Could alcohol consumption have an impact on breast cancer screening? Plus, how has the HPV vaccine impacted CIN2+ rates. And: Can metformin plus changes in lifestyle mitigate PCOS.
Results of a population-based Swedish study may make women at high risk of breast cancer think twice about their drinking habits. Published in the British Journal of Cancer, the data show an association between alcohol consumption, mammographic density, and breast cancer risk.
For the analysis, researchers looked at data from a web-based self-administered questionnaire completed by a cross-sectional sample of 53,060 Swedish women aged 40 to 74. All had participated in the Swedish national mammography screening program and had baseline mammograms. Women who drank more than 40 bottles of beer per week or >50 g of alcohol per day were excluded. The mammograms used to assess density were mediolateral oblique images, the view routinely used in Sweden.
On the questionnaire, the participants were asked to provide information about how frequently they consumed alcohol and in what quantity at least once per month during the months before the study. Each woman’s risk of developing breast cancer over the next decade was calculated using the Tyrer-Cuzick prediction model, which takes into consideration factors such as family history, personal reproductive history, and history of breast disease.
The researchers found a clear association between higher absolute and percent breast density, which was most pronounced in women at the highest (≥5%) Tyrer-Cuzick 10-year risk of breast cancer. For high-risk women compared with non-drinkers, the estimated increase in absolute dense volume in those consuming 5.0-99, 10.0-19.9, 20.0-29.9, and 30.0-40.0 g per day of alcohol was 2.6 cm3 (95% CI, 0.2-49), 2.9 cm3 (95% CI, -0.6-6.3), 4.6 cm3 (95% CI, 1.5-7.7) and 10.8 cm3 (95% CI, 4.8-17.0), respectively. Expressed another way, absolute breast volume increased 2.4 cm3 (95% CI, 1.4-3.5) for each additional 10 g of alcohol consumed per day. A trend toward increasing alcohol consumption and higher absolute dense volume was seen in women at low (≤3%) risk, but not in those at moderate (3.0%-4.9%) risk of breast cancer.
Of the dose-response relationship between alcohol consumption and breast density, the authors said, “there is a clear modifying effect by background breast cancer risk, with considerably steeper dose-response curves for women with high risk compared with women with low and moderate risk.” Their study, they believe, is the first to evaluate the influence of background breast cancer risk when determining the effect of alcohol consumption on mammographic density.
Among the limitations of the research noted were the cross-sectional design, which did not allow them to rule out reverse causation between alcohol consumption and mammographic density. Unlike previous studies, this analysis used volumetric measures of breast density, which the authors believe is a strength because it takes into account thickness and hence may better reflect the actual amount of fibroglandular tissue in the breast.
The impact of the HPV vaccination on CIN2+ rates
A 4-state review of human papillomavirus (HPV) detection in young women underscores the challenges of interpreting ecologic trends for the disease in the era of HPV vaccination. Led by an investigator from the Centers from Disease Control and Prevention, the study shows that CIN2+ is declining, likely due to less screening, but vaccination itself may be having an impact.
The research looked at 9119 cases of CIN2+ among women aged 18 to 39 years old in California, Connecticut, New York, and Oregon from 2008 to 2012. The cases were reported to the HPV-IMPACT Project, a sentinel system set up to monitor the population impact of the HPV vaccine. Each area's CIN2+ incidence rates were age-stratified. Annual rates of cervical screening were estimated for each area, except for Connecticut, using administrative and survey data. Trends were examined using the Cochran-Armitage test.
Over the course of the studied period, the incidence of CIN2+ significantly decreased among women aged 18 to 20 years (California, from 94 to 5 per 100,000 women; Connecticut, from 450 to 57 per 100,000 women; New York, from 299 to 43 per 100,000 women; and Oregon, from 202 to 37 per 100,000 women; Ptrend < .0001). Rates of CIN2+ also differed significantly among women aged 21 to 29 in Connecticut (from 762 to 589 per 100,000 women) and New York (from 770 to 465 per 100,000 women; Ptrend < .001) y. No change in rates was seen among women aged 30 to 39 in any of the geographic areas. During the same period, the rate of screening also decreased, with the largest declined seen among women aged 18 to 20 (from 67% in Oregon to 88% in California. Smaller decreases were seen among women aged 21 to 29 (13% to 27%) and 30 to 39 (3% to 21%).
Investigators believe that the decline in detection of CIN2+ is likely due to decreased screening, but potentially shows the impact of the HPV vaccine. They also believe that the data illustrate the need to determine the HPV types of lesions detected to ascertain the impact of vaccination on cervical precancers.
Combining metformin with lifestyle changes may help PCOS
A systematic review supports the conclusion that taking metformin while making lifestyle changes improves menstruation and lowers weight in women with polycystic ovary syndrome (PCOS).
For the study, which included meta-analysis, investigators searched MEDLINE, EMBASE, Pubmed, Scopus, Cochrane, PsycINFO, CINAHL, Clinical Trials registry, and ANZCTR for randomized controlled trials (RCTs) conducted in humans and published in English through August 2014. Inclusion criteria were a diagnosis of PCOS based on Rotterdam criteria, at any age and at any body mass index (BMI). The reports selected looked at the impact on PCOS of taking metformin at any dose and for any duration combined with making lifestyle changes versus lifestyle changes plus or minus placebo, and of metformin alone versus lifestyle changes plus placebo.
Data on 608 women with PCOS were reflected in the 12 RCTs selected. Lifestyle plus metformin was linked to lower BMI (mean difference (MD) −0.73 kg/m2, 95% confidence intervals [CI] −1.14, −0.32, P = 0.0005), subcutaneous adipose tissue (MD −92.49 cm2, 95% CI −164.14, −20.84, P = 0.01), and increased number of menstrual cycles (MD 1.06, 95% CI 0.30, 1.82, P = 0.006) after 6 months compared with lifestyle plus placebo. No other anthropometric, metabolic, or reproductive differences were seen after 6 months between lifestyle changes plus metformin versus lifestyle plus placebo. After the same duration of treatment, weight and BMI were similar for metformin alone versus lifestyle combined with placebo, but the drug alone produced lower levels of testosterone.
The investigators concluded that lifestyle changes plus metformin lower BMI and improve menstruation in women with PCOS compared with just lifestyle changes plus a placebo. Study limitations included small sample sizes, short durations, and risk of bias. Additional studies with larger sizes and appropriate duration are needed, the authors said, to clarify what role metformin may play in managing PCOS.