Journal of Clinical Oncology, Vol 18, Issue 19
(October), 2000: 3360-3369
© 2000 American Society for Clinical Oncology
Effect of Radiotherapy After Breast-Conserving Treatment in Women With Breast Cancer and Germline BRCA1/2 Mutations
By Lori J. Pierce,
Myla Strawderman,
Steven A. Narod,
Ivo Oliviotto,
Andrea Eisen,
Laura Dawson,
David Gaffney,
Lawrence J. Solin,
Asa Nixon,
Judy Garber,
Christine Berg,
Claudine Isaacs,
Ruth Heimann,
Olufunmilayo I. Olopade,
Bruce Haffty,
Barbara L. Weber
From the Department of Radiation Oncology, University of Michigan, and University of Michigan Cancer Center Biostatistics Core, Ann Arbor, MI; Center for Research in Women’s Health, University of Toronto, Toronto; Radiation Therapy Program, British Columbia Cancer Agency, Vancouver, Canada; Departments of Medicine, Genetics, and Radiation Oncology, University of Pennsylvania, Philadelphia, PA; Department of Radiation Oncology, University of Utah, Salt Lake City, UT; Joint Center for Radiotherapy and Dana-Farber Cancer Institute, Harvard University, Boston, MA; Department of Radiation Oncology and Division Hematology/Oncology, Lombardi Cancer Center, Georgetown University, Washington, DC; Departments of Radiation and Cellular Oncology and Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL; and Department of Therapeutic Radiology, Yale University, New Haven, CT.
Address reprint requests to Lori J. Pierce, MD, Department of Radiation Oncology, University of Michigan School of Medicine, UH-B2C490, Box 0010, 1500 E Medical Center Dr, Ann Arbor, MI 48109-0010; email ljpierce{at}umich.edu
PURPOSE: Recent laboratory data suggest a role for BRCA1/2 in the cellular response to DNA damage. There is a paucity of clinical data, however, examining the effect of radiotherapy (RT), which causes double-strand breaks, on breast tissue from BRCA1/2 mutation carriers. Thus the goals of this study were to compare rates of radiation-associated complications, in-breast tumor recurrence, and distant relapse in women with BRCA1/2 mutations treated with breast-conserving therapy (BCT) using RT with rates observed in sporadic disease.
PATIENTS AND METHODS: Seventy-one women with a BRCA1/2 mutation and stage I or II breast cancer treated with BCT were matched 1:3 with 213 women with sporadic breast cancer. Conditional logistic regression models were used to compare matched cohorts for rates of complications and recurrence.
RESULTS: Tumors from women in the genetic cohort were associated with high histologic (P = .0004) and nuclear (P = .009) grade and negative estrogen (P = .0001) and progesterone (P = .002) receptors compared with tumors from the sporadic cohort. Using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity scoring, there were no significant differences in acute or chronic morbidity in skin, subcutaneous tissue, lung, or bone. The 5-year actuarial overall survival, relapse-free survival, and rates of tumor control in the treated breast for the patients in the genetic cohort were 86%, 78%, and 98%, respectively, compared with 91%, 80%, and 96%, respectively, for the sporadic cohort (P = not significant).
CONCLUSION: There was no evidence of increased radiation sensitivity or sequelae in breast tissue heterozygous for a BRCA1/2 germline mutation compared with controls, and rates of tumor control in the breast and survival were comparable between BRCA1/2 carriers and controls at 5 years. Although additional follow-up is needed, these data may help in discussing treatment options in the management of early-stage hereditary breast cancer and should provide reassurance regarding the safety of administering RT to carriers of a germline BRCA1/2 mutation.
Presented in part at the Thirty-Fifth Annual Meeting of the American Society of Clinical Oncology, May 15-18, 1999, Atlanta, GA.
This article has been cited by other articles:
|
|
|
|
 
K. D. Graves, L. M. Moss, C. L. Jasper, T. A. DeMarco, B. N. Peshkin, C. Isaacs, and M. D. Schwartz
Predictors of Enrollment into a Familial Cancer Registry by Individuals at High Risk for BRCA1/2
Cancer Epidemiol. Biomarkers Prev.,
December 1, 2007;
16(12):
2763 - 2767.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Morrogh, P. I. Borgen, and T. A. King
The Importance of Local Control in Early-Stage Breast Cancer: A Historical Review and a Discussion of Ongoing Issues
Ann. Surg. Oncol.,
December 1, 2007;
14(12):
3310 - 3320.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Brewster, E. P. Wileyto, L. Kessler, A. Collier, B. Weathers, J. E. Stopfer, S. Domchek, and C. H. Halbert
Sociocultural Predictors of Breast Cancer Risk Perceptions in African American Breast Cancer Survivors
Cancer Epidemiol. Biomarkers Prev.,
February 1, 2007;
16(2):
244 - 248.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Shanley, K. McReynolds, A. Ardern-Jones, R. Ahern, I. Fernando, J. Yarnold, G. Evans, D. Eccles, S. Hodgson, S. Ashley, et al.
Late Toxicity Is Not Increased in BRCA1/BRCA2 Mutation Carriers Undergoing Breast Radiotherapy in the United Kingdom
Clin. Cancer Res.,
December 1, 2006;
12(23):
7025 - 7032.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. J. Pierce, A. M. Levin, T. R. Rebbeck, M. A. Ben-David, E. Friedman, L. J. Solin, E. E. Harris, D. K. Gaffney, B. G. Haffty, L. A. Dawson, et al.
