Regional lymphadenopathy following COVID-19 vaccination: Literature review and considerations for patient management in breast cancer care.

PURPOSE: Over 1 billion doses of COVID-19 vaccines have been already administered across the United States, the United Kingdom and the European Union at the time of writing. Furthermore, 1.82 million booster doses have been administered in the US since 13th August, and similar booster programmes are currently planned or under consideration in the UK and the EU beginning in the autumn of 2021. Early reports showed an association between vaccine administration and the development of ipsilateral axillary and supraclavicular lymphadenopathy, which could interfere with the diagnosis, treatment and follow-up of breast cancer patients. In this paper, we review the available evidence on vaccine-related lymphadenopathy, and we discuss the clinical implications of the same on breast cancer diagnosis and management. METHODS: A literature search was performed - PubMed, Ovid Medline, Scopus, CINHAL, Springer Nature, ScienceDirect, Academic Search Premier and the Directory of Open Access Journals were searched for articles reporting on regional palpable or image-detected lymphadenopathy following COVID-19 vaccination. Separately, we compiled a series of case studies from the University Hospitals of Derby and Burton, United Kingdom and the Mayo Clinic in Minnesota, United States of America, to illustrate the impact that regional lymphadenopathy post-COVID-19 vaccination can have on the diagnosis and management of patients being seen in diagnostic and therapeutic breast clinics. RESULTS: From the literature search, 15 studies met the inclusion criteria (n = 2057 patients, 737 with lymphadenopathy). The incidence of lymphadenopathy ranged between 14.5% and 53% and persisted for >6 weeks in 29% of patients. CONCLUSIONS: Clinicians managing breast cancer patients should be aware that the COVID-19 vaccination may result in regional lymphadenopathy in a significant number of patients, which can result in unnecessary investigations, treatment and increased patient anxiety. An accurate COVID-19 vaccination history should be collected from all patients where regional lymphadenopathy is a clinical and/or an imaging finding and then combined with clinical judgement when managing individual cases.

Radiological audit of interval breast cancers: Estimation of tumour growth rates.

INTRODUCTION: This multicentre, retrospective study aimed to establish correlation between estimated tumour volume doubling times (TVDT) from a series of interval breast cancers with their clinicopathological features. The potential impact of delayed diagnosis on prognosis was also explored. MATERIALS AND METHODS: Interval cancers, where screening mammograms demonstrated changes that were retrospectively classified as either uncertain or suspicious, were reviewed from five screening units within the UK NHS Breast Screening Programme (NHSBSP). Data collected included the time interval between screening mammogram and cancer diagnosis, the size of the initial mammographic abnormality and of the subsequent cancer, demographics, mammographic density and tumour biology. We estimated volume doubling times and the estimated change in size and node status, which would have followed if these cancers had been detected at the previous screen. RESULTS: 306 interval cancers meeting the inclusion criteria were identified. Average time from screening to diagnosis was 644 days (SD 276 days). 19% were diagnosed in the first twelve months, 42% in the subsequent twelve months and 39% thereafter. Overall average estimated TVDT was 167 days (95% CI 151-186). Significant differences were noted with age (p = 0.01), grade (p < 0.001) and ER status (p < 0.001) with women under 60, grade 3 cancers and ER negative cancers having shorter TVDTs. HER2 positive tumours had shorter doubling times than HER2 negative, but this difference was not statistically significant. It was estimated that diagnosing these cancers at the previous screen would have increased ten-year survival from 82% to 86%. CONCLUSION: High grade, ER negativity and younger age were associated with shorter durations of TVDT. The role of HER2 status on interval cancer growth rate requires further assessment. It is likely that the delayed diagnosis of interval cancers confers a 4% reduction in ten-year survival.

Effect of second timed appointments for non-attenders of breast cancer screening in England: a randomised controlled trial.

