Relation of Quantitative Histologic and Radiologic Breast Tissue Composition Metrics With Invasive Breast Cancer Risk.

Background: Benign breast disease (BBD) is a strong breast cancer risk factor, but identifying patients that might develop invasive breast cancer remains a challenge. Methods: By applying machine-learning to digitized hematoxylin and eosin-stained biopsies and computer-assisted thresholding to mammograms obtained circa BBD diagnosis, we generated quantitative tissue composition metrics and determined their association with future invasive breast cancer diagnosis. Archival breast biopsies and mammograms were obtained for women (18-86 years of age) in a case-control study, nested within a cohort of 15 395 BBD patients from Kaiser Permanente Northwest (1970-2012), followed through mid-2015. Patients who developed incident invasive breast cancer (ie, cases; n = 514) and those who did not (ie, controls; n = 514) were matched on BBD diagnosis age and plan membership duration. All statistical tests were 2-sided. Results: Increasing epithelial area on the BBD biopsy was associated with increasing breast cancer risk (odds ratio [OR]Q4 vs Q1 = 1.85, 95% confidence interval [CI] = 1.13 to 3.04; P trend = .02). Conversely, increasing stroma was associated with decreased risk in nonproliferative, but not proliferative, BBD (P heterogeneity = .002). Increasing epithelium-to-stroma proportion (ORQ4 vs Q1 = 2.06, 95% CI =1.28 to 3.33; P trend = .002) and percent mammographic density (MBD) (ORQ4 vs Q1 = 2.20, 95% CI = 1.20 to 4.03; P trend = .01) were independently and strongly predictive of increased breast cancer risk. In combination, women with high epithelium-to-stroma proportion and high MBD had substantially higher risk than those with low epithelium-to-stroma proportion and low MBD (OR = 2.27, 95% CI = 1.27 to 4.06; P trend = .005), particularly among women with nonproliferative (P trend = .01) vs proliferative (P trend = .33) BBD. Conclusion: Among BBD patients, increasing epithelium-to-stroma proportion on BBD biopsies and percent MBD at BBD diagnosis were independently and jointly associated with increasing breast cancer risk. These findings were particularly striking for women with nonproliferative disease (comprising approximately 70% of all BBD patients), for whom relevant predictive biomarkers are lacking.

Antepartum Depression and Preterm Birth: Pathophysiology, Epidemiology, and Disparities due to structural racism.

PURPOSE OF REVIEW: Informed by the evidence of links between physiology of stress and parturition, we review recent epidemiologic evidence (2015-2020) of antenatal depression as a risk factor for preterm birth (PTB). We also explain racial/ethnic disparities in depression and preterm birth as a consequence of structural racism. RECENT FINDINGS: Epidemiologic evidence is consistent in linking antepartum depression with an elevated risk of PTB. Antidepressant usage has been linked with an elevated risk of PTB. However, recent evidence suggests that severity of depression is the underlying driver of the elevated risk attributed to antidepressant usage. The number of depressive symptoms, as a proxy for severity of maternal stress, may be a more informative predictor of PTB than criterion based predictors. Across various study designs, measurement modalities, and populations, antenatal depression predicts an elevated risk of delivering preterm. The physiology of stress provides a plausible explanation for this observation. Excessive stress-induced elevations in maternal and then fetal HPA hormones can alter maternal and fetal homeostasis and hasten the timing of parturition. Antenatal depression and exposure to structural racism are two stressors that can trigger the maternal stress response. Chronically elevated levels of stress hormones among women of color in the USA provide a likely physiologic explanation for Black-White disparities in the risk of PTB. Focusing on the number of depressive symptoms as the more informative predictor of PTB raises several questions. We consider these questions as well as directions for future research in the context of recent advances in the field.