Study shows women with breast cancer treated with radiotherapy using tangential fields have increased risk of developing cancer in the 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, warns a 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 tumours in both breasts, such as a genetic tendency to breast cancer or hormonal risk factors.

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 around one in ten of all contralateral breast cancers in women having traditional radiotherapy for their initial breast cancer could be attributed to their radiation treatment. But few research studies have looked at whether modern radiotherapy and chemotherapy affect this risk, and the results have been inconclusive. So a large study was carried out to assess the long-term risk of contralateral breast cancer in young women, focusing 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 centres in the Netherlands, the Netherlands Cancer Institute, Amsterdam, and the Erasmus Medical Center, Rotterdam, between 1970 and 1986. The researchers 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.

Results showed that radiotherapy did not significantly 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 (surgery to remove a small area of the breast) showed a 1.5-fold increased risk of breast cancer in their other breast compared with those who had radiotherapy after mastectomy (removal of the entire breast).

The researchers, led by Maartje Hooning, from the Netherlands Cancer Institute, Amsterdam, 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.”
They noted that radiation techniques for treating breast cancer have improved over the last few years. Strategies 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 pre-existing tumour 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.

Commenting on the study, Jacques Bernier, from the Department of Radio-Oncology, Genolier Swiss Medical Network, Genolier and Geneva, Switzerland, said: “This is the first time the potential relationship between radiotherapy and the risk of contralateral breast cancer has been investigated with so much precise data on irradiation doses to the contralateral breast.” He explained how it has built on what was suspected previously: “The increased risk of contralateral breast cancer in young patients with a positive family history of breast cancer had been alluded to in the past but never really quantified, at least never with the degree of precision reached in this study.”

Dr Bernier explained that tangential fields (oblique anterior and oblique posterior) are used after both mastectomy and breast conserving surgery. “The dose delivered to the contralateral breast is a function of the field angles and extension of the irradiation to the midline in the case, for instance, of tumours located in one of the inner quadrants or when the post-surgical scar extends to the sternum. Thus, the dose to the contralateral breast is conditioned more by the anatomy of the patient or post-surgical conditions than by the type of surgery.”
He considered that the study was well designed, with the main limitation being that it covered a time window (1970-1986) when technology was not very sophisticated and radiotherapy doses delivered to the contralateral breast were higher than with current treatment, using conformal therapy with doses more focused to the target volume. “The risk levels calculated in this paper might overestimate those linked with modern radiotherapy,” he considered.

In terms of the implications of the study for the clinical management of patients, Dr Bernier said: “Obviously, the indication for post-operative radiotherapy should not be questioned even in patients with the highest risk of contralateral breast cancer, except in very specific cases with particular breast or chest wall anatomy. But it is clear that, in this group of patients, the irradiation plan should be set up with more caution as regards the level of dose delivered to the contralateral breast.

“In young patients with a positive family of breast cancer, the treatment plan should take into account their higher potential risk of contralateral breast cancer. Further efforts should be made to increase the conformality of radiotherapy techniques,” Dr Bernier concluded.

Research Paper:

Hooning MJ, Aleman BMP, Hauptmann M et al. Roles of Radiotherapy and Chemotherapy in the Development of Contralateral Breast Cancer. Published online in the Journal of Clinical Oncology