Therapy-related myeloid neoplasms (t-MN) are rare and deadly hematologic malignancies that develop following exposure to cytotoxic therapies such as radiation, chemotherapy, and poly (adenosine diphosphate-ribose)-ADP polymerase (PARP) inhibitors. Preliminary evidence suggests that germline BRCA1 and BRCA2 pathogenic and likely pathogenic (P/LP) variants may increase susceptibility to t-MNs due to the genes’ established role in DNA damage response. There is also evidence that individuals with BRCA1/2 P/LP variants may be more susceptible to developing primary hematologic malignancies. We reviewed medical records of 706 individuals with BRCA1/2 P/LP variants to assess hematologic malignancy diagnoses and t-MN development. Our study population was 5.1% male and 94.9% female, 58% had BRCA1 P/LP variants and 42% had BRCA2 P/LP variants, and the majority (59.92%) identified as Caucasian. Twenty-one hematologic malignancies were identified (2.97%): non-Hodgkin lymphoma in 9/706 individuals (1.27%), chronic myeloid leukemia and multiple myeloma each in 2/706 individuals (0.28%), respectively, and acute myeloid leukemia, unspecified leukemia, and Hodgkin lymphoma each in 1/706 individuals (0.14%). Therapy-related myeloid neoplasms were seen in 5/706 individuals (0.71%), a significantly higher incidence than 0.13/100,000 (0.0013%) observed in the general population (p-value: 0.000001). The estimated 20-year risk of t-MN development is 2.11% (95% CI 0.74 – 5.96). This study supports the assertation that germline BRCA1/2 P/LP variants increase the risk of t-MNs.
","abstract_html":"<p>Therapy-related myeloid neoplasms (t-MN) are rare and deadly hematologic malignancies that develop following exposure to cytotoxic therapies such as radiation, chemotherapy, and poly (adenosine diphosphate-ribose)-ADP polymerase (PARP) inhibitors. Preliminary evidence suggests that germline <em>BRCA1</em> and <em>BRCA2</em> pathogenic and likely pathogenic (P/LP) variants may increase susceptibility to t-MNs due to the genes’ established role in DNA damage response. There is also evidence that individuals with <em>BRCA1/2</em> P/LP variants may be more susceptible to developing primary hematologic malignancies. We reviewed medical records of 706 individuals with <em>BRCA1/2</em> P/LP variants to assess hematologic malignancy diagnoses and t-MN development. Our study population was 5.1% male and 94.9% female, 58% had <em>BRCA1</em> P/LP variants and 42% had <em>BRCA2</em> P/LP variants, and the majority (59.92%) identified as Caucasian. Twenty-one hematologic malignancies were identified (2.97%): non-Hodgkin lymphoma in 9/706 individuals (1.27%), chronic myeloid leukemia and multiple myeloma each in 2/706 individuals (0.28%), respectively, and acute myeloid leukemia, unspecified leukemia, and Hodgkin lymphoma each in 1/706 individuals (0.14%). Therapy-related myeloid neoplasms were seen in 5/706 individuals (0.71%), a significantly higher incidence than 0.13/100,000 (0.0013%) observed in the general population (p-value: 0.000001). The estimated 20-year risk of t-MN development is 2.11% (95% CI 0.74 – 5.96). This study supports the assertation that germline <em>BRCA1/2</em> P/LP variants increase the risk of t-MNs.</p>","abstract_has_math":false,"creators":["Rogers, Rosemary","https://orcid.org/0000-0002-1799-238X
"],"institution":null,"degree_name":"Masters of Science (MS)","degree_level":"Thesis (MS)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Courtney DiNardo, MD, MSCE","Sarah Bannon, MS, CGC","S. Shahrukh Hashmi, MD, PhD, MPH"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-05-01T07:00:00Z","date_published":"2021-05-01T07:00:00Z","updated_at":"2026-07-24T05:50:47Z","subjects":["hematologic malignancy","HBOC","therapy-related myeloid neoplasms","leukemia","lymphoma","VR","Genetics and Genomics","Medicine and Health Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1097","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Courtney DiNardo, MD, MSCE","Sarah Bannon, MS, CGC","S. Shahrukh Hashmi, MD, PhD, MPH"]},{"key":"dc:creator","label":"Author","values":["Rogers, Rosemary","https://orcid.org/0000-0002-1799-238X
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"]},{"key":"dc:title","label":"Title","values":["Spectrum and Incidence of Primary and Therapy-Related Hematologic Malignancies In Individuals With Brca1 and Brca2 Pathogenic Variants"]}]}],"canonical_facts":{"dc:contributor":["Courtney DiNardo, MD, MSCE","Sarah Bannon, MS, CGC","S. Shahrukh Hashmi, MD, PhD, MPH"],"dc:creator":["Rogers, Rosemary","https://orcid.org/0000-0002-1799-238X
"],"dc:date.available":["2022-05-06T07:00:00Z"],"dc:description.abstract":["Therapy-related myeloid neoplasms (t-MN) are rare and deadly hematologic malignancies that develop following exposure to cytotoxic therapies such as radiation, chemotherapy, and poly (adenosine diphosphate-ribose)-ADP polymerase (PARP) inhibitors. Preliminary evidence suggests that germline BRCA1 and BRCA2 pathogenic and likely pathogenic (P/LP) variants may increase susceptibility to t-MNs due to the genes’ established role in DNA damage response. There is also evidence that individuals with BRCA1/2 P/LP variants may be more susceptible to developing primary hematologic malignancies. We reviewed medical records of 706 individuals with BRCA1/2 P/LP variants to assess hematologic malignancy diagnoses and t-MN development. Our study population was 5.1% male and 94.9% female, 58% had BRCA1 P/LP variants and 42% had BRCA2 P/LP variants, and the majority (59.92%) identified as Caucasian. Twenty-one hematologic malignancies were identified (2.97%): non-Hodgkin lymphoma in 9/706 individuals (1.27%), chronic myeloid leukemia and multiple myeloma each in 2/706 individuals (0.28%), respectively, and acute myeloid leukemia, unspecified leukemia, and Hodgkin lymphoma each in 1/706 individuals (0.14%). Therapy-related myeloid neoplasms were seen in 5/706 individuals (0.71%), a significantly higher incidence than 0.13/100,000 (0.0013%) observed in the general population (p-value: 0.000001). The estimated 20-year risk of t-MN development is 2.11% (95% CI 0.74 – 5.96). This study supports the assertation that germline BRCA1/2 P/LP variants increase the risk of t-MNs.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1097"],"dc:subject":["hematologic malignancy","HBOC","therapy-related myeloid neoplasms","leukemia","lymphoma","VR","Genetics and Genomics","Medicine and Health Sciences"],"dc:title":["Spectrum and Incidence of Primary and Therapy-Related Hematologic Malignancies In Individuals With Brca1 and Brca2 Pathogenic Variants"],"thesis:degree_level":["Thesis (MS)"],"thesis:degree_name":["Masters of Science (MS)"]},"updated_at":"2026-07-24T05:50:47Z"}