LETTER TO THE EDITOR
Have We Given Up on Breast Cancer Metastasis? Global Trends in Breast Cancer Metastasis Research Productivity To the Editor: Breast cancer is the most common cancer among women worldwide according to the World Health Organization, with an estimated 1.7 million new cases diagnosed in 2012. It is the leading cause of cancer death in women from less developed regions resulting in 324,000 deaths per year and in more developed regions, 198,000 cancer deaths per year, second only to lung cancer (1). In the USA, approximately 200,000 women are diagnosed with breast cancer each year, of which 5–6% of the patients are diagnosed with distant metastasis (stage 4). Currently, no cure exists for metastatic breast cancer and 40,000 people die in the USA of this disease annually (1–4). Unfortunately, the survival rates for stage four breast cancer patients has not improved with the most recent data indicating a decrease in the 5 year survival rates in mortality to 24% in 2003–2009 compared with 26.7% in 1996–2003 (1–4). The purpose of this bibliometric study was to assess the global effort in breast cancer metastasis research by evaluating relevant research articles published worldwide from 1992 to 2012. This retrospective bibliometric analysis of public data was exempt from Institutional Review Board approval. Articles with “Breast Neoplasms” as a major medical subject heading (MeSH) term published between 1992 and 2012 were identified in the National Library of Medicine MEDLINE data-base. Articles related to metastases were identified if they also had the subheading “Secondary” or “Neoplasm Metastasis” as a major MeSH term. If specified, the country of origin, article methodology, study topic, and source of funding were
Address correspondence and reprint requests to: Richard Ha, MD, Assistant Professor of Radiology, Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Ave., 10th Floor, New York, NY 10032, USA, or e-mail: [email protected] DOI: 10.1111/tbj.12436 © 2015 Wiley Periodicals, Inc., 1075-122X/15 The Breast Journal, Volume 21 Number 4, 2015 442–444
recorded. Growth was analyzed by using linear and nonlinear regression statistical analysis. From 1992 to 2012, a total of 113,721 breast cancer research articles were published worldwide, of which 8,533 (7.5%) had breast cancer metastasis as an additional major topic. Among all countries, USA demonstrated the largest contribution to these research efforts (24.6%, 2,104/8,533). However, looking at metastasis research productivity as a percentage of overall breast cancer research, USA ranked 9th worldwide (6.3%, 2,104/34,155; Table 1). The top five countries were Japan (11.3%, 496/4,386), Germany (10.2%, 336/3,308), Italy (9.6%, 405/4,224), Australia (8.8%, 136/1,552), and Canada (8.2%, 246/ 2,999). The number of breast cancer metastasis articles from 1992 to 2012 originating from the USA displayed a logistic growth pattern while the number of articles in the remaining countries worldwide displayed a linear growth pattern (p < 0.0001 for each, Fig. 1). Breast cancer metastasis articles were most frequently published in Breast Cancer Research and Treatment, followed by Cancer and the Journal of Clinical Oncology (Table 2). Worldwide, the most frequent type of breast cancer metastasis article was case reports (44.1%), followed by review articles (20.6%),
Table 1. Top 10 Countries with the Highest Metastasis Research Productivity as a Percentage of Overall Breast Cancer Research Country Japan Germany Italy Australia Canada Netherlands UK France USA China
Metastasis research/All breast cancer research (%) 496/4386 336/3308 405/4224 136/1552 246/2999 155/2021 558/7532 214/2939 2104/33462 175/2913
(11.30) (10.20) (9.60) (8.80) (8.20) (7.70) (7.40) (7.30) (6.30) (6.00)
Letter to the Editor • 443
Figure 1. The growth trend in the number of breast cancer metastasis articles originating from the USA (logistic growth, p < 0.0001) versus other countries worldwide (linear growth, p < 0.0001) from 1992-2012.
