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Published in: Breast Cancer Research and Treatment 1/2017

01-01-2017 | Epidemiology

3D conformal radiotherapy is not associated with the long-term cardiac mortality in breast cancer patients: a retrospective cohort study in Germany (PASSOS-Heart Study)

Authors: Hiltrud Merzenich, Detlef Bartkowiak, Heinz Schmidberger, Marcus Schmidt, Lukas Schwentner, Thomas Wiegel, Achim Woeckel, Daniel Wollschläger, Maria Blettner

Published in: Breast Cancer Research and Treatment | Issue 1/2017

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Abstract

Purpose

In breast cancer patients treated in the 1970s and 1980s, radiation therapy (RT) for left-sided tumors has been associated with an elevated risk of cardiac mortality. In recent years, improved RT techniques have reduced radiation exposure of the heart and major coronary vessels, but some exposure remains unavoidable. In a retrospective cohort study, we investigated the long-term cardiac mortality risk of breast cancer survivors treated with modern RT in Germany.

Methods

A total of 11,982 women were included who were treated for breast cancer between 1998 and 2008. A systematic mortality follow-up was conducted until December 2012. The effect of breast cancer laterality on cardiac mortality and on overall mortality was investigated as a surrogate measure of exposure. Using Cox regression, we analyzed survival time as the primary outcome measure, taking potential confounding factors into account.

Results

We found no evidence for an effect of tumor laterality on mortality in irradiated patients (N = 9058). For cardiac mortality, the hazard ratio was 0.94 (95% CI 0.64–1.38) for left-sided versus right-sided tumors. For all causes of death, the hazard ratio was 0.95 (95% CI 0.85–1.05). A diagnosis of cardiac illness prior to breast cancer treatment increased both cardiac mortality risk and overall mortality risk.

