Grade Dictates Treatment of Primary NHL of the Breast

CHICAGO—Low-grade primary non-Hodgkin’s lymphoma (NHL) of the breast may be treated with local surgical excision with or without radiation therapy. Intermediate- or high-grade disease requires chemotherapy, however, said William Wong, MD, radiation oncologist, Mayo Clinic, Scottsdale, Arizona, at the 86th Annual Meeting of the Radiological Society of North America (RSNA).

Although 55,000 new cases of non-Hodgkin’s lymphoma will be diagnosed in the United States this year, an extremely small number will involve the breast. A retrospective study of all patients with non-Hodgkin’s lymphoma of the breast treated at the Rochester and Scottsdale Mayo Clinics between 1973 and 1998 uncovered only 25 women and one man with breast involvement.

These individuals were studied to gain insight into this rare disease by identifying relevant patient characteristics and prognostic factors, the natural history of this form of lymphoma, and the effect of various forms of treatment, Dr. Wong said.

Most of the patients in the study presented with a palpable breast mass; the median tumor size was 3.6 cm. Ten patients had lymphoma in the left breast, 14 in the right breast, and two in both breasts.

Based on the Working Formulation, 11 patients were classified as having low-grade non-Hodgkin’s lymphoma, 14 had intermediate-grade disease, and one patient had high-grade disease. Using the Ann Arbor staging method, 21 patients were determined to have stage I non-Hodgkin’s lymphoma and 5 had stage II disease.

Most patients (23) underwent local excision of the breast mass, while three had mastectomy, Dr. Wong said. Sixteen patients received radiotherapy after surgery, with the radiation dose ranging from 20 to 50.4 Gy (median, 35 Gy). Ten patients had radiation field therapy that included the breast, chest wall, and regional lymph nodes, and four patients had radiation field therapy confined to the breast.

Ten patients received chemotherapy as part of their initial treatment strategy. Nine of these patients had combination chemotherapy, and one was treated with a single chemotherapeutic agent for low-grade non-Hodgkin’s lymphoma.

Twenty-five of 26 patients had a complete clinical response to initial therapy. One patient with a low-grade lymphoma showed signs of local relapse after the tumor was excised. The 5-year survival rate for the entire group of patients was 70%; local control was achieved in 75% of patients, distant control in 51%, and relapse-free survival in 42%.

Overall, patients with low-grade disease had a 5-year survival rate of 91%, local control rate of 91%, distant control rate of 70%, and relapse-free survival rate of 61%. Individuals with high-grade disease, in contrast, had a 5-year survival rate of 53%, local control rate of 64%, distant control rate of 34%, and relapse-free survival rate of 29%.

Metastasis developed in 14 patients, including 11 of 15 patients with intermediate- or high-grade lymphoma. Chemotherapy was necessary to control the distant spread of disease in these patients. All six patients who did not undergo chemotherapy developed distant failure, compared with five of nine patients who had chemotherapy.

Three patients had brain metastases, which is in keeping with incidence reports by other investigators in the literature. "My feeling is we should watch these patients carefully. If they develop neurological symptoms, we should evaluate them for brain metastasis. One of the patients in this study with brain metastasis was salvaged with subsequent treatment without any additional problems," Dr. Wong said.

Prognostic Factors

According to a univariate analysis, the only significant prognostic factor for survival was stage of disease. For patients with intermediate-grade lymphoma, the use of chemotherapy was a significant prognostic factor for distant control; 52% of patients who received chemotherapy had no distant failure at 5 years, compared with 17% of those who did not have chemotherapy.

Dr. Wong concluded that "for the treatment of low-grade primary NHL of the breast, local therapy alone would be adequate. If radiation therapy is used, the dose should be 30 Gy or higher, because we did not have any failures with those patients. We may consider local excision alone for selected patients, mainly those with small lesions when the excision is complete and there are negative surgical margins. The role of chemotherapy for patients with primary low-grade NHL is not clear."

For those with intermediate- or high-grade disease, however, chemotherapy combined with local therapy is the treatment of choice, he said. The radiation therapy dose for patients with advanced-stage disease should be between 40 Gy and 50 Gy.