Sophia Zackrisson

Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

E. Senkus1, S. Kyriakides2, F. Penault-Llorca3,4, P. Poortmans5, A. Thompson6, S. Zackrisson7 & F. Cardoso8,9, on behalf of the ESMO Guidelines Working Group* Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland; Europa Donna Cyprus, Nicosia, Cyprus; Department of Pathology, Centre Jean Perrin, Clermont-Ferrand; EA 4677 Universite d’Auvergne, Clermont-Ferrand, France; Institute Verbeeten, Tilburg, The Netherlands; Dundee Cancer Centre, University of Dundee, Dundee, UK; Diagnostic Radiology, Lund University, Malmo, Sweden; European School of Oncology, Milan, Italy; Breast Cancer Unit, Champalimaud Centre Center, Lisbon, Portugal

Rate of over-diagnosis of breast cancer 15 years after end of Malmö mammographic screening trial: follow-up study

Abstract Objective To evaluate the rate of over-diagnosis of breast cancer 15 years after the end of the Malmö mammographic screening trial. Design Follow-up study. Setting Malmö, Sweden. Subjects 42 283 women aged 45-69 years at randomisation. Interventions Screening for breast cancer with mammography or not (controls). Screening was offered at the end of the randomisation design to both groups aged 45-54 at randomisation but not to groups aged 55-69 at randomisation. Main outcome measures Rate of over-diagnosis of breast cancer (in situ and invasive), calculated as incidence in the invited and control groups, during period of randomised design (period 1), during period after randomised design ended (period 2), and at end of follow-up. Results In women aged 55-69 years at randomisation the relative rates of over-diagnosis of breast cancer (95% confidence intervals) were 1.32 (1.14 to 1.53) for period 1, 0.92 (0.79 to 1.06) for period 2, and 1.10 (0.99 to 1.22) at the end of follow-up. Conclusion Conclusions on over-diagnosis of breast cancer in the Malmö mammographic screening trial can be drawn mainly for women aged 55-69 years at randomisation whose control groups were never screened. Fifteen years after the trial ended the rate of over-diagnosis of breast cancer was 10% in this age group.

Breast tomosynthesis and digital mammography: a comparison of breast cancer visibility and BIRADS classification in a population of cancers with subtle mammographic findings

The main purpose was to compare breast cancer visibility in one-view breast tomosynthesis (BT) to cancer visibility in one- or two-view digital mammography (DM). Thirty-six patients were selected on the basis of subtle signs of breast cancer on DM. One-view BT was performed with the same compression angle as the DM image in which the finding was least/not visible. On BT, 25 projections images were acquired over an angular range of 50 degrees, with double the dose of one-view DM. Two expert breast imagers classified one- and two-view DM, and BT findings for cancer visibility and BIRADS cancer probability in a non-blinded consensus study. Forty breast cancers were found in 37 breasts. The cancers were rated more visible on BT compared to one-view and two-view DM in 22 and 11 cases, respectively, (p < 0.01 for both comparisons). Comparing one-view DM to one-view BT, 21 patients were upgraded on BIRADS classification (p < 0.01). Comparing two-view DM to one-view BT, 12 patients were upgraded on BIRADS classification (p < 0.01). The results indicate that the cancer visibility on BT is superior to DM, which suggests that BT may have a higher sensitivity for breast cancer detection.

Effectiveness of Population-Based Service Screening With Mammography for Women Ages 40 to 49 Years Evaluation of the Swedish Mammography Screening in Young Women (SCRY) Cohort

The effectiveness of mammography screening for women ages 40 to 49 years still is questioned, and few studies of the effectiveness of service screening for this age group have been conducted.