Table 2. Top 10 Journals Publishing Breast Cancer Metastasis Research Worldwide Journal title
Table 3. Type of Breast Cancer Metastasis Research Articles Published Worldwide
Number of metastasis research articles (%) Article type
Breast Cancer Res Treat Cancer J Clin Oncol Gan To Kagaku Ryoho Ann Oncol Ann Surg Oncol Breast J Br J Cancer Anticancer Res Eur J Surg Oncol
271 208 193 160 151 148 125 122 115 111
(3.2) (2.4) (2.3) (1.9) (1.8) (1.7) (1.5) (1.4) (1.3) (1.3)
and comparative studies (14.5%; Table 3). The three specialties contributing the most to breast cancer metastasis research were surgery (18.5%), medicine (16.6%), and pathology (10.6%; Table 4). In the USA, 25.6% (539/2,104) of published articles specific for breast cancer metastasis were funded by the NIH. In comparison, 41.8% (13,395/32,051) of nonmetastasis research publications were funded by the NIH. Worldwide breast cancer metastasis research productivity is low, representing only 7.5% of breast cancer research publications over 20 years. Even this low number is likely an overestimation of metastasis research productivity given 44.1% of publications were case reports and 20.6% review articles, which
Case Reports Review Articles Comparative Studies Clinical Trials Multicenter Studies Evaluation Studies Meta-Analysis
Number of metastasis research articles
Percentage among metastasis research articles
2299 1075 756 744 294 156 40
44.1 20.6 14.5 14.3 5.6 3.0 0.8
are less likely to have meaningful clinical impact. More clinically relevant studies, such as clinical trials represent only 14.3% of breast cancer metastasis research articles. Additional analysis demonstrates, of the 9,489 breast cancer clinical trial publications, only 744 (7.8%) were specific for metastatic disease. Currently, the USA is the most productive nation worldwide in terms of the number of breast cancer research publications. However, metastasis specific research publications in the USA only represent a small percentage (6.3%) of the overall breast cancer research ranking behind eight other nations. This may be related to the lack of NIH funding regarding metastasis research evidenced by lower percentage (25.6%) of NIH funded articles specific to metastasis
444 • letter to the editor
Table 4. Medical Sub-specialty Contribution to the Breast Cancer Metastasis Research Worldwide Medical subspecialty Surgery Surgery Surgical Oncology Medicine Medical Oncology Internal Medicine OB-GYN RadOnc Genetics Pharmacy Surgical Pathology Biochemistry Nursing Pathology Radiology Radiology Nuclear Medicine Imaging Basic Science Biotech Biology Research Engineering Epidemiology/ Public Health Epidemiology Public Health Family Medicine
Number of metastasis research articles
Percentage of overall metastasis research
1582 1575 7 1413 559 127 283 182 83 106 2 66 5 903 684 475 207 2 533 18 168 319 28 49
18.5%
16.6%
10.6% 8.0%
6.2%
0.6%
43 4 2
research compared to the percentage of NIH funded studies not specific for metastasis (41.8%). In addition, the trend of plateauing growth in metastasis research productivity for the past 20 years in the USA
is concerning especially given the decrease in 5 year survival rates in patients with stage 4 breast cancer. Improvements in survival rates and even a possible cure in patients with breast cancer metastasis will undoubtedly result from dedicated high quality research. The USA, as the global leader in breast cancer research should consider refocusing efforts on breast cancer metastasis research as a priority in our nation’s research agenda. Richard Ha, MD Daniel Chow, MD Victoria Mango, MD Lauren Friedlander, MD Elise Desperito, MD Ralph Wynn, MD Department of Radiology Columbia University Medical Center New York New York REFERENCES 1. Forman D, Bray F, Brewster DH, et al. Cancer Incidence in Five Continents, Vol. X (electronic version). Lyon: IARC, 2013. 2. DeSantis C, Siegel R, Jemal A, American Cancer Society. Breast Cancer Facts & Figures 2007-2008. Atlanta: American Cancer Society, Inc, 2007. 3. DeSantis C, Siegel R, Jemal A, American Cancer Society. Breast Cancer Facts & Figures 2013-2014. Atlanta: American Cancer Society, Inc, 2013. 4. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2010. Bethesda, MD: National Cancer Institute, 2013.