Conclusions

Contemporary RT seems not to be associated with an increased risk of cardiac mortality or overall mortality for left-sided breast cancer relative to right-sided RT. However, an extended follow-up period and exact dosimetry might be necessary to confirm this observation.
Literature
1.
go back to reference International Agency for Research on Cancer (2014) Cancer in five continents, Vol X, IARC Scientific Publications No. 164. Lyon International Agency for Research on Cancer (2014) Cancer in five continents, Vol X, IARC Scientific Publications No. 164. Lyon
2.
go back to reference Robert-Koch-Institut und GEKID (2015) Krebs in Deutschland 2011/2012. Berlin Robert-Koch-Institut und GEKID (2015) Krebs in Deutschland 2011/2012. Berlin
3.
go back to reference Schwentner L, Wöckel A, König J, Janni W, Ebner F, Blettner M, Kreienberg R, Van Ewijk R (2013) Adherence to treatment guidelines and survival in triple-negative breast cancer: a retrospective multi-center cohort study with 9156 patients. BMC Cancer 13:487–499CrossRefPubMedPubMedCentral Schwentner L, Wöckel A, König J, Janni W, Ebner F, Blettner M, Kreienberg R, Van Ewijk R (2013) Adherence to treatment guidelines and survival in triple-negative breast cancer: a retrospective multi-center cohort study with 9156 patients. BMC Cancer 13:487–499CrossRefPubMedPubMedCentral
4.
go back to reference Travis LB, Ng AK, Allan JM, Pui CH, Kennedy AR, Xu XG, Purdy JA, Applegate K, Yahalom J, Constine LS, Gilbert ES, Boice JD (2014) Second malignant neoplasms and cardiovascular disease following radiotherapy. Health Phys 106(2):229–246CrossRefPubMed Travis LB, Ng AK, Allan JM, Pui CH, Kennedy AR, Xu XG, Purdy JA, Applegate K, Yahalom J, Constine LS, Gilbert ES, Boice JD (2014) Second malignant neoplasms and cardiovascular disease following radiotherapy. Health Phys 106(2):229–246CrossRefPubMed
5.
go back to reference Borghini A, Gianicolo EAL, Picano E, Andreassi MG (2013) Ionizing radiation and atherosclerosis: current knowledge and future challenges. Atherosclerosis 230:40–47CrossRefPubMed Borghini A, Gianicolo EAL, Picano E, Andreassi MG (2013) Ionizing radiation and atherosclerosis: current knowledge and future challenges. Atherosclerosis 230:40–47CrossRefPubMed
6.
go back to reference Steward FA, Hoving S, Russell NS (2010) Vascular damage as an underlying mechanism of cardiac and cerebral toxicity in irradiated cancer patients. Radiat Res 174:865–869CrossRef Steward FA, Hoving S, Russell NS (2010) Vascular damage as an underlying mechanism of cardiac and cerebral toxicity in irradiated cancer patients. Radiat Res 174:865–869CrossRef
7.
go back to reference Early Breast Cancer Trialists´ Collaborative Group (2000) Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomized trials. Lancet 355:1757–1770CrossRef Early Breast Cancer Trialists´ Collaborative Group (2000) Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomized trials. Lancet 355:1757–1770CrossRef
8.
go back to reference Early Breast Cancer Trialists´ Collaborative Group (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomized trials. Lancet 366:2087–2106CrossRef Early Breast Cancer Trialists´ Collaborative Group (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomized trials. Lancet 366:2087–2106CrossRef
9.
go back to reference Darby SC, McGale P, Taylor CW, Peto R (2005) Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries. Lancet Oncol 6:557–565CrossRefPubMed Darby SC, McGale P, Taylor CW, Peto R (2005) Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries. Lancet Oncol 6:557–565CrossRefPubMed
10.
go back to reference Darby S, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Bronnum D, Correa C, Cutter D, Gagliardi G, Gigante B, Jensen MB, Nisbet A, Peto R, Rahimi K, Taylor C, Hall P (2013) Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 11:987–998CrossRef Darby S, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Bronnum D, Correa C, Cutter D, Gagliardi G, Gigante B, Jensen MB, Nisbet A, Peto R, Rahimi K, Taylor C, Hall P (2013) Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 11:987–998CrossRef
11.
go back to reference Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E et al (2015) Primary breast cancer: eSMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 26(supplement 5):8–30CrossRef Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E et al (2015) Primary breast cancer: eSMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 26(supplement 5):8–30CrossRef
12.
