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Key Words

Breast cancer, mastectomy, chemotherapy, radiation therapy, lymph nodes. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ³.)

Summary

Women with moderate- to high-risk early breast cancer who received radiation therapy in addition to mastectomy and chemotherapy were more likely to be alive after 20 years of follow-up than women who received surgery and chemotherapy alone, Canadian researchers report.

Source

Journal of the National Cancer Institute, January 19, 2005.

Background

It's not clear whether all women who have a mastectomy for breast cancer that has spread to the lymph nodes benefit from adjuvant (additional) radiation therapy. Current guidelines recommend radiation therapy for women whose tumors are larger than five centimeters in diameter or who have more than four cancerous lymph nodes. This group of patients is at the highest risk for breast cancer recurrence.

Women with smaller tumors or less than four cancerous lymph nodes have a less elevated risk of recurrence. For this moderate-risk group, studies have not clearly shown that the benefits of radiation outweigh the potential risks of radiation-induced second cancers, heart problems, and other concerns.

The Study

This study was designed to find out whether radiation to the lymph nodes and chest wall, in addition to mastectomy and chemotherapy, would improve patients' long-term survival. It involved 318 premenopausal women with stage I or stage II breast cancer that had spread to one or more lymph nodes. The patients were assigned at random to receive radiation or no further treatment after mastectomy and chemotherapy. The women were treated between 1979 and 1986 in British Columbia, Canada.

In an earlier report after 15 years of follow-up, researchers had found that women who received radiation were less likely to die of breast cancer but that their overall survival was no better than that of women who did not receive radiation. In the current report, researchers looked at outcomes after 20 years of follow-up. The lead author of the report is Joseph Ragaz, M.D., of McGill University Health Center in Montreal, Canada.

Results

After 20 years of follow-up, 190 of the 318 patients had died (170 died of breast cancer, 20 of other causes). Forty-seven percent of the women treated with radiation were still alive, compared with 37 percent of the women who got no additional treatment. Breast cancer recurred more frequently in patients who did not receive radiation. Radiation therapy resulted in a 32 percent reduction in deaths from breast cancer and a 27 percent reduction in all deaths.

What's more, moderate-risk women who had one to three cancerous lymph nodes benefited from radiation just as much as higher-risk women who had four or more affected nodes. “Our data show that implementing radiation therapy soon after diagnosis in the adjuvant setting is important,” Ragaz and his colleagues write. Radiation given later, after a patient’s cancer had recurred, generally did not cure the disease, they add.

Comments

The higher rate of breast cancer recurrence among patients not treated with radiation shows that microscopic disease survives both mastectomy and chemotherapy and is the origin of subsequent tumor recurrences, the study authors assert. “Our data indicate that radiation therapy can effectively eradicate this source of metastases in more than 30 percent of patients,” they write. This reduction in the rate of disease recurrence helps to explain the survival advantage seen in women who received radiation therapy.

The finding that radiation therapy reduces disease recurrence is an important one, says C. Norman Coleman, M.D., who heads the radiation oncology branch of the National Cancer Institute’s Center for Cancer Research. “It shows that radiation therapy can not only eliminate local residual disease but also reduce the risk of the disease spreading to other tissues and organs,” he says. Moreover, he adds, the side effects of radiation therapy did not negate its benefits, as has happened in previous studies.

Limitations

The results of this study support earlier findings suggesting that radiation may benefit patients with relatively few cancerous nodes who are at moderate risk for breast cancer recurrence, says Coleman. However, uncertainty remains because it is difficult to show a treatment benefit when the risk of recurrence is low to begin with. In an accompanying editorial, Timothy Whelan, M.D., and Mark Levine, M.D., of the Juravinski Cancer Center in Hamilton, Canada, urge that a clinical trial be conducted to address the remaining uncertainties about the benefits of radiation therapy for moderate-risk patients.

Also, many changes have occurred in breast cancer treatment since 1979, when this study began enrolling patients. The multidrug chemotherapy regimen given to patients in this study (cyclosphosphamide, methotrexate, and 5-fluorouracil) is rarely used today. Patients did not receive the hormonal drug tamoxifen because the trial began before studies elsewhere demonstrated the benefits of this drug in preventing breast cancer recurrence.

In recent years other studies have shown that, for women with small breast tumors (less than four centimeters in diameter), long-term survival is similar with either breast-conserving surgery (lumpectomy with or without radiation) or mastectomy (see the related article ⁴). Nevertheless, in some parts of the United States many breast cancer patients continue to be treated with mastectomy.

Glossary Terms

Surgery to remove abnormal tissue or cancer from the breast and a small amount of normal tissue around it. It is a type of breast-sparing surgery.

Surgery to remove the breast (or as much of the breast tissue as possible).

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.