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Assessment and Counseling for Women With a Family History of Breast Cancer: Title and subTitle BreakA Guide for Clinicians FREE

Kent F. Hoskins, MD; Jill E. Stopfer, MS; Kathleen A. Calzone, RN, BSN; Sofia D. Merajver, MD, PhD; Timothy R. Rebbeck, PhD; Judy E. Garber, MD; Barbara L. Weber, MD
[+] Author Affiliations

Reprint requests to the University of Pennsylvania Medical Center, Biomedical Research Bldg I, Room 1009, 422Curie Blvd, Philadelphia, PA 19104-6100(Dr Weber).


JAMA. 1995;273(7):577-585. doi:10.1001/jama.1995.03520310075033
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More women in all risk categories are seeking information regarding their individual breast cancer risk, and there is a need for their primary care clinicians to be able to assess familial risk factors for breast cancer, provide individualized risk information, and offer surveillance recommendations. Estimates of the number of women with a family history of breast cancer range from approximately 5% to 20%, depending on the population surveyed. Many of these women will not have a family history that suggests the presence of a highly penetrant breast cancer susceptibility gene. However, a small subset of such women will come from families with a striking incidence of breast and other cancers often associated with inherited mutations. The development and refinement of risk prediction models provide an epidemiologic basis for counseling women with a family history that does not appear related to a dominant susceptibility gene. In contrast, the recent isolation of BRCA1, the localization of BRCA2, and the acknowledgment that additional breast cancer susceptibility genes must exist provide a molecular basis for counseling some high-risk women. We present a guide for primary care clinicians that may be helpful in defining families as moderate or high risk, in determining individual risk in women with a family history of breast cancer based on this distinction, and for counseling women in a setting where the data necessary to design surveillance and prevention strategies are lacking. We include criteria for selecting women who may be candidates for detection of inherited mutations in breast cancer susceptibility genes.

(JAMA. 1995;273:577-585)

REFERENCES

Kelsey JL, Gammon MD.  The epidemiology of breast cancer. CA Cancer J Clin . 1991;;41:147-165.
Holford TR, Roush GC, McKay LA.  Trends in female breast cancer in Connecticut and the United States. J Clin Epidemiol . 1991;;44:29-39.
Gail MH, Brinton LA, Byar DP, et al.  Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst . 1989;;81:1879-1886.
Polednak AP, Lane DA, Burg MA.  Risk perception, family history, and use of breast cancer screening tools. Cancer Detect Prev . 1991;;15:257-263.
Skinner CS, Strecher VJ, Hospers H.  Physicians' recommendations for mammography: do tailored messages make a difference? Am J Public Health . 1994;;84:43-49.
Mulvihill JJ.  Prospects for cancer control and prevention through genetics. Clin Genet . 1989;;36: 313-319.
Collins FS, Benjamin LJ, Botstein D, et al.  Statement on use of DNA testing for presymptomatic identification of cancer risk. JAMA . 1994;;271:785.
Andrews LB, Fullarton JE, Holtzman NA, Motulsky AG, eds. Assessing Genetic Risks: Implications for Health and Social Policy . Washington, DC: Committee on Assessing Genetic Risks, Division of Health Sciences Policy, Institute of Medicine; National Academy Press; 1994;:1-28.
Murray TH.  Ethical issues in human genome research. FASEB J . 1991;;5:55-60.
Huggins M, Bloch M, Kanani S, et al.  Ethical and legal dilemmas arising during predictive testing for adult-onset disease: the experience of Huntington disease. Am J Hum Genet . 1990;;47:4-12.
Biesecker BB, Boehnke M, Calzone K, et al.  Genetic counseling for families with inherited susceptibility to breast and ovarian cancer. JAMA . 1993;;269:1970-1974.
Bowcock AM, Biesecker BB, Collins F, et al.  Statement of the American Society of Human Genetics on genetic testing for breast and ovarian cancer predisposition. Am J Hum Genet . 1994;;55:i-iv.
Feuer EJ, Wun L-M, Boring CC, Flanders WD, Timmel MJ, Tong T.  The lifetime risk of developing breast cancer. J Natl Cancer Inst . 1993;;85:892-897.
Colditz GA, Willett WC, Hunter DJ, et al.  Family history, age, and risk of breast cancer. JAMA . 1993;;270:338-343.
Slattery ML, Kerber RA.  A comprehensive evaluation of family history and breast cancer risk. JAMA . 1993;;270:1563-1568.
Claus EB, Risch N, Thompson WD.  Genetic analysis of breast cancer in the Cancer and Steroid Hormone study. Am J Hum Genet . 1991;;48:232-242.
