 |
|
Breast Cancer Following Radiotherapy and Chemotherapy Among Young Women With Hodgkin Disease
Lois B. Travis, MD;
Deirdre A. Hill, PhD;
Graça M. Dores, MD;
Mary Gospodarowicz, MD;
Flora E. van Leeuwen, PhD;
Eric Holowaty, MD;
Bengt Glimelius, MD;
Michael Andersson, MD;
Tom Wiklund, MD;
Charles F. Lynch, MD;
Mars B. Van't Veer, MD;
Ingrid Glimelius, MD;
Hans Storm, MD;
Eero Pukkala, PhD;
Marilyn Stovall, PhD;
Rochelle Curtis, MA;
John D. Boice, Jr, ScD;
Ethel Gilbert, PhD
JAMA. 2003;290:465-475.
Context Second cancer is the leading cause of death in long-term survivors of Hodgkin disease (HD), with exceptionally high risks of breast cancer among women treated at a young age. Quantitative associations between radiotherapy dose delivered to the breast and administered chemotherapy have not been reported to date in large series, nor has the influence of ovarian exposures on subsequent risk.
Objective To quantify the long-term risk of breast cancer associated with use of radiotherapy and chemotherapy to treat young women with HD.
Design, Setting, and Subjects Matched case-control study of breast cancer within a cohort of 3817 female 1-year survivors of HD diagnosed at age 30 years or younger, between January 1, 1965, and December 31, 1994, and within 6 population-based cancer registries. The study was conducted March 1, 1996, through September 30, 1998.
Main Outcome Measures Relative risk (RR) of breast cancer associated with radiation dose delivered to site of breast cancer or to ovaries and with cumulative dose of alkylating agents.
Results Breast cancer occurred in 105 patients with HD who were matched to 266 patients with HD but without breast cancer. A radiation dose of 4 Gy or more delivered to the breast was associated with a 3.2-fold (95% confidence interval [CI], 1.4-8.2) increased risk, compared with the risk in patients who received lower doses and no alkylating agents. Risk increased to 8-fold (95% CI, 2.6-26.4) with a dose of more than 40 Gy (P<.001 for trend). Radiation risk did not vary appreciably by age at exposure or reproductive history. Increased risks persisted for 25 or more years following radiotherapy (RR, 2.3; 95% CI, 0.5-16.5; P = .03 for trend with dose). Treatment with alkylating agents alone resulted in a reduced risk (RR, 0.6; 95% CI, 0.2-2.0) of breast cancer, and combined alkylating agents and radiotherapy in a 1.4-fold (95% CI, 0.6-3.5) increased risk. Risk of breast cancer decreased with increasing number of alkylating agent cycles (P = .003 for trend). Risk also was low (RR, 0.4; 95% CI, 0.1-1.1) among women who received 5 Gy or more delivered to ovaries compared with those who received lower doses.
Conclusions Hormonal stimulation appears important for the development of radiation-induced breast cancer, as evidenced by the reduced risk associated with ovarian damage from alkylating agents or radiation. The high radiation-related risk, which did not diminish at the highest doses or the longest follow-up, however, suggests the need for lifetime surveillance and programs of patient and public awareness.
Author Affiliations: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Md (Drs Travis, Hill, Dores, and Gilbert and Ms Curtis); Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Dr Gospodarowicz); Netherlands Cancer Institute, Amsterdam (Dr van Leeuwen); Cancer Care Ontario, Toronto (Dr Holowaty); Uppsala University, Uppsala, Sweden (Drs B. Glimelius and I. Glimelius); Danish Cancer Society, Copenhagen (Drs Andersson and Storm); Helsinki University Central Hospital, Helsinki, Finland (Dr Wiklund); The University of Iowa, Iowa City (Dr Lynch); The Dr Daniel den Hoed Cancer Center, Rotterdam, the Netherlands (Dr Van't Veer); Finnish Cancer Registry, Helsinki (Dr Pukkala); the University of Texas M. D. Anderson Cancer Center, Houston (Dr Stovall); and International Epidemiology Institute, Rockville, Md, and Vanderbilt University Medical Center, Nashville, Tenn (Dr Boice).
RELATED ARTICLE
Breast Cancer After Hodgkin Disease: Hope for a Safer Cure
Joachim Yahalom
JAMA. 2003;290(4):529-531.
EXTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Systematic Review: Using Magnetic Resonance Imaging to Screen Women at High Risk for Breast Cancer
Warner et al.
ANN INTERN MED 2008;148:671-679.
ABSTRACT
| FULL TEXT
Secondary malignancies after therapy of indolent non-Hodgkin's lymphoma
Friedberg
haematol 2008;93:336-338.
FULL TEXT
Polymorphic MLH1 and risk of cancer after methylating chemotherapy for Hodgkin lymphoma
Worrillow et al.
J. Med. Genet. 2008;45:142-146.
ABSTRACT
| FULL TEXT
Increased risk of breast cancer among survivors of allogeneic hematopoietic cell transplantation: a report from the FHCRC and the EBMT-Late Effect Working Party
Friedman et al.
Blood 2008;111:939-944.
ABSTRACT
| FULL TEXT
Multiple Primary Cancers: An Overview of the National Cancer Institute's Surveillance, Epidemiology, and End Results Program
Travis
Am Soc Clin Oncol Ed Book 2008;2008:413-417.
