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April 21, 1993, Vol 269, No. 15 >
ARTICLE | April 21, 1993

Inherited Breast and Ovarian Cancer: Title and subTitle BreakWhat Are the Risks? What Are the Choices? FREE

Mary-Claire King, PhD; Sarah Rowell, MPH; Susan M. Love, MD
[+] Author Affiliations

Reprint requests to 140 Warren Hall, University of California, Berkeley, Berkeley, CA 94720 (Dr King).


JAMA. 1993;269(15):1975-1980. doi:10.1001/jama.1993.03500150087033
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References

IT IS now clear that susceptibility to breast and ovarian cancer is inherited in some families. Between 5% and 10% of breast cancer1,2 and ovarian cancer3 can be attributed to inheritance of a gene conferring high risk, followed by genetic changes specific to the target epithelial cells of the breast or ovary. For decades, there has been no doubt that cancer is genetic, in the sense that transformation of a normal cell to invasive and malignant growth is due to changes in the DNA. But most cancer is genetic only at the level of the transformed cell, not in the germline cells of patients. Consequently, most cancer is not inherited in families. Not all that is genetic is inherited.

Meanwhile, it has been observed for centuries that breast cancer clusters in families.4 Of course, given the very high incidence of breast cancer in our times, there are

REFERENCES

1 +
Newman B, Austin MA, Lee M, King M-C.  Inheritance of human breast cancer: evidence for autosomal dominant transmission in high-risk families. Proc Natl Acad Sci USA . 1988;;85:3044-3048.
2 +
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.
3 +
Schildkraut JM, Thompson WD.  Familial ovarian cancer: a population-based case-control study. Am J Epidemiol . 1988;;128:456-466.
4 +
Broca P. Traite des Tumeurs . Paris, France: Asselin; 1866;.
5 +
Hall JM, Lee MK, Morrow J, et al.  Linkage of early-onset familial breast cancer to chromosome 17q21. Science . 1990;;250:1684-1689.
6 +
Malkin D, Li FP, Strong LC, et al.  Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science . 1990;;250: 1233-1238.
7 +
King M-C.  Breast cancer genes: how many, where, and who are they? Nature Genet . 1992;;2: 89-90.
8 +
Sideransky D, Tokino T, Helzlsouer K, et al.  Inherited p53 gene mutations in breast cancer. Cancer Res . 1992;;52:2984-2986.
9 +
Coles C, Condie A, Chetty U, Steel CM, Evans HJ, Prosser J.  p53 mutations in breast cancer. Cancer Res . 1992;;52:5291-5298.
10 +
Hall JM, Friedman L, Guenther C, et al.  Closing in on a breast cancer gene on chromosome 17q. Am J Hum Genet . 1992;;50:1235-1242.
11 +
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 . In press.
12 +
Collins FS.  Positional cloning: let's not call it reverse anymore. Nature Genet . 1992;;1:3-6.
13 +
Bowcock AM, Anderson LA, Black DM, et al.  Polymorphisms in THRAl and D17S183 flank an interval of <4 cM for the breast-ovarian cancer gene on chromosome 17q. Am J Hum Genet . In press.
14 +
Smith SA, Easton DF, Evans DGR, Ponder BAJ.  Allele losses in the region 17q12-21 in familial breast and ovarian cancer involve the wild-type chromosome. Nature Genet . 1992;;2:128-131.
15 +
Zuppan PJ, Hall JM, Lee MK, Ponglikitmongkol M, King M-C.  Possible linkage of the estrogen receptor gene to breast cancer in a family with late-onset disease. Am J Hum Genet . 1991;;48:1065-1068.
16 +
Callahan R, Cropp CS, Merlo GR, Liscia DS, Cappa APM, Lidereau R.  Somatic mutations and human breast cancer. Cancer . 1992;;69( (suppl) ):1582-1588.
17 +
Hollstein M, Sidransky D, Vogelstein B, Harris CC.  p53 mutations in human cancers . Science . 1991;; 253:49-53.
18 +
Van de Vijver MJ, Nusse R.  The molecular biology of breast cancer. Biochim Biophys Acta . 1991;;1072:33-50.
19 +
Xiong Y, Connolly T, Futcher B, Beach D.  Human D-type cyclin. Cell . 1991;;65:691-699.
20 +
