A Markov Chain Method to Estimate the Tumour Progression Rate from Preclinical to Clinical Phase, Sensitivity and Positive Predictive Value for Mammography in Breast Cancer Screening

Author(s):  
H. H. Chen ◽  
S. W. Duffy ◽  
Laszlo Tabar
Author(s):  
Jennifer A. Cooper ◽  
David Jenkinson ◽  
Chris Stinton ◽  
Matthew G. Wallis ◽  
Sue Hudson ◽  
...  

Abstract Objectives In breast cancer screening, two readers separately examine each woman’s mammograms for signs of cancer. We examined whether preventing the two readers from seeing each other’s decisions (blinding) affects behaviour and outcomes. Methods This cohort study used data from the CO-OPS breast-screening trial (1,119,191 women from 43 screening centres in England) where all discrepant readings were arbitrated. Multilevel models were fitted using Markov chain Monte Carlo to measure whether reader 2 conformed to the decisions of reader 1 when they were not blinded, and the effect of blinding on overall rates of recall for further tests and cancer detection. Differences in positive predictive value (PPV) were assessed using Pearson’s chi-squared test. Results When reader 1 recalls, the probability of reader 2 also recalling was higher when not blinded than when blinded, suggesting readers may be influenced by the other’s decision. Overall, women were less likely to be recalled when reader 2 was blinded (OR 0.923; 95% credible interval 0.864, 0.986), with no clear pattern in cancer detection rate (OR 1.029; 95% credible interval 0.970, 1.089; Bayesian p value 0.832). PPV was 22.1% for blinded versus 20.6% for not blinded (p < 0.001). Conclusions Our results suggest that when not blinded, reader 2 is influenced by reader 1’s decisions to recall (alliterative bias) which would result in bypassing arbitration and negate some of the benefits of double-reading. We found a relationship between blinding the second reader and slightly higher PPV of breast cancer screening, although this analysis may be confounded by other centre characteristics. Key Points • In Europe, it is recommended that breast screening mammograms are analysed by two readers but there is little evidence on the effect of ‘blinding’ the readers so they cannot see each other’s decisions. • We found evidence that when the second reader is not blinded, they are more likely to agree with a recall decision from the first reader and less likely to make an independent judgement (alliterative error). This may reduce overall accuracy through bypassing arbitration. • This observational study suggests an association between blinding the second reader and higher positive predictive value of screening, but this may be confounded by centre characteristics.


Author(s):  
Julie E. Buring ◽  
I-Min Lee

One hundred women over the age of 50 received mammograms at a mobile breast cancer screening unit. Twenty-seven women had findings suspicious for malignancy on the mammogram; 19 of these women were confirmed as having breast cancer by biopsy. One woman had a negative mammogram but in the subsequent year developed breast cancer and is assumed to have had the disease at the time of screening. What is the sensitivity of the mammogram? The specificity? And the predictive value of a positive screening test?


2018 ◽  
Vol 26 (3) ◽  
pp. 147-153 ◽  
Author(s):  
AMWM Aarts ◽  
SW Duffy ◽  
SME Geurts ◽  
DP Vulkan ◽  
JDM Otten ◽  
...  

Objectives We investigated whether changes in mammographic technique and screening policy have improved mammographic sensitivity, and elongated the mean sojourn time, since the introduction of biennial breast cancer screening in Nijmegen, the Netherlands, in 1975. Methods Maximum likelihood estimation, non-linear regression, and Markov Chain Monte Carlo simulation were used to estimate test sensitivity, mean sojourn time, and underlying breast cancer incidence in four time periods, covering 40 years of breast cancer screening in Nijmegen (1975–2012). Results Maximum likelihood estimation generated an estimated test sensitivity of approximately 90% and a mean sojourn time around three years, while the estimates based on non-linear regression and Markov Chain Monte Carlo simulation were 80% and four years, respectively. All three methods estimated a rise in the underlying breast cancer incidence over time, with approximately one case more per 1000 women per year in the final period compared with the first period. Conclusions The three methods showed a slightly higher mammographic sensitivity and a longer mean sojourn time in the last period, after the introduction of digital mammography. Estimates were more realistic for the more sophisticated methods, non-linear regression and Markov Chain Monte Carlo simulation, while the simple closed form approximation of maximum likelihood estimation led to rather high estimates for sensitivity in the early periods.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17025-e17025
Author(s):  
Tetsuji Kurokawa ◽  
Akiko Shinagawa ◽  
Yoko Chino ◽  
Motohiro Kobayashi ◽  
Yoshio Yoshida

