LOS ANGELES — Increased risk of breast cancer after successful treatment for Hodgkin's lymphoma “definitely exists,” and is very much a matter of time, according to a researcher who reviewed records for 248 women cured of Hodgkin's lymphoma from 1964 through 2001.
Women who were younger than 30 years of age at the time of radiotherapy and those who survive 15 years or more after their treatments face the greatest risk of breast cancer, Dr. Mohamed Alm El-Din of Massachusetts General Hospital, Boston, reported at the annual meeting of the American Society for Therapeutic Radiation and Oncology.
Radiation dose and technique were not significant predictors when Dr. Alm El-Din and his coinvestigators compared the records of 36 women diagnosed with breast cancer with the rest of the survivors. Neither was a history of splenectomy, mediastinal disease, or chemotherapy with alkylating agents.
Perhaps the most striking finding, Dr. Alm El-Din noted, was that 11 (31%) of the 36 had bilateral breast cancer. Whether these women had other risk factors, such as a BRCA 1 or 2 gene or family history of breast cancer, is not known. Although slightly more than half (56%) of the breast cancers were detected by mammography, 11% were found incidentally during elective mastectomies.
“The younger the patient at the time of treatment for Hodgkin's lymphoma, the higher the risk, and the longer the time since radiation, the higher the risk,” Dr. Alm El-Din said in an interview. Patients who were irradiated for the disease at a young age “should be counseled about the higher risk, and we should design long-term surveillance, so we can detect any breast cancer very early and enhance their chances for a cure again.”
The presentation expanded upon an earlier Massachusetts General Hospital study of 111 Hodgkin's lymphoma patients, 14 of whom developed breast cancer (Cancer 1997;79:1203–10).
In the larger updated group, the median age at the time of supradiaphragmatic irradiation (SDI) was 26 years and median follow-up 15.2 years. Among the 36 women who developed breast cancer, the median age at first breast cancer diagnosis was 43.8 years, and the median time since radiation for Hodgkin's lymphoma was 18.4 years. Of these patients, 19 had their breast cancer treated at Massachusetts General. They developed 28 cancers: 9 ductal carcinomas in situ and 17 invasive ductal carcinomas. One had a mixed ductal and lobular tumor, and another had unknown histology.
Overall, the researchers reported a standardized morbidity ratio (SMR) of 9.78 for a woman developing a first breast cancer after SDI for Hodgkin's lymphoma. The ratio represents the number of observed breast cancers in a cohort divided by the number of breast cancers expected based on age-specific and calendar-year specific incidence rates from the Surveillance, Epidemiology, and End Results (SEER) database.
The highest SMR, 279.23, was for those irradiated before the age of 14 years. For all women treated before the age of 30, the SMR was significantly higher compared with those who were 30 years of age or older when originally treated: 19.05 vs. 4.64.
Looking at the interval between radiation and the diagnosis of a first breast cancer, the researchers found a peak SMR of 18.90 for the period 15–20 years afterward during which 14 women were diagnosed with breast cancer. Dr. Alm El-Din said survivors had an SMR of 14.34 when they were 15 or more years past radiotherapy as opposed to 5.01 when they were within 15 years of treatment.
In his conclusion, he recommended that all female survivors of Hodgkin's lymphoma, but especially those treated before the age of 30, be counseled about their increased risk. He said breast MRI, chemoprevention, and intensive screening should be considered for high-risk Hodgkin's survivors, many of whom are likely to be in primary care. Prophylactic mastectomy might be considered, he added, “in view of the high incidence of bilaterality and cases discovered incidentally.”
Physicians at Massachusetts General have already started to contact these patients to put them on long-term screening protocols. “Prophylactic mastectomy could be an option, but it is a very personal decision that should be discussed between doctor and patient.”