Ten-Year Multi-Institutional Results of Breast-Conserving Surgery and Radiotherapy in BRCA1/2-Associated Stage I/II Breast Cancer
J. Clin. Oncol.,
June 1, 2006;
24(16):
2437 - 2443.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. K. Plevritis, A. W. Kurian, B. M. Sigal, B. L. Daniel, D. M. Ikeda, F. E. Stockdale, and A. M. Garber
Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging.
JAMA,
May 24, 2006;
295(20):
2374 - 2384.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. E. Jacobi, N. J.D. Nagelkerke, J. C. van Houwelingen, and G. H. de Bock
Breast Cancer Screening, Outside the Population-Screening Program, of Women from Breast Cancer Families without Proven BRCA1/BRCA2 Mutations: a Simulation Study.
Cancer Epidemiol. Biomarkers Prev.,
March 1, 2006;
15(3):
429 - 436.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D. Schwartz, C. Lerman, B. Brogan, B. N. Peshkin, C. Isaacs, T. DeMarco, C. Hughes Halbert, M. Pennanen, and C. Finch
Utilization of BRCA1/BRCA2 Mutation Testing in Newly Diagnosed Breast Cancer Patients
Cancer Epidemiol. Biomarkers Prev.,
April 1, 2005;
14(4):
1003 - 1007.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Narod and K. Offit
Prevention and Management of Hereditary Breast Cancer
J. Clin. Oncol.,
March 10, 2005;
23(8):
1656 - 1663.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. A. Newman and H. M. Kuerer
Advances in Breast Conservation Therapy
J. Clin. Oncol.,
March 10, 2005;
23(8):
1685 - 1697.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Metcalfe, H. T. Lynch, P. Ghadirian, N. Tung, I. Olivotto, E. Warner, O. I. Olopade, A. Eisen, B. Weber, J. McLennan, et al.
Contralateral Breast Cancer in BRCA1 and BRCA2 Mutation Carriers
J. Clin. Oncol.,
June 15, 2004;
22(12):
2328 - 2335.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. B. Daly
Tailoring Breast Cancer Treatment to Genetic Status: The Challenges Ahead
J. Clin. Oncol.,
May 15, 2004;
22(10):
1776 - 1777.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D. Schwartz, C. Lerman, B. Brogan, B. N. Peshkin, C. Hughes Halbert, T. DeMarco, W. Lawrence, D. Main, C. Finch, C. Magnant, et al.
Impact of BRCA1/BRCA2 Counseling and Testing on Newly Diagnosed Breast Cancer Patients
J. Clin. Oncol.,
May 15, 2004;
22(10):
1823 - 1829.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. El-Tamer, D. Russo, A. Troxel, L. P. Bernardino, R. Mazziotta, A. Estabrook, B.-A. Ditkoff, F. Schnabel, and M. Mansukhani
Survival and Recurrence After Breast Cancer in BRCA1/2 Mutation Carriers
Ann. Surg. Oncol.,
February 1, 2004;
11(2):
157 - 164.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. N. Weitzel, S. M. McCaffrey, R. Nedelcu, D. J. MacDonald, K. R. Blazer, and C. A. Cullinane
Effect of Genetic Cancer Risk Assessment on Surgical Decisions at Breast Cancer Diagnosis
Arch Surg,
December 1, 2003;
138(12):
1323 - 1328.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Mincey
Genetics and the Management of Women at High Risk for Breast Cancer
Oncologist,
October 1, 2003;
8(5):
466 - 473.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Smith, D. Saslow, K. Andrews Sawyer, W. Burke, M. E. Costanza, W. P. Evans III, R. S. Foster Jr., E. Hendrick, H. J. Eyre, and S. Sener
American Cancer Society Guidelines for Breast Cancer Screening: Update 2003
CA Cancer J Clin,
May 1, 2003;
53(3):
141 - 169.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. T. Lynch, C. L. Snyder, J. F. Lynch, B. D. Riley, and W. S. Rubinstein
Hereditary Breast-Ovarian Cancer at the Bedside: Role of the Medical Oncologist
J. Clin. Oncol.,
February 15, 2003;
21(4):
740 - 753.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Vlastos, N. Q. Mirza, F. Meric, K. K. Hunt, A. N. Mirza, L. A. Newman, F. C. Ames, H. M. Kuerer, M. I. Ross, B. Feig, et al.
Breast-Conservation Therapy in Early-Stage Breast Cancer Patients With a Positive Family History
Ann. Surg. Oncol.,
November 1, 2002;
9(9):
912 - 919.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Ben David, A. Chetrit, G. Hirsh-Yechezkel, E. Friedman, B.D. Beck, U. Beller, G. Ben-Baruch, A. Fishman, H. Levavi, F. Lubin, et al.
Effect of BRCA Mutations on the Length of Survival in Epithelial Ovarian Tumors
J. Clin. Oncol.,
January 15, 2002;
20(2):
463 - 466.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. N. Peshkin, T. A. DeMarco, B. M. Brogan, C. Lerman, and C. Isaacs
BRCA1/2 Testing: Complex Themes in Result Interpretation
J. Clin. Oncol.,
May 1, 2001;
19(9):
2555 - 2565.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Unnithian, R. Macklis, and B. G. Haffty
Breast Cancer Radiotherapy: Safe for All?
J. Clin. Oncol.,
December 1, 2000;
18(23):
4000 - 4001.
[Full Text]
[PDF]
|
|
|
|
