Abstract
Pre-treatment and sequential post-treatment (at 3 months, 6 months, 1, 2, 3, 4 and 5 years) examination of general immune competence was performed in 185 consecutive breast cancer patients. The patients were followed for 5 to 11 years to monitor the dynamic relationship between host immunity and cancer and to examine the effect of the treatment method. The tests of immune competence used were immunoglobulins IgG, IgA, IgM, leucocyte counts, percentage and total lymphocyte counts and Mantoux and DNCB skin hypersensitivity tests.
Serum IgG and IgA showed no change relating to treatment method in recurrence-free patients; but IgG levels were higher when recurrent disease was imminent or established; IgM diminished (P<0.001) after treatment and this continued at 5 years in all patient groups. Simple lymphocyte counts showed the most interesting changes. They remained depressed for as long as 60 months following radiotherapy (P<0.01). After treatment by surgery, lymphocyte counts rose in patients without recurrence, but fell when systemic recurrence was imminent or established. This effect was not seen in patients with local recurrence only. There was no change in immune competence immediately before recurrence sufficient to be of clinical usefulness, but a low pre-treatment lymphocyte count with a steady rise after surgery carried a good prognosis. Similarly a high initial lymphocyte count with a fall after surgery was indicative of recurrence. Universal and prolonged depression of lymphocyte counts following radiotherapy was confirmed, and the effect was additive to that of tumour load in recurrent disease.
Because of the large number of statistical calculations carried out, some of the apparently significant findings may be due to chance. However, the general trends emerging suggest that similar long-term studies, using the more sophisticated measures of lymphocyte function now available, might