Motokura T, Bloom T, Kim HG, et al.  A novel cyclin encoded by a bell-linked candidate oncogene. Nature . 1991;;350:512-515.
21 +
Slamon DJ, Godophin W, Jones LA, et al.  Studies of the HER2/neu proto-oncogene in human breast and ovarian cancer. Science . 1989;;244:707-712.
22 +
Tsuda H, Hirohashi S, Shimosato Y, Hirota T, et al.  Correlation between long-term survival in breast cancer patients and amplification of two putative oncogene-coamplification units: hst-1/int-2 and c-erbB-2/ear-1. Cancer Res . 1989;;49:3104-3108.
23 +
Bevilacqua G, Sobel ME, Liotta LA, Steeg PS.  Association of low nm23 RNA levels in human primary infiltrating ductal breast carcinomas with lymph node involvement and other histopathological indicators of high metastatic potential. Cancer Res . 1989;;49:5185-5190.
24 +
Weinberg RA.  Tumor suppressor genes. Science . 1991;;254:1138-1146.
25 +
Ries LAG, Hankey BF, Edwards BK, eds. Cancer Statistics Review, 1973-1987 . Bethesda Md: National Institutes of Health; 1990;. National Institutes of Health publication 90-2789.
26 +
Henderson BE, Ross RK, Pike MC.  Toward the primary prevention of cancer. Science . 1991;:1131-1138.
27 +
Pike MC, Kraile MD, Henderson BE, Casagrande JT, Hoel DG.  `Hormonal' risk factors, `breast tissue age' and the age-incidence of breast cancer. Nature . 1983;;303:767-770.
28 +
McGregor DH, Land CE, Choi K, et al.  Breast cancer incidence among atomic bomb survivors, Hiroshima and Nagasaki, 1950-1969. J Natl Cancer Inst . 1977;;59:799-811.
29 +
Boice JD Jr, Monson RR.  Breast cancer in women after repeated fluoroscopic examinations of the chest. J Natl Cancer Inst . 1977;;59:823-832.
30 +
King M-C.  Genetic analysis of cancer in families. Cancer Surv . 1991;;9:417-435.
31 +
Anderson LA, Friedman LS, Osborne-Lawrence S, et al.  High-density genetic map of the BRCA1 region of chromosome 17q12-q21. Genomics . In press.
32 +
Claus EB, Schildkraut JM, Thompson WD, Risch N.  An analysis of the genetic relationship between breast and ovarian cancer. Am J Hum Genet . In press.
33 +
Miller AB, Baines CJ, To T, Wall C.  Canadian national breast screening study, 1: breast cancer detection and death rates among women aged 40 to 49 years. Can Med Assoc J . 1992;;147:1459-1476.
34 +
Baker LH.  BCDDP: five-year summary report. CA Cancer J Clin . 1982;;32:194-225.
35 +
LaFrancis IE, Cooper RB.  Second primary malignancies associated with primary female breast cancer: a review of the Danbury Hospital experience. Conn Med . 1992;;56:411-414.
36 +
Runowicz CD.  Advances in the screening and treatment of ovarian cancer. CA Cancer J Clin . 1992;;42:327-349.
37 +
Zeigler LD, Kroll SS.  Primary breast cancer after prophylactic mastectomy. Am J Clin Oncol . 1991;;14:451-454.
38 +
Nelson H, Miller SH, Buck D, Demuth RJ, Fletcher WS, Buehler P.  Effectiveness of prophylactic mastectomy in the prevention of breast tumors in C3H mice. Plast Reconstr Surg . 1989;;83: 662-669.
39 +
Goodnight JE Jr, Quagliana JM, Morton DL.  Failure of subcutaneous mastectomy to prevent the development of breast cancer. J Surg Oncol . 1984;;26:198-201.
40 +
Temple WJ, Lindsay RL, Magi E, Urbanski SJ.  Technical considerations for prophylactic mastectomy in patients at high risk for breast cancer. Am J Surg . 1991;;161:413-414.
41 +
Irwin KL, Lee NC, Peterson HB, Rubin GL, Wingo PA, Mandel MG.  Hysterectomy, tubal sterilization, and the risk of breast cancer. Am J Epidemiol . 1988;;127:1192-1201.
42 +
Cruickshank DJ, Haites N, Anderson S, et al.  The multidisciplinary management of a family with epithelial ovarian cancer. Br J Obstet Gynaecol . 1992;;99:226-231.
43 +
Weber AM, Hewett WJ, Gajewski WH, Curry SL.  Serous carcinoma of the peritoneum after oophorectomy. Obstet Gynecol . 1992;;80:558-560.
44 +
Nayfield SG, Karp JE, Ford LG, Dorr FA, Kramer BS.  Potential role of tamoxifen in prevention of breast cancer. J Natl Cancer Inst . 1991;;83: 1450-1459.

