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      Second solid cancers after radiotherapy for breast cancer in SEER cancer registries

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          Abstract

          Background:

          Radiotherapy for breast cancer reduces disease recurrence and breast cancer mortality. However, it has also been associated with increased second cancer risks in exposed sites.

          Methods:

          We evaluated long-term second cancer risks among 182 057 5-year survivors of locoregional invasive breast cancer diagnosed between 1973 and 2000 and reported to US NCI-SEER Program cancer registries. Multivariate Poisson regression was used to estimate the relative risk (RR) and excess cases of second cancer in women who had surgery and radiotherapy, compared with those who had surgery alone. Second cancer sites were grouped according to doses received from typical tangential breast fields.

          Results:

          By the end of 2005 (median follow-up=13.0 years), 15 498 second solid cancers had occurred, including 6491 contralateral breast cancers. The RRs for radiotherapy were 1.45 (95% confidence interval (CI)=1.33–1.58) for high-dose second cancer sites (1+ Gy: lung, oesophagus, pleura, bone and soft tissue) and 1.09 (1.04–1.15) for contralateral breast cancer (≈1 Gy). These risks decreased with increasing age and year of treatment. There was no evidence of elevated risks for sites receiving medium (0.5–0.99 Gy, RR=0.89 (0.74–1.06)) or low doses (<0.5 Gy, RR=1.01 (0.95–1.07)). The estimated excess cases of cancer in women treated with radiotherapy were as follows: 176 (95% CI=69–284) contralateral breast cancers or 5% (2–8%) of the total in all 1+year survivors, and 292 (222–362) other solid cancers or 6% (4–7%) of the total.

          Conclusions:

          Most second solid cancers in breast cancer survivors are not related to radiotherapy.

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          Most cited references29

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          Dose to the contralateral breast from radiotherapy and risk of second primary breast cancer in the WECARE study.

          To quantify the risk of second primary breast cancer in the contralateral breast (CB) after radiotherapy (RT) for first breast cancer. The study population included participants in the Women's Environmental, Cancer, and Radiation Epidemiology study: 708 cases (women with asynchronous bilateral breast cancer) and 1399 controls (women with unilateral breast cancer) counter-matched on radiation treatment. Participants were 1.0 Gy of absorbed dose to the specific quadrant of the CB had a 2.5-fold greater risk for CB cancer than unexposed women (RR = 2.5, 95% CI 1.4-4.5). No excess risk was observed in women >40 years of age. Women 5 years had a RR of 3.0 (95% CI 1.1-8.1), and the dose response was significant (excess RR per Gy of 1.0, 95% CI 0.1-3.0). Women 1.0 Gy to the CB had an elevated, long-term risk of developing a second primary CB cancer. The risk is inversely related to age at exposure and is dose dependent.
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            Risk of second primary cancer in the contralateral breast in women treated for early-stage breast cancer: a population-based study.

