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Breast Cancer Risk After Chest Radiotherapy in Hodgkin Lymphoma Survivors: A Comprehensive Overview.

Amanda Caruso1, Filomena Emanuela Laddaga2, Alba Fiorentino3

  • 1Department of Medicine and Surgery, LUM University "Giuseppe Degennaro", Bari, Italy; Unit of Clinical Pathology, "F. Miulli" University Hospital, Bari, Italy.

Clinical Lymphoma, Myeloma & Leukemia
|November 6, 2025
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Summary

Female survivors of Hodgkin lymphoma treated with chest radiotherapy face high secondary breast cancer risks, comparable to BRCA mutations. Risk factors include radiation dose, age at exposure, and genetics, necessitating personalized surveillance and prevention strategies.

Keywords:
Background parenchymal enhancementMRIScreeningSecondary breast cancerSurvivorship

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Area of Science:

  • Oncology
  • Radiotherapy Research
  • Cancer Epidemiology

Background:

  • Secondary breast cancer (SBC) is a significant concern for female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT).
  • Radiation doses of ≥10 Gy before age 30 elevate SBC risk, rivaling BRCA1/2 mutation carrier risks.
  • These excess cases emerge approximately 8 years post-RT and persist throughout life.

Purpose of the Study:

  • To review the multifaceted factors contributing to SBC development in HL survivors.
  • To elucidate the interplay between radiation parameters, patient-specific factors, and micro-environmental influences.
  • To discuss current and emerging strategies for SBC surveillance and prevention.

Main Methods:

  • Synthesis of epidemiological data, mechanistic evidence, and clinical studies.
  • Analysis of radiation dose, field, age at exposure, systemic therapies, host genomics, and micro-environmental factors.
  • Review of current surveillance guidelines and preventive interventions.

Main Results:

  • Radiation-associated SBCs exhibit distinct characteristics, including earlier onset and frequent bilaterality.
  • Risk is influenced by radiation dose, field, age at exposure, chemotherapy, host genetics, and micro-environment.
  • Emerging biomarkers like MRI background parenchymal enhancement and polygenic risk scores show promise.

Conclusions:

  • HL survivors treated with chest RT require tailored surveillance and prevention strategies for SBC.
  • Personalized survivorship care, informed by biomarkers, is crucial for managing radiation-induced secondary breast cancer.
  • Future research should focus on refining risk stratification and preventive measures.