Have We Given Up on Breast Cancer Metastasis? Global Trends in Breast Cancer Metastasis Research Productivity To the Editor: Breast cancer is the most common cancer among women worldwide according to the World Health Organization, with an estimated 1.7 million new cases diagnosed in 2012. It is the leading cause of cancer death in women from less developed regions resulting in 324,000 deaths per year and in more developed regions, 198,000 cancer deaths per year, second only to lung cancer (1). In the USA, approximately 200,000 women are diagnosed with breast cancer each year, of which 5–6% of the patients are diagnosed with distant metastasis (stage 4). Currently, no cure exists for metastatic breast cancer and 40,000 people die in the USA of this disease annually (1–4). Unfortunately, the survival rates for stage four breast cancer patients has not improved with the most recent data indicating a decrease in the 5 year survival rates in mortality to 24% in 2003–2009 compared with 26.7% in 1996–2003 (1–4). The purpose of this bibliometric study was to assess the global effort in breast cancer metastasis research by evaluating relevant research articles published worldwide from 1992 to 2012. This retrospective bibliometric analysis of public data was exempt from Institutional Review Board approval. Articles with “Breast Neoplasms” as a major medical subject heading (MeSH) term published between 1992 and 2012 were identified in the National Library of Medicine MEDLINE data-base. Articles related to metastases were identified if they also had the subheading “Secondary” or “Neoplasm Metastasis” as a major MeSH term. If specified, the country of origin, article methodology, study topic, and source of funding were
Address correspondence and reprint requests to: Richard Ha, MD, Assistant Professor of Radiology, Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Ave., 10th Floor, New York, NY 10032, USA, or e-mail: [email protected] DOI: 10.1111/tbj.12436 © 2015 Wiley Periodicals, Inc., 1075-122X/15 The Breast Journal, Volume 21 Number 4, 2015 442–444
recorded. Growth was analyzed by using linear and nonlinear regression statistical analysis. From 1992 to 2012, a total of 113,721 breast cancer research articles were published worldwide, of which 8,533 (7.5%) had breast cancer metastasis as an additional major topic. Among all countries, USA demonstrated the largest contribution to these research efforts (24.6%, 2,104/8,533). However, looking at metastasis research productivity as a percentage of overall breast cancer research, USA ranked 9th worldwide (6.3%, 2,104/34,155; Table 1). The top five countries were Japan (11.3%, 496/4,386), Germany (10.2%, 336/3,308), Italy (9.6%, 405/4,224), Australia (8.8%, 136/1,552), and Canada (8.2%, 246/ 2,999). The number of breast cancer metastasis articles from 1992 to 2012 originating from the USA displayed a logistic growth pattern while the number of articles in the remaining countries worldwide displayed a linear growth pattern (p < 0.0001 for each, Fig. 1). Breast cancer metastasis articles were most frequently published in Breast Cancer Research and Treatment, followed by Cancer and the Journal of Clinical Oncology (Table 2). Worldwide, the most frequent type of breast cancer metastasis article was case reports (44.1%), followed by review articles (20.6%),
Table 1. Top 10 Countries with the Highest Metastasis Research Productivity as a Percentage of Overall Breast Cancer Research Country Japan Germany Italy Australia Canada Netherlands UK France USA China
Metastasis research/All breast cancer research (%) 496/4386 336/3308 405/4224 136/1552 246/2999 155/2021 558/7532 214/2939 2104/33462 175/2913
(11.30) (10.20) (9.60) (8.80) (8.20) (7.70) (7.40) (7.30) (6.30) (6.00)
Letter to the Editor • 443
Figure 1. The growth trend in the number of breast cancer metastasis articles originating from the USA (logistic growth, p < 0.0001) versus other countries worldwide (linear growth, p < 0.0001) from 1992-2012.
Table 2. Top 10 Journals Publishing Breast Cancer Metastasis Research Worldwide Journal title
Table 3. Type of Breast Cancer Metastasis Research Articles Published Worldwide
Number of metastasis research articles (%) Article type
Breast Cancer Res Treat Cancer J Clin Oncol Gan To Kagaku Ryoho Ann Oncol Ann Surg Oncol Breast J Br J Cancer Anticancer Res Eur J Surg Oncol
271 208 193 160 151 148 125 122 115 111
(3.2) (2.4) (2.3) (1.9) (1.8) (1.7) (1.5) (1.4) (1.3) (1.3)
and comparative studies (14.5%; Table 3). The three specialties contributing the most to breast cancer metastasis research were surgery (18.5%), medicine (16.6%), and pathology (10.6%; Table 4). In the USA, 25.6% (539/2,104) of published articles specific for breast cancer metastasis were funded by the NIH. In comparison, 41.8% (13,395/32,051) of nonmetastasis research publications were funded by the NIH. Worldwide breast cancer metastasis research productivity is low, representing only 7.5% of breast cancer research publications over 20 years. Even this low number is likely an overestimation of metastasis research productivity given 44.1% of publications were case reports and 20.6% review articles, which
Case Reports Review Articles Comparative Studies Clinical Trials Multicenter Studies Evaluation Studies Meta-Analysis
Number of metastasis research articles
Percentage among metastasis research articles
2299 1075 756 744 294 156 40
44.1 20.6 14.5 14.3 5.6 3.0 0.8
are less likely to have meaningful clinical impact. More clinically relevant studies, such as clinical trials represent only 14.3% of breast cancer metastasis research articles. Additional analysis demonstrates, of the 9,489 breast cancer clinical trial publications, only 744 (7.8%) were specific for metastatic disease. Currently, the USA is the most productive nation worldwide in terms of the number of breast cancer research publications. However, metastasis specific research publications in the USA only represent a small percentage (6.3%) of the overall breast cancer research ranking behind eight other nations. This may be related to the lack of NIH funding regarding metastasis research evidenced by lower percentage (25.6%) of NIH funded articles specific to metastasis
444 • letter to the editor
Table 4. Medical Sub-specialty Contribution to the Breast Cancer Metastasis Research Worldwide Medical subspecialty Surgery Surgery Surgical Oncology Medicine Medical Oncology Internal Medicine OB-GYN RadOnc Genetics Pharmacy Surgical Pathology Biochemistry Nursing Pathology Radiology Radiology Nuclear Medicine Imaging Basic Science Biotech Biology Research Engineering Epidemiology/ Public Health Epidemiology Public Health Family Medicine
Number of metastasis research articles
Percentage of overall metastasis research
1582 1575 7 1413 559 127 283 182 83 106 2 66 5 903 684 475 207 2 533 18 168 319 28 49
18.5%
16.6%
10.6% 8.0%
6.2%
0.6%
43 4 2
research compared to the percentage of NIH funded studies not specific for metastasis (41.8%). In addition, the trend of plateauing growth in metastasis research productivity for the past 20 years in the USA
is concerning especially given the decrease in 5 year survival rates in patients with stage 4 breast cancer. Improvements in survival rates and even a possible cure in patients with breast cancer metastasis will undoubtedly result from dedicated high quality research. The USA, as the global leader in breast cancer research should consider refocusing efforts on breast cancer metastasis research as a priority in our nation’s research agenda. Richard Ha, MD Daniel Chow, MD Victoria Mango, MD Lauren Friedlander, MD Elise Desperito, MD Ralph Wynn, MD Department of Radiology Columbia University Medical Center New York New York REFERENCES 1. Forman D, Bray F, Brewster DH, et al. Cancer Incidence in Five Continents, Vol. X (electronic version). Lyon: IARC, 2013. 2. DeSantis C, Siegel R, Jemal A, American Cancer Society. Breast Cancer Facts & Figures 2007-2008. Atlanta: American Cancer Society, Inc, 2007. 3. DeSantis C, Siegel R, Jemal A, American Cancer Society. Breast Cancer Facts & Figures 2013-2014. Atlanta: American Cancer Society, Inc, 2013. 4. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2010. Bethesda, MD: National Cancer Institute, 2013.
