Paula Stavrinos

Uptake of tamoxifen in consecutive premenopausal women under surveillance in a high-risk breast cancer clinic.

Background:Randomised trials of tamoxifen versus placebo indicate that tamoxifen reduces breast cancer risk by approximately 33%, yet uptake is low. Approximately 10% of women in our clinic entered the IBIS-I prevention trial. We assess the uptake of tamoxifen in a consecutive series of premenopausal women not in a trial and explore the reasons for uptake through interviews.Methods:All eligible women between 33 and 46 years at ⩾17% lifetime risk of breast cancer and undergoing annual mammography in our service were invited to take a 5-year course of tamoxifen. Reasons for accepting (n=15) or declining (n=15) were explored using semi-structured interviews.Results:Of 1279 eligible women, 136 (10.6%) decided to take tamoxifen. Women >40 years (74 out of 553 (13.4%)) and those at higher non-BRCA-associated risk were more likely to accept tamoxifen (129 out of 1109 (11.6%)). Interviews highlighted four themes surrounding decision making: perceived impact of side effects, the impact of others’ experience on beliefs about tamoxifen, tamoxifen as a ‘cancer drug’, and daily reminder of cancer risk.Conclusions:Tamoxifen uptake was similar to previously ascertained uptake in a randomised controlled trial (IBIS-I). Concerns were similar in women who did or did not accept tamoxifen. Decision making appeared to be embedded in the experience of significant others.

Prevention of breast cancer in the context of a national breast screening programme.

Abstract.  Howell A, Astley S, Warwick J, Stavrinos P, Sahin S, Ingham S, McBurney H, Eckersley B, Harvie M, Wilson M, Beetles U, Warren R, Hufton A, Sergeant J, Newman W, Buchan I, Cuzick J, Evans DG (Genesis Prevention Centre and Nightingale Breast Screening Centre, University Hospital of South Manchester; School of Cancer and Enabling Sciences, University of Manchester, Manchester; Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London; School of Community Based Medicine, University of Manchester, Manchester; Genetic Medicine, Manchester Academic Health Sciences Centre, University of Manchester and Central Manchester Foundation Trust, Manchester; and Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge; UK). Prevention of breast cancer in the context of a national breast screening programme (Review). J Intern Med 2012; 271: 321–330.

Prevention of Breast Cancer on the context of National Breast Screening Programme.

Abstract.  Howell A, Astley S, Warwick J, Stavrinos P, Sahin S, Ingham S, McBurney H, Eckersley B, Harvie M, Wilson M, Beetles U, Warren R, Hufton A, Sergeant J, Newman W, Buchan I, Cuzick J, Evans DG (Genesis Prevention Centre and Nightingale Breast Screening Centre, University Hospital of South Manchester; School of Cancer and Enabling Sciences, University of Manchester, Manchester; Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London; School of Community Based Medicine, University of Manchester, Manchester; Genetic Medicine, Manchester Academic Health Sciences Centre, University of Manchester and Central Manchester Foundation Trust, Manchester; and Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge; UK). Prevention of breast cancer in the context of a national breast screening programme (Review). J Intern Med 2012; 271: 321–330.

Breast cancer risk feedback to women in the UK NHS breast screening population.

Introduction:There are widespread moves to develop risk-stratified approaches to population-based breast screening. The public needs to favour receiving breast cancer risk information, which ideally should produce no detrimental effects. This study investigates risk perception, the proportion wishing to know their 10-year risk and whether subsequent screening attendance is affected.Methods:Fifty thousand women attending the NHS Breast Screening Programme completed a risk assessment questionnaire. Ten-year breast cancer risks were estimated using a validated algorithm (Tyrer-Cuzick) adjusted for visually assessed mammographic density. Women at high risk (⩾8%) and low risk (<1%) were invited for face-to-face or telephone risk feedback and counselling.Results:Of those invited to receive risk feedback, more high-risk women, 500 out of 673 (74.3%), opted to receive a consultation than low-risk women, 106 out of 193 (54.9%) (P<0.001). Women at high risk were significantly more likely to perceive their risk as high (P<0.001) and to attend their subsequent mammogram (94.4%) compared with low-risk women (84.2%; P=0.04) and all attendees (84.3%; ⩽0.0001).Conclusions:Population-based assessment of breast cancer risk is feasible. The majority of women wished to receive risk information. Perception of general population breast cancer risk is poor. There were no apparent adverse effects on screening attendance for high-risk women whose subsequent screening attendance was increased.

