Julie Horn

Reproductive history and the risk of molecular breast cancer subtypes in a prospective study of Norwegian women

PurposeBreast cancer can be classified into molecular subtypes that differ in clinical characteristics and prognosis. There is some but conflicting evidence that reproductive risk factors may differ between distinct breast cancer subtypes.MethodsWe investigated associations of reproductive factors with the risk for six molecular breast cancer subtypes in a cohort of 21,532 Norwegian women who were born between 1886 and 1928 and followed up for breast cancer incidence between 1961 and 2008. We obtained stored tumor tissue from incident breast cancers and used immunohistochemistry and in situ hybridization to classify 825 invasive tumors into three luminal subtypes [Luminal A, Luminal B (HER2−) and Luminal B (HER2+)] and three non-luminal subtypes [human epidermal growth factor receptor 2 (HER2) subtype, basal-like phenotype (BP) and five negative phenotype (5NP)]. We used Cox regression to assess reproductive factors and risk for each subtype.ResultsWe found that young age at menarche, old age at first birth and low parity were associated with increased risk for luminal breast cancer subtypes. For the HER2 subtype, we either found no association or associations in the opposite direction compared to the luminal subtypes. The BP subtype appeared to have a similar reproductive risk profile as the luminal subtypes. Breastfeeding was associated with a reduced risk for HER2 and 5NP subtypes, but was not associated with any other subtype.ConclusionsThe results suggest that molecular breast cancer subtypes differ in their reproductive risk factors, but associations with non-luminal subtypes are still poorly understood and warrant further study.

Validity of a selection of pregnancy complications in the Medical Birth Registry of Norway

The validity of information on pregnancy complications in the Medical Birth Registry of Norway (MBRN) is insufficiently studied. The objective was to examine the validity of information on gestational age, birthweight, medically initiated delivery, and gestational hypertension in the MBRN.

Anthropometric factors and risk of molecular breast cancer subtypes among postmenopausal Norwegian women

Adult height and body weight are positively associated with breast cancer risk after menopause, but few studies have investigated these factors according to molecular breast cancer subtype. A total of 18,562 postmenopausal Norwegian women who were born between 1886 and 1928 were followed up for breast cancer incidence from the time (between 1963 and 1975) height and weight were measured until 2008. Immunohistochemical and in situ hybridization techniques were used to subtype 734 incident breast cancer cases into Luminal A, Luminal B [human epidermal growth factor receptor 2 (HER2−)], Luminal B (HER2+), HER2 subtype, basal‐like phenotype (BP) and five‐negative phenotype (5NP). We used Cox regression analysis to assess adult height and body mass index (BMI) in relation to risk of these subtypes. We found a positive association of height with risk of Luminal A breast cancer (ptrend, 0.004), but there was no clear association of height with any other subtype. BMI was positively associated with risk of all luminal breast cancer subtypes, including Luminal A (ptrend, 0.002), Luminal B (HER2−) (ptrend, 0.02), Luminal B (HER2+) (ptrend, 0.06), and also for the HER2 subtype (ptrend, 0.04), but BMI was not associated with risk of the BP or 5NP subtypes. Nonetheless, statistical tests for heterogeneity did not provide evidence that associations of height and BMI differed across breast cancer subtypes. This study of breast cancer risk among postmenopausal women suggests that height is positively associated with risk of Luminal A breast cancer. BMI is positively associated with risk of all luminal subtypes and for the HER2 subtype.

Reproductive and hormonal risk factors of breast cancer: a historical perspective

The complexity of breast cancer etiology has puzzled scientists for more than 300 years. In this brief review, we emphasize the importance of reproductive and hormonal factors in relation to the risk of breast cancer. By following the historical course of how various risk factors have been determined, this study attempts to illustrate the origin of hypotheses, their subsequent rejection, and development of new hypotheses. Starting with the contributions of Italian physicians in the 18th century and covering the activity of British epidemiologists before World War II, this review ends up with the international collaboration that became increasingly important in the second half of the 20th century.

