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Plus: research on systemic HT, type II diabetes and post-pregnancy obesity
A multicenter study of breast biopsy interpretation that compared diagnoses by an expert consensus panel and pathologists in clinical practice found that they disagreed in 52% of cases involving atypia.
The research, based on data from pathologists who interpret breast biopsies in 8 states, suggests that a second opinion may be warranted for women diagnosed with atypia before they begin intensive surveillance or treatment to reduce risk.
Published in JAMA, the analysis focused on independent interpretation of slides from 60 breast biopsies (240 cases, 1 slide per case) and spanned November 2011 to May 2014. Included were 23 cases of invasive breast cancer, 73 ductal carcinoma in situ (DCIS), 72 atypical hyperplasia (atypia), and 2 benign cases without atypia. The cases were randomly identified from a cohort of nearly 20,000 in pathology registries affiliated with the Breast Cancer Surveillance Consortium and from core needle and excisional biopsies. Nearly half of the specimens were from women aged 40 to 49.
First all 240 cases were reviewed independently and rated for difficulty by each of 3 pathologists who are internationally recognized as experts in diagnostic breast pathology. In the 25% of cases in which the diagnosis was not unanimous, consensus was reached via discussion.
Pathologists in 8 states who had interpreted breast biopsies for at least 1 year were then invited to review the same specimens. Of the 115 who participated, 50.5% said that breast pathology was challenging and 44.3% said it made them more nervous than other types of pathology, but more than half (51%) said they had seen cases of the type presented.
For the atypia cases (2070 interpretations), the rate of concordance between the diagnoses of the expert panel and the community pathologists was 48% (95% CI, 44%-52%), 35% (95% CI, 31%-39%) were under-interpreted, and 3% (95% CI, 2%-4%) were over-interpreted. The rate of concordance was 84% (95% CI, 82%-86%) for DCIS cases (2097 interpretations), with 13% (95% CI, 12%-15%) under-interpreted and 3% (95% CI, 2%-4%) over-interpreted. For cases of invasive carcinoma (663 interpretations), the concordance rate was 96% (95% CI, 94%-97%) and 4% (95% CI, 3%-6%) were under-interpreted.
The authors found that pathologists were statistically significantly less likely to agree with the diagnosis of the expert panel if they were from outside academic settings, interpreted low weekly volumes of breast cases, or were from small practices. “The variability of pathology interpretations,” they concluded, “is relevant to concerns about over-diagnosis of atypia and DCIS.
When a biopsy is over-interpreted (eg, interpreted as DCIS by a pathologist when the consensus-derived diagnosis is atypia), a woman may undergo unnecessary surgery, radiation, or hormonal therapy.”
A Swedish study of more than 40,000 postmenopausal women taking statins suggests that it may be time to rethink the ban on use of hormonal therapy (HT) in this population. The report, from a register-based cohort, showed a reduced risk of all-cause mortality associated with combined use of statins and semi-natural 17β-estradiol, in contrast to the negative findings with conjugated equine estrogen (CEE) in a healthy population in the Women’s Health Initiative (WHI).
Included in the analysis, which was published in Menopause, were 40,958 women aged 40 to 74 years who filled a first statin prescription between 2006 and 2007. Of them, 2,862 (7%) used HT and 38,096 did not. The mean ages of HT users and nonusers were 61 and 62, respectively. The women were followed for a mean of 4.0 years for emigration, cardiovascular event, death, or change in HT. Seventy percent of those who used HT did so for primary prevention.
Among the HT users, the rate of cardiovascular events was 250/10,000 person-years, compared with 267/10,000 for the nonusers (hazard ratio [HR] 1.04; 95% confidence interval [CI] 0.88-1.22). The rate of cardiovascular death among the HT users was 5 per 10,000 person-years, compared with 18 for nonusers (HR 0.53; 95% CI 0.34-0.81). All-cause mortality rates were 33 and 87, respectively, and the HR was 0.53 (95% CI 0.34-0.81). The pattern was similar for primary and secondary prevention.
Only estrogens with systemic effects were considered in the study. CEE, which was used in the WHI, is not sold in Sweden. The authors theorize that “estradiol may be less thrombogenic or atherosclerogenic than conjugated estrogens, which may explain the more beneficial effect of HT in the present study.” They underscored that the findings from this study are not applicable to all women with cardiovascular disease (CVD) because it did not include women at risk of CVD who were not on statins.
Risk of developing type 2 diabetes is significantly elevated in obese women with gestational diabetes who gain weight after delivery, according to a new study using data from the Nurses’ Health Study II (NHS II).
Researchers included 1695 women who had incident gestational diabetes mellitus between 1991 and 2001 from the Diabetes & Women’s Health study, taken from NHS II. The women were followed until the return of a 2009 questionnaire. Incident type 2 diabetes and body weight were reported every 2 years. Baseline was defined as the questionnaire period when the women reported an incident gestational diabetes mellitus pregnancy. Cox proportional hazards models were used to estimate 95% confidence intervals (CIs) and hazard ratios (HRs).
In the course of 18 years of follow-up, the researchers were able to document 259 incident cases of type 2 diabetes. The adjusted HRs for type 2 diabetes that were associated with each 1 kg/m2 increase in body mass index (BMI) were 1.16 (95% CI 1.12, 1.19) for baseline BMI and 1.16 (95% CI 1.13, 1.20) for the most recent BMI. The researchers found that each 5-kg increment of weight gain after development of gestational diabetes was associated with a 27% greater risk of type 2 diabetes (adjusted HR 1.27; 95% CI 1.04, 1.54). Women who had a BMI ≥30.0 kg/m2 at baseline and gained ≥5 kg after developing gestational diabetes mellitus were 43 times more likely to develop type 2 diabetes than their counterparts who had a BMI <25.0 kg/m2 at baseline and gained 5 kg or less after a pregnancy complicated by gestational diabetes (adjusted HR 43.19; 95% CI, 13.60-137.11).
The investigators concluded that baseline BMI, current BMI, and weight gain following a diagnosis of gestational diabetes mellitus were all positively and significantly associated with the risk of further progression from gestational diabetes to type 2 diabetes.