival (RFS; all locations) of the elderly patients ≥ 70 years. Grouping is based on ApoD_CN and ERα expression in the cytoplasm. A significant difference in RFS (p = 0.004) was found between group 1 (ERα + /ApoD_CN−) and group 2 (ERα + /ApoD_CN+). Of note is the observation of no significant difference (p=0.39) in RFS between group 2 (ERα + /ApoD_CN+) and group 3 (ERα − /ApoD_CN+). We excluded the ERα − /ApoD_CN− tumors from the analysis in this age group, due to a low number of patients (n = 4).B. Breast cancer specific survival (BCSS; dead of breast cancer) in the elderly patients > 70 years. Stratification is based on ERα/ApoD_CN category of the primary tumor. A statistically significant survival difference (p = 0.004) between group 1 (ERα + /ApoD_CN−) and group 2 (ERα + /ApoD_CN+) was observed, and also between group 2 and group 3 (ERα − /ApoD_CN+) (p = 0.03). We excluded the ERα − /ApoD_CN− tumors from the analysis in this age group, due to a low number of patients (n = 4).

Table II.  Univariate survival analysis of patients ≥70 years of age (n = 76)

	Events/ at risk	% censored	p	HR	95% CI
Relapse Free Survival (RFS)
pN0	17/51	66		1
pN+	28/40	30	<0.0001	3.2	1.2–5.8
pT1	14/41	66		1
pT2	30/49	39	0.01	2.3	1.2–4.3
WHO grade 1	4/15	73		1
WHO grade 2	26/53	51	0.16	2.2	0.8–6.2
WHO grade 3	15/23	35	0.01	4.1	1.4–12.4
PR +	29/66	56		1
PR −	11/17	35	0.09	1.8	0.9–3.7
Overall ERα/ApoD	36/76	53	<0.0001	1.6	1.2–2.2
ERα + /ApoDCN−	15/45	67		1
ERα + /ApoDCN+	11/17	35	0.007	3.0	1.3–6.6
ERα − /ApoDCN+	10/14	29	<0.0001	5.0	2.1–11.8
Breast Cancer Specific Survival (BCSS)
pN0	14/51	73		1
pN+	24/40	40	<0.0001	3.3	1.7–6.6
pT1	11/41	73		1
pT2	26/49	47	0.01	2.6	1.3–5.2
WHO grade 1	2/15	87
WHO grade 2	22/53	59	0.05	4.2	1.0–17.9
WHO grade 3	14/23	39	0.003	9.9	2.2–43.8
PR +	23/66	65
PR −	10/17	67	0.04	2.2	1.0–4.6
Overall ERα/ApoD	30/76	61	<0.0001	2.2	1.6–3.0
ERα + /ApoDCN−	10/45	78		1
ERα + /ApoDCN+	10/17	41	0.007	3.4	1.4–8.2
ERα − /ApoDCN+	10/14	29	<0.0001	11.1	4.2–29.0

Table III.  Multivariate analysis of patients ≥70 years of age (n = 72)

	Relapse Free Survival			Breast Cancer Specific Survival
	p	HR	95% CI	p	HR	95% CI
pN0		1			1
pN+	<0.0001	4.1	1.9–8.8	0.003	3.7	1.5–8.7
WHO grade 1		1			1
WHO grade 2	0.04	3.6	1.1–12.5	0.016	7.1	1.4–35.0
WHO grade 3	0.007	6.8	1.7–27.8	0.001	22.1	3.9–127.1
ERα + /ApoDCN−		1			1
ERα + /ApoDCN+	0.01	3.3	1.3–8.3	0.005	4.3	1.6–11.9
ERα − /ApoDCN+	0.03	3.3	1.1–9.5	0.007	5.0	1.6–15.8

Figure 3.  A. Breast cancer specific survival (BCSS) in the ApoD_CN− tumors of postmenopausal patients enrolled in a prospective randomized adjuvant study (Adjuvant study NBCG − 1) on 20 mg tamoxifen (TAM) for 2 years vs. placebo (i.e. Control = Ctr) [13].B. Breast cancer specific survival (BCSS) in the ApoD_CN+ tumors of postmenopausal patients enrolled in the prospective randomized adjuvant study (Adjuvant study NBCG – 1) on 20 mg tamoxifen (TAM) for 2 years vs. placebo (i.e. Control = Ctr) [13].