Light In and Sound Out: Emerging Translational Strategies for Photoacoustic Imaging

Photoacoustic imaging (PAI) has the potential for real-time molecular imaging at high resolution and deep inside the tissue, using nonionizing radiation and not necessarily depending on exogenous imaging agents, making this technique very promising for a range of clinical applications. The fact that PAI systems can be made portable and compatible with existing imaging technologies favors clinical translation even more. The breadth of clinical applications in which photoacoustics could play a valuable role include: noninvasive imaging of the breast, sentinel lymph nodes, skin, thyroid, eye, prostate (transrectal), and ovaries (transvaginal); minimally invasive endoscopic imaging of gastrointestinal tract, bladder, and circulating tumor cells (in vivo flow cytometry); and intraoperative imaging for assessment of tumor margins and (lymph node) metastases. In this review, we describe the basics of PAI and its recent advances in biomedical research, followed by a discussion of strategies for clinical translation of the technique.

Breast tomosynthesis and digital mammography: a comparison of diagnostic accuracy

OBJECTIVE Our aim was to compare the ability of radiologists to detect breast cancers using one-view breast tomosynthesis (BT) and two-view digital mammography (DM) in an enriched population of diseased patients and benign and/or healthy patients. METHODS All participants gave informed consent. The BT and DM examinations were performed with about the same average glandular dose to the breast. The study population comprised patients with subtle signs of malignancy seen on DM and/or ultrasonography. Ground truth was established by pathology, needle biopsy and/or by 1-year follow-up by mammography, which retrospectively resulted in 89 diseased breasts (1 breast per patient) with 95 malignant lesions and 96 healthy or benign breasts. Two experienced radiologists, who were not participants in the study, determined the locations of the malignant lesions. Five radiologists, experienced in mammography, interpreted the cases independently in a free-response study. The data were analysed by the receiver operating characteristic (ROC) and jackknife alternative free-response ROC (JAFROC) methods, regarding both readers and cases as random effects. RESULTS The diagnostic accuracy of BT was significantly better than that of DM (JAFROC: p=0.0031, ROC: p=0.0415). The average sensitivity of BT was higher than that of DM (∼90% vs ∼79%; 95% confidence interval of difference: 0.036, 0.108) while the average false-positive fraction was not significantly different (95% confidence interval of difference: -0.117, 0.010). CONCLUSION The diagnostic accuracy of BT was superior to DM in an enriched population.

Non-attendance in breast cancer screening is associated with unfavourable socio-economic circumstances and advanced carcinoma.

Our first objective was to assess changes in non‐attendance, proportion of advanced breast cancer and survival in Malmö Mammographic Service Screening Program, MMSSP, compared to a former trial, Malmö Mammographic Screening Trial, MMST. Our second objective was to describe non‐attenders in MMSSP in socio‐economic terms and risk for advanced breast cancer compared to attenders. Information from hospital and national registers was used to identify 33,800 women invited to service screening in MMSSP 1990–93. Attendance rates at first screening, the proportion of advanced breast cancers (Stage II–IV) and survival among non‐attenders in MMSSP were compared to the non‐attenders and with the control group of the former trial, MMST. Various socio‐economic factors were assessed as potential predictors of non‐attendance in MMSSP. Odds ratios (OR) and 95% confidence interval (CI) were computed. Incidence of breast cancer during a 10‐year‐period, relative risks and 95% CI among non‐attenders compared to attenders in MMSSP were computed. Attendance rates were significantly lower in MMSSP but a lower proportion of advanced breast cancers and a somewhat better survival among breast cancer cases (not significant) was seen in non‐attenders in MMSSP compared to MMST. In MMSSP non‐attendance was associated with being unmarried, being born abroad, being not currently employed, crowded housing conditions and low income. Incidence of advanced breast cancer was significantly higher among non‐attenders than among attenders. Attendance has decreased over time and potential reasons are discussed. Stage distribution and survival among non‐attenders seem to have improved. Several socio‐economic factors predict non‐attendance and non‐attenders are at higher risk for advanced breast cancer.

Breast tomosynthesis: Accuracy of tumor measurement compared with digital mammography and ultrasonography.

