Reviewer ’s report  
 
Title: Retrospective observation on contribution and limitations of screening for breast cancer  
with mammography in Korea: Detection rate of breast cancer and incidence rate of interval  
cancer  of the breast  
 
Version: 0 Date: 13 Sep 2016  
 
Reviewer: A Alain  
 
Reviewer's report:  
 
This manuscript is well written and clearly presented. It addresses the interesting issue of 
estimating the benefits and limitations of screening for breast c ancer using X -ray mammography. 
The authors use several millions of participants in breast cancer screening conducted by NHIS in 
Korea over 6 years from 2009 to 2014. By comparing data from breast cancer screening and 
health insurance claim data, they repor t quite convincing results that clearly demonstrate that not 
only the positive predictive value of breast cancer screening but also the incidence rate of 
interval cancer of the breast have increased during that period, which explains that both the 
sensitiv ity and specificity do not vary so much. They conclude that to increase the detection rate 
of breast cancer (i) the participation rate should be higher, and (ii) active quality control of the 
equipment and facility used for mammography, mammograms and read ing is required. Overall, 
the results reported in this manuscript are scientifically sound and of interest for people involved 
in improving breast cancer diagnosis. They certainly deserve publication provided some 
additional informations are given by the a uthors.  
 
Indeed I have some remarks and comments that could help the authors to improve their 
manuscript and hopefully to contribute to the future impact of their work.  
 
Point 1. The authors do not specify the screening protocole used to detect breast canc er. From the 
discussion « Third, a known lesion is seen on the previous screen mammogram ; this is an 
interpretive error on the part of the reader (retrospectively visible interval cancer). Fourth, a 
second reader may discover the lesion .... », one can gu ess that only one reader was used ? A few 
words about how this reader diagnosis breast cancer (microcalcifications, lesion, ...) should be 
very helpful for a non specialist.  
 
Point 2. As regards to the increase in PPV of breast cancer screening, the author s agree that « 
According to the guidelines on reporting results and recommendations of the Korea National 
Cancer Screening Program, deferred cases are those in which a judgment of normal, benign 
lesion, or suspected cancer cannot be maded only on the prese nt examination, and additional 
examinations, such as ultrasound and magnified views, comparison with previous mammograms, 
or re -examination after some period is recommended for accurate diagnosis ». Some recent 
progress has been reported in the analysis of  Infrared Thermograms in the following 
publications : 
 
Multifractal analysis of dynamic infrared imaging of breast cancer.  
E. GERASIMOVA, B. AUDIT, S. ROUX, A. KHALIL, F. ARGOUL, O. NAIMARK & A. 
ARNEODO, Europhys. Lett. 104, 68001 (2013)  
￼￼  
Wavelet -based m ultifractal analysis of dynamic infrared thermograms to assist in early breast 
cancer diagnosis.  
E. GERASIMOVA, B. AUDIT, S.G. ROUX, A. KHALIL, O. GILEVA, F. ARGOUL, O. 
NAIMARK & A. ARNEODO, Front. Physiol. 5, 176 (2014)  
 
Thermograms should be added to the  list of additional screening techniques.  
 
Point 3. As regards to the increase in PPV of breast cancer screening, the authors emphasize the 
limitations of mammogram reading and the need of improving the reading : « NHIS conducts 
quality control by introduc ing guidelines and performing periodic checkups on the human 
resources, equipment, facilities, and environments, as well as providing diverse types of 
education aimed at the radiologists and radiology technicians who read the results ». In this 
context I a m quite suprised that the authors do not mention the possibility to use computer -aided 
diagnostic (CAD) methods. Here is a list of rather recent articles about CAD methods :  
 
Computer -aided diagnostic models in breast cancer screening.  
T. AYER, M.U. AYVACI , Z.X. LIU, O. ALAGOZ & E.S. BURNSIDE, Imaging Med. 2, 313 
(2010)  
 
Characterizing mammographic images by using generic texture features.  
L. HABERLE, F. WAGNER, P.A. FASCHING, S.M. JUD, et al., Breast Cancer Res. 14, R59 
(2012)  
 
A statistical based feature  extraction method for breast cancer diagnosis in digital mammogram 
using multiresolution representation.  
M. MESELHY ELTOUKHY, I. FAYE & B. BELHAOUARI SAMIR, Comput. Biol. Med. 42, 
123 (2012)  
 
In particular, in the following articles a wavelet -based method has been proposed to quantify the 
roughness fluctuations in mammographic images and to segment these images into dense tissue 
regions, fat tissue regions and microcalcifications. This segmenta tion was shown to be of great 
help for overcoming the difficulty of detecting lesions in dense breasts.  
 
Wavelet -based multifractal formalism to assist in diagnosis in digitized mammograms.  
P. KESTENER, J. M. LINA, P. SAINT -JEAN & A. ARNEODO, Image Anal. S tereol. 20, 169 
(2001)  
 
A wavelet -based method for multifractal image analysis : from theoretical concepts to 
experimental applications.  
A. ARNEODO, N. DECOSTER, P. KESTENER & S.G. ROUX, Advances in Imaging and 
Electron Physics 126, 1 (2003).  
 
Wavelet -based 3D reconstructioon of microcalcification clusters from two mammographic views 
: new evidence that fractal tumors are malignant and Euclidean tumors are benign.  
K.A. BATCHELDER, A.B. TANENBAUM, S. ALBERT, L. GUIMOND, P. KESTENER, A. 
ARNEODO & A. KHALIL, P LOS ONE 9, e107580 (2014)  
 
Point 4. As a breakthrough to early breast cancer diagnosis, the just appeared following 
publication :  
 
Comparative multifractal analysis of dynamic infrared thermograms and X -ray mammograms 
enlightens changes in the environment of malignant tumors.  
E. GERASIMOVA -CHECHKINA, B. TONER, Z. MARIN, B. AUDIT, S.G. ROUX, F. 
ARGOUL, A. KHALIL, O. GILEVA, O. NAIMARK & A. ARNEODO, Front. Physiol. 7, 336 
(2016)  
 
has reported very promising analysis suggesting that combining sparse and someti mes painful 
and quite uncomfortable mammography examinations with more frequent inexpensive, quick 
and painless IR thermography examinations could become a very efficient routine breast cancer 
screening method to identify, as early as possible, women with high risk of breast cancer.  
 
To conclude, I recommend that the manuscript be returned to the authors and that it be revised 
taking into account the above comments and suggestions.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please sp ecify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
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3. Do you hold or are you currently applying for any patents relating to the content of the  
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