Anderson DE, Badzioch MD.  Risk of familial breast cancer. Cancer . 1985;;56:383-387.
Claus ER, Risch NJ, Thompson WD.  Age at diagnosis as an indicator of familial risk of breast cancer. Am J Epidemiol . 1990;;131:961-972.
Claus EB, Risch N, Thompson WD.  Autosomal dominant inheritance of early onset breast cancer. Cancer . 1994;;73:643-651.
Easton DF, Bishop DT, Ford D, Crockford GP, and the Breast Cancer Linkage Consortium.  Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. Am J Hum Genet . 1993;;52:678-701.
Narod SA, Feuteun J, Lynch HT, et al.  Familial breast-ovarian cancer locus on chromosome 17q12-23. Lancet . 1991;;338:82-83.
Wooster R, Neuhausen S, Mangion J, et al.  Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science . 1994;; 265:2088-2090.
Sattin RW, Rubin GL, Webster LA, et al.  Family history and the risk of breast cancer. JAMA . 1985;;253:1908-1913.
Offit K, Brown, K.  Quantitation of familial cancer risk: a resource for clinical oncologists. J Clin Oncol . 1994;;12:1724-1736.
Bondy ML, Lustbader ED, Halabi S, Ross E, Vogel V.  Validation of a breast cancer risk assessment model in women with a positive family history. J Natl Cancer Inst . 1994;;86:620-625.
Benichou J.  A computer program for estimating individualized probabilities of breast cancer. Comput Biomed Res . 1993;;26:373-382.
Easton DF, Narod SA, Ford D, Steel M.  The genetic epidemiology of BRCA1. Lancet . 1994;;344: 761.
Miki Y, Swensen J, Shattuck-Eidens D, et al.  A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science . 1994;;266:66-71.
Futreal A, Liu Q, Shattuck-Eidens D, et al.  BRCA1 mutations in primary breast and ovarian carcinomas. Science . 1994;;266:120-122.
Hall JM, Lee MK, Newman B, et al.  Linkage of early onset breast cancer to chromosome 17q21. Science . 1990;;250:1684-1689.
Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE, and the Breast Cancer Linkage Consortium.  Risk of cancer in BRCA1 mutation carriers. Lancet . 1994;;343:692-695.
Lynch HT, Marcus J, Watson P, Page D.  Distinctive clinicopathologic features of BRCA1-linked hereditary breast cancer. Proc ASCO . 1994;;13:56.
Stratton M, Ford D, Neuhasen S, et al.  Familial male breast cancer is not linked to the BRCA1 locus on chromosome 17q. Nat Genet . 1994;;7:103-107.
Shattuck-Eidens D, McClure M, Simard J, et al.  A collaborative study of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene: implications for presymptomatic genetic testing and screening. JAMA . 1995;;273:535-541.
Li FP, Fraumeni JF Jr.  Soft-tissue sarcomas, breast cancer, and other neoplasms: a familial syndrome? Ann Intern Med . 1969;;71:747-752.
Malkin D, Li FP, Strong LC, et al.  Germline p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science . 1990;;250: 1233-1238.
Hall NR, Murday VA, Chapman P.  Genetic linkage in Muir-Torre syndrome to the same chromosomal region as cancer family syndrome. Eur J Cancer . 1994;;30A:180-182.
Li FP, Fraumeni JF Jr, Mulvihill JJ, et al.  A cancer family syndrome in twenty-four kindreds. Cancer Res . 1988;;48:5358-5362.
McIntyre LF, Smith-Sorensen B, Friend SH, et al.  Germline mutations of the p53 tumor suppressor gene in children with osteosarcoma. J Clin Oncol . 1994;;12:925-930.
Li FP, Garber JE, Friend SH, et al.  Recommendations on predictive testing for germline p53 mutations among cancer-prone individuals. J Natl Cancer Inst . 1992;;84:1156-1160.
Hartley AL, Birch JM, Marsden HB, et al.  Breast cancer risk in mothers of children with osteosarcoma and chondrosarcoma. Br J Cancer . 1986;; 54:819-823.
Wood DA, Darling HH.  A cancer family manifesting multiple occurrences of bilateral carcinoma of the breast. Cancer Res . 1943;;3:509-514.
Brownstein MH, Wolf M, Bikowski JB.  Cowden's disease: a cutaneous marker of breast cancer. Cancer . 1978;;41:2393-2398.
Starink TM.  Cowden's disease: analysis of 14 new cases. J Am Acad Dermatol . 1984;;11:1127-1141.
