Serum immuno-oncology markers carry independent prognostic information in patients with newly diagnosed metastatic breast cancer, from a prospective observational study

Gunnarsdottir, Frida Björk; Bendahl, Pär-Ola; Johansson, Alexandra; Benfeitas, Rui; Rydén, Lisa; Bergenfelz, Caroline; Larsson, Anna-Maria

doi:10.1186/s13058-023-01631-6

Table 3 Odds ratios of top serum protein levels by patient and tumor clinicopathological features

From: Serum immuno-oncology markers carry independent prognostic information in patients with newly diagnosed metastatic breast cancer, from a prospective observational study

				ADA			CAIX			CASP8			CD244			CD8A
Clinicopathological features		N	OR	95%CI	P value	OR	95%CI	P value	OR	95%CI	P value	OR	95%CI	P value	OR	95%CI	P value
Age	< 65	65	1			1			1			1			1
	≥ 65	71	0.52	0.26–1.03	0.086^a	1.06	0.54–2.08	1.00^a	0.94	0.48–1.85	1.00^a	0.94	0.48–1.85	1.00^a	0.59	0.30–1.16	0.17^a
ECOG	0	75	1			1			1			1
	1	36	1.27	0.57–2.82	0.55^b	1.14	0.51–2.53	0.75^b	3.36	1.46–7.75	0.005^b	0.83	0.37–1.84	0.65^b	0.78	0.35–1.73	0.54^b
	2	21	2.55	0.92–7.03	0.071^b	3.18	1.11–9.10	0.031^b	3.36	1.21–9.32	0.020^b	0.33	0.12–0.95	0.039^b	1.07	0.41–2.82	0.89^b
NHG	I-II	68	1			1			1			1
	III	42	1.53	0.71–3.32	0.33^a	1.06	0.49–2.29	1.00^a	1.15	0.53–2.49	0.84^a	0.81	0.37–1.75	0.7^a	0.59	0.27–1.29	0.24^a
PT tumor size	1	49	1			1			1			1
	2	46	1.88	0.83–4.25	0.13b	1.05	0.47–2.34	0.91^b	1.03	0.46–2.31	0.94^b	1.03	0.46–2.31	0.94^b	1.23	0.55–2.75	0.62^b
	3	17	1.40	0.46–4.27	0.55^b	0.52	0.17–1.64	0.27^b	1.09	0.36–3.30	0.88^b	3.99	1.14–13.98	0.031^b	1.38	0.46–4.17	0.57^b
	4	17	2.90	0.92–9.13	0.070^b	1.08	0.36–3.26	0.89^b	2.25	0.72–7.06	0.16^b	1.75	0.57–5.36	0.33^b	2.25	0.72–7.06	0.16^b
PT node status	Neg	39	1			1			1			1
