The Risk Of Second Primary Lymphatic And Hematopoietic Malignancy Among Survivors Of Breast Cancer

Background Breast cancer chemotherapy have ameliorated to a large extent for the past few decades.There are a growing number of breast cancer survivors,this population is at the risk of developing second primary lymphatic and hematopoietic malignancies.We described the incidence of second primary lymphatic and hematopoietic malignancy among breast cancer survivors and assessed the temporal trend in risk of developing second primary acute myeloid leukemia among breast cancer patients who recived chemotherapy.In addition,we assessed the impact of radiotherapy on the risk of second primary acute myeloid leukemia and identify risk factors related to second primary acute myeloid leukemia after breast cancer.Methods We conducted two studies.The first study included 548130 patients with first primary breast cancer identified in the Surveillance,Epidemiology,and End Results(SEER)9 database of the United States.All patients were diagnosed between1975 and 2016 and followed up to December 2016.The risks of second primary lymphatic and hematopoietic malignancies were quantified by standardized incidence ratio(SIR).In addition,we performed stratified sub-analyses according to chemotherapy.Multivariable Poisson regression models were used to assess the risk temporal trends of second primary acute myeloid leukemia in breast cancer patients who recived chemotherapy.In addition,we conducted a case-control study among breast cancer patients who diagonsed between 1990 and 2015 in SEER 9database.And the risk factors for second primary acute myeloid leukemia were identified using Cox proportional hazards regression models.Results The second primary lymphatic and hematopoietic malignancies overall SIR was decreased(SIR = 0.96).For survivors who have received chemotherapy,the SIRs for second primary acute myeloid leukemia increased from 4.93 after breast cancer diagnosis in 1975 through 1979 to 6.05 in 2010 through 2016.In multivariable Poisson regression model accounting for age at the time of breast cancer diagnosis,latency and receipt of radiotherapy,the trend in SIR not increased significantly from1975 through 2016 for second primary acute myeloid leukemia(P for linear trend=0.2366).The risk of second primary acute myeloid leukemia was related to the following variables: radiotherapy(HR = 1.331,95%CI:1.128-1.57),chemotherapy(HR = 1.852,95 % CI : 1.511-2.27),age(40-49 vs <40,HR = 0.89,95%CI :0.613-1.292;50-59 vs <40,HR = 1.172,95%CI: 0.819-1.676;60-69 vs <40,HR =2.131,95%CI:1.499-3.031;≥70 vs <40,HR= 2.294,95%CI:1.584-3.324),distant lymph node metastasis(N2 vs N0,HR= 1.379,95%CI:1.018-1.87;N3 vs N0,HR=2.05,95%CI:1.437-2.925).Conclusions: Our study indicated that breast cancer patients who did receive chemotherapy had an obvious added hazard of developing second primary acute myeloid leukemia.Although breast cancer chemotherapy have evolved to a large extent for the last several decades,we observed nonsignificant variation in second primary acute myeloid leukemia risk with time.In addition,risk factors for second primary acute myeloid leukemia following breast cancer include radiotherapy,chemotherapy,older age and distant lymph node metastasis.