Radiation Therapy for Breast Cancer Increases the Risk of Esophageal Cancer

ABSTRACT & COMMENTARY

Radiation therapy is an important component of breast-conserving primary treatment for breast cancer. The features of radiation therapy that define success include the following: use of supervoltage equipment (e.g., a 6-mV linear accelerator), treatment planning and simulation of tangential fields to treat the breast while limiting lung volume, whole breast dose around 45-50 Gy given at 1.8-2.0 Gy/d, and use of boost to primary tumor if margins are positive or close. The field generally includes the ipsilateral internal mammary nodes, supraclavicular nodes, chest wall, and axilla.

Radiation is known to be carcinogenic. Much has been written about the potential for breast irradiation to induce a second breast cancer. However, the susceptibility of the breast to radiation carcinogenesis is influenced by the dose of radiation and the age of the host, and both of these factors tend to mitigate the risk in breast cancer patients. The relationship between radiation dose and cancer incidence appears to be a bell-shaped curve where risk increases linearly up to about 10 Gy and then decreases again at higher (therapeutic) radiation doses. Thus, the ipsilateral breast is at very low risk. It has been estimated that the uninvolved breast receives 1-3 Gy from a course of radiation to the involved breast.1 However, the breast becomes substantially less susceptible to radiation-induced cancers after age 40. Thus, the risk for women with breast cancer over age 40 is very, very low,2 though not zero.

Sarcomas (particularly angiosarcomas)3 and lung cancers4 may also be increased in women who receive breast radiation therapy. The cumulative risk of a sarcoma is less than 1% in 30 years. The lung cancer risk is greatly amplified in smokers, but, overall, lung cancer is about three times more common in women who receive breast radiation therapy.

The key feature of susceptibility to radiation carcinogenesis is that the cancer occurs within or adjacent to the radiation field. Thus, any organ in the field may be a candidate for increased secondary cancer incidence. Ahsan and Neugut have noted a significant increase in the risk of esophageal cancer in women with breast cancer who are treated with radiation therapy. They examined data from the NCI Surveillance, Epidemiology, and End Results Program (SEER) for the period 1973-1993. Among 220,806 women who had breast cancer in this period (over 1 million years of follow-up), 116 primary esophageal cancers were noted, where 75 were expected, for a relative risk of 1.54. However, all of the increased risk occurred in the group that received radiation therapy. For those who received radiation therapy, the relative risk of squamous cell carcinoma of the esophagus was 5.42, and for adenocarcinoma of the esophagus, relative risk was 4.22. No increased risk of either type of esophageal cancer was seen in women who did not receive radiation therapy. Women whose tumors were in the inner half of the breast and who received radiation therapy had a relative risk of 7.59. (Ahsan H, Neugut AI. Ann Intern Med 1998;128:114-117.)

COMMENTARY

These data suggest that, like other organs within the radiation field, the esophagus of women who receive radiation therapy as part of the primary treatment of breast cancer is at an increased risk to develop cancer, particularly after 10 years of follow-up. Not clear from these results is what impact, if any, was exerted by smoking. Furthermore, the data may reflect a lag in the institution of technical improvements in the delivery of breast radiation therapy that would be expected to further decrease the exposure of the esophagus to radiation.

These results should have a negligible impact on women’s choice of treatment for their breast cancer. Even with nearly a quarter of a million women in the study sample largely treated with suboptimal, or at least outmoded, technique, and followed for up to 20 years, the number of excess cases of esophageal cancer was about 40. This is not a public health problem. Nor should (or can) physicians heighten surveillance for this potential complication. However, given the important goal of trying to develop effective cancer preventions, it seems to me that we should be mounting serious, large-scale clinical trials of new preventions in people who have received radiation therapy for primary cancers of a variety of sites and who are likely to survive 20 years as a consequence of effective treatment. They are at greater risk of developing cancer than most others in the general population, and that risk should be amenable to modification.

References

1. Fraas B, et al. Int J Radiat Oncol Biol Phys 1985;11: 485-489.

2. Storm H, et al. J Natl Cancer Inst. 1992;84:1245-1250.

3. Wijnmaalen A, et al. Int J Radiat Oncol Biol Phys 1993;26:135-139.

4. Neugat A, et al. Cancer 1993;71:3054-3058.

Radiation therapy for primary breast cancer:

a. is a crucial component of breast-conserving therapy.

b. produces an unacceptably high rate of second malignancy.

c. is associated with an increased risk of ovarian cancer.

d. produces contralateral breast cancer in 30% of treated patients.

e. does not appreciably increase the rate of local tumor control after conservative surgery.