	Pos	79	0.84	0.39–1.80	0.70^a	0.65	0.30–1.40	0.33^a	0.55	0.26–1.20	0.17^a	1.62	0.75–3.53	0.24^a	1.47	0.68–3.18	0.43^a
MFI	0	28	1			1			1			1
	0–3	25	1.27	0.43–3.76	0.66^b	1.73	0.58–5.16	0.33^b	1.10	0.37–3.26	0.86^b	1.78	0.59–5.36	0.31^b	1.08	0.37–3.19	0.88^b
	> 3	83	0.93	0.40–2.19	0.87^b	1.07	0.46–2.53	0.87^b	0.77	0.33–1.81	0.55^b	0.84	0.36–1.99	0.70^b	0.98	0.41–2.30	0.96^b
Metastatic sites	< 3	96	1			1			1			1
	≥ 3	40	2.39	1.11–5.13	0.038^a	1.33	0.63–2.79	0.57^a	2.79	1.28–6.05	0.014^a	1	0.48–2.09	1.00^a	1.33	0.63–2.79	0.57^a
Site of metastasis	Non-visceral	56	1			1			1			1
	Visceral	80	1.28	0.64–2.53	0.60^a	2.37	1.18–4.78	0.023^a	1.63	0.82–3.24	0.22^a	1.13	0.57–2.24	0.86^a	1.13	0.57–2.24	0.86^a
First line	Endocrine	55	1			1			1			1
treatment	Chemotherapy	60	3.08	1.44–6.62	0.004^b	1.98	0.94–4.17	0.072^b	2.14	1.01–4.52	0.047^b	0.72	0.35–1.51	0.39^b	1.19	0.57–2.47	0.65^b
	HER2 targeted	13	4.63	1.25–17.07	0.021^b	2.59	0.75–8.98	0.13^b	2.80	0.81–9.73	0.11^b	0.66	0.20–2.23	0.51^b	0.46	0.13–1.68	0.24^b
CTC	< 5	65	1			1			1			1
	≥ 5	69	3.44	1.69–7.00	0.001^a	1.27	0.65–2.51	0.50^a	1.62	0.82–3.21	0.17^a	0.62	0.31–1.22	0.17^a	1.20	0.61–2.36	0.73^a
CTC clusters	Neg	108	1			1			1			1
	Pos	26	4.49	1.67–12.08	0.002^a	2.27	0.93–5.55	0.082^a	2.27	0.93–5.55	0.082^a	0.54	0.22–1.29	0.19^a	1.21	0.51–2.86	0.83^a
PAM50 subtype	Luminal A	39	1			1			1			1
	Luminal B	41	6.25	2.35–16.55	0.0002^b	1.13	0.46–2.78	0.78^b	2.56	1.03–6.33	0.043^b	1.83	0.75–4.44	0.18^b	0.90	0.37–2.17	0.81^b
	HER2 enriched	13	6.53	1.64–25.93	0.0077^b	3.60	0.94–13.79	0.062^b	4.50	1.16–17.41	0.029^b	1.11	0.31–3.91	0.87^b	0.38	0.10–1.45	0.16^b
	Basal like	14	2.90	0.81–10.33	0.10^b	4.00	1.06–15.08	0.041^b	3.60	1.00–12.95	0.050^b	1.29	0.38–4.40	0.68^b	0.86	0.25–2.91	0.81^b