Breast cancer risk in young women in the national breast screening programme: implications for applying NICE guidelines for additional screening and chemoprevention.

In the United Kingdom, women at moderate and high risk of breast cancer between the ages of 40 and 49 years are eligible for annual mammographic screening and preventive therapy with tamoxifen. Here, we estimate the numbers of women in a population eligible for this service and the proportion of breast cancers detected in this group compared with the whole population. Women <50 attending for mammographic screening in the National Health Service Breast Screening Programme (NHSBSP) completed a risk questionnaire. The proportion at moderate and high risk according to National Institute of Health Care Excellence (NICE) guidelines was estimated. An estimate was also made using a different model of risk estimation (Tyrer–Cuzick). The numbers of cancers detected in the moderate/high risk groups were compared with numbers detected in the whole population. Completed questionnaires were available for 4,360 women between ages 46 and 49 years. Thirty women [0.7%; 95% confidence interval (CI), 0.5–1.0%] were at high risk and 130 (3.0%, 2.5–3.5%) were at moderate risk according to NICE guidelines. Thirty-seven cancers were detected by mammography in the whole group. Five of these were found in the moderate-/high-risk group giving a 3.2-fold increase in detection compared with the standard risk group. More women were assigned to the moderate- or high-risk group using the Tyrer–Cuzick model (N = 384), but the numbers of cancers in this group were not appreciably increased (N = 8). Systematic assessment of family history in primary care or through population-based screening will identify appreciable numbers of women in their forties, eligible for additional surveillance and chemoprevention Cancer Prev Res; 7(10); 993–1001. ©2014 AACR.

Volumetric and area-based breast density measurement in the predicting risk of cancer at screening (PROCAS) study

Mammographic density, defined as the proportion of the breast area in a mammogram that contains fibroglandular tissue, is associated with risk of breast cancer. However, measures of mammographic density are subject to variation in the underlying imaging process and in the assessments of observers. Automatic volumetric measures of breast density remove much of this variability, but their association with risk is less well established. We present density measurements produced using area-based visual analogue scales (VAS) and by volumetric assessment software (QuantraTM, Hologic Inc.) in the PROCAS study. The distributions of VAS scores (n = 22 327) and volumetric quantities (n = 11 653) are given, as are their relationships for subjects with results by both (n = 11 096), but these are not directly comparable as one is area-based and the other volumetric. Inter-observer variability in visual area-based estimation is examined by a scatter plot matrix.

The impact of a panel of 18 SNPs on breast cancer risk in women attending a UK familial screening clinic: a case–control study