BACKGROUND: In England, participation in breast cancer screening has been decreasing in the past 10 years, approaching the national minimum standard of 70%. Interventions aimed at improving participation need to be investigated and put into practice to stop this downward trend. We assessed the effect on participation of sending invitations for breast screening with a timed appointment to women who did not attend their first offered appointment within the NHS Breast Screening Programme (NHSBSP). METHODS: In this open, randomised controlled trial, women in six centres in the NHSBSP in England who were invited for routine breast cancer screening were randomly assigned (1:1) to receive an invitation to a second appointment with fixed date and time (intervention) or an invitation letter with a telephone number to call to book their new screening appointment (control) in the event of non-attendance at the first offered appointment. Randomisation was by SX number, a sequential unique identifier of each woman within the NHSBSP, and at the beginning of the study a coin toss decided whether women with odd or even SX numbers would be allocated to the intervention group. Women aged 50-70 years who did not attend their first offered appointment were eligible for the analysis. The primary endpoint was participation (ie, attendance at breast cancer screening) within 90 days of the date of the first offered appointment; we used Poisson regression to compare the proportion of women who participated in screening in the study groups. All analyses were by intention to treat. This trial is registered with Barts Health, number 009304QM. FINDINGS: We obtained 33 146 records of women invited for breast cancer screening at the six centres between June 2, 2014, and Sept 30, 2015, who did not attend their first offered appointment. 26 054 women were eligible for this analysis (12 807 in the intervention group and 13 247 in the control group). Participation within 90 days of the first offered appointment was significantly higher in the intervention group (2861 [22%] of 12 807) than in the control group (1632 [12%] of 13 247); relative risk of participation 1·81 (95% CI 1·70-1·93; p<0·0001). INTERPRETATION: These findings show that a policy of second appointments with fixed date and time for non-attenders of breast screening is effective in improving participation. This strategy can be easily implemented by the screening sites and, if combined with simple interventions, could further increase participation and ensure an upward shift in the participation trend nationally. Whether the policy should vary by time since last attended screen will have to be considered. FUNDING: National Health Service Cancer Screening Programmes and Department of Health Policy Research Programme.

Accuracy of GE digital breast tomosynthesis vs supplementary mammographic views for diagnosis of screen-detected soft-tissue breast lesions.

OBJECTIVE: To compare the accuracy of standard supplementary views and GE digital breast tomosynthesis (DBT) for assessment of soft-tissue mammographic abnormalities. METHODS: Women recalled for further assessment of soft-tissue abnormalities were recruited and received standard supplementary views (typically spot compression views) and two-view GE DBT. The added value of DBT in the assessment process was determined by analysing data collected prospectively by radiologists working up the cases. Following anonymization of cases, there was also a retrospective multireader review. The readers first read bilateral standard two-view digital mammography (DM) together with the supplementary mammographic views and gave a combined score for suspicion of malignancy on a five-point scale. The same readers then read bilateral standard two-view DM together with two-view DBT. Pathology data were obtained. Differences were assessed using receiver operating characteristic analysis. RESULTS: The study population was 342 lesions in 322 patients. The final diagnosis was malignant in 113 cases (33%) and benign/normal in 229 cases (67%). In the prospective analysis, the performance of two-view DM plus DBT was at least equivalent to the performance of two-view DM and standard mammographic supplementary views-the area under the curve (AUC) was 0.946 and 0.922, respectively, which did not reach statistical significance. Similar results were obtained for the retrospective review-AUC was 0.900 (DBT) and 0.873 (supplementary views), which did not reach statistical significance. CONCLUSION: The accuracy of GE DBT in the assessment of screen detected soft-tissue abnormalities is equivalent to the use of standard supplementary mammographic views. ADVANCES IN KNOWLEDGE: The vast majority of evidence relating to the use of DBT has been gathered from research using Hologic equipment. This study provides evidence for the use of the commercially available GE DBT system demonstrating that it is at least equivalent to supplementary mammographic views in the assessment of soft-tissue screen-detected abnormalities.

The use of lower resolution viewing devices for mammographic interpretation: implications for education and training.

AIMS: To establish whether lower resolution, lower cost viewing devices have the potential to deliver mammographic interpretation training. METHODS: On three occasions over eight months, fourteen consultant radiologists and reporting radiographers read forty challenging digital mammography screening cases on three different displays: a digital mammography workstation, a standard LCD monitor, and a smartphone. Standard image manipulation software was available for use on all three devices. Receiver operating characteristic (ROC) analysis and ANOVA (Analysis of Variance) were used to determine the significance of differences in performance between the viewing devices with/without the application of image manipulation software. The effect of reader's experience was also assessed. RESULTS: Performance was significantly higher (p < .05) on the mammography workstation compared to the other two viewing devices. When image manipulation software was applied to images viewed on the standard LCD monitor, performance improved to mirror levels seen on the mammography workstation with no significant difference between the two. Image interpretation on the smartphone was uniformly poor. Film reader experience had no significant effect on performance across all three viewing devices. CONCLUSION: Lower resolution standard LCD monitors combined with appropriate image manipulation software are capable of displaying mammographic pathology, and are potentially suitable for delivering mammographic interpretation training. KEY POINTS: • This study investigates potential devices for training in mammography interpretation. • Lower resolution standard LCD monitors are potentially suitable for mammographic interpretation training. • The effect of image manipulation tools on mammography workstation viewing is insignificant. • Reader experience had no significant effect on performance in all viewing devices. • Smart phones are not suitable for displaying mammograms.