Breast Cancer Risk After Radiation Therapy for Hodgkin Lymphoma: Influence of Gonadal Hormone Exposure

Inge M. Krul; Annemieke W.J. Opstal-van Winden; Berthe M.P. Aleman; Cécile P.M. Janus; Anna M. van Eggermond; Marie L. De Bruin; Michael Hauptmann; Augustinus D.G. Krol; Michael Schaapveld; Annegien Broeks; Karen R. Kooijman; Sandra Fase; Marnix L. Lybeert; Josée M. Zijlstra; Richard W.M. van der Maazen; Ausrele Kesminiene; Ibrahima Diallo; Florent de Vathaire; Nicola S. Russell; Flora E. van Leeuwen

doi:10.1016/j.ijrobp.2017.07.016

Breast Cancer Risk After Radiation Therapy for Hodgkin Lymphoma: Influence of Gonadal Hormone Exposure

Inge M. Krul, Annemieke W.J. Opstal-van Winden, Berthe M.P. Aleman, Cécile P.M. Janus, Anna M. van Eggermond, Marie L. De Bruin, Michael Hauptmann, Augustinus D.G. Krol, Michael Schaapveld, Annegien Broeks, Karen R. Kooijman, Sandra Fase, Marnix L. Lybeert, Josée M. Zijlstra, Richard W.M. van der Maazen, Ausrele Kesminiene, Ibrahima Diallo, Florent de Vathaire, Nicola S. Russell, Flora E. van Leeuwen^*

^*Corresponding author for this work

17 Citations (Scopus)

Abstract

Background Young women treated with chest radiation therapy (RT) for Hodgkin lymphoma (HL) experience a strongly increased risk of breast cancer (BC). It is unknown whether endogenous and exogenous gonadal hormones affect RT-associated BC risk. Methods We conducted a nested case-control study among female 5-year HL survivors treated before age 41. Hormone exposure and HL treatment data were collected through medical records and questionnaires for 174 BC case patients and 466 control patients. Radiation dose to breast tumor location was estimated based on RT charts, simulation films, and mammography reports. Results We observed a linear radiation dose-response curve with an adjusted excess odds ratio (EOR) of 6.1%/Gy (95% confidence interval [CI]: 2.1%-15.4%). Women with menopause <30 years (caused by high-dose procarbazine or pelvic RT) had a lower BC risk (OR, 0.13; 95% CI, 0.03-0.51) than did women with menopause ≥50 years. BC risk increased by 6.4% per additional year of post-RT intact ovarian function (P<.001). Among women with early menopause (<45 years), hormone replacement therapy (HRT) use for ≥2 years did not increase BC risk (OR, 0.86; 95% CI, 0.32-2.32), whereas this risk was nonsignificantly increased among women without early menopause (OR, 3.69; 95% CI, 0.97-14.0; P for interaction:.06). Stratification by duration of post-RT intact ovarian function or HRT use did not statistically significantly modify the radiation dose-response curve. Conclusions BC risk in female HL survivors increases linearly with radiation dose. HRT does not appear to increase BC risk for HL survivors with therapy-induced early menopause. There are no indications that endogenous and exogenous gonadal hormones affect the radiation dose-response relationship.

Original language	English
Journal	International Journal of Radiation Oncology Biology Physics
Volume	99
Issue number	4
Pages (from-to)	843-853
Number of pages	11
ISSN	0360-3016
DOIs	https://doi.org/10.1016/j.ijrobp.2017.07.016
Publication status	Published - 2017

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Krul, I. M., Opstal-van Winden, A. W. J., Aleman, B. M. P., Janus, C. P. M., van Eggermond, A. M., De Bruin, M. L., Hauptmann, M., Krol, A. D. G., Schaapveld, M., Broeks, A., Kooijman, K. R., Fase, S., Lybeert, M. L., Zijlstra, J. M., van der Maazen, R. W. M., Kesminiene, A., Diallo, I., de Vathaire, F., Russell, N. S., & van Leeuwen, F. E. (2017). Breast Cancer Risk After Radiation Therapy for Hodgkin Lymphoma: Influence of Gonadal Hormone Exposure. International Journal of Radiation Oncology Biology Physics, 99(4), 843-853. https://doi.org/10.1016/j.ijrobp.2017.07.016

Breast Cancer Risk After Radiation Therapy for Hodgkin Lymphoma: Influence of Gonadal Hormone Exposure. / Krul, Inge M.; Opstal-van Winden, Annemieke W.J.; Aleman, Berthe M.P. et al.
In: International Journal of Radiation Oncology Biology Physics, Vol. 99, No. 4, 2017, p. 843-853.

