TY - JOUR
T1 - Doxorubicin Exposure and Breast Cancer Risk in Survivors of Adolescent and Adult Hodgkin Lymphoma
AU - Neppelenbroek, Suzanne I.M.
AU - Geurts, Yvonne M.
AU - Aleman, Berthe M.P.
AU - Lugtenburg, Pieternella J.
AU - Rademakers, Saskia E.
AU - De Weijer, Roel J.
AU - Schippers, Maaike G.A.
AU - Ta, Bastiaan D.P.
AU - Plattel, Wouter J.
AU - Zijlstra, Josée M.
AU - Van Der Maazen, Richard W.M.
AU - Nijziel, Marten R.
AU - Ong, Francisca
AU - Schimmel, Erik C.
AU - Posthuma, Eduardus F.M.
AU - Kersten, Marie José
AU - Böhmer, Lara H.
AU - Muller, Karin
AU - Koene, Harry R.
AU - te Boome, LCJ
AU - Bilgin, Yavuz M.
AU - De Jongh, Eva
AU - Janus, Cécile P.M.
AU - Van Leeuwen, Flora E.
AU - Schaapveld, Michael
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2024/6/1
Y1 - 2024/6/1
N2 - PURPOSEFemale Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) at a young age have a strongly increased risk of breast cancer (BC). Studies in childhood cancer survivors have shown that doxorubicin exposure may also increase BC risk. Although doxorubicin is the cornerstone of HL chemotherapy, the association between doxorubicin and BC risk has not been examined in HL survivors treated at adult ages.METHODSWe assessed BC risk in a cohort of 1,964 female 5-year HL survivors, treated at age 15-50 years in 20 Dutch hospitals between 1975 and 2008. We calculated standardized incidence ratios, absolute excess risks, and cumulative incidences. Doxorubicin exposure was analyzed using multivariable Cox regression analyses.RESULTSAfter a median follow-up of 21.6 years (IQR, 15.8-27.1 years), 252 women had developed invasive BC or ductal carcinoma in situ. The 30-year cumulative incidence was 20.8% (95% CI, 18.2 to 23.4). Survivors treated with a cumulative doxorubicin dose of >200 mg/m2 had a 1.5-fold increased BC risk (95% CI, 1.08 to 2.1), compared with survivors not treated with doxorubicin. BC risk increased 1.18-fold (95% CI, 1.05 to 1.32) per additional 100 mg/m2 doxorubicin (Ptrend =.004). The risk increase associated with doxorubicin (yes v no) was not modified by age at first treatment (hazard ratio [HR]age <21 years, 1.5 [95% CI, 0.9 to 2.6]; HRage ≥21 years, 1.3 [95% CI, 0.9 to 1.9) or chest RT (HRwithout mantle/axillary field RT, 1.9 [95% CI, 1.06 to 3.3]; HRwith mantle/axillary field RT, 1.2 [95% CI, 0.8 to 1.8]).CONCLUSIONThis study shows that treatment with doxorubicin is associated with increased BC risk in both adolescent and adult HL survivors. Our results have implications for BC surveillance guidelines for HL survivors and treatment strategies for patients with newly diagnosed HL.
AB - PURPOSEFemale Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) at a young age have a strongly increased risk of breast cancer (BC). Studies in childhood cancer survivors have shown that doxorubicin exposure may also increase BC risk. Although doxorubicin is the cornerstone of HL chemotherapy, the association between doxorubicin and BC risk has not been examined in HL survivors treated at adult ages.METHODSWe assessed BC risk in a cohort of 1,964 female 5-year HL survivors, treated at age 15-50 years in 20 Dutch hospitals between 1975 and 2008. We calculated standardized incidence ratios, absolute excess risks, and cumulative incidences. Doxorubicin exposure was analyzed using multivariable Cox regression analyses.RESULTSAfter a median follow-up of 21.6 years (IQR, 15.8-27.1 years), 252 women had developed invasive BC or ductal carcinoma in situ. The 30-year cumulative incidence was 20.8% (95% CI, 18.2 to 23.4). Survivors treated with a cumulative doxorubicin dose of >200 mg/m2 had a 1.5-fold increased BC risk (95% CI, 1.08 to 2.1), compared with survivors not treated with doxorubicin. BC risk increased 1.18-fold (95% CI, 1.05 to 1.32) per additional 100 mg/m2 doxorubicin (Ptrend =.004). The risk increase associated with doxorubicin (yes v no) was not modified by age at first treatment (hazard ratio [HR]age <21 years, 1.5 [95% CI, 0.9 to 2.6]; HRage ≥21 years, 1.3 [95% CI, 0.9 to 1.9) or chest RT (HRwithout mantle/axillary field RT, 1.9 [95% CI, 1.06 to 3.3]; HRwith mantle/axillary field RT, 1.2 [95% CI, 0.8 to 1.8]).CONCLUSIONThis study shows that treatment with doxorubicin is associated with increased BC risk in both adolescent and adult HL survivors. Our results have implications for BC surveillance guidelines for HL survivors and treatment strategies for patients with newly diagnosed HL.
UR - http://www.scopus.com/inward/record.url?scp=85194927938&partnerID=8YFLogxK
U2 - 10.1200/JCO.23.01386
DO - 10.1200/JCO.23.01386
M3 - Article
C2 - 38359378
AN - SCOPUS:85194927938
SN - 0732-183X
VL - 42
SP - 1903
EP - 1913
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 16
ER -