Background: Mammographic tumor size measurement can be difficult because breast structures are superimposed onto a two-dimensional (2D) plane, potentially obscuring the tumor outline. Breast tomosynthesis (BT) is a 3D X-ray imaging technique in which low-dose images are acquired over a limited angular range at a total dose comparable to digital mammography (DM). These low-dose images are used to mathematically reconstruct a 3D image volume of the breast, thus reducing the problem of superimposed tissue. Purpose: To investigate whether breast cancer size can be more accurately assessed with breast tomosynthesis than with digital mammography and ultrasonography (US), by reducing the disturbance effect of the projected anatomy. Material and Methods: A prototype BT system was used. The main inclusion criterion for BT examination was subtle but suspicious findings of breast cancer on 2D mammography. Sixty-two women with 73 breast cancers were included. BT, DM, and US sizes were measured independently by experienced radiologists without knowledge of the pathology results, which were used as reference. Results: The tumor outline could be determined in significantly more cases with BT (63) and US (60) than DM (49). BT and US size correlated well with pathology (R=0.86 and R=0.85, respectively), and significantly better than DM size (R=0.71). Accordingly, staging was significantly more accurate with BT than with DM. Conclusion: The study indicates that BT is superior to DM in the assessment of breast tumor size and stage.

Social Inequalities and Mortality in Europe - Results from a Large Multi-National Cohort

Background Socio-economic inequalities in mortality are observed at the country level in both North America and Europe. The purpose of this work is to investigate the contribution of specific risk factors to social inequalities in cause-specific mortality using a large multi-country cohort of Europeans. Methods A total of 3,456,689 person/years follow-up of the European Prospective Investigation into Cancer and Nutrition (EPIC) was analysed. Educational level of subjects coming from 9 European countries was recorded as proxy for socio-economic status (SES). Cox proportional hazard models with a step-wise inclusion of explanatory variables were used to explore the association between SES and mortality; a Relative Index of Inequality (RII) was calculated as measure of relative inequality. Results Total mortality among men with the highest education level is reduced by 43% compared to men with the lowest (HR 0.57, 95% C.I. 0.52–0.61); among women by 29% (HR 0.71, 95% C.I. 0.64–0.78). The risk reduction was attenuated by 7% in men and 3% in women by the introduction of smoking and to a lesser extent (2% in men and 3% in women) by introducing body mass index and additional explanatory variables (alcohol consumption, leisure physical activity, fruit and vegetable intake) (3% in men and 5% in women). Social inequalities were highly statistically significant for all causes of death examined in men. In women, social inequalities were less strong, but statistically significant for all causes of death except for cancer-related mortality and injuries. Discussion In this European study, substantial social inequalities in mortality among European men and women which cannot be fully explained away by accounting for known common risk factors for chronic diseases are reported.

THE DIAGNOSTIC ACCURACY OF DUAL-VIEW DIGITAL MAMMOGRAPHY, SINGLE-VIEW BREAST TOMOSYNTHESIS AND A DUAL-VIEW COMBINATION OF BREAST TOMOSYNTHESIS AND DIGITAL MAMMOGRAPHY IN A FREE-RESPONSE OBSERVER PERFORMANCE STUDY

The purpose of the present study was to compare the diagnostic accuracy of dual-view digital mammography (DM), single-view breast tomosynthesis (BT) and BT combined with the opposite DM view. Patients with subtle lesions were selected to undergo BT examinations. Two radiologists who are non-participants in the study and have experience in using DM and BT determined the locations and extents of lesions in the images. Five expert mammographers interpreted the cases using the free-response paradigm. The task was to mark and rate clinically reportable findings suspicious for malignancy and clinically relevant benign findings. The marks were scored with reference to the outlined regions into lesion localization or non-lesion localization, and analysed by the jackknife alternative free-response receiver operating characteristic method. The analysis yielded statistically significant differences between the combined modality and dual-view DM (p < 0.05). No differences were found between single-view BT and dual-view DM or between single-view BT and the combined modality.