Dr. Susan Love Research Foundation | Breast Cancer

A new analysis by Danish researchers has found that radiation after mastectomy reduces the risk that a woman with an aggressive tumor will develop a local or regional recurrence or metastatic disease. These findings underscore the importance of women who are at high risk for recurrence receiving radiation therapy following their mastectomy.

Most women who have a mastectomy don't need radiation. That's because the surgery removes all of the cancer in the breast. But there is a small group of women for whom radiation is necessary. These women are believed to be at high risk for a local or regional recurrence in the skin or lymph nodes because they had four or more positive lymph nodes, a tumor over 5cm in size, close margins (cancer cells at the edge of the mastectomy), or a significant amount of cancer cells seen in the lymphatic or blood vessels in the breast tissue.

The new analysis by Danish researchers focused on the 3,083 women enrolled in the Danish Breast Cancer Cooperative Group 82 b and c trials. All of the women in these trials had a tumor larger than 5cm, positive axillary nodes, and/or cancer cells that had been found in the skin or pectoral fascia (the connective tissue surrounding the muscle), which the researchers thought put them at high risk for recurrence.

The women were randomly assigned to two groups. One group received radiation; the other group did not. The women who received radiation had eight cycles of CMF chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil). The women who did not receive radiation had nine CMF cycles. The chemotherapy and radiation were given in what is referred to as a sandwich technique, with the radiation given after the first cycle of chemotherapy. All of the postmenopausal women received tamoxifen for one year.

The women in this trial have now been followed for an average of 18 years. As of November 2004, 30 percent of the women who received radiation were alive with no evidence of recurrence compared with 19 percent of the women who did not receive radiation.

Overall, radiation was found to reduce the risk of metastases, with distant metastases seen in 59 percent (919 of 1,545) of the women who did not receive radiation compared with 50 percent (768 of 1,538) of the women who did.

Radiation also affected the type of first recurrence a woman had. The study found that the first form of recurrence for women who did not receive radiation was more likely to be a local or regional recurrence. Thirty percent (456) of the women who did not receive radiation experienced a local or regional recurrence as their first type of recurrence compared with 5 percent (79) of the women who did receive radiation. In contrast, the women who had radiation were more likely to have their first form of recurrence be distant metastases. The study found that 41 percent of the women who received radiation had distant metastases as their first form of recurrence compared with 28 percent of the women who did not receive radiation.

Based on these findings the researchers conclude, "postmastectomy radiation therapy changes the pattern [of recurrence] in high-risk breast cancer patients; fewer patients have a local or regional recurrence as the first site of recurrence, and overall fewer patients have distant metastases."

Susan says:

There are some differences between the type of treatment the women in this study received when the trial was started 18 years ago and the type of treatment women would receive today. For example, all the women received CMF chemotherapy. But a chemotherapy combination that contains doxorubicin is now more likely to be used in women at high risk for recurrence. This means the rate of local or regional recurrence seen in the study among women who did not receive radiation might be lower today.

Also, all of the postmenopausal women in the study were given one year of hormone therapy with tamoxifen. Today, only the women whose tumors were hormone-sensitive would receive hormone therapy, they might be given tamoxifen or an aromatase inhibitor, and they would take the drug for five years, not one. This also could have affected the rate of local or regional recurrence seen in the study among the women who did not receive radiation.

Even so, there is a lot we can learn from this study, as it illustrates why women who are at high risk for recurrence should be given radiation therapy. The women who received this treatment not only had a lower risk of recurrence, they had a lower risk of dying of breast cancer.

The key point is that the women who received radiation went longer before they experienced a recurrence: 3.9 years among those who did not have radiation compared with 7.9 years among those who did. And you can argue that the longer you go without a recurrence, the better.

There has been some controversy as to what a local recurrence means. Some researchers have argued that it's not the local recurrence that spreads to other places. Instead, they have maintained, the local recurrence is an indicator that a woman is at higher risk of distant recurrence and that it is just that the local recurrence shows up first. But, as this study indicates, there may be some instances when local recurrence does in fact lead to the spread of the disease.

Previous studies have found that postmastectomy radiation reduces the chance of a local recurrence by 50–75 percent. This means that if the risk of local recurrence overall is 5–10 percent, then the risk of recurrence following radiation would be 3–5 percent. But if a woman's risk of recurrence were high, then the benefit would be greater.

So, why doesn't every woman who had a mastectomy have radiation, just to be on the safe side? Because radiation has its own risks. Studies show that people who have had cancer on the left side and got radiation had an increased risk of developing heart disease, although this risk has decreased substantially as radiation techniques have improved. Thus, it's a balance of risk versus benefit. When the risk of local recurrence is high enough after a mastectomy, radiation is worthwhile. And as this study illustrates, for those women who are at high risk for recurrence, the benefit is worth the risk.