Muir EG, Yates-Bell AJ, Barlow KA.  Multiple primary carcinomata of the colon, duodenum, and larynx associated with keratoacanthomata of the face. Br J Surg . 1967;;54:191-195.
Spigelman AD, Murray V, Phillips RKS.  Cancer and the Peutz-Jeghers syndrome. Gut . 1989;;30: 1588-1590.
Morrell D, Cromartie E, Swift M.  Mortality and cancer incidence in 263 patients with ataxia-telangiectasia. J Natl Cancer Inst . 1986;;77:89-92.
Swift M, Morrell D, Massey RB, Chase CL.  Incidence of cancer in 161 families affected by ataxiatelangiectasia. N Engl J Med . 1987;;325:1831-1836.
Castilla LH, Couch FJ, Erdos MR, et al.  Mutations in the BRCA1 gene in families with early onset breast and ovarian cancer. Nat Genet . 1994;; 8:387-391.
Simard J, Tonin P, Durocher F, et al.  Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families. Nat Genet . 1994;;8:392-398.
Friedman LS, Ostermeyer EA, Szabo CI, et al.  Confirmation of BRCA1 by analysis of germline mutations linked to breast and ovarian cancer in 10 families. Nat Genet . 1994;;8:399-404.
Shapiro DE, Boggs SR, Melamed BG, Graham-Pole J.  The effect of varied physician affect on recall, anxiety, and perceptions in women at risk for breast cancer: an analogue study. Health Psychol . 1992;;11:61-66.
Wender RC.  Cancer screening and prevention in primary care: obstacles for physicians. Cancer Suppl . 1993;;72:1093-1099.
Kelly PT.  Informational needs of individuals and families with hereditary cancers. Semin Oncol Nurs . 1992;;8:288-292.
Lerman C, Rimer B, Trock B, Balshem A, Engstrom P.  Factors associated with repeat adherence to breast cancer screening. Prev Med . 1990;;19:279-290.
Stefanek ME, Wilcox P, Huelskamp AM.  Breast self-examination proficiency and training effects: women at increased risk of breast cancer. Cancer Epidemiol Biomarkers Prev . 1992;;1:591-596.
Becker MH. The Health Belief Model and Personal Health Behavior . Thorofare, NJ: Charles B Slack Inc; 1974;.
Wellisch DK, Gritz ER, Schain W, Wang H, Siau J.  Psychosocial functioning of daughters of breast cancer patients part II: characterizing the distressed daughter of the breast cancer patient. Psychosomatics . 1992;;33:171-179.
Evans DL, Burnell LD, Hopwood P, Howell A.  Perception of risk in women with a family history of breast cancer. Br J Cancer . 1992;;67:612-614.
Champion VL.  The relationship of selected variables to breast cancer detection behaviors in women 35 and older. Oncol Nurs Forum . 1991;;18:733-739.
Kash KM, Holland JC, Halper MS, Miller DG.  Psychological distress and surveillance behaviors of women with a family history of breast cancer. J Natl Cancer Inst . 1992;;84:24-30.
Lerman C, Trock B, Rimer B, Jepson C, Brody D, Boyce A.  Psychological side effects of breast cancer screening. Health Psychol . 1991;;10:259-267.
Taplin S, Anderman C, Grothaus L.  Breast cancer risk and participation in mammographic screening. Am J Public Health . 1989;;79:1494-1498.

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Kelsey JL, Gammon MD.  The epidemiology of breast cancer. CA Cancer J Clin . 1991;;41:147-165.
Holford TR, Roush GC, McKay LA.  Trends in female breast cancer in Connecticut and the United States. J Clin Epidemiol . 1991;;44:29-39.
Gail MH, Brinton LA, Byar DP, et al.  Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst . 1989;;81:1879-1886.
Polednak AP, Lane DA, Burg MA.  Risk perception, family history, and use of breast cancer screening tools. Cancer Detect Prev . 1991;;15:257-263.
Skinner CS, Strecher VJ, Hospers H.  Physicians' recommendations for mammography: do tailored messages make a difference? Am J Public Health . 1994;;84:43-49.
Mulvihill JJ.  Prospects for cancer control and prevention through genetics. Clin Genet . 1989;;36: 313-319.
Collins FS, Benjamin LJ, Botstein D, et al.  Statement on use of DNA testing for presymptomatic identification of cancer risk. JAMA . 1994;;271:785.
Andrews LB, Fullarton JE, Holtzman NA, Motulsky AG, eds. Assessing Genetic Risks: Implications for Health and Social Policy . Washington, DC: Committee on Assessing Genetic Risks, Division of Health Sciences Policy, Institute of Medicine; National Academy Press; 1994;:1-28.
