No Association of BRCA Mutations with Therapy-Related Myelodysplastic Syndrome or Acute Myeloid Leukemia in Patients Treated for Breast or Ovarian Cancer

Abstract

Abstract 4259 Background:Patients with defective DNA repair mechanisms are at higher risk for developing cancer. BRCA1 and BRCA2 are proteins that coordinate DNA repair by homologous-recombination. Mutations in BRCA1 and BRCA2 are associated with an increased risk of cancers, namely breast, ovarian, and pancreatic, thus making these patients more likely to receive chemo- or radiation therapy. Additionally, secondary malignancies can be an unfortunate consequence of treatment with chemo- or radiation therapy. Although tumors with defective DNA repair mechanisms may be more susceptible to therapy, we hypothesized that patients with BRCA mutations that underwent chemotherapy or radiotherapy for treatment of breast or ovarian cancer would be at a higher risk of developing therapy- related myelodysplastic syndrome (t-MDS) or acute myeloid leukemia (t-AML). Methods:We accessed patient data from our institution maintained by the Mayo Clinic Life Sciences System using the Data Discovery and Query Builder. We searched for patients whose notes and diagnoses included the terms BRCA, and breast or ovarian cancer, and myelodysplastic syndrome or acute myeloid leukemia. We searched our records from 1/1/1995–7/15/2011. We cross-referenced our findings to a database of patients who were diagnosed with a BRCA mutation through our department of medical genetics. Secondly, we searched the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) database for female patients who developed AML after the diagnosis or breast or ovarian cancer from the years 1973–2008 using ratio and multiple primaries standardized incidence ratios sessions. Results:We identified 220 patients with a BRCA mutation, of which 73 received chemotherapy. There were two patients with BRCA mutations that developed t-AML following treatment for breast cancer, and one patient with a BRCA mutation who developed t-AML following treatment for ovarian cancer (Table 1). Manual data extraction from the list of patients with BRCA mutations diagnosed at our institution only identified one of these patients, as two obtained their testing through another institution. We did not identify any patients with BRCA mutations who developed t-MDS following treatment for breast or ovarian cancer. The latency between diagnosis of the primary cancer and the diagnosis or t-AML was 24 months for two patients, and 22 years for the other.Table 1Age at Primary DxPrimary CancerStage of PrimaryRx of PrimaryMutationLatency to AML (months)AML CytogeneticsOutcome149yBreast, IDCUnknownCMFBRCA1, 1675delA26443–48,XX, add(3)(p13)[7],del(4)(p11)[7],+8[18],del(9)(q10)[3],del(11)(p13)[8],der(11)t(11;15) (p13;q11.2)[5],-13, -14, -15[5],add(16)(p11.2)[15],-18[3], add(19)(p13.3),-22[17],+13mar[cp19]/46,XX[1]Deceased234yBreast, IDCIIIC (T2, N3, M0)ddAC+T and Bev, 6,640cGyBRCA124add(3)(q12), t(11;15)(q23,q15), MLL and EVI1Deceased354yOvarian(carcino-sarcoma)IB(T1b, N0, M0)Ifos/CispCarbo/taxolBRCA124Normal at Dx;at relapse:-7, inv (16)(p13.1q22),+r[9]/46XXCR2From our search of the SEER database we found 649 patients who developed AML after a diagnosis of breast cancer, and 98 patients who developed AML after a diagnosis of ovarian cancer. These patients represented 0.1% and 0.2% of evaluable breast and ovarian cases respectively. The latency from time of diagnosis of the primary cancer to that of AML was 58 months (29–113 interquartile range) for breast cancer and 47 months (29–91) for ovarian cancer. The observed number of patients with AML following the diagnosis of breast or ovarian cancer was 1.68 and 4.74 times higher than that expected of the general population, respectively (both p<0.05). We were not able to stratify patients based on the presence of a BRCA mutation due to the limitations of the database. Conclusions:We identified three patients with confirmed BRCA mutations and t-AML at our institution. Although this does not represent a strong association, patients at risk for BRCA mutations do not always undergo testing. Thus, our results may not fully represent whether there is an association with BRCA mutations and t-MDS or t-AML. Using the SEER database, we confirmed that patients who were diagnosed with breast or ovarian cancer subsequently had a higher incidence of AML than the general population, although we were not able to test if patients with BRCA mutations are at higher risk of t-MDS or t-AML. Disclosures:No relevant conflicts of interest to declare.