Skip to main content
Top
Published in: Breast Cancer Research and Treatment 2/2011

01-06-2011 | Epidemiology

Circulating levels of inflammatory markers and mammographic density among postmenopausal women

Authors: Katherine W. Reeves, Joel L. Weissfeld, Francesmary Modugno, Brenda Diergaarde

Published in: Breast Cancer Research and Treatment | Issue 2/2011

Login to get access

Abstract

Mammographic density is strongly associated with breast cancer risk. Inflammation is involved in breast carcinogenesis, perhaps through effects on mammographic density. We evaluated associations between inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) and mammographic density among postmenopausal women. Plasma IL-6, TNF-α, and CRP levels were measured in 145 women with benign breast disease (benign controls) and 397 women with a negative screening mammogram (well controls) enrolled in the Mammograms and Masses Study. Associations between the inflammatory markers and mammographic density were evaluated separately for benign and well controls through correlation analyses and linear regressions. Age-adjusted mean CRP levels were higher among benign controls (2.07 μg/ml) compared to well controls (1.63 μg/ml; P = 0.02), while IL-6 and TNF-α levels were similar between groups. Using linear regression, IL-6, TNF-α, and CRP were not statistically significantly associated with dense breast area within either group. Statistically significant positive associations were observed between all three markers and nondense breast area in both groups; statistically significant negative associations were observed between IL-6 and percent density among benign controls, and between all three markers and percent density among well controls. These associations were all attenuated and non-significant upon adjustment for body mass index. IL-6, TNF-α, and CRP levels were not independently associated with dense breast area, nondense breast area, or percent density in this study population. Our results suggest that these inflammatory factors do not impact breast carcinogenesis through independent effects on mammographic density.
Literature
1.
go back to reference Boyd NF, Martin LJ, Rommens JM et al (2009) Mammographic density: a heritable risk factor for breast cancer. Methods Mol Biol 472:343–360PubMedCrossRef Boyd NF, Martin LJ, Rommens JM et al (2009) Mammographic density: a heritable risk factor for breast cancer. Methods Mol Biol 472:343–360PubMedCrossRef
2.
go back to reference Wolfe JN (1976) Breast patterns as an index of risk for developing breast cancer. Am J Roentgenol 126:1130–1137 Wolfe JN (1976) Breast patterns as an index of risk for developing breast cancer. Am J Roentgenol 126:1130–1137
3.
4.
go back to reference Torres-Mejia G, De Stavola B, Allen DS et al (2005) Mammographic features and subsequent risk of breast cancer: a comparison of qualitative and quantitative evaluations in the Guernsey prospective studies. Cancer Epidemiol Biomarkers Prev 14:1052–1059PubMedCrossRef Torres-Mejia G, De Stavola B, Allen DS et al (2005) Mammographic features and subsequent risk of breast cancer: a comparison of qualitative and quantitative evaluations in the Guernsey prospective studies. Cancer Epidemiol Biomarkers Prev 14:1052–1059PubMedCrossRef
5.
go back to reference Kato I, Beinart C, Bleich A et al (1995) A nested case-control study of mammographic patterns, breast volume, and breast cancer. Cancer Causes Control 6:431–438PubMedCrossRef Kato I, Beinart C, Bleich A et al (1995) A nested case-control study of mammographic patterns, breast volume, and breast cancer. Cancer Causes Control 6:431–438PubMedCrossRef
6.
go back to reference Byrne C, Schairer C, Wolfe J et al (1995) Mammographic features and breast cancer risk: effects with time, age, and menopause status. J Natl Cancer Inst 87:1622–1629PubMedCrossRef Byrne C, Schairer C, Wolfe J et al (1995) Mammographic features and breast cancer risk: effects with time, age, and menopause status. J Natl Cancer Inst 87:1622–1629PubMedCrossRef
7.
