Table 2.

The association between tumor mutation burden (TMB) of neuroendocrine pathways and breast cancer prognosis

Pathway	Somatic Mutation a	WCH + TCGA			WCH			TCGA			P for heterogeneity
		Cases	Controls	Odds ratio b	Cases	Controls	Odds ratio	Cases	Controls	Odds ratios
Adrenergic	No mutation	77	75	Ref	38	49	Ref	39	26	Ref	-
	Any mutation	131	133	1.16 (0.74, 1.81)	58	47	2.01 (1.06, 3.8)	73	86	0.66 (0.34, 1.29)	0.02
	TMB	208	208	1.07 (0.91, 1.24)	96	96	1.28 (1.02, 1.59)	112	112	0.89 (0.7, 1.12)	0.03
Glucocorticoid	No mutation	122	137	Ref	55	65	Ref	67	82	Ref	-
	Any Mutation	86	71	1.66 (1.07, 2.58)	41	31	1.81 (0.95, 3.44)	45	40	1.57 (0.84, 2.95)	0.76
	TMB	208	208	1.17 (1.02, 1.35)	96	96	1.22 (0.99, 1.51)	112	112	1.12 (0.91, 1.38)	0.57
Dopaminergic	No mutation	135	138	Ref	59	68	Ref	76	70	Ref	-
	Any Mutation	73	70	1.07 (0.69, 1.66)	37	28	1.84 (0.95, 3.56)	36	42	0.7 (0.37, 1.33)	0.04
	TMB	208	208	1.02 (0.89, 1.17)	96	96	1.2 (0.98, 1.46)	112	112	0.88 (0.72, 1.08)	0.03
Serotonergic	No mutation	135	140	Ref	60	70	Ref	75	70	Ref	-
	Any Mutation	73	68	1.04 (0.66, 1.62)	36	26	1.74 (0.9, 3.36)	37	42	0.61 (0.32, 1.18)	0.03
	TMB	208	208	1.02 (0.89, 1.18)	96	96	1.2 (0.98, 1.47)	112	112	0.85 (0.68, 1.05)	0.02
Cholinergic	No mutation	61	76	Ref	30	49	Ref	21	27	Ref	-
	Any Mutation	147	132	1.59 (1.01, 2.53)	66	47	2.75 (1.42, 5.32)	81	85	0.87 (0.44, 1.72)	0.02
	TMB	208	208	1.14 (0.97, 1.34)	96	96	1.33 (1.06, 1.67)	112	112	0.95 (0.74, 1.21)	0.05

^aSomatic mutation burden of candidate genes in each pathway were firstly categorized as mutated or nonmutated, and then treated as a continuous variable (log2 scale)

^bOdds ratios were estimated using logistic regression models and adjusted for cohort membership, age at diagnosis, menopausal status at diagnosis, molecular subtype, and cancer stage

^cBetween-cohort heterogeneity was calculated using Q-statistics