				CSF1			FasL			IL-6			IL-8			IL-10
Clinicopathological features		N	OR	95%CI	P value	OR	95%CI	P value	OR	95%CI	P value	OR	95%CI	P value	OR	95%CI	P value
Age	< 65	65	1			1			1			1			1
	≥ 65	71	1.34	0.68–2.64	0.49^a	0.66	0.34–1.30	0.30^a	1.19	0.61–2.34	0.73^a	0.84	0.43–1.64	0.73^a	1.19	0.61–2.34	0.73^a
ECOG	0	75	1			1			1			1			1
	1	36	3.77	1.63–8.74	0.002^b	0.42	0.19–0.96	0.039^b	2.97	1.30–6.78	0.010^b	2.50	1.11–5.64	0.027^b	1.68	0.75–3.74	0.20^b
	2	21	4.71	1.63–13.59	0.004^b	0.33	0.12–0.92	0.034^b	2.73	1.01–7.40	0.049^b	19.00	4.10–88.10	< 0.001^b	2.69	0.97–7.42	0.057^b
NHG	I-II	68	1			1			1			1			1
	III	42	1.24	0.57–2.67	0.70^a	0.63	0.29–1.36	0.33^a	1.39	0.64–3.02	0.44^a	1.45	0.67–3.13	0.43^a	1.02	0.47–2.21	1.00^a
PT tumor size	1	49	1			1			1			1			1
	2	46	1.59	0.71–3.57	0.26^b	1.04	0.46–2.32	0.93^b	1.46	0.65–3.27	0.36^b	1.46	0.65–3.28	0.36^b	0.95	0.42–2.13	0.90^b
	3	17	0.93	0.31–2.86	0.90^b	2.71	0.83–8.87	0.099^b	0.93	0.31–2.86	0.90^b	1.09	0.36–3.30	0.88^b	1.62	0.53–4.94	0.40^b
	4	17	2.44	0.78–7.68	0.13^b	1.27	0.42–3.84	0.67^b	3.20	0.98–10.49	0.055^b	1.38	0.46–4.17	0.57^b	1.62	0.53–4.94	0.40^b
PT node status	Neg	39	1			1			1			1			1
	Pos	79	0.88	0.41–1.90	0.85^a	1.2	0.55–2.58	0.7^a	1.03	0.48–2.22	1.00^a	0.76	0.35–1.63	0.56^a	0.80	0.37–1.72	0.70^a
MFI	0	28	1			1			1			1			1
	0–3	25	1.50	0.50–4.46	0.47^b	1.73	0.58–5.16	0.33^b	0.82	0.28–2.46	0.73^b	1.10	0.37–3.26	0.86^b	0.58	0.19–1.72	0.33^b
	> 3	83	0.89	0.38–2.09	0.78^b	1.07	0.46–2.53	0.87^b	0.52	0.22–1.25	0.14^b	0.77	0.33–1.81	0.55^b	0.93	0.40–2.20	0.87^b
Metastatic sites	< 3	96	1			1			1			1			1
	≥ 3	40	2.79	1.28–6.05	0.014^a	0.87	0.42–1.82	0.85^a	3.27	1.49–7.19	0.004^a	2.79	1.28–6.05	0.014^a	2.39	1.11–5.13	0.038^a
Site of metastasis	Non-visceral	56	1			1			1			1			1
	Visceral	80	2.09	1.04–4.19	0.055^a	1.28	0.64–2.53	0.60^a	2.70	1.33–5.47	0.009^a	1.85	0.92–3.68	0.12^a	1.63	0.82–3.24	0.22^a
First line	Endocrine	55	1			1			1			1			1
treatment	Chemotherapy	60	1.59	0.76–3.33	0.22^b	0.71	0.34–1.49	0.37^b	1.85	0.88–3.89	0.11^b	1.85	0.88–3.89	0.11^b	1.71	0.82–3.60	0.15^b
	HER2 targeted	13	1.62	0.48–5.47	0.44^b	0.2	0.049–0.81	0.024^b	1.89	0.56–6.39	0.31^b	1.89	0.56–6.39	0.31^b	1.29	0.38–4.34	0.69^b
CTC	< 5	65	1			1			1			1			1
	≥ 5	69	1.83	0.92–3.63	0.088^a	1	0.51–1.97	1.00^a	1.44	0.73–2.84	0.31^a	2.07	1.04–4.12	0.04^a	1.52	0.77–3.01	0.30^a
CTC clusters	Neg	108	1			1			1			1			1
	Pos	26	1.52	0.64–3.62	0.39^a	0.8	0.34–1.88	0.67^a	1.04	0.44–2.44	1.00^a	8	2.58–24.82	< 0.001^a	4.33	1.61–11.63	0.004^a
PAM50 subtype	Luminal A	39	1			1			1			1			1
	Luminal B	41	2.02	0.83–4.95	0.12^b	1.34	0.56–3.24	0.51^b	1.23	0.51–2.97	0.64^b	2.28	0.93–5.61	0.072^b	1.11	0.46–2.67	0.81^b
	HER2 enriched	13	1.00	0.28–3.52	1.00^b	0.47	0.12–1.78	0.27^b	1.51	0.43–5.33	0.52^b	4.02	1.04–15.46	0.043^b	1.36	0.39–4.79	0.63^b
	Basal like	14	0.88	0.26–3.00	0.83^b	0.79	0.23–2.70	0.71^b	2.33	0.66–8.24	0.19^b	4.46	1.18–16.90	0.028^b	2.92	0.78–10.91	0.11^b

