Secondary Breast Cancer in a Woman Treated for Hodgkin Lymphoma as a Child

October 1, 2007

Overall survival of Hodgkin lymphoma (HL) is 90%; however, survival decreases with time owing to late complications, including subsequent malignancy. Female survivors of pediatric HL have increased morbidity and mortality associated with secondary effects of radiation therapy, most specifically the development of secondary breast cancer. It is estimated that female HL survivors have a 35- to 75-fold excess risk of developing breast cancer, with the greatest risk occurring 15 to 20 years after initial diagnosis. This risk time frame is more than 20 years before the median age (61 years) of breast cancer diagnosis among the general population. This equates to an HL survivor reaching the cumulative lifetime incidence of breast cancer by 40 years of age when compared with the general population.

Overall survival of Hodgkin lymphoma (HL) is 90%; however, survival decreases with time owing to late complications, including subsequent malignancy.[1,2] Female survivors of pediatric HL have increased morbidity and mortality associated with secondary effects of radiation therapy, most specifically the development of secondary breast cancer.[1–6] It is estimated that female HL survivors have a 35- to 75-fold excess risk of developing breast cancer, with the greatest risk occurring 15 to 20 years after initial diagnosis. This risk time frame is more than 20 years before the median age (61 years) of breast cancer diagnosis among the general population.[3,7,8] This equates to an HL survivor reaching the cumulative lifetime incidence of breast cancer by 40 years of age when compared with the general population.[3,9]

PATIENT OVERVIEW

BG is a 36-year-old white female who was diagnosed at 16 years of age with Hodgkin lymphoma after a 1-month history of cervical adenopathy. At initial presentation to a pediatric oncology institution, a cervical lymph node biopsy was consistent with classical nodular sclerosing (NS) HL. Additionally, computed tomography of BG's neck, chest, axilla, and abdomen was positive for bilateral cervical and mediastinal disease. Clinical history was negative for B symptoms, which include fever, night sweats, and/or 10% weight loss. The patient was staged as having IIA NS Hodgkin lymphoma.

BG was entered on the institutional HL protocol, receiving six cycles of chemotherapy and 20 Gray (Gy) thoracic radiation. The patient obtained a complete remission and received all chemotherapy and radiation without significant side effects. At 25 years of age, BG was permanently discharged from the treating pediatric oncology institution and transitioned into adult follow-up. The patient and primary care physician were informed that heightened surveillance should be given to radiation and chemotherapy late effects, which included risk of hypothyroidism, increased breast cancer risk 15–20 years post-radiation, and infertility.

BG did well until a routine screening mammogram at 30 years of age revealed a calcified right breast lesion. An ultrasound-guided biopsy confirmed infiltrating ductal carcinoma with positive estrogen and progesterone receptors. The patient underwent a bilateral mastectomy (owing to risk of contralateral disease), as well as chemotherapy and antiestrogen therapy. BG is now 6 years post secondary breast cancer, with no evidence of disease recurrence.

 

NURSING MANAGEMENT IN MONITORING LATE EFFECTS

This case study exemplifies the important role that nurses play in informing and educating the patient about potential late effects of cancer therapy. After BG's HL therapy and remission, she had annual follow-up examinations, which included a review of systems and personal health habits, and an extensive educational program regarding effects of cancer treatment. BG was instructed about her increased breast cancer risk and the importance of preventive health habits. Furthermore, she was taught how to perform monthly breast self-examination, referred to a local physician for biannual breast examinations, and instructed to get yearly mammograms after 25 years of age.

The advanced practice nurse and clinic nurse were instrumental in providing the patient and primary care physician with education and a rationale for the heightened surveillance measures. The primary care physician was given a detailed summary of BG's treatment, including doses of chemotherapy/radiation; a summary of hospitalizations during therapy; and potential late effects and specific monitoring necessary, including early mammography. Additionally, the Children's Oncology Group (COG) Late Effects Guidelines offer information about monitoring for all survivors of childhood cancers and are an excellent resource for nurses and physicians. The guidelines may be accessed athttp://www.survivorshipguidelines.org/.[10] For BG, these preventive monitoring measures provided early breast cancer detection and likely contributed to an excellent prognosis.

 

DISCUSSION

The mechanism for secondary breast cancer among HL survivors is not understood. While all childhood cancer survivors are at an increased risk for a second cancer, the greatest risk occurs in females treated at a younger age, those treated with radiation and/or chemotherapy, primary disease of Hodgkin lymphoma or sarcoma, and first-degree relative with cancer.[2,3,6,11–13] Breast cancer is the most common secondary cancer among childhood cancer survivors and it remains unclear if the primary disease is an independent factor, or whether secondary malignancy results from an interaction between the primary therapy and host-related factors including gene-gene/gene-environment interactions.[2,3,12,13] It is known that thoracic radiation is the strongest risk factor for secondary breast cancer; however, it is unclear if lower radiation doses will decrease the individual risk. The dose of 40 Gy to the thorax has been associated with the highest risk of secondary cancer, with a 23.3-fold increase in comparison to a radiation dose of 20–39 Gy, which carries a 5.9-fold increase in risk.[14] Another study, however, found that the risk of secondary breast cancer was increased in female HL survivors compared with the general population, regardless of the radiation dose; as described in this case study, the patient received a dose of 20 Gy thoracic radiation and developed secondary breast cancer approximately 14 years after therapy.[5] In addition to dose of radiation, the age at which the radiation is given is known to be a risk factor. The greatest risk of secondary breast cancer has been found in women treated for HL prior to the age of 30 years. The American Cancer Society (ACS) therefore recommends that any woman who received thoracic radiation between the ages of 10 and 30 years undergo yearly breast magnetic resonance imaging screening as an adjunct to mammography.[15]

The ACS does not delineate age recommendations for the initiation of breast cancer screening, but notes that screening is most productive if initiated at an early age and individual risk factors are taken into consideration.[15] While ACS recommendations are not age-specific, the COG recommendations for annual screening mammography advise that patients start screening at age 25 years or 8 years after completion of radiation therapy, whichever occurs last.[10]

With improved therapy, it is now estimated that 1 of every 300 adults in the US is a survivor of childhood cancer.[9] As these survivors transition into adult care, it is important that they and their physicians have an understanding of potential late effects. Identification of genetic risk factors associated with development of secondary breast cancers could facilitate identification of at-risk patients. Such identification also could permit modification of therapy and heightened surveillance that may reduce the morbidity and mortality related to secondary cancers. While genetic factors may identify those at greatest risk, all women who were treated with thoracic radiation at an early age, or who have a primary diagnosis of HL or sarcoma (with or without thoracic radiation) and a familial cancer history, should be apprised of their breast cancer risk.

References:

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2. Mertens AC, Yasui Y, Neglia JP, et al: Late mortality experience in five-year survivors of childhood and adolescent cancer: The Childhood Cancer Survivor Study. J Clin Oncol 19(13):3163–3172, 2001.

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15. Saslow D, Boetes C, Burke W, et al: American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 57(3):75–89, 2007.