These women need to be followed for at least 40 years, perhaps with more-intensive screening regimens, say the investigators from the England and Wales Hodgkin Lymphoma Follow-Up Group in a report online June 25 in the Journal of Clinical Oncology.
“Supradiaphragmatic radiotherapy is still widely used although techniques and doses keep changing,” first author Dr. Anthony J. Swerdlow, from the Institute of Cancer Research, Sutton, Surrey, England, commented in an email to Reuters Health.
He and his colleagues documented the clinical characteristics, treatment, and subsequent outcomes of 5,002 women with HL treated with supradiaphragmatic radiation (mantle-field in two thirds of the population) in England and Wales from 1956 to 2003. The women were younger than 36 at the time of treatment and were followed through the end of 2008.
The researchers used modeling to describe specific, cumulative breast cancer risk at given time points during follow-up according to age at diagnosis, treatment type (inclusion of alkylating agents or pelvic radiation), radiation dose, and time from first treatment.
A total of 373 women developed breast cancer or ductal carcinoma in situ during follow up, yielding a standardized incidence ratio (SIR) of 5.0.
SIRs were greatest for those treated at age 14 years (47.2) and “continued to remain high for at least 40 years. The maximum absolute excess risk was at attained ages 50 to 59 years,” the investigators report. Alkylating chemotherapy or pelvic radiotherapy diminished the risk, but only for women treated at age 20 or older, not for those treated when younger.
The authors tabulated “in detail” cumulative risks of breast cancer based on various factors. For example, the cumulative risk of breast cancer in a woman 20 to 24 years old at the time of treatment with supradiaphragmatic radiation is 3.5% at 20 years and 29.2% at 40 years. For those treated with supradiaphragmatic radiation plus alkylating chemo and/or pelvic radiotherapy, the corresponding risks are 3.6% and 11.5%.
“I think the clinical implications (of the article) are in the provision of risk statistics to use to advise patients,” Dr. Swerdlow said.
In an accompanying commentary, Dr. Michael Crump, from Princess Margaret Hospital and University of Toronto in Canada says, “The legacy of curative extended-field radiation for HL is a large survivor population that is at an increased lifetime risk of second cancer, in particular breast, lung and GI cancer. The article by Swerdlow et al … offers additional information to address the challenge of individual risk assessment.”
This is largest cohort of survivors of HL yet evaluated for breast cancer risk, Dr. Crump notes, and the results confirm those of others. Namely, that breast cancer risk is “highest in women treated with mantle radiotherapy around puberty, decreases with increasing age at treatment (although still elevated for women treated in their thirties, the median age at diagnosis of HL in most countries), and decreases with smaller radiation field sizes and lower radiation doses. Gonadotoxic therapy (alkylating agents or radiation) reduced subsequent breast cancer risk but only for women treated after age 20 years.”
Dr. Swerdlow and colleagues say the “large cumulative risks of breast cancer we found 20 to 39 years after supradiaphragmatic radiotherapy, especially in patients treated at age 20 years, are similar to or higher than the risks by the same ages in BRCA1 and BRCA2 carriers. They suggest that intensive breast screening programs for such women may need to continue for 40 years and longer after initial radiotherapy.”
They also say their data showing maximum absolute excess risk at ages 50 to 59 years suggest that “more-intensive screening (eg, annual screening with magnetic resonance imaging) may be needed.”
In his editorial, Dr. Crump points out that “Both the American Cancer Society and the United Kingdom Notification Risk Assessment and Screening Programme recommend magnetic resonance imaging (MRI) as an adjunct to annual mammography for women who have received thoracic irradiation younger than age 36 years, starting 8 years after treatment. Available data suggest that efforts to enroll high-risk women onto screening programs are falling short, and less than half of women treated during adolescence or as young adults currently receive annual mammography.”
Continuing, Dr. Crump says, “The United Kingdom guideline recommends commencing screening at age 25 years but returns women to standard mammography once every three years once they have reached age 50 years. The report by Swerdlow et al suggests that this upper age limit should be reconsidered in light of the very high cumulative risk faced by women even beyond 30 years of follow-up,” he concludes.