Murray TH.  Ethical issues in human genome research. FASEB J . 1991;;5:55-60.
Huggins M, Bloch M, Kanani S, et al.  Ethical and legal dilemmas arising during predictive testing for adult-onset disease: the experience of Huntington disease. Am J Hum Genet . 1990;;47:4-12.
Biesecker BB, Boehnke M, Calzone K, et al.  Genetic counseling for families with inherited susceptibility to breast and ovarian cancer. JAMA . 1993;;269:1970-1974.
Bowcock AM, Biesecker BB, Collins F, et al.  Statement of the American Society of Human Genetics on genetic testing for breast and ovarian cancer predisposition. Am J Hum Genet . 1994;;55:i-iv.
Feuer EJ, Wun L-M, Boring CC, Flanders WD, Timmel MJ, Tong T.  The lifetime risk of developing breast cancer. J Natl Cancer Inst . 1993;;85:892-897.
Colditz GA, Willett WC, Hunter DJ, et al.  Family history, age, and risk of breast cancer. JAMA . 1993;;270:338-343.
Slattery ML, Kerber RA.  A comprehensive evaluation of family history and breast cancer risk. JAMA . 1993;;270:1563-1568.
Claus EB, Risch N, Thompson WD.  Genetic analysis of breast cancer in the Cancer and Steroid Hormone study. Am J Hum Genet . 1991;;48:232-242.
Anderson DE, Badzioch MD.  Risk of familial breast cancer. Cancer . 1985;;56:383-387.
Claus ER, Risch NJ, Thompson WD.  Age at diagnosis as an indicator of familial risk of breast cancer. Am J Epidemiol . 1990;;131:961-972.
Claus EB, Risch N, Thompson WD.  Autosomal dominant inheritance of early onset breast cancer. Cancer . 1994;;73:643-651.
Easton DF, Bishop DT, Ford D, Crockford GP, and the Breast Cancer Linkage Consortium.  Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. Am J Hum Genet . 1993;;52:678-701.
Narod SA, Feuteun J, Lynch HT, et al.  Familial breast-ovarian cancer locus on chromosome 17q12-23. Lancet . 1991;;338:82-83.
Wooster R, Neuhausen S, Mangion J, et al.  Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science . 1994;; 265:2088-2090.
Sattin RW, Rubin GL, Webster LA, et al.  Family history and the risk of breast cancer. JAMA . 1985;;253:1908-1913.
Offit K, Brown, K.  Quantitation of familial cancer risk: a resource for clinical oncologists. J Clin Oncol . 1994;;12:1724-1736.
Bondy ML, Lustbader ED, Halabi S, Ross E, Vogel V.  Validation of a breast cancer risk assessment model in women with a positive family history. J Natl Cancer Inst . 1994;;86:620-625.
Benichou J.  A computer program for estimating individualized probabilities of breast cancer. Comput Biomed Res . 1993;;26:373-382.
Easton DF, Narod SA, Ford D, Steel M.  The genetic epidemiology of BRCA1. Lancet . 1994;;344: 761.
Miki Y, Swensen J, Shattuck-Eidens D, et al.  A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science . 1994;;266:66-71.
Futreal A, Liu Q, Shattuck-Eidens D, et al.  BRCA1 mutations in primary breast and ovarian carcinomas. Science . 1994;;266:120-122.
Hall JM, Lee MK, Newman B, et al.  Linkage of early onset breast cancer to chromosome 17q21. Science . 1990;;250:1684-1689.
Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE, and the Breast Cancer Linkage Consortium.  Risk of cancer in BRCA1 mutation carriers. Lancet . 1994;;343:692-695.
Lynch HT, Marcus J, Watson P, Page D.  Distinctive clinicopathologic features of BRCA1-linked hereditary breast cancer. Proc ASCO . 1994;;13:56.
Stratton M, Ford D, Neuhasen S, et al.  Familial male breast cancer is not linked to the BRCA1 locus on chromosome 17q. Nat Genet . 1994;;7:103-107.
Shattuck-Eidens D, McClure M, Simard J, et al.  A collaborative study of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene: implications for presymptomatic genetic testing and screening. JAMA . 1995;;273:535-541.
Li FP, Fraumeni JF Jr.  Soft-tissue sarcomas, breast cancer, and other neoplasms: a familial syndrome? Ann Intern Med . 1969;;71:747-752.
Malkin D, Li FP, Strong LC, et al.  Germline p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science . 1990;;250: 1233-1238.
Hall NR, Murday VA, Chapman P.  Genetic linkage in Muir-Torre syndrome to the same chromosomal region as cancer family syndrome. Eur J Cancer . 1994;;30A:180-182.