ABSTRACT
| FULL TEXT
Second Cancers after Hodgkin's Lymphoma: Long-term Risks
Ng
Am Soc Clin Oncol Ed Book 2008;2008:418-422.
ABSTRACT
| FULL TEXT
Reducing Second Breast Cancers: A Potential Role for Prophylactic Mammary Irradiation
Brenner et al.
JCO 2007;25:4868-4872.
FULL TEXT
Treatment-Adjusted Predisposition to Second Malignant Neoplasms After a Solid Cancer in Childhood: A Case-Control Study
Guerin et al.
JCO 2007;25:2833-2839.
ABSTRACT
| FULL TEXT
Risk of Second Malignant Neoplasms After Childhood Leukemia and Lymphoma: An International Study
Maule et al.
JNCI J Natl Cancer Inst 2007;99:790-800.
ABSTRACT
| FULL TEXT
Long-Term Solid Cancer Risk Among 5-Year Survivors of Hodgkin's Lymphoma
Hodgson et al.
JCO 2007;25:1489-1497.
ABSTRACT
| FULL TEXT
The Late Effects of Childhood Cancer Therapy
Dickerman
Pediatrics 2007;119:554-568.
ABSTRACT
| FULL TEXT
Dexrazoxane-Associated Risk for Acute Myeloid Leukemia/Myelodysplastic Syndrome and Other Secondary Malignancies in Pediatric Hodgkin's Disease
Tebbi et al.
JCO 2007;25:493-500.
ABSTRACT
| FULL TEXT
An Affair of the Heart
Boice
JNCI J Natl Cancer Inst 2007;99:186-187.
FULL TEXT
Breast cancer in Hodgkin's disease and non-Hodgkin's lymphoma survivors
Sanna et al.
Ann Oncol 2007;18:288-292.
ABSTRACT
| FULL TEXT
Evaluation of the Risk of Therapy-Associated Complications in Survivors of Hodgkin Lymphoma
Travis
ASH Education Book 2007;2007:192-196.
ABSTRACT
| FULL TEXT
The impact of treatment on the risk of second malignancy after Hodgkin's disease
Ng and Mauch
Ann Oncol 2006;17:1727-1729.
FULL TEXT
The Epidemiology of Second Primary Cancers
Travis
Cancer Epidemiol. Biomarkers Prev. 2006;15:2020-2026.
ABSTRACT
| FULL TEXT
Don't Throw Out the Baby With the Bathwater: On Optimizing Cure and Reducing Toxicity in Hodgkin's Lymphoma
Yahalom
JCO 2006;24:544-548.
FULL TEXT
Combined-Modality Therapy Versus Radiotherapy Alone for Treatment of Early-Stage Hodgkin's Disease: Cure Balanced Against Complications
Koontz et al.
JCO 2006;24:605-611.
ABSTRACT
| FULL TEXT
Cancer Survivorship--Genetic Susceptibility and Second Primary Cancers: Research Strategies and Recommendations
Travis et al.
JNCI J Natl Cancer Inst 2006;98:15-25.
ABSTRACT
| FULL TEXT
The Management of Patients with Limited-Stage Classical Hodgkin Lymphoma
Gospodarowicz and Meyer
ASH Education Book 2006;2006:253-258.
ABSTRACT
| FULL TEXT
Breast cancer risk following radiotherapy for Hodgkin lymphoma: modification by other risk factors
Hill et al.
Blood 2005;106:3358-3365.
ABSTRACT
| FULL TEXT
Cumulative Absolute Breast Cancer Risk for Young Women Treated for Hodgkin Lymphoma
Travis et al.
JNCI J Natl Cancer Inst 2005;97:1428-1437.
ABSTRACT
| FULL TEXT
Solid tumor risks after high doses of ionizing radiation
Sachs and Brenner
Proc. Natl. Acad. Sci. USA 2005;102:13040-13045.
ABSTRACT
| FULL TEXT
Advances in the biology and therapy of diffuse large B-cell lymphoma: moving toward a molecularly targeted approach
Abramson and Shipp
Blood 2005;106:1164-1174.
ABSTRACT
| FULL TEXT
Development of Risk-Based Guidelines for Pediatric Cancer Survivors: The Children's Oncology Group Long-Term Follow-Up Guidelines From the Children's Oncology Group Late Effects Committee and Nursing Discipline
Landier et al.
JCO 2004;22:4979-4990.
ABSTRACT
| FULL TEXT
Treatment of stage I and II Hodgkin's lymphoma with ABVD chemotherapy: results after 7 years of a prospective study
Rueda Dominguez et al.
Ann Oncol 2004;15:1798-1804.
ABSTRACT
| FULL TEXT
Risk-Adapted, Combined-Modality Therapy With VAMP/COP and Response-Based, Involved-Field Radiation for Unfavorable Pediatric Hodgkin's Disease
Hudson et al.
JCO 2004;22:4541-4550.
ABSTRACT
| FULL TEXT
Breast Cancer after Childhood Cancer: A Report from the Childhood Cancer Survivor Study
Kenney et al.
ANN INTERN MED 2004;141:590-597.
ABSTRACT
| FULL TEXT
Breast Cancer After Hodgkin Disease: Hope for a Safer Cure
Yahalom
JAMA 2003;290:529-531.
FULL TEXT
|