				MCP2			MUC16			TNFRSF4
Clinicopathological features		N	OR	95%CI	P value	OR	95%CI	P value	OR	95%CI	P value
Age	< 65	65	1			1			1
	≥ 65	71	1.34	0.68–2.64	0.49^a	1.19	0.61–2.34	0.73^a	1.06	0.54–2.08	1.00^a
ECOG	0	75	1			1			1
	1	36	1.60	0.72–3.57	0.25^b	1.77	0.80–3.96	0.16^b	1.68	0.75–3.74	0.20^b
	2	21	1.04	0.39–2.74	0.94^b	5.08	1.68–15.35	0.004^b	2.18	0.81–5.89	0.12^b
NHG	I-II	68	1			1			1
	III	42	0.94	0.44–2.04	1.00^a	0.96	0.45–2.08	1.00^a	1.06	0.49–2.29	1.00^a
PT tumor size	1	49	1			1			1
	2	46	0.75	0.33–1.67	0.48^b	0.88	0.39–1.96	0.75^b	2.05	0.91–4.65	0.085^b
	3	17	0.72	0.24–2.19	0.57^b	1.49	0.49–4.55	0.49^b	1.78	0.58–5.40	0.31^b
	4	17	0.92	0.30–2.77	0.88^b	1.17	0.39–3.54	0.78^b	2.90	0.92–9.13	0.070^b
PT node status	Neg	39	1			1			1
	Pos	79	1.39	0.65–3.01	0.44^a	1.26	0.58–2.72	0.70^a	1.33	0.61–2.87	0.056^a
MFI	0	28	1			1			1
	0–3	25	1.07	0.36–3.14	0.91^b	1.73	0.58–5.16	0.33^b	1.18	0.50–2.79	0.70^b
	> 3	83	1.24	0.53–2.93	0.62^b	1.07	0.46–2.53	0.87^b	0.95	0.39–2.31	0.90^b
Metastatic sites	< 3	96	1			1			1
	≥ 3	40	2.39	1.11–5.13	0.038^a	3.27	1.49–7.19	0.004^a	2.79	1.28–6.05	0.014^a
Site of metastasis	Non-visceral	56	1			1			1
	Visceral	80	2.37	1.18–4.78	0.023^a	2.09	1.04–4.19	0.055^a	1.63	0.82–3.24	0.22^a
First line	Endocrine	55	1			1			1
treatment	Chemotherapy	60	0.83	0.40–1.74	0.63^b	2.17	1.02–4.60	0.044^b	1.58	0.76–3.30	0.22^b
	HER2 targeted	13	0.37	0.10–1.35	0.13^b	4.26	1.16–15.68	0.029^b	0.81	0.23–2.78	0.74^b
CTC	< 5	65	1			1			1
	≥ 5	69	0.74	0.38–1.46	0.49^a	3.44	1.69–7.00	< 0.001^a	1.52	0.77–3.01	0.30^a
CTC clusters	Neg	108	1			1			1
	Pos	26	0.56	0.23–1.34	0.28^a	5.88	2.06–16.76	< 0.001^a	3.39	1.32–8.74	0.015^a
PAM50 subtype	Luminal A	39	1			1			1
	Luminal B	41	0.99	0.41–2.39	0.99^b	1.84	0.76–4.46	0.18^b	1.83	0.75–4.44	0.18^b
	HER2 enriched	13	0.54	0.15–1.93	0.34^b	1.68	0.47–5.93	0.42^b	0.81	0.22–2.92	0.75^b
	Basal like	14	0.86	0.25–2.91	0.81^b	3.59	0.96–13.50	0.058^b	2.33	0.66–8.24	0.19^b

CTC circulating tumor cells; ECOG Eastern Cooperative Oncology Group; HER2 human epidermal growth factor receptor 2; MFI metastasis-free interval; NHG Nottingham histological grade; PT primary tumor
^aP value from Fisher’s exact test
^bP value from logistic regression

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