Research output: Contribution to journal › Journal article › Research › peer-review

Krul, IM, Opstal-van Winden, AWJ, Aleman, BMP, Janus, CPM, van Eggermond, AM, De Bruin, ML, Hauptmann, M, Krol, ADG, Schaapveld, M, Broeks, A, Kooijman, KR, Fase, S, Lybeert, ML, Zijlstra, JM, van der Maazen, RWM, Kesminiene, A, Diallo, I, de Vathaire, F, Russell, NS & van Leeuwen, FE 2017, 'Breast Cancer Risk After Radiation Therapy for Hodgkin Lymphoma: Influence of Gonadal Hormone Exposure', International Journal of Radiation Oncology Biology Physics, vol. 99, no. 4, pp. 843-853. https://doi.org/10.1016/j.ijrobp.2017.07.016

@article{57bceb79fbbb479cb68d85bfb2b05a70,

title = "Breast Cancer Risk After Radiation Therapy for Hodgkin Lymphoma: Influence of Gonadal Hormone Exposure",

abstract = "Background Young women treated with chest radiation therapy (RT) for Hodgkin lymphoma (HL) experience a strongly increased risk of breast cancer (BC). It is unknown whether endogenous and exogenous gonadal hormones affect RT-associated BC risk. Methods We conducted a nested case-control study among female 5-year HL survivors treated before age 41. Hormone exposure and HL treatment data were collected through medical records and questionnaires for 174 BC case patients and 466 control patients. Radiation dose to breast tumor location was estimated based on RT charts, simulation films, and mammography reports. Results We observed a linear radiation dose-response curve with an adjusted excess odds ratio (EOR) of 6.1%/Gy (95% confidence interval [CI]: 2.1%-15.4%). Women with menopause <30 years (caused by high-dose procarbazine or pelvic RT) had a lower BC risk (OR, 0.13; 95% CI, 0.03-0.51) than did women with menopause ≥50 years. BC risk increased by 6.4% per additional year of post-RT intact ovarian function (P<.001). Among women with early menopause (<45 years), hormone replacement therapy (HRT) use for ≥2 years did not increase BC risk (OR, 0.86; 95% CI, 0.32-2.32), whereas this risk was nonsignificantly increased among women without early menopause (OR, 3.69; 95% CI, 0.97-14.0; P for interaction:.06). Stratification by duration of post-RT intact ovarian function or HRT use did not statistically significantly modify the radiation dose-response curve. Conclusions BC risk in female HL survivors increases linearly with radiation dose. HRT does not appear to increase BC risk for HL survivors with therapy-induced early menopause. There are no indications that endogenous and exogenous gonadal hormones affect the radiation dose-response relationship.",

author = "Krul, {Inge M.} and {Opstal-van Winden}, {Annemieke W.J.} and Aleman, {Berthe M.P.} and Janus, {C{\'e}cile P.M.} and {van Eggermond}, {Anna M.} and {De Bruin}, {Marie L.} and Michael Hauptmann and Krol, {Augustinus D.G.} and Michael Schaapveld and Annegien Broeks and Kooijman, {Karen R.} and Sandra Fase and Lybeert, {Marnix L.} and Zijlstra, {Jos{\'e}e M.} and {van der Maazen}, {Richard W.M.} and Ausrele Kesminiene and Ibrahima Diallo and {de Vathaire}, Florent and Russell, {Nicola S.} and {van Leeuwen}, {Flora E.}",

year = "2017",

doi = "10.1016/j.ijrobp.2017.07.016",

language = "English",

volume = "99",

pages = "843--853",

journal = "International Journal of Radiation Oncology Biology Physics",

issn = "0360-3016",

publisher = "Elsevier",

number = "4",

}

TY - JOUR

T1 - Breast Cancer Risk After Radiation Therapy for Hodgkin Lymphoma

T2 - Influence of Gonadal Hormone Exposure

AU - Krul, Inge M.

AU - Opstal-van Winden, Annemieke W.J.

AU - Aleman, Berthe M.P.

AU - Janus, Cécile P.M.