Li FP, Fraumeni JF Jr, Mulvihill JJ, et al.  A cancer family syndrome in twenty-four kindreds. Cancer Res . 1988;;48:5358-5362.
McIntyre LF, Smith-Sorensen B, Friend SH, et al.  Germline mutations of the p53 tumor suppressor gene in children with osteosarcoma. J Clin Oncol . 1994;;12:925-930.
Li FP, Garber JE, Friend SH, et al.  Recommendations on predictive testing for germline p53 mutations among cancer-prone individuals. J Natl Cancer Inst . 1992;;84:1156-1160.
Hartley AL, Birch JM, Marsden HB, et al.  Breast cancer risk in mothers of children with osteosarcoma and chondrosarcoma. Br J Cancer . 1986;; 54:819-823.
Wood DA, Darling HH.  A cancer family manifesting multiple occurrences of bilateral carcinoma of the breast. Cancer Res . 1943;;3:509-514.
Brownstein MH, Wolf M, Bikowski JB.  Cowden's disease: a cutaneous marker of breast cancer. Cancer . 1978;;41:2393-2398.
Starink TM.  Cowden's disease: analysis of 14 new cases. J Am Acad Dermatol . 1984;;11:1127-1141.
Muir EG, Yates-Bell AJ, Barlow KA.  Multiple primary carcinomata of the colon, duodenum, and larynx associated with keratoacanthomata of the face. Br J Surg . 1967;;54:191-195.
Spigelman AD, Murray V, Phillips RKS.  Cancer and the Peutz-Jeghers syndrome. Gut . 1989;;30: 1588-1590.
Morrell D, Cromartie E, Swift M.  Mortality and cancer incidence in 263 patients with ataxia-telangiectasia. J Natl Cancer Inst . 1986;;77:89-92.
Swift M, Morrell D, Massey RB, Chase CL.  Incidence of cancer in 161 families affected by ataxiatelangiectasia. N Engl J Med . 1987;;325:1831-1836.
Castilla LH, Couch FJ, Erdos MR, et al.  Mutations in the BRCA1 gene in families with early onset breast and ovarian cancer. Nat Genet . 1994;; 8:387-391.
Simard J, Tonin P, Durocher F, et al.  Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families. Nat Genet . 1994;;8:392-398.
Friedman LS, Ostermeyer EA, Szabo CI, et al.  Confirmation of BRCA1 by analysis of germline mutations linked to breast and ovarian cancer in 10 families. Nat Genet . 1994;;8:399-404.
Shapiro DE, Boggs SR, Melamed BG, Graham-Pole J.  The effect of varied physician affect on recall, anxiety, and perceptions in women at risk for breast cancer: an analogue study. Health Psychol . 1992;;11:61-66.
Wender RC.  Cancer screening and prevention in primary care: obstacles for physicians. Cancer Suppl . 1993;;72:1093-1099.
Kelly PT.  Informational needs of individuals and families with hereditary cancers. Semin Oncol Nurs . 1992;;8:288-292.
Lerman C, Rimer B, Trock B, Balshem A, Engstrom P.  Factors associated with repeat adherence to breast cancer screening. Prev Med . 1990;;19:279-290.
Stefanek ME, Wilcox P, Huelskamp AM.  Breast self-examination proficiency and training effects: women at increased risk of breast cancer. Cancer Epidemiol Biomarkers Prev . 1992;;1:591-596.
Becker MH. The Health Belief Model and Personal Health Behavior . Thorofare, NJ: Charles B Slack Inc; 1974;.
Wellisch DK, Gritz ER, Schain W, Wang H, Siau J.  Psychosocial functioning of daughters of breast cancer patients part II: characterizing the distressed daughter of the breast cancer patient. Psychosomatics . 1992;;33:171-179.
Evans DL, Burnell LD, Hopwood P, Howell A.  Perception of risk in women with a family history of breast cancer. Br J Cancer . 1992;;67:612-614.
Champion VL.  The relationship of selected variables to breast cancer detection behaviors in women 35 and older. Oncol Nurs Forum . 1991;;18:733-739.
Kash KM, Holland JC, Halper MS, Miller DG.  Psychological distress and surveillance behaviors of women with a family history of breast cancer. J Natl Cancer Inst . 1992;;84:24-30.
Lerman C, Trock B, Rimer B, Jepson C, Brody D, Boyce A.  Psychological side effects of breast cancer screening. Health Psychol . 1991;;10:259-267.
Taplin S, Anderman C, Grothaus L.  Breast cancer risk and participation in mammographic screening. Am J Public Health . 1989;;79:1494-1498.
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