go back to reference Boyd NF, Dite GS, Stone J et al (2002) Heritability of mammographic density, a risk factor for breast cancer. N Engl J Med 347:886–894PubMedCrossRef Boyd NF, Dite GS, Stone J et al (2002) Heritability of mammographic density, a risk factor for breast cancer. N Engl J Med 347:886–894PubMedCrossRef
8.
go back to reference Greendale GA, Reboussin BA, Slone S et al (2003) Postmenopausal hormone therapy and change in mammographic density. J Natl Cancer Inst 95:30–37PubMedCrossRef Greendale GA, Reboussin BA, Slone S et al (2003) Postmenopausal hormone therapy and change in mammographic density. J Natl Cancer Inst 95:30–37PubMedCrossRef
9.
go back to reference Morimoto LM, White E, Chen Z et al (2002) Obesity, body size, and risk of postmenopausal breast cancer: the Women’s Health Initiative. Cancer Causes Control 13:741–751PubMedCrossRef Morimoto LM, White E, Chen Z et al (2002) Obesity, body size, and risk of postmenopausal breast cancer: the Women’s Health Initiative. Cancer Causes Control 13:741–751PubMedCrossRef
10.
go back to reference Harvey JA, Pinkerton JV, Herman CR (1997) Short-term cessation of hormone replacement therapy and improvement of mammographic specificity. J Natl Cancer Inst 89:1623–1625PubMedCrossRef Harvey JA, Pinkerton JV, Herman CR (1997) Short-term cessation of hormone replacement therapy and improvement of mammographic specificity. J Natl Cancer Inst 89:1623–1625PubMedCrossRef
11.
go back to reference Ursin G, Parisky YR, Pike MC et al (2001) Mammographic density changes during the menstrual cycle. Cancer Epidemiol Biomarkers Prev 10:141–142PubMed Ursin G, Parisky YR, Pike MC et al (2001) Mammographic density changes during the menstrual cycle. Cancer Epidemiol Biomarkers Prev 10:141–142PubMed
12.
go back to reference Key T, Appleby P, Barnes I et al (2002) Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94:606–616PubMed Key T, Appleby P, Barnes I et al (2002) Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94:606–616PubMed
13.
go back to reference Kaaks R, Rinaldi S, Key TJ et al (2005) Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition. Endocr Relat Cancer 12:1071–1082PubMedCrossRef Kaaks R, Rinaldi S, Key TJ et al (2005) Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition. Endocr Relat Cancer 12:1071–1082PubMedCrossRef
14.
go back to reference Reeves GK, Beral V, Green J et al (2006) Hormonal therapy for menopause and breast-cancer risk by histological type: a cohort study and meta-analysis. Lancet Oncol 7:910–918PubMedCrossRef Reeves GK, Beral V, Green J et al (2006) Hormonal therapy for menopause and breast-cancer risk by histological type: a cohort study and meta-analysis. Lancet Oncol 7:910–918PubMedCrossRef
15.
go back to reference Shah NR, Borenstein J, Dubois RW (2005) Postmenopausal hormone therapy and breast cancer: a systematic review and meta-analysis. Menopause 12:668–678PubMedCrossRef Shah NR, Borenstein J, Dubois RW (2005) Postmenopausal hormone therapy and breast cancer: a systematic review and meta-analysis. Menopause 12:668–678PubMedCrossRef
16.
go back to reference Cotterchio M, Kreiger N, Sloan M et al (2001) Nonsteroidal anti-inflammatory drug use and breast cancer risk. Cancer Epidemiol Biomarkers Prev 10:1213–1217PubMed Cotterchio M, Kreiger N, Sloan M et al (2001) Nonsteroidal anti-inflammatory drug use and breast cancer risk. Cancer Epidemiol Biomarkers Prev 10:1213–1217PubMed
17.
go back to reference Harris RE, Chlebowski RT, Jackson RD et al (2003) Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women’s Health Initiative. Cancer Res 63:6096–6101PubMed Harris RE, Chlebowski RT, Jackson RD et al (2003) Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women’s Health Initiative. Cancer Res 63:6096–6101PubMed
18.