go back to reference Thariat J, Hannoun-Levi JM, Sun Myint A, Vuong T, Gérard JP (2012) Past, present, and future of radiotherapy for the benefit of patients. Nat Rev Clin Oncol 10:52–60CrossRefPubMed Thariat J, Hannoun-Levi JM, Sun Myint A, Vuong T, Gérard JP (2012) Past, present, and future of radiotherapy for the benefit of patients. Nat Rev Clin Oncol 10:52–60CrossRefPubMed
13.
go back to reference Taylor CW, Wang Z, Macaulay E, Jagsi R, Duane F, Darby SC (2015) Exposure of the heart in breast cancer radiation therapy: a systematic review of heart doses published during 2003 to 2013. Int J Radiat Oncol Biol Phys 93:845–853CrossRefPubMed Taylor CW, Wang Z, Macaulay E, Jagsi R, Duane F, Darby SC (2015) Exposure of the heart in breast cancer radiation therapy: a systematic review of heart doses published during 2003 to 2013. Int J Radiat Oncol Biol Phys 93:845–853CrossRefPubMed
14.
go back to reference Killander F, Anderson H, Kjellen E, Malmström P (2014) Increased cardio and cerebrovascular mortality in breast cancer patients treated with postmastectomy radiotherapy—25 year follow-up of a randomized trial from the South Sweden Breast cancer Group. European J Cancer 50:2201–2210CrossRef Killander F, Anderson H, Kjellen E, Malmström P (2014) Increased cardio and cerebrovascular mortality in breast cancer patients treated with postmastectomy radiotherapy—25 year follow-up of a randomized trial from the South Sweden Breast cancer Group. European J Cancer 50:2201–2210CrossRef
15.
go back to reference Wollschläger D, Karle H, Stockinger M, Bartkowiak D, Buhrdel S, Merzenich H, Wiegel T, Blettner M, Schmidberger H (2016) Radiation dose distribution in functional heart regions from tangential breast cancer radiotherapy. Radiother Oncol 119:65–70CrossRefPubMed Wollschläger D, Karle H, Stockinger M, Bartkowiak D, Buhrdel S, Merzenich H, Wiegel T, Blettner M, Schmidberger H (2016) Radiation dose distribution in functional heart regions from tangential breast cancer radiotherapy. Radiother Oncol 119:65–70CrossRefPubMed
16.
go back to reference Wollschläger D, Karle H, Stockinger M, Bartkowiak D, Buhrdel S, Merzenich H, Wiegel T, Schmidberger H, Blettner M (2016) Predicting heart dose in breast cancer patients who received 3D conformal radiation therapy. Health Phys 119:65–70 Wollschläger D, Karle H, Stockinger M, Bartkowiak D, Buhrdel S, Merzenich H, Wiegel T, Schmidberger H, Blettner M (2016) Predicting heart dose in breast cancer patients who received 3D conformal radiation therapy. Health Phys 119:65–70
17.
go back to reference Cox DR, Oakes D (1984) Analysis of survival data. Chapman and Hall, New York Cox DR, Oakes D (1984) Analysis of survival data. Chapman and Hall, New York
18.
go back to reference Core Team R (2016) A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna Core Team R (2016) A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna
19.
go back to reference Therneau TM, Grambsch PM (2000) Modeling survival data: extending the Cox model. Springer, New YorkCrossRef Therneau TM, Grambsch PM (2000) Modeling survival data: extending the Cox model. Springer, New YorkCrossRef
20.
go back to reference American Joint Committee on Cancer (2010) AJCC cancer staging handbook, 7th edn. Springer, New YorkCrossRef American Joint Committee on Cancer (2010) AJCC cancer staging handbook, 7th edn. Springer, New YorkCrossRef
21.
go back to reference Robert-Koch-Institut (2010) GEDA-Survey „Gesundheit in Deutschland 2010“. Gesundheitsberichterstattung des Bundes, Berlin Robert-Koch-Institut (2010) GEDA-Survey „Gesundheit in Deutschland 2010“. Gesundheitsberichterstattung des Bundes, Berlin
22.
go back to reference Henson KE, McGale P, Taylor C, Darby SC (2013) Radiation-related mortality from heart disease and lung cancer more than 20 years after radiotherapy for breast cancer. Br J Cancer 108:179–182CrossRefPubMed Henson KE, McGale P, Taylor C, Darby SC (2013) Radiation-related mortality from heart disease and lung cancer more than 20 years after radiotherapy for breast cancer. Br J Cancer 108:179–182CrossRefPubMed
23.
go back to reference McGale P, Darby SC, Hall P, Adolfson J, Bengtsson NO, Bennet AM, Fornander T, Gigante B, Jensen MB, Peto R, Rahimi K, Taylor WT, Ewertz M (2011) Incidence of heart disease in 35,000 women treated with radiotherapy for breast cancer in Denmark and Sweden. Radiother Oncol 100(2):167–175CrossRefPubMed McGale P, Darby SC, Hall P, Adolfson J, Bengtsson NO, Bennet AM, Fornander T, Gigante B, Jensen MB, Peto R, Rahimi K, Taylor WT, Ewertz M (2011) Incidence of heart disease in 35,000 women treated with radiotherapy for breast cancer in Denmark and Sweden. Radiother Oncol 100(2):167–175CrossRefPubMed
24.
