The TP53 mutation rate differs in breast cancers that arise in women with high or low mammographic density.

Mammographic density (MD) influences breast cancer risk, but how this is mediated is unknown. Molecular differences between breast cancers arising in the context of the lowest and highest quintiles of mammographic density may identify the mechanism through which MD drives breast cancer development. Women diagnosed with invasive or in situ breast cancer where MD measurement was also available (n = 842) were identified from the Lifepool cohort of >54,000 women participating in population-based mammographic screening. This group included 142 carcinomas in the lowest quintile of MD and 119 carcinomas in the highest quintile. Clinico-pathological and family history information were recorded. Tumor DNA was collected where available (n = 56) and sequenced for breast cancer predisposition and driver gene mutations, including copy number alterations. Compared to carcinomas from low-MD breasts, those from high-MD breasts were significantly associated with a younger age at diagnosis and features associated with poor prognosis. Low- and high-MD carcinomas matched for grade, histological subtype, and hormone receptor status were compared for somatic genetic features. Low-MD carcinomas had a significantly increased frequency of TP53 mutations, higher homologous recombination deficiency, higher fraction of the genome altered, and more copy number gains on chromosome 1q and losses on 17p. While high-MD carcinomas showed enrichment of tumor-infiltrating lymphocytes in the stroma. The data demonstrate that when tumors were matched for confounding clinico-pathological features, a proportion in the lowest quintile of MD appear biologically distinct, reflective of microenvironment differences between the lowest and highest quintiles of MD.

The impact of translated reminder letters and phone calls on mammography screening booking rates: Two randomised controlled trials.

INTRODUCTION: Participation in mammographic screening for breast cancer in Australia is approximately 54% among the general population, but screening among women from some culturally and linguistically diverse (CALD) backgrounds is lower. BreastScreen Victoria apply strategies to increase screening including reminder letters and phone calls; however, these are usually provided in English. Using intervention strategies generated from the Ophelia (OPtimise HEalth LIteracy and Access) community co-design process, translated mammography reminder letters and in-language phone calls were tested within two randomised control trials (RCTs). METHODS AND ANALYSIS: Women aged 50-75 years who were due for their 2-yearly screening mammography (for RCT#1) or were under-screened, i.e. ≥27 months since last screen (for RCT#2) were randomised into intervention or control groups. RCT#1 compared sending women routine reminder letters (English only) with translated (Arabic or Italian) letters. RCT#2 compared reminder telephone calls to women in their preferred language (Arabic or Italian) to no telephone call. The primary outcome for each trial was screening booking rates within 14-days. Primary outcomes were tested using Pearson's chi-square test. Rates within language group (incidence ratio: IR) were compared using the Cochran-Mantel-Haenszel test. RESULTS: For RCT#1 (letters) 1,032 women were randomised into the intervention arm or to usual care. Uptake of screening bookings was similar between both groups, with no differences observed by language group. For RCT#2 (phone calls), 195 women were randomised to the intervention group or to usual care. Overall, 64.2% of women in the intervention arm and 6% in the control arm booked a screening appointment within 14 days (p<0.0001). The IR (95%CI) of booking was 10.1 (3.9, 26.3) times higher among Italian women, and 11.6 (2.9, 46.5) times higher among Arabic women in the intervention compared to usual care groups. DISCUSSION AND CONCLUSION: A service improvement initiative derived from community members and breast screen providers was found to be highly effective. This evidence informed the service provider, BreastScreen Victoria, who have implemented these improvements into routine practice to improve screening among CALD groups and reduce health inequalities.

Pilot trial of digital breast tomosynthesis (3D mammography) for population-based screening in BreastScreen Victoria.

OBJECTIVES: To estimate detection measures for tomosynthesis and standard mammography; to assess the feasibility of using tomosynthesis in population-based screening for breast cancer. DESIGN, SETTING: Prospective pilot trial comparing tomosynthesis (with synthesised 2D images) and standard mammography screening of women attending Maroondah BreastScreen, a BreastScreen Victoria service in the eastern suburbs of Melbourne. PARTICIPANTS: Women at least 40 years of age who presented for routine breast screening between 18 August 2017 and 8 November 2018. MAIN OUTCOME MEASURES: Cancer detection rate (CDR); proportion of screens that led to recall for further assessment. RESULTS: 5018 tomosynthesis and 5166 standard mammography screens were undertaken in 10 146 women; 508 women (5.0% of screens) opted not to undergo tomosynthesis screening. With tomosynthesis, 49 cancers (40 invasive, 9 in situ) were detected (CDR, 9.8 [95% CI, 7.2-13] per 1000 screens); with standard mammography, 34 cancers (30 invasive, 4 in situ) were detected (CDR, 6.6 [95% CI, 4.6-9.2] per 1000 screens). The estimated difference in CDR was 3.2 more detections (95% CI, -0.32 to 6.8) per 1000 screens with tomosynthesis; the difference was greater for repeat screens and for women aged 60 years or more. The recall rate was greater for tomosynthesis (4.2%; 95% CI, 3.6-4.8%) than standard mammography (3.0%; 95% CI, 2.6-3.5%; estimated difference, 1.2%; 95% CI, 0.46-1.9%). The median screen reading time for tomosynthesis was 67 seconds (interquartile range [IQR] 46-105 seconds); for standard mammography, 16 seconds (IQR, 10-29 seconds). CONCLUSIONS: Breast cancer detection, recall for assessment, and screen reading time were each higher for tomosynthesis than for standard mammography. Our preliminary findings could form the basis of a large scale comparative evaluation of tomosynthesis and standard mammography for breast screening in Australia. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12617000947303.

Using an automated measure of breast density to explore the association between ethnicity and mammographic density in Australian women.