e17025 Background:The estimated age-standardized incidence rate for cervical cancer is higher in Japan than in North America and the UK. It is important to improve cancer screening. The introduction of HPV testing with cytology for triage of those that test positive for cervical cancer screening has been challenging. The Fukui Cervical Cancer Screening (FCCS) study was designed to determine the best cervical cancer screening method in the Japanese population. We performed a subanalysis using baseline data of FCCS study to determine the performance of cytology, the human papillomavirus (HPV) testing and cotesting with cytology and HPV testing, and to evaluate whether the stratification of HPV16, HPV18, and 12 other hrHPV types appropriately balances risks and harms in the Japanese cancer screening population. Methods:The study enrolled 7,584 women aged 25 years or older undergoing routine screening. All women underwent liquid-based cytology (LBC) and cobas HPV testing. Women with abnormal cytology regardless of the HPV status, women with positive hrHPV results regardless of cytology results, and women randomly selected from among those with normal cytology and negative hrHPV results were referred for colposcopy. Results:The prevalence of hrHPV, HPV16, and HPV18 was 6.8%, 1.2%, and 0.5%, respectively. The estimated sensitivities for cervical intraepithelial neoplasia (CIN) 2 or worse for cytology, HPV testing, and cotesting with cytology and HPV testing were 71%, 92%, and 100%, respectively. The estimated positive predictive values for cytology, HPV testing, and cotesting with cytology and HPV testing were 33%, 21% and 21%, respectively. Using a strategy whereby those with abnormal cytology or positive HPV16 genotype undergo colposcopy and biopsy results in a sensitivity of 85% and a positive predictive value of 33%. This strategy results in improved sensitivity while at the same time maintains the positive predictive value compared to screening with cytology alone. Conclusions:Baseline data from the FCCS study suggests that strategy of using colposcopy for women with abnormal cytology and/or HPV16 positivity appropriately balances risks and harms for Japanese women. Clinical trial information: UMIN000025977.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12074-e12074
Author(s):  
Alexander Petrovsky ◽  
Nafset Khakurinova ◽  
Vladimir Sholokhov ◽  
Ramiz Valiev ◽  
Sergey Berdnikov ◽  
...  

e12074 Background: Patients with operable breast cancer (BC) and clinically negative lymph nodes (CNLN) usually undergo sentinel lymph node biopsy (SNLB) or axillary lymph nodes dissection (ALND). AUS followed by fine-needle aspiration (FNA) or core-needle biopsy (CNB) could decrease number of unnecessary SNLBs and allow to assign patient to ALND directly. On the other hand, new AUS techniques such as SWE could enhance AUS specificity and allow to avoid SNLB in some patients. Aim: To assess sensitivity, specificity and negative predictive value of the AUS+SWE followed by FNA or CNB in patients with operable BC. Methods: Since Sep 2012 to Jan 2018 150 pts with operable BC and were enrolled. We include 30 pts in training cohort with clinically positive lymph nodes to verify AUS+SWE sensitivity and specificity. In validation cohort only those pts who were candidates for SNLB and who presented with tumor staging up to T3, and clinically negative axillae were included (n=120). All patients underwent preoperative AUS in B-mode, SWE, followed by FNA or CNB in case of suspicious nodes were detected. All pts underwent axilla surgery (SNLB = 46, ALND =74) and final pathology outcomes were available for all pts. Results: In training cohort of 30 patients with clinically positive lymph nodes the overall AUS+SWE sensitivity was set at 89.2%. The positive predictive value was calculated to be 96.1%. In the assessment of invasive breast tumors stages T1- T3 with clinically negative lymph nodes the sensitivity was 74.2%, specificity 95.5% positive predictive value was 85.2% and negative predictive value 91.4% If FNA or CNB follow the AUS+SWE in patients with CNLN the sensitivity was 86.7%, specificity 85.7% positive predictive value was 92.8% and negative predictive value was 75% (FNA or CNB was performed in 40 patients of 120 in validation set). Area under the ROC-curve was calculated as 0.860 [95% CI 0.766 to 0.954] for the US+SWE and 0.705 [95% CI 0.581 to 0.828] for the US+SWE followed by FNA or CNB. Conclusions: Axillary US+SWE should be included in the preoperative staging of all patients with invasive breast cancer. The addition US+SWE (not obviously followed by FNA or CNB) could lead to avoiding of unnecessary SNLB or ALND in patients with clinically and pathologically negative lymph nodes with negative predictive value of 91.4%. On the other hand in patients with US+SWE positive lymph nodes SNLB could also be skipped and the time interval to definitive therapy became shorter. Clinical trial information: BCA_US_SWE_001.


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