go back to reference Boero IJ, Paravati AJ, Triplett DP, Hwang L, Matsuno RK, Gillespie EF, Yashar CM, Moiseenko V, Einck JP, Mell LK, Parikh SA, Murphy JD (2015) Modern radiation therapy and cardiac outcomes in breast cancer. Int J Radiation Oncol Biol Phys 94(4):700–708CrossRef Boero IJ, Paravati AJ, Triplett DP, Hwang L, Matsuno RK, Gillespie EF, Yashar CM, Moiseenko V, Einck JP, Mell LK, Parikh SA, Murphy JD (2015) Modern radiation therapy and cardiac outcomes in breast cancer. Int J Radiation Oncol Biol Phys 94(4):700–708CrossRef
25.
go back to reference Rutter CE, Chagpar AB, Evans SB (2014) Breast cancer laterality does not influence survival in a large modern cohort: implications for radiation-related cardiac mortality. Int J Radiation Oncol Biol Phys 90(2):329–334CrossRef Rutter CE, Chagpar AB, Evans SB (2014) Breast cancer laterality does not influence survival in a large modern cohort: implications for radiation-related cardiac mortality. Int J Radiation Oncol Biol Phys 90(2):329–334CrossRef
26.
go back to reference Bouchardy C, Rapiti E, Usel M, Balmer Majno S, Vlastos G, Benhamou S, Mirabell R, Neyroud-Caspar I, Verkooijen HM, Vinh-Hung V (2010) Excess of cardiovascular mortality among node-negative breast cancer patients irradiated for inner-quadrant tumors. Ann Oncol 21:459–465CrossRefPubMed Bouchardy C, Rapiti E, Usel M, Balmer Majno S, Vlastos G, Benhamou S, Mirabell R, Neyroud-Caspar I, Verkooijen HM, Vinh-Hung V (2010) Excess of cardiovascular mortality among node-negative breast cancer patients irradiated for inner-quadrant tumors. Ann Oncol 21:459–465CrossRefPubMed
27.
go back to reference Schmitz KH, Prosnitz RG, Schwartz AL, Carver JR (2012) Prospective surveillance and management of cardiac toxicity and health in breast cancer survivors. Cancer 118(8 suppl):2270–2276CrossRefPubMed Schmitz KH, Prosnitz RG, Schwartz AL, Carver JR (2012) Prospective surveillance and management of cardiac toxicity and health in breast cancer survivors. Cancer 118(8 suppl):2270–2276CrossRefPubMed
28.
go back to reference Lloyd-Jones DM, Leip EP, Larson MG, D’Agostino RB, Beiser A, Wilson PW, Wolf PA, Levy D (2006) Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation 113:791–798CrossRefPubMed Lloyd-Jones DM, Leip EP, Larson MG, D’Agostino RB, Beiser A, Wilson PW, Wolf PA, Levy D (2006) Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation 113:791–798CrossRefPubMed
29.
go back to reference Rothman KJ (1986) Modern Epidemiology. Little,Brown & Company, Boston/Toronto Rothman KJ (1986) Modern Epidemiology. Little,Brown & Company, Boston/Toronto
30.
go back to reference Roychoudhuri R, Robinson D, Putcha V, Cuzick J, Darby S, Moller H (2007) Increased cardiovascular mortality more than fifteen years after radiotherapy for breast cancer A population based study. BMC Cancer 7:9CrossRefPubMedPubMedCentral Roychoudhuri R, Robinson D, Putcha V, Cuzick J, Darby S, Moller H (2007) Increased cardiovascular mortality more than fifteen years after radiotherapy for breast cancer A population based study. BMC Cancer 7:9CrossRefPubMedPubMedCentral
31.
go back to reference Darby SC, McGale P, Granath F Peto R, Hall P, Ekbom A (2003) Mortality from cardiovascular disease more than 10 years after radiotherapy for breast cancer: nationwide cohort study of 90,000 Swedish women. BMJ 326:256–257CrossRefPubMedPubMedCentral Darby SC, McGale P, Granath F Peto R, Hall P, Ekbom A (2003) Mortality from cardiovascular disease more than 10 years after radiotherapy for breast cancer: nationwide cohort study of 90,000 Swedish women. BMJ 326:256–257CrossRefPubMedPubMedCentral
32.
go back to reference Schubert-Fritschle G, Eckel R, Eisenmenger W, Hölzel D (2002) Qualität der Angaben von Todesbescheinigungen. Dt. Ärzteblatt 99(1–2):C36–C41 Schubert-Fritschle G, Eckel R, Eisenmenger W, Hölzel D (2002) Qualität der Angaben von Todesbescheinigungen. Dt. Ärzteblatt 99(1–2):C36–C41
33.
go back to reference Vittinghoff E, McCulloch CE (2007) Relaxing the rule of ten events per variable in logistic and Cox regression. Am J Epidemiol 165(6):710–718CrossRefPubMed Vittinghoff E, McCulloch CE (2007) Relaxing the rule of ten events per variable in logistic and Cox regression. Am J Epidemiol 165(6):710–718CrossRefPubMed
Metadata
Title
3D conformal radiotherapy is not associated with the long-term cardiac mortality in breast cancer patients: a retrospective cohort study in Germany (PASSOS-Heart Study)
Authors
Hiltrud Merzenich
Detlef Bartkowiak
Heinz Schmidberger
Marcus Schmidt
Lukas Schwentner
Thomas Wiegel
Achim Woeckel
Daniel Wollschläger
Maria Blettner
Publication date
01-01-2017
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-016-4042-2

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