Figures

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Newman B, Austin MA, Lee M, King M-C.  Inheritance of human breast cancer: evidence for autosomal dominant transmission in high-risk families. Proc Natl Acad Sci USA . 1988;;85:3044-3048.
2 +
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.
3 +
Schildkraut JM, Thompson WD.  Familial ovarian cancer: a population-based case-control study. Am J Epidemiol . 1988;;128:456-466.
4 +
Broca P. Traite des Tumeurs . Paris, France: Asselin; 1866;.
5 +
Hall JM, Lee MK, Morrow J, et al.  Linkage of early-onset familial breast cancer to chromosome 17q21. Science . 1990;;250:1684-1689.
6 +
Malkin D, Li FP, Strong LC, et al.  Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science . 1990;;250: 1233-1238.
7 +
King M-C.  Breast cancer genes: how many, where, and who are they? Nature Genet . 1992;;2: 89-90.
8 +
Sideransky D, Tokino T, Helzlsouer K, et al.  Inherited p53 gene mutations in breast cancer. Cancer Res . 1992;;52:2984-2986.
9 +
Coles C, Condie A, Chetty U, Steel CM, Evans HJ, Prosser J.  p53 mutations in breast cancer. Cancer Res . 1992;;52:5291-5298.
10 +
Hall JM, Friedman L, Guenther C, et al.  Closing in on a breast cancer gene on chromosome 17q. Am J Hum Genet . 1992;;50:1235-1242.
11 +
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 . In press.
12 +
Collins FS.  Positional cloning: let's not call it reverse anymore. Nature Genet . 1992;;1:3-6.
13 +
Bowcock AM, Anderson LA, Black DM, et al.  Polymorphisms in THRAl and D17S183 flank an interval of <4 cM for the breast-ovarian cancer gene on chromosome 17q. Am J Hum Genet . In press.
14 +
Smith SA, Easton DF, Evans DGR, Ponder BAJ.  Allele losses in the region 17q12-21 in familial breast and ovarian cancer involve the wild-type chromosome. Nature Genet . 1992;;2:128-131.
15 +
Zuppan PJ, Hall JM, Lee MK, Ponglikitmongkol M, King M-C.  Possible linkage of the estrogen receptor gene to breast cancer in a family with late-onset disease. Am J Hum Genet . 1991;;48:1065-1068.
16 +
Callahan R, Cropp CS, Merlo GR, Liscia DS, Cappa APM, Lidereau R.  Somatic mutations and human breast cancer. Cancer . 1992;;69( (suppl) ):1582-1588.
17 +
Hollstein M, Sidransky D, Vogelstein B, Harris CC.  p53 mutations in human cancers . Science . 1991;; 253:49-53.
18 +
Van de Vijver MJ, Nusse R.  The molecular biology of breast cancer. Biochim Biophys Acta . 1991;;1072:33-50.
19 +
Xiong Y, Connolly T, Futcher B, Beach D.  Human D-type cyclin. Cell . 1991;;65:691-699.
20 +
Motokura T, Bloom T, Kim HG, et al.  A novel cyclin encoded by a bell-linked candidate oncogene. Nature . 1991;;350:512-515.
21 +
Slamon DJ, Godophin W, Jones LA, et al.  Studies of the HER2/neu proto-oncogene in human breast and ovarian cancer. Science . 1989;;244:707-712.
22 +
Tsuda H, Hirohashi S, Shimosato Y, Hirota T, et al.  Correlation between long-term survival in breast cancer patients and amplification of two putative oncogene-coamplification units: hst-1/int-2 and c-erbB-2/ear-1. Cancer Res . 1989;;49:3104-3108.
23 +
Bevilacqua G, Sobel ME, Liotta LA, Steeg PS.  Association of low nm23 RNA levels in human primary infiltrating ductal breast carcinomas with lymph node involvement and other histopathological indicators of high metastatic potential. Cancer Res . 1989;;49:5185-5190.
