Is the Risk of Breast Cancer Increased after Hematopoietic Cell Transplantation?.

Survivors of hematopoietic stem cell transplantation (HSCT) are at risk for second malignant neoplasms (SMN). As secondary breast cancer is now reported in excess among survivors of a variety of cancers treated with conventional chemoradiotherapy, we sought to explore the risk among HSCT survivors. Among 4,805 allogeneic transplant recipients treated at the Fred Hutchinson Cancer Research Center between November, 1969 and April, 2003, who survived at least 100 days post transplant, there were 27 females and 1 male with secondary breast cancer, representing the largest single diagnostic group of secondary solid tumors post transplant, following cancers of the skin and mucosa. Confining the analysis to the 2,042 female HSCT recipients, the cumulative incidence of secondary breast cancer at 25 years was 5.4% (95% Confidence Interval [CI]: 3.0%, 8.9%). The risk was twice that of the general population, using US SEER data for expected values (Age and race adjusted standardized incidence ratio = 2.3; 95% CI = 1.5, 3.3). The time to second breast cancer from transplant was 1-24.8 (median 9.3) years. In Cox regression, using time from transplant as the time scale, risk increased with increasing age at time of transplant, with hazard ratios [HR] of 12.6 (95% CI 1.6,97.9) for patients 18–39 years and 54.7 (95% CI 6.6,450.8) for those ≥ 40 years. However, when age was used as the time scale, this age effect was no longer seen (HR: 0.56; 95% CI: 0.06,5,3). We also investigated the role of preparatory regimen and graft versus host disease (GVHD) and found no associations with increased breast cancer risk. Specifically, use of TBI in the conditioning regimen (HR: 1.9; 95% CI: 0.8,4.7), type of alkylating agent used in the conditioning regimen (Busulfan HR: 2.0; 95% CI: 0.1,32.0; Cytoxan HR: 1.3 95%; CI: 0.2,10.5; Busulfan plus Cytoxan HR: 0.8; 95% CI: 0.1,6.7), donor type (related versus unrelated; HR: 1.3; 95% CI 0.5,3.2), nor acute (HR: 1.2; 95% CI: 0.5,2.6) or chronic GVHD (HR: 1.5; 95% CI: 0.7,3.3) increased risk for secondary breast cancer. The only treatment-related risk factor identified was the use of single fraction (versus fractionated) TBI, where the hazard ratio was 4.8 (95% CI: 1.5,16.2). Among 1,015 100+ day survivors of autologous transplants, excluding those transplanted for primary breast cancer, there were 2 female and 1 male breast cancer reported. These data suggest that, in contrast to the risk reported following conventional chemoradiotherapy, transplant preparatory regimens do not significantly increase risk for secondary breast cancer. In addition, GVHD, which is a risk factor for a number of SMNs following HSCT, does not appear to increase the risk for secondary breast cancer. Risk factors other than therapy should therefore be investigated to better understand the increased risk of breast cancer following HSCT and to develop appropriate preventive strategies.