Pre-pregnancy blood pressure and offspring sex in the HUNT Study, Norway

To the Editor: We read with great interest the recent paper by Retnakaran et al.1 describing an association between higher maternal pre-pregnancy systolic blood pressure and increased probability of delivering a boy. As the authors suggested this finding needs replication, which we aimed to do using the Norwegian HUNT Study. In the HUNT Study, the entire adult population of Nord-Trøndelag county, Norway, has been invited to health surveys since the 1980s.2 By linking HUNT Study data with the Medical Birth Registry of Norway,3 which has prospectively recorded all births in Norway since 1967, we identified 2,427 women with blood pressure recorded in the HUNT2 (1995–97) or HUNT3 (2006–08) surveys prior to a singleton first pregnancy. Blood pressure was measured at rest by trained staff 3 times at 1-minute intervals using an automatic oscillometric method (Dinamap, Critikon, FL). We used the mean of the second and third measurements, or the second measurement for women (n = 163) who did not have a third measurement. Associations between pre-first pregnancy systolic blood pressure and sex of the offspring of first pregnancy were analyzed with logistic and linear regression models using Stata. In a very similar fashion to Retnakaran et al., we adjusted for the highest obtained education level, age, current smoking, body mass index, waist circumference, nonfasting serum glucose, high-density and non-high-density lipoprotein cholesterol, and triglycerides. We also adjusted for HUNT survey occasion (HUNT2 or HUNT3). Overall, mean (SD) pre-pregnancy blood pressure among the 2,427 women was 121 (11) mm Hg systolic and 70 (9) mm Hg diastolic. There were 1,267 (52%) boys and 1,160 (48%) girls (sex ratio 1.09). Median time from blood pressure recording to pregnancy was 3 years. Unadjusted pre-pregnancy systolic and diastolic blood pressure was similar before pregnancies with male (121/70 mm Hg) and female (121/70 mm Hg) offspring. The adjusted differences in pre-pregnancy systolic and diastolic blood pressure between mothers of male and female offspring were 0.2 mm Hg (95% confidence interval, −0.6 to 1.1) and −0.1 mm Hg (95% confidence interval, −0.8 to 0.5), respectively. We found no meaningful association of systolic blood pressure with the probability of male offspring. Overall, each one mm Hg higher systolic blood pressure was associated with an adjusted odds ratio of male offspring of 1.002 (95% confidence interval, 0.994–1.010). The predicted probabilities of having a boy by quintiles of systolic blood pressure are shown in Figure 1. As time from blood pressure measurement to pregnancy was shorter (median: 26.3 weeks) in the study by Retnakaran et al., we repeated the analysis in a subgroup of females with blood pressure measurements taken less than 3 years before pregnancy (n = 1210); the odds ratio of having a boy per one mm Hg higher systolic blood pressure was 1.005 (95% confidence interval, 0.994–1.015). Findings were similar for diastolic blood pressure and sex of offspring. The blood pressure measurement protocol did not substantially differ between our study and the study by Retnakaran et al. Retnakaran et al. studied a Chinese population whilst our study population was predominantly Caucasian, included both planned and unintended pregnancies, and was restricted to first births. However, we do not expect that any causal effect of maternal blood pressure on offspring sex would differ by these characteristics. In summary, these results from a Norwegian population-based cohort of greater size than that of Retnakaran et al., do not support the suggestion that maternal pre-pregnancy blood pressure influences the probability of delivering a boy.

Impact of eating disorders on obstetric outcomes in a large clinical sample: A comparison with the HUNT study

OBJECTIVE Current evidence from clinical studies suggests that having an active eating disorder (ED) during pregnancy is associated with unfavorable obstetric outcomes. However, the role of a lifetime diagnosis of ED is not fully understood. Variations in findings suggest a need for additional studies of maternal ED. This study aims to identify associations between a lifetime ED and obstetric outcomes. METHOD Data from a hospital patient register and a population-based study (The HUNT Study) were linked to the Medical Birth Registry in Norway. Register based information of obstetric complications (preeclampsia, preterm birth, perinatal deaths, small for gestational age (SGA), large for gestational age (LGA), Caesarean sections, and 5-min Apgar score) were acquired for 532 births of women with ED and 43,657 births of non-ED women. Multivariable regression in generalized estimating equations was used to account for clusters within women as they contributed multiple births to the dataset. RESULTS After adjusting for parity, maternal age, marital status, and year of delivery, lifetime history of anorexia nervosa was associated with increased odds of having offspring who were SGA (Odds ratio (OR) 2.7, 95% Confidence Interval (CI) 1.4-5.2). Women with a lifetime history of bulimia nervosa had higher odds of having a Caesarian section (OR 1.7 95% CI 1.1-2.5). Women with EDNOS/sub-threshold ED had a higher likelihood of having a low Apgar score at 5 min (OR 3.1, 95% CI 1.1-8.8). CONCLUSION Our study corroborates available evidence on the associations between maternal ED and adverse obstetric outcomes.

Correction to: The impact of parity on life course blood pressure trajectories: the HUNT study in Norway

The article was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 24 January 2018 without open access.

Early or late pregnancy loss and development of clinical cardiovascular disease risk factors: a prospective cohort study

To assess the association between the outcome of a womans first pregnancy and risk of clinical cardiovascular disease risk factors.