24 +
Weinberg RA.  Tumor suppressor genes. Science . 1991;;254:1138-1146.
25 +
Ries LAG, Hankey BF, Edwards BK, eds. Cancer Statistics Review, 1973-1987 . Bethesda Md: National Institutes of Health; 1990;. National Institutes of Health publication 90-2789.
26 +
Henderson BE, Ross RK, Pike MC.  Toward the primary prevention of cancer. Science . 1991;:1131-1138.
27 +
Pike MC, Kraile MD, Henderson BE, Casagrande JT, Hoel DG.  `Hormonal' risk factors, `breast tissue age' and the age-incidence of breast cancer. Nature . 1983;;303:767-770.
28 +
McGregor DH, Land CE, Choi K, et al.  Breast cancer incidence among atomic bomb survivors, Hiroshima and Nagasaki, 1950-1969. J Natl Cancer Inst . 1977;;59:799-811.
29 +
Boice JD Jr, Monson RR.  Breast cancer in women after repeated fluoroscopic examinations of the chest. J Natl Cancer Inst . 1977;;59:823-832.
30 +
King M-C.  Genetic analysis of cancer in families. Cancer Surv . 1991;;9:417-435.
31 +
Anderson LA, Friedman LS, Osborne-Lawrence S, et al.  High-density genetic map of the BRCA1 region of chromosome 17q12-q21. Genomics . In press.
32 +
Claus EB, Schildkraut JM, Thompson WD, Risch N.  An analysis of the genetic relationship between breast and ovarian cancer. Am J Hum Genet . In press.
33 +
Miller AB, Baines CJ, To T, Wall C.  Canadian national breast screening study, 1: breast cancer detection and death rates among women aged 40 to 49 years. Can Med Assoc J . 1992;;147:1459-1476.
34 +
Baker LH.  BCDDP: five-year summary report. CA Cancer J Clin . 1982;;32:194-225.
35 +
LaFrancis IE, Cooper RB.  Second primary malignancies associated with primary female breast cancer: a review of the Danbury Hospital experience. Conn Med . 1992;;56:411-414.
36 +
Runowicz CD.  Advances in the screening and treatment of ovarian cancer. CA Cancer J Clin . 1992;;42:327-349.
37 +
Zeigler LD, Kroll SS.  Primary breast cancer after prophylactic mastectomy. Am J Clin Oncol . 1991;;14:451-454.
38 +
Nelson H, Miller SH, Buck D, Demuth RJ, Fletcher WS, Buehler P.  Effectiveness of prophylactic mastectomy in the prevention of breast tumors in C3H mice. Plast Reconstr Surg . 1989;;83: 662-669.
39 +
Goodnight JE Jr, Quagliana JM, Morton DL.  Failure of subcutaneous mastectomy to prevent the development of breast cancer. J Surg Oncol . 1984;;26:198-201.
40 +
Temple WJ, Lindsay RL, Magi E, Urbanski SJ.  Technical considerations for prophylactic mastectomy in patients at high risk for breast cancer. Am J Surg . 1991;;161:413-414.
41 +
Irwin KL, Lee NC, Peterson HB, Rubin GL, Wingo PA, Mandel MG.  Hysterectomy, tubal sterilization, and the risk of breast cancer. Am J Epidemiol . 1988;;127:1192-1201.
42 +
Cruickshank DJ, Haites N, Anderson S, et al.  The multidisciplinary management of a family with epithelial ovarian cancer. Br J Obstet Gynaecol . 1992;;99:226-231.
43 +
Weber AM, Hewett WJ, Gajewski WH, Curry SL.  Serous carcinoma of the peritoneum after oophorectomy. Obstet Gynecol . 1992;;80:558-560.
44 +
Nayfield SG, Karp JE, Ford LG, Dorr FA, Kramer BS.  Potential role of tamoxifen in prevention of breast cancer. J Natl Cancer Inst . 1991;;83: 1450-1459.

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