AU - van Eggermond, Anna M.

AU - De Bruin, Marie L.

AU - Hauptmann, Michael

AU - Krol, Augustinus D.G.

AU - Schaapveld, Michael

AU - Broeks, Annegien

AU - Kooijman, Karen R.

AU - Fase, Sandra

AU - Lybeert, Marnix L.

AU - Zijlstra, Josée M.

AU - van der Maazen, Richard W.M.

AU - Kesminiene, Ausrele

AU - Diallo, Ibrahima

AU - de Vathaire, Florent

AU - Russell, Nicola S.

AU - van Leeuwen, Flora E.

PY - 2017

Y1 - 2017

N2 - Background Young women treated with chest radiation therapy (RT) for Hodgkin lymphoma (HL) experience a strongly increased risk of breast cancer (BC). It is unknown whether endogenous and exogenous gonadal hormones affect RT-associated BC risk. Methods We conducted a nested case-control study among female 5-year HL survivors treated before age 41. Hormone exposure and HL treatment data were collected through medical records and questionnaires for 174 BC case patients and 466 control patients. Radiation dose to breast tumor location was estimated based on RT charts, simulation films, and mammography reports. Results We observed a linear radiation dose-response curve with an adjusted excess odds ratio (EOR) of 6.1%/Gy (95% confidence interval [CI]: 2.1%-15.4%). Women with menopause <30 years (caused by high-dose procarbazine or pelvic RT) had a lower BC risk (OR, 0.13; 95% CI, 0.03-0.51) than did women with menopause ≥50 years. BC risk increased by 6.4% per additional year of post-RT intact ovarian function (P<.001). Among women with early menopause (<45 years), hormone replacement therapy (HRT) use for ≥2 years did not increase BC risk (OR, 0.86; 95% CI, 0.32-2.32), whereas this risk was nonsignificantly increased among women without early menopause (OR, 3.69; 95% CI, 0.97-14.0; P for interaction:.06). Stratification by duration of post-RT intact ovarian function or HRT use did not statistically significantly modify the radiation dose-response curve. Conclusions BC risk in female HL survivors increases linearly with radiation dose. HRT does not appear to increase BC risk for HL survivors with therapy-induced early menopause. There are no indications that endogenous and exogenous gonadal hormones affect the radiation dose-response relationship.

AB - Background Young women treated with chest radiation therapy (RT) for Hodgkin lymphoma (HL) experience a strongly increased risk of breast cancer (BC). It is unknown whether endogenous and exogenous gonadal hormones affect RT-associated BC risk. Methods We conducted a nested case-control study among female 5-year HL survivors treated before age 41. Hormone exposure and HL treatment data were collected through medical records and questionnaires for 174 BC case patients and 466 control patients. Radiation dose to breast tumor location was estimated based on RT charts, simulation films, and mammography reports. Results We observed a linear radiation dose-response curve with an adjusted excess odds ratio (EOR) of 6.1%/Gy (95% confidence interval [CI]: 2.1%-15.4%). Women with menopause <30 years (caused by high-dose procarbazine or pelvic RT) had a lower BC risk (OR, 0.13; 95% CI, 0.03-0.51) than did women with menopause ≥50 years. BC risk increased by 6.4% per additional year of post-RT intact ovarian function (P<.001). Among women with early menopause (<45 years), hormone replacement therapy (HRT) use for ≥2 years did not increase BC risk (OR, 0.86; 95% CI, 0.32-2.32), whereas this risk was nonsignificantly increased among women without early menopause (OR, 3.69; 95% CI, 0.97-14.0; P for interaction:.06). Stratification by duration of post-RT intact ovarian function or HRT use did not statistically significantly modify the radiation dose-response curve. Conclusions BC risk in female HL survivors increases linearly with radiation dose. HRT does not appear to increase BC risk for HL survivors with therapy-induced early menopause. There are no indications that endogenous and exogenous gonadal hormones affect the radiation dose-response relationship.

U2 - 10.1016/j.ijrobp.2017.07.016

DO - 10.1016/j.ijrobp.2017.07.016

M3 - Journal article

C2 - 28888722

AN - SCOPUS:85028745257

SN - 0360-3016

VL - 99

SP - 843

EP - 853

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

IS - 4

ER -

Breast Cancer Risk After Radiation Therapy for Hodgkin Lymphoma: Influence of Gonadal Hormone Exposure

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