Women with preeclampsia may have reduced risk of breast cancer: a meta-analysis of cohort studies with 7.8 million participants

Figures & data

Figure 1. Study flow chart.

Table 1. Details of included studies.

Study	Location	Database	Type	Sample size	PE (%)	Breast cancer (%)	Identification of PE	Identification of breast cancer	Parity	Pre or post-menopausal Breast cancer	Confounders adjusted	Follow-up (years)	NOS score
Cohn 2001 (14)	USA	Child Health and Development Studies Cohort	P	3804	2.3	3.8	Medical records	Medical records	Any	NR	Maternal age, year of birth, age at first pregnancy, maternal weight gain, and parity	19	9
Mogren 2001 (13)	Sweden	The Swedish Cancer Registry	R	40951	8.3	2.1	ICD codes	Medical records	Primiparous	NR	Maternal age, parity, year of birth, and hospital of delivery	25	9
Calderon-Margalit 2009 (5)	Israel	Jerusalem Perinatal study cohort	R	37033	2.9	2.6	Medical records	ICD codes	Any	NR	Maternal age, parity, ethnicity, religion, and diabetes	30	9
Ma 2010 (15)	USA	California Teachers Study	P	52464	NR	5.4	Patient reported	Medical records	Any	Post	Maternal age, year of birth, and parity	NR	7
Bhattacharya 2012 (16)	UK	Aberdeen Maternity and Neonatal Databank	R	34845	5.8	2.6	Medical records	Medical records	Primiparous	NR	Year of birth, social class and smoking	25	8
Opdahl 2012 (17)	Norway	Cancer Registry in Norway	P	919712	2.8	1.7	ICD codes	ICD codes	Any	Both	Maternal age, year of birth, age at first pregnancy, length of gestation, marital status, and parity	21	9
Pacheco 2015 (18)	Denmark	Danish Medical Birth Registry and Cancer registry	R	778701	3.6	1.3	ICD codes	ICD codes	Any	Both	Maternal age, year of birth, and parity	16	9
Walfisch 2015 (6)	Israel	Hospital of the Negev	R	103180	8.1	0.5	ICD codes	ICD codes	Any	NR	Maternal age, year of birth, and parity	12	8
Yang 2018 (8)	Sweden	Nationwide cohort Karolinska Mammography Project	R	1337934 55044	5 5	2 4.5	ICD codes Patient reported	ICD codes Mammograms	Any	Both	Calender period, number of births, age at first birth, weight status categories, smoking status and education level. Second cohort also adjusted for alcohol use, age at menarche, body shape at age 18 years, physical activity at age 18 years and irregular menstrual cycles in adult life	21.6 29.2	9
Serrand 2021 (19)	France	Registries of French Hospitals	R	4322970	1.1	0.001	ICD codes	ICD codes	Primiparous	NR	Age, insurance status, year of first-detected pregnancy, and comorbidities (obesity, high blood pressure, history of diabetes, dyslipidemia, history of kidney or liver failure, chronic obstructive pulmonary disease or asthma, and history of cardiovascular disease)	8	8
Nichols 2023 (7)	UK, USA	Premenopausal Breast Cancer Collaborative Group (Four cohorts)	P	152055	NR	1.8	Patient-reported/Medical records	Patient-reported/Medical records	Any	Pre	Age, education, smoking in young adulthood, body mass index	10	7

Figure 2. Meta-analysis of association between PE and subsequent risk of breast cancer.

Figure 3. Funnel plot to assess publication bias.

Table 2. Details of sensitivity analysis.

Excluded study	Risk ratio (95% confidence intervals)	P value
Cohn 2001 (14)	0.89 [0.83, 0.95]	<.001
Mogren 2001 (13)	0.87 [0.82, 0.93]	<.001
Calderon-Margalit 2009 (5)	0.87 [0.84, 0.91]	<.001
Ma 2010 (15)	0.88 [0.82, 0.95]	<.001
Bhattacharya 2012 (16)	0.89 [0.83, 0.96]	.002
Opdahl 2012 (17)	0.89 [0.82, 0.97]	.009
Pacheco 2015 (18)	0.90 [0.83, 0.97]	.005
Walfisch 2015 (6)	0.89 [0.82, 0.95]	.001
Yang 2018’ (8)	0.89 [0.81, 0.97]	.008
Yang 2018 (8)	0.90 [0.84, 0.96]	.003
Serrand 2021 (19)	0.89 [0.83, 0.96]	.002
Nichols 2023 (7)	0.89 [0.82, 0.97]	.005

Table 3. Subgroup analyses.

Variable	Groups	Studies	Risk ratio (95% confidence intervals)
Location	USA Europe Israel	2 6 2	0.95 [0.72, 1.27] 0.86 [0.81, 0.92] 1.12 [0.74, 1.69]
Study type	Prospective Retrospective	4 7	0.87 [0.81, 0.93] 0.90 [0.81, 1.00]
Parity	Primaparous Any	3 8	0.89 [0.72, 1.10] 0.88 [0.82, 0.95]
Data extraction	Patient reported Medical records/ICD codes	3* 9*	0.84 [0.75, 0.95] 0.90 [0.83, 0.98]
Incidence of breast cancer	≥2% <2%	6 5	0.95 [0.82, 1.09] 0.85 [0.80, 0.90]
Follow-up	<20 years ≥20 years	5 5	0.83 [0.77, 0.90] 0.92 [0.82, 1.03]

ICD, international classification of diseases.

*no of cohorts.

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