            To study the potential risk factors, including radiotherapy (RT) for contralateral breast cancer (CBC), in patients treated for early-stage breast cancer. The Surveillance, Epidemiology, and End Results database (1973-1996) was used to study the incidence of CBC after breast cancer. The Cox proportional hazards regression model was used to estimate the relative risk (RR) of CBC, with adjustment for confounders, including age, race, histologic subtype, and use of RT. Information on the use of hormonal therapy and chemotherapy was not available in the Surveillance, Epidemiology, and End Results database. A CBC was documented in 5679 (4.2%) of the 134501 localized invasive or intraductal breast cancer patients surviving at least 3 months. The 10- and 20-year actuarial rate of CBC was 6.1% and 12%, respectively. In multivariate analysis, medullary carcinoma (RR = 1.18, 95% confidence interval [CI] 1.02-1.37), black race (RR = 1.20, 95% CI 1.08-1.33), and age >55 years at initial diagnosis (RR = 1.15, 95% CI 1.08-1.22) were associated with increased CBC risk. A total of 1234 (3.3%) of 37,379 patients who received RT developed CBC, and 4445 (4.6%) of 97122 patients who did not receive RT developed CBC. Overall, RT was not associated with an increased risk of CBC (RR = 1.04, 95% CI 0.97-1.10) in multivariate analysis. The CBC risk associated with RT varied substantially with the length of follow-up. During the first 5 years of follow-up, RT was not associated with an increased CBC risk (age-adjusted RR = 0.96, 95% CI 0.88-1.04). For patients surviving for >5 years, RT was associated with a 14% increase in CBC risk (RR = 1.14, 95% CI 1.03-1.26). The increased CBC risk with RT was evident in patients aged 55 years (RR = 1.15, p = 0.04) at initial diagnosis. The 5-, 10-, 15-, and 20-year actuarial rate of CBC was 2.9%, 6.5%, 10.2%, and 13.4%, respectively, for patients with RT; the corresponding rates were 3.0%, 6.0%, 8.9%, and 11.8% for patients without RT. The absolute increase in CBC risk associated with RT was 0.5%, 1.3%, and 1.6% in the 10-, 15-, and 20-year actuarial rate, respectively. CBC is not uncommon after breast cancer, especially for certain subsets of patients. RT was associated with a very small increased long-term CBC risk. This minimal increase in CBC risk should not affect clinical decision-making in treatment selection for patients with localized invasive breast cancer or ductal carcinoma in situ. Unnecessary radiation exposure to the contralateral breast should be avoided for all patients with early-stage breast cancer.
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              Cancer in the contralateral breast after radiotherapy for breast cancer.

              Patients with breast cancer have a threefold increase in the risk that a second breast cancer will develop. Radiation treatment for the initial cancer can result in moderately high doses to the contralateral breast, possibly contributing to this heightened risk. We conducted a case-control study in a cohort of 41,109 women diagnosed with breast cancer between 1935 and 1982 in Connecticut. We reviewed the medical records of 655 women in whom a second breast cancer developed five or more years after the initial tumor and compared their radiation exposure with that of 1189 matched controls from the cohort who did not have a second cancer. The dose of radiation to the contralateral breast was estimated from the original radiotherapy records. Among the exposed women, the average radiation dose to the contralateral breast was 2.82 Gy (maximum, 7.10). Overall, 23 percent of the women who had a second breast cancer and 20 percent of the controls had received radiotherapy (relative risk of a second breast cancer associated with radiotherapy, 1.19). Among women who survived for at least 10 years, radiation treatment was associated with a small but marginally significant elevation in the risk of a second breast cancer (relative risk, 1.33); the risk increased significantly with the dose of radiation. An increase in risk in association with radiotherapy was evident only among women who were under 45 years of age when they were treated (relative risk, 1.59) and not among older women (relative risk, 1.01). Radiotherapy for breast cancer contributes little to the already high risk of a second cancer in the opposite breast. Fewer than 3 percent of all second breast cancers in this study could be attributed to previous radiation treatment; the risk, however, was significantly increased among women who underwent irradiation at a relatively young age (less than 45 years). Radiation exposure after the age of 45 entails little, if any, risk of radiation-induced breast cancer.
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                Author and article information

                Journal
                Br J Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                24 November 2009
                05 January 2010
                05 January 2010
                : 102
                : 1
                : 220-226
                Affiliations
                [1 ]Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute Bethesda, MD 20814, USA
                [2 ]Early Detection Research Group, Division of Cancer Prevention, National Cancer Institute Bethesda, MD 20814, USA
                [3 ]Department of Radiation Physics, University of Texas M.D. Anderson Cancer Center Houston, TX 70330, USA
                Author notes
                [* ]Author for correspondence: berringtona@ 123456mail.nih.gov
                Article
                6605435
                10.1038/sj.bjc.6605435
                2813734
                19935795
                b0f4f0b7-0580-456c-bab3-87990b3c4545
                Copyright 2010, Cancer Research UK
                History
                : 16 September 2009
                : 16 October 2009
                : 19 October 2009
                Categories
                Epidemiology

                Oncology & Radiotherapy
                risk,breast cancer,radiotherapy,radiation,second primary neoplasms
                Oncology & Radiotherapy
                risk, breast cancer, radiotherapy, radiation, second primary neoplasms

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