go back to reference Khuder SA, Mutgi AB (2001) Breast cancer and NSAID use: a meta-analysis. Br J Cancer 84:1188–1192PubMedCrossRef Khuder SA, Mutgi AB (2001) Breast cancer and NSAID use: a meta-analysis. Br J Cancer 84:1188–1192PubMedCrossRef
19.
go back to reference Terry MB, Gammon MD, Zhang FF et al (2004) Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. JAMA 291:2433–2440PubMedCrossRef Terry MB, Gammon MD, Zhang FF et al (2004) Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. JAMA 291:2433–2440PubMedCrossRef
20.
go back to reference Gallicchio L, McSorley MA, Newschaffer CJ et al (2006) Nonsteroidal antiinflammatory drugs, cyclooxygenase polymorphisms, and the risk of developing breast carcinoma among women with benign breast disease. Cancer 106:1443–1452PubMedCrossRef Gallicchio L, McSorley MA, Newschaffer CJ et al (2006) Nonsteroidal antiinflammatory drugs, cyclooxygenase polymorphisms, and the risk of developing breast carcinoma among women with benign breast disease. Cancer 106:1443–1452PubMedCrossRef
21.
go back to reference DuBois RN (2004) Aspirin and breast cancer prevention: the estrogen connection. JAMA 291:2488–2489PubMedCrossRef DuBois RN (2004) Aspirin and breast cancer prevention: the estrogen connection. JAMA 291:2488–2489PubMedCrossRef
22.
go back to reference Reed MJ, Purohit A (1997) Breast cancer and the role of cytokines in regulating estrogen synthesis: an emerging hypothesis. Endocr Rev 18:701–715PubMedCrossRef Reed MJ, Purohit A (1997) Breast cancer and the role of cytokines in regulating estrogen synthesis: an emerging hypothesis. Endocr Rev 18:701–715PubMedCrossRef
23.
go back to reference Purohit A, Reed MJ (2002) Regulation of estrogen synthesis in postmenopausal women. Steroids 67:979–983PubMedCrossRef Purohit A, Reed MJ (2002) Regulation of estrogen synthesis in postmenopausal women. Steroids 67:979–983PubMedCrossRef
24.
go back to reference Carr BR, Bradshaw KD (2001) Disorders of the ovary and female reproductive tract. In: Braunwald E, Fauci AS, Kasper DL et al (eds) Harrison’s principles of internal medicine, 15th edn. McGraw-Hill, New York, NY Carr BR, Bradshaw KD (2001) Disorders of the ovary and female reproductive tract. In: Braunwald E, Fauci AS, Kasper DL et al (eds) Harrison’s principles of internal medicine, 15th edn. McGraw-Hill, New York, NY
25.
go back to reference Bogaty P, Brophy JM, Noel M et al (2004) Impact of prolonged cyclooxygenase-2 inhibition on inflammatory markers and endothelial function in patients with ischemic heart disease and raised C-reactive protein: a randomized placebo-controlled study. Circulation 110:934–939PubMedCrossRef Bogaty P, Brophy JM, Noel M et al (2004) Impact of prolonged cyclooxygenase-2 inhibition on inflammatory markers and endothelial function in patients with ischemic heart disease and raised C-reactive protein: a randomized placebo-controlled study. Circulation 110:934–939PubMedCrossRef
26.
go back to reference Il’yasova D, Colbert LH, Harris TB et al (2005) Circulating levels of inflammatory markers and cancer risk in the health aging and body composition cohort. Cancer Epidemiol Biomarkers Prev 14:2413–2418PubMedCrossRef Il’yasova D, Colbert LH, Harris TB et al (2005) Circulating levels of inflammatory markers and cancer risk in the health aging and body composition cohort. Cancer Epidemiol Biomarkers Prev 14:2413–2418PubMedCrossRef
27.
