Effect of postoperative radiotherapy on peripheral blood lymphocytes in patients with carcinoma of the breast

Abstract

The effect of prophylactic postoperative radiotherapy in patients with carcinoma of the breast was determined on cells in the peripheral blood. Controls had carcinoma of the breast treated by radical mastectomy. Results were also compared with those in patients with carcinoma of the cervix treated by radiotherapy. None had recurrent disease. Radiotherapy of carcinoma of the breast decreased the total white blood cell count by 15% during the period of the first 6 months but did not alter the granulocyte count. The total white cell and granulocyte counts did not change in those with carcinoma of the cervix. The lymphocyte count was decreased by one third for 12 months in patients given radiotherapy for carcinoma of the breast and for 24 months in those with carcinoma of the cervix. The lymphopenia persisted in many for 60 months. Function of the lymphocytes was determined by their ability to synthesize nucleic acids when grown in tissue culture with the strong mitogen phytohemagglutinin (PHA). Radiotherapy produced 50% increase in DNA synthesis for 12 months in patients with carcinoma of the breast and for 60 months in those with carcinoma of the cervix. Treatment had no effect on RNA synthesis in patients with carcinoma of the breast but caused a 25% decrease in RNA synthesis for 60 months in those with carcinoma of the cervix. We are unable to explain the prolonged lymphopenia and the decrease in RNA synthesis. Lymphocytes transformed by PHA are mostly thymic‐dependent and responsible for cellular immune response. Since the lymphocyte count was decreased by one third and DNA synthesis increased by a greater amount, the number of thymic dependent lymphocytes did not change or may have increased. The cellular immune response to cancer is unlikely to be impaired by local radiotherapy.

Horizontal studies of cell mediated immune reactions to autologous tumour antigens in patients with operable mammary carcinoma

“…The two methods gave comparable results (Table I) (Meyer, 1970;McCredie, Inch and Sutherland, 1972) and reduced PHA induced blast transformation (Stjernsward et al, 1972) In the 7 day tests, 47% of patients reacted to autologous and 40% to allogeneic breast tumour antigens; 28/45 (62%) patients positive to autologous antigens also reacted to allogeneic tumour preparations, while only 7143 (16%) patients negative to autologous antigens cross-reacted with allogeneic tumours (P < 0-001, Chi-squared with Yates' correction). This might indicate that negative in vitro results truly indicated a lack of reactivity on the part of the patient and were not due to variations in the fractionation of tumours.…”

A comparison of the acute effects of radiation therapy, including or excluding the thymus, on the lymphocyte subpopulations of cancer patients.

“…Although methods have varied and results differed, most workers agree that RT causes a decrease in the response to mitogens (5,(34)(35)(36)(37)(38). A few have found that RT does not effect the lymphocyte response to mitogens (37,39,40). The time after cessation of RT at which the mitogen stimulation is measured is crucial (see Fig.…”

Long term effects of radiation of T and B lymphocytes in peripheral blood of patients with Hodgkin's disease.

“…On the other hand, the impaired response in untreated patients appears to be due to a factor which interferes with the capacity of the circulating lymphocytes to form E rosettes and to respond adequately to PHA.2 We have recently been able to demonstrate such a factor in the serum and in extracts from the spleens of untreated patients with Hodgkin's disease,3 and to reverse the impaired responses of peripheral blood lymphocytes from these patients by overnight incubation in 20% fetal calf serum. 2 Lymphocyte stimulation by Con A was also impaired in both untreated patients and in patients in long term remission after radiotherapy (Fig. 2).…”

“…Radiation induced alterations in the number and function of peripheral blood lymphocytes have recently been described in patients treated with radiotherapy for carcinoma of the breast (1-6), lung (7)(8)(9), bladder (7)(8)(9)(10), uterine cervix (2,6,11). testicular seminoma and carcinoma (12.…”

“…However, at the completion of treatment, the mean total lymphocyte count of 503/mm3 was 4 SD below the mean for normal controls. Acute lymphocytopenia after a course of radiation has been described in a variety of clinical situations involving localized or extended field radiotherapy (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Recovery usually begins shortly after completion of treatment (6,7,12), and continues through the next 1-2 yr.…”