Radiotherapy Using Tangential Fields Increase Risk of Cancer in Other Breast

Women with breast cancer treated with radiotherapy using tangential fields (where radiation is directed at an angle to the breast) after lumpectomy show increased risk of breast cancer in the other breast, with an even higher risk in younger women and in those with family members who have had breast cancer, cautions a recent study.

Women who have had breast cancer have a three to four times higher risk of developing a new primary cancer in their other breast (contralateral breast cancer), compared with the risk of a first primary breast cancer in other women. This increased risk could be due to a common cause for the tumors in both breasts, such as hormonal risk factors a genetic tendency to breast cancer.

Researchers have suggested that the treatment of the first breast cancer may also play a role in increasing the risk of a new cancer in the other breast. One study estimated that about one in 10 of all contralateral breast tumors in women having conventional radiotherapy for their initial breast cancer could be attributed to their radiation treatment. However, few research studies have looked at whether advanced radiotherapy and chemotherapy affect this risk, and the results have been inconclusive. Therefore, a large study was carried out to evaluate the long-term risk of contralateral breast cancer in young women, centering on the effects of the radiation dose they were given, their chemotherapy, and their family history of breast cancer.

The study included 7,221 predominantly young women treated for breast cancer at two centers in The Netherlands, The Netherlands Cancer Institute (Amsterdam, The Netherlands), and the Erasmus Medical Center (Rotterdam, The Netherlands), between 1970 and 1986. The investigators searched the patients' records for information on the treatment they were given for their primary cancers, including surgery, radiotherapy, chemotherapy, and hormonal treatment; whether they suffered recurrent cancer; and their family history of breast cancer.

The study's results showed that radiotherapy did not considerably increase the risk of contralateral breast cancer overall. However, the risk associated with radiotherapy was higher in younger women. Those who were younger than 35 years at first treatment had nearly twice the risk of breast cancer associated with radiotherapy occurring in the other breast (hazard ratio [HR] 1.78; 95% confidence interval [CI], 0.85 to 3.72) compared to women over 45 years (HR 1.09; 95% CI, 0.82 to 1.45).

The risk of contralateral breast cancer also depended on the type of radiotherapy used, which was determined by the location and stage of the primary breast cancer. Women treated before the age of 45 years with radiotherapy after lumpectomy showed a 1.5-fold increased risk of breast cancer in their other breast compared with those who had radiotherapy after mastectomy.

The researchers, led by Dr. Maartje Hooning, from The Netherlands Cancer Institute, explained why this difference might have occurred, "Postmastectomy radiotherapy using direct electron fields led to a significantly lower radiation exposure to the contralateral breast than postlumpectomy radiotherapy using tangential fields."

The investigators noted that radiation techniques for treating breast cancer have improved over the last few years. Newer approaches to improve the angle of delivery of radiation to the breast and the introduction of intensity-modulated radiotherapy have led to a lower dose of radiation to the other breast. "These policies will have the impact of reducing, though not eliminating, any potential increased risk of contralateral breast cancer owing to radiotherapy," they suggested.

The joint effects of postlumpectomy radiotherapy and a strong family history for breast cancer on the risk of contralateral breast cancer were greater than expected when individual risks were summed up (HR 3.52; 95% CI, 2.07 to 6.02; p departure from additivity = 0.043).

Treatment with adjuvant chemotherapy (cyclophosphamide, methotrexate, and fluorouracil) was associated with a nonsignificantly decreased risk of contralateral breast cancer in the first five years of follow-up but did not reduce the risk in subsequent years. "Our data suggest that chemotherapy primarily affects contralateral breast cancer risk by eradicating preexisting tumor cells in the contralateral breast," the researchers suggested.

"Young patients with breast cancer irradiated with breast tangentials experience increased risk of contralateral breast cancer, especially in those with a positive family history of breast cancer," concluded Dr. Hooning and her co-researchers. "This finding should be taken into account when advising breast radiation with tangential fields to young patients with breast cancer.

The study was published in the October 14, 2008, issue of the Journal of Clinical Oncology.

Related Links:
The Netherlands Cancer Institute
Erasmus Medical Center