Parity-related molecular signatures and breast cancer subtypes by estrogen receptor status

Table 3 Associations between parity in PVLSI and PBCS data sets and gene expression enrichment ^a

	PVLSI signature		SHL signature		UICH signature
PVLSI normal tissues
GSEA ES^b	0.98		-0.52		0.71
GSEA FWER^b	0% (sig)		N/A		3% (sig)
Creighton analysis^c	Negative	Positive	Negative	Positive	Negative	Positive
Nulliparous	37 (69%)	17 (31%)	22 (41%)	32 (59%)	33 (61%)	21 (39%)
Parous	27 (36%)	49 (64%)	45 (59%)	31 (41%)	30 (39%)	46 (61%)
OR (95% CI)^d	3.95 (1.88 to 8.29)		0.47 (0.23 to 0.96)		2.4 (1.18 to 4.92)
P-value^e	0.0002 (sig)		N/A		0.015 (sig)
PBCS cancer-adjacent normal tissues
GSEA ES^b	0.52		0.24		0.60
GSEA FWER^b	5% (sig)		37%		14% (sig)
Creighton analysis^c	Negative	Positive	Negative	Positive	Negative	Positive
Nulliparous	17 (57%)	13 (43%)	16 (53%)	14 (47%)	15 (50%)	15 (50%)
Parous	58 (49%)	61 (51%)	62 (52%)	57 (48%)	62 (52%)	57 (48%)
OR (95% CI)^d	1.38 (0.61 to 3.08)		1.05 (0.47 to 2.34)		0.92 (0.41 to 2.05)
P-value^e	0.44		0.90		0.84
PBCS tumor tissues
GSEA ES^b	0.47		0.40		0.58
GSEA FWER^b	18%		24%		21%
Creighton analysis^c	Negative	Positive	Negative	Positive	Negative	Positive
Nulliparous	16 (53%)	14 (47%)	14 (47%)	16 (53%)	21 (70%)	9 (30%)
Parous	58 (49%)	61 (51%)	55 (46%)	64 (54%)	65 (55%)	54 (45%)
OR (95% CI)^d	1.20 (0.54 to 2.68)		1.02 (0.56 to 2.27)		1.94 (0.82 to 4.58)
P-value^e	0.65		0.96		0.13

^aCI, Confidence interval; ES, Enrichment score; FDR, False discovery rate; FWER, Family-wise error rate; GSEA, Gene set enrichment analysis; OR, Odds ratio; N/A, Not applicable; PVLSI, Samples obtained from normal breast tissue of 130 women who underwent reduction mammoplasty surgery at Baystate Medical Center in Springfield, MA, USA, and banked at the Pioneer Valley Life Sciences Institute; SHL, Normal breast samples from 107 postmenopausal healthy volunteers recruited at the Sunderby Hospital in Luleå, Sweden; UICH, Mammoplasty benign biopsy specimens from 24 premenopausal women from the University of Illinois at Chicago Hospital. ^bIn GSEA analysis, ES indicates the GSEA enrichment score and FWER is the corresponding family-wise error rate and considered significant (sig) if ≤ 15%. ^cIn Creighton analysis, “Positive” and “Negative” indicate enriched and not enriched expression of parity signature, respectively. ^dIn Creighton analysis, odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by unconditional logistic regression analysis with observed parity as the outcome variable and nulliparity as the reference. ^eIn Creighton analysis, P-values were obtained by χ² test or Fisher’s exact test if the expected cell count was less than five, and considered significant (sig) if ≤ 0.05.

ISSN: 1465-542X