Background Breast cancer familial risk clinics offer screening and preventive strategies. While BRCA1/BRCA2 genetic testing provides important risk information for some women, panels of more common breast cancer risk genetic variants may have relevance to greater numbers of women with familial risk. Methods Three polygenic risk scores (PRS) based on 18 SNPs were investigated in a case–control study of women attending a familial risk clinic. PRS were derived from published general European population allele ORs and frequencies (18-SNPs (SNP18)). In women with BRCA1/BRCA2 mutations, 3 SNPs/13 SNPs, respectively, generated the PRS estimates. In total, 364 incident breast cancer cases (112 with BRCA1/2 mutations) were matched with 1605 controls (691 BRCA1/2) by age last mammogram and BRCA1/2 genetic test result. 87 women with cancer before attendance were also considered. Logistic regression was used to measure PRS performance through ORs per IQR and calibration of the observed to expected (O/E) logarithm relative risk when unadjusted and adjusted for phenotypic risk factors assessed by the Tyrer-Cuzick (TC) model. Results SNP18 was predictive for non-carriers of BRCA1/2 mutations (IQR OR 1.55, 95% CI 1.29 to 1.87, O/E 96%). Findings were unaffected by adjustment from TC (IQR OR 1.56, 95% CI 1.29 to 1.89) or when prior cancers were included (IQR OR 1.55, 95% CI 1.30 to 1.87). There was some evidence to support polygenic scores with weights for individuals with BRCA1/2 mutations (BRCA1 IQR OR 1.44, 95% CI 1.17 to 1.76; BRCA2 IQ OR 1.44, 95% CI 0.90 to 2.31). Conclusions PRS may be used to refine risk assessment for women at increased familial risk who test negative/have low likelihood of BRCA1/2 mutations. They may alter the recommended prevention strategy for many women attending family history clinics.

Local mammographic density as a predictor of breast cancer

High overall mammographic density is associated with both an increased risk of developing breast cancer and the risk of cancer being masked. We compared local density at cancer sites in diagnostic images with corresponding previous screening mammograms (priors), and matched controls. VolparaTM density maps were obtained for 54 mammograms showing unilateral breast cancer and their priors which had been previously read as normal. These were each matched to 3 controls on age, menopausal status, hormone replacement therapy usage, body mass index and year of prior. Local percent density was computed in 15mm square regions at lesion sites and similar locations in the corresponding images. Conditional logistic regression was used to predict case-control status. In diagnostic and prior images, local density was increased at the lesion site compared with the opposite breast (medians 21.58%, 9.18%, p<0.001 diagnostic; 18.82%, 9.45%, p <0.001 prior). Women in the highest tertile of local density in priors were more likely to develop cancer than those in the lowest tertile (OR 42.09, 95% CI 5.37-329.94). Those in the highest tertile of VolparaTM gland volume were also more likely to develop cancer (OR 2.89, 95% CI 1.30-6.42). Local density is increased where cancer will develop compared with corresponding regions in the opposite breast and matched controls, and its measurement could enhance computer-aided mammography.

Volumetric and area-based measures of mammographic density in women with and without cancer

We compare mammographic density in 44 women with screen-detected breast cancer and a control group of 923 women with normal screening mammograms. Multiple regression was used to compare the effects of case-control status on breast density of the contra-lateral breast. Two breast density measures were investigated: the average visual assessment, recorded on a visual analogue scale (VAS), for the two views and two independent readers; and volumetric percentage density measured by QuantraTM. We adjusted for confounding factors of BMI, HRT use, age and menopausal status. Initially there was no significant difference in mean percentage density between cases and controls using either measure of density: VAS (cases 27.5%, controls 26.9%) and QuantraTM (cases 17.2%, controls 18.2%). However, when confounding factors were controlled for, case-control status had a statistically significant effect on breast density as measured by QuantraTM (adjusted means: cases 19.2%, controls 14.8%; p = 0.002) but not by VAS.

Use of Volumetric Breast Density Measures for the Prediction of Weight and Body Mass Index

Body Mass Index (BMI) is an important confounding factor for breast density assessment, particularly where a relative measure (percentage density) is used. Since height and weight are not routinely collected at screening, we investigated the relationship between breast and fat volumes computed by QuantraTM and VolparaTM and weight/BMI in 6898 women for whom self-reported values are available. A significant positive correlation was found between breast volume and fat volume with both weight and BMI. BMI and VolparaTM average fat volume showed the strongest positive relationship (r = 0.728, p<0.001). Using these results we predicted weight and BMI for a separate group of women; these showed moderate intraclass correlation (ICC) agreement with self-reported weight and BMI. The strongest relationship was with weight predicted using QuantraTM average fat volume (ICC = 0.634, CI = 0.573-0.689, p<0.001), however our results suggest that it is not possible to accurately predict individuals’ weight and BMI from volumetric breast density measures.