INTRODUCTION: The aim of this study was to investigate mammographic density in a sample of Victorian women and explore a possible association between mammographic density and ethnicity. METHODS: Categories of mammographic density, using Volpara Density Grade, were reported using two editions of Volpara automated software in a data set of women attending two Victorian sites for mammographic screening. The variables available for analysis were age, self-reported exposure to menopausal hormone therapy (MHT) and ethnicity based on country of birth. RESULTS: Data from 16,943 women were available for analysis. Using the VDG 4th edition, 40% of women were classified in the higher two categories (42% for the 5th edition) and 76.9% of women were in the same VDG category using both systems. In the sample, 87.7% of women were in the age range currently invited for screening in Victoria (50-74 years). Of the total group, 82.5% could be classified on the basis of country of birth. In multivariable logistic regression analyses examining factors associated with higher VDG, age (protective), use of MHT (risk factor) and being born in a country with predominantly Asian ancestry (risk factor) were all statistically significant at P < 0.001 for both editions irrespective of whether the reference category was the lowest two or three VDG categories. CONCLUSIONS: Mammographic density as assessed by VDG was positively associated with ever exposure to MHT and inversely associated with age. Being born in a country with predominantly Asian ancestry was associated with higher VDG when controlled for age and MHT exposure.

Barriers to Breast Cancer Screening among Diverse Cultural Groups in Melbourne, Australia.

This study explored the association between health literacy, barriers to breast cancer screening, and breast screening participation for women from culturally and linguistically diverse (CALD) backgrounds. English-, Arabic- and Italian-speaking women (n = 317) between the ages of 50 to 74 in North West Melbourne, Australia were recruited to complete a survey exploring health literacy, barriers to breast cancer screening, and self-reported screening participation. A total of 219 women (69%) reported having a breast screen within the past two years. Results revealed that health literacy was not associated with screening participation. Instead, emotional barriers were a significant factor in the self-reported uptake of screening. Three health literacy domains were related to lower emotional breast screening barriers, feeling understood and supported by healthcare providers, social support for health and understanding health information well enough to know what to do. Compared with English- and Italian-speaking women, Arabic-speaking women reported more emotional barriers to screening and greater challenges in understanding health information well enough to know what to do. Interventions that can improve breast screening participation rates should aim to reduce emotional barriers to breast screening, particularly for Arabic-speaking women.

Treatment Intensity Differences After Early-Stage Breast Cancer (ESBC) Diagnosis Depending on Participation in a Screening Program.

BACKGROUND: While population mammographic screening identifies early-stage breast cancers (ESBCs; ductal carcinoma in situ [DCIS] and invasive disease stages 1-3A), commentaries suggest that harms from overdiagnosis and overtreatment may outweigh the benefits. Apparent benefits to patients with screen-detected cancers may be due to selection bias from exclusion of interval cancers (ICs). Treatment intensity is rarely discussed, with an assumption that all ESBCs are treated similarly. We hypothesized that women diagnosed while in a screening program would receive less-intense treatment than those never or not recently screened (NRS). METHODS: This was a retrospective analysis of all women aged 50-69 years managed for ESBC (invasive or DCIS) during the period 2007-2013 within a single service, comparing treatment according to screening status. Data on demographics, detection, pathology, and treatment were derived from hospital, cancer registry, and screening service records. RESULTS: Overall, 622 patients were active screeners (AS) at diagnosis (569 screen-detected and 53 ICs) and 169 patients were NRS. AS cancers were smaller (17 mm vs. 26 mm, p < 0.0001), less likely to involve nodes (26% vs. 48%, p < 0.0001), and lower grade. For invasive cancer, NRS patients were more likely to be recommended for mastectomies [35% vs. 16%; risk ratio(RR) 2.2, p < 0.0001], axillary dissection (43% vs. 19%; RR 2.3, p < 0.0001), adjuvant chemotherapy (65% vs. 37%; RR 1.7, p < 0.0001), and postmastectomy radiotherapy (58% vs. 39%; RR 1.5, p = 0.04). CONCLUSION: Participants in population screening diagnosed with ESBC receive substantially less-intense treatment than non-participants. Differences persist when potential overdiagnosis is taken into account; these differences should be factored into debates around mammographic screening.

Uptake of adjuvant breast cancer treatments recommended by multi-disciplinary meetings.

BACKGROUND: Adjuvant therapy for breast cancer is routinely discussed and recommended in multi-disciplinary meetings (MDMs). Current literature explores how treatments received by patients differ from national guidelines; however, it does not explore whether treatment is concordant with MDMs. This study provides an Australian perspective on the uptake of MDM recommendations and reasons for non-concordance. METHODS: A retrospective cohort study of patients with breast cancer presented at The Royal Melbourne Hospital MDM in 2010 and 2014 to investigate the concordance between MDM recommendations and treatment received. RESULTS: The study group comprised 441 patients (161 from 2010 and 280 from 2014). A total of 375 patients were included in the analyses. Overall, 82% of patients had perfect concordance between recommended and received treatment for all modes of adjuvant therapy. Concordance to endocrine therapy was higher for invasive cancers than ductal carcinoma in situ (97% versus 81%, P < 0.0001). Concordance to radiotherapy was high and did not differ according to type of cancer or surgery (ranging from 88 to 91%). Concordance to chemotherapy recommendations was high overall (92%) and did not vary with nodal status. Women aged over 65 years were least likely to be recommended for adjuvant therapy but most likely to concordant with the recommendation. CONCLUSIONS: Uptake of MDM-recommended treatments is high. There is a minority of patients in whom MDM recommendations are not followed, highlighting that there are extra steps between recommendations at an MDM and decisions with patients. More attention to this issue is appropriate, and the reasons for non-concordance warrant further study.