go back to reference Heikkila K, Harris R, Lowe G et al (2009) Associations of circulating C-reactive protein and interleukin-6 with cancer risk: findings from two prospective cohorts and a meta-analysis. Cancer Causes Control 20:15–26PubMedCrossRef Heikkila K, Harris R, Lowe G et al (2009) Associations of circulating C-reactive protein and interleukin-6 with cancer risk: findings from two prospective cohorts and a meta-analysis. Cancer Causes Control 20:15–26PubMedCrossRef
28.
go back to reference Bhandare D, Nayar R, Bryk M et al (2005) Endocrine biomarkers in ductal lavage samples from women at high risk for breast cancer. Cancer Epidemiol Biomarkers Prev 14:2620–2627PubMedCrossRef Bhandare D, Nayar R, Bryk M et al (2005) Endocrine biomarkers in ductal lavage samples from women at high risk for breast cancer. Cancer Epidemiol Biomarkers Prev 14:2620–2627PubMedCrossRef
29.
go back to reference Gonullu G, Ersoy C, Ersoy A et al (2005) Relation between insulin resistance and serum concentrations of IL-6 and TNF-alpha in overweight or obese women with early stage breast cancer. Cytokine 31:264–269PubMedCrossRef Gonullu G, Ersoy C, Ersoy A et al (2005) Relation between insulin resistance and serum concentrations of IL-6 and TNF-alpha in overweight or obese women with early stage breast cancer. Cytokine 31:264–269PubMedCrossRef
30.
go back to reference Caras I, Grigorescu A, Stavaru C et al (2004) Evidence for immune defects in breast and lung cancer patients. Cancer Immunol Immunother 53:1146–1152PubMedCrossRef Caras I, Grigorescu A, Stavaru C et al (2004) Evidence for immune defects in breast and lung cancer patients. Cancer Immunol Immunother 53:1146–1152PubMedCrossRef
31.
go back to reference DeKeyser FG, Wainstock JM, Rose L et al (1998) Distress, symptom distress, and immune function in women with suspected breast cancer. Oncol Nurs Forum 25:1415–1422PubMed DeKeyser FG, Wainstock JM, Rose L et al (1998) Distress, symptom distress, and immune function in women with suspected breast cancer. Oncol Nurs Forum 25:1415–1422PubMed
32.
go back to reference Krajcik RA, Massardo S, Orentreich N (2003) No association between serum levels of tumor necrosis factor-alpha (TNF-alpha) or the soluble receptors sTNFR1 and sTNFR2 and breast cancer risk. Cancer Epidemiol Biomarkers Prev 12:945–946PubMed Krajcik RA, Massardo S, Orentreich N (2003) No association between serum levels of tumor necrosis factor-alpha (TNF-alpha) or the soluble receptors sTNFR1 and sTNFR2 and breast cancer risk. Cancer Epidemiol Biomarkers Prev 12:945–946PubMed
33.
go back to reference Campbell MJ, Scott J, Maecker HT et al (2005) Immune dysfunction and micrometastases in women with breast cancer. Breast Cancer Res Treat 91:163–171PubMedCrossRef Campbell MJ, Scott J, Maecker HT et al (2005) Immune dysfunction and micrometastases in women with breast cancer. Breast Cancer Res Treat 91:163–171PubMedCrossRef
34.
go back to reference Sheen-Chen SM, Chen WJ, Eng HL et al (1997) Serum concentration of tumor necrosis factor in patients with breast cancer. Breast Cancer Res Treat 43:211–215PubMedCrossRef Sheen-Chen SM, Chen WJ, Eng HL et al (1997) Serum concentration of tumor necrosis factor in patients with breast cancer. Breast Cancer Res Treat 43:211–215PubMedCrossRef
35.
go back to reference Allin KH, Bojesen SE, Nordestgaard BG (2009) Baseline C-reactive protein is associated with incident cancer and survival in patients with cancer. J Clin Oncol 27:2217–2224PubMedCrossRef Allin KH, Bojesen SE, Nordestgaard BG (2009) Baseline C-reactive protein is associated with incident cancer and survival in patients with cancer. J Clin Oncol 27:2217–2224PubMedCrossRef
36.
go back to reference Zhang SM, Lin J, Cook NR et al (2007) C-reactive protein and risk of breast cancer. J Natl Cancer Inst 99:890–894PubMedCrossRef Zhang SM, Lin J, Cook NR et al (2007) C-reactive protein and risk of breast cancer. J Natl Cancer Inst 99:890–894PubMedCrossRef
37.
go back to reference Trichopoulos D, Psaltopoulou T, Orfanos P et al (2006) Plasma C-reactive protein and risk of cancer: a prospective study from Greece. Cancer Epidemiol Biomarkers Prev 15:381–384PubMedCrossRef Trichopoulos D, Psaltopoulou T, Orfanos P et al (2006) Plasma C-reactive protein and risk of cancer: a prospective study from Greece. Cancer Epidemiol Biomarkers Prev 15:381–384PubMedCrossRef
38.
go back to reference Siemes C, Visser LE, Coebergh JW et al (2006) C-reactive protein levels, variation in the C-reactive protein gene, and cancer risk: the Rotterdam Study. J Clin Oncol 24:5216–5222PubMedCrossRef Siemes C, Visser LE, Coebergh JW et al (2006) C-reactive protein levels, variation in the C-reactive protein gene, and cancer risk: the Rotterdam Study. J Clin Oncol 24:5216–5222PubMedCrossRef
39.
go back to reference Lithgow D, Nyamathi A, Elashoff D et al (2007) C-reactive protein in nipple aspirate fluid associated with Gail model factors. Biol Res Nurs 9:108–116PubMedCrossRef Lithgow D, Nyamathi A, Elashoff D et al (2007) C-reactive protein in nipple aspirate fluid associated with Gail model factors. Biol Res Nurs 9:108–116PubMedCrossRef
40.
go back to reference Reeves KW, Gierach GL, Modugno F (2007) Recreational physical activity and mammographic breast density characteristics. Cancer Epidemiol Biomarkers Prev 16:934–942PubMedCrossRef Reeves KW, Gierach GL, Modugno F (2007) Recreational physical activity and mammographic breast density characteristics. Cancer Epidemiol Biomarkers Prev 16:934–942PubMedCrossRef
41.
go back to reference Hudson AG, Gierach GL, Modugno F et al (2008) Nonsteroidal anti-inflammatory drug use and serum total estradiol in postmenopausal women. Cancer Epidemiol Biomarkers Prev 17:680–687PubMedCrossRef Hudson AG, Gierach GL, Modugno F et al (2008) Nonsteroidal anti-inflammatory drug use and serum total estradiol in postmenopausal women. Cancer Epidemiol Biomarkers Prev 17:680–687PubMedCrossRef
42.
go back to reference Palomares MR, Machia JR, Lehman CD et al (2006) Mammographic density correlation with Gail model breast cancer risk estimates and component risk factors. Cancer Epidemiol Biomarkers Prev 15:1324–1330PubMedCrossRef Palomares MR, Machia JR, Lehman CD et al (2006) Mammographic density correlation with Gail model breast cancer risk estimates and component risk factors. Cancer Epidemiol Biomarkers Prev 15:1324–1330PubMedCrossRef
43.
go back to reference Haars G, van Noord PA, van Gils CH et al (2005) Measurements of breast density: no ratio for a ratio. Cancer Epidemiol Biomarkers Prev 14:2634–2640PubMedCrossRef Haars G, van Noord PA, van Gils CH et al (2005) Measurements of breast density: no ratio for a ratio. Cancer Epidemiol Biomarkers Prev 14:2634–2640PubMedCrossRef
44.
go back to reference Boyd NF, Martin LJ, Sun L et al (2006) Body size, mammographic density, and breast cancer risk. Cancer Epidemiol Biomarkers Prev 15:2086–2092PubMedCrossRef Boyd NF, Martin LJ, Sun L et al (2006) Body size, mammographic density, and breast cancer risk. Cancer Epidemiol Biomarkers Prev 15:2086–2092PubMedCrossRef
45.
go back to reference Reeves KW, Stone RA, Modugno F et al (2009) Longitudinal association of anthropometry with mammographic breast density in the Study of Women’s Health Across the Nation. Int J Cancer 124:1169–1177PubMedCrossRef Reeves KW, Stone RA, Modugno F et al (2009) Longitudinal association of anthropometry with mammographic breast density in the Study of Women’s Health Across the Nation. Int J Cancer 124:1169–1177PubMedCrossRef
46.
go back to reference Woolcott CG, Cook LS, Courneya KS et al (2010) Associations of overall and abdominal adiposity with area and volumetric mammographic measures among postmenopausal women. Int J Cancer. doi:10.1002/ijc.25676 Woolcott CG, Cook LS, Courneya KS et al (2010) Associations of overall and abdominal adiposity with area and volumetric mammographic measures among postmenopausal women. Int J Cancer. doi:10.​1002/​ijc.​25676
47.
go back to reference Himmerich H, Fulda S, Linseisen J et al (2006) TNF-alpha, soluble TNF receptor and interleukin-6 plasma levels in the general population. Eur Cytokine Netw 17:196–201PubMed Himmerich H, Fulda S, Linseisen J et al (2006) TNF-alpha, soluble TNF receptor and interleukin-6 plasma levels in the general population. Eur Cytokine Netw 17:196–201PubMed
48.
go back to reference Bochud M, Marquant F, Marques-Vidal PM et al (2009) Association between C-reactive protein and adiposity in women. J Clin Endocrinol Metab 94:3969–3977PubMedCrossRef Bochud M, Marquant F, Marques-Vidal PM et al (2009) Association between C-reactive protein and adiposity in women. J Clin Endocrinol Metab 94:3969–3977PubMedCrossRef
49.
go back to reference Weisberg SP, McCann D, Desai M et al (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808PubMed Weisberg SP, McCann D, Desai M et al (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808PubMed
50.
go back to reference Sunderkotter C, Steinbrink K, Goebeler M et al (1994) Macrophages and angiogenesis. J Leukoc Biol 55:410–422PubMed Sunderkotter C, Steinbrink K, Goebeler M et al (1994) Macrophages and angiogenesis. J Leukoc Biol 55:410–422PubMed
51.
go back to reference Garcia-Macedo R, Sanchez-Munoz F, Almanza-Perez JC et al (2008) Glycine increases mRNA adiponectin and diminishes pro-inflammatory adipokines expression in 3T3–L1 cells. Eur J Pharmacol 587:317–321PubMedCrossRef Garcia-Macedo R, Sanchez-Munoz F, Almanza-Perez JC et al (2008) Glycine increases mRNA adiponectin and diminishes pro-inflammatory adipokines expression in 3T3–L1 cells. Eur J Pharmacol 587:317–321PubMedCrossRef
52.
go back to reference Kolsum U, Roy K, Starkey C et al (2009) The repeatability of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein in COPD patients over one year. Int J Chron Obstruct Pulmon Dis 4:149–156PubMed Kolsum U, Roy K, Starkey C et al (2009) The repeatability of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein in COPD patients over one year. Int J Chron Obstruct Pulmon Dis 4:149–156PubMed
53.
go back to reference Karakas M, Baumert J, Greven S et al (2010) Reproducibility in serial C-reactive protein and interleukin-6 measurements in post-myocardial infarction patients: results from the AIRGENE study. Clin Chem 56:861–864PubMedCrossRef Karakas M, Baumert J, Greven S et al (2010) Reproducibility in serial C-reactive protein and interleukin-6 measurements in post-myocardial infarction patients: results from the AIRGENE study. Clin Chem 56:861–864PubMedCrossRef
Metadata
Title
Circulating levels of inflammatory markers and mammographic density among postmenopausal women
Authors
Katherine W. Reeves
Joel L. Weissfeld
Francesmary Modugno
Brenda Diergaarde
Publication date
01-06-2011
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2011
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-010-1249-5

Other articles of this Issue 2/2011

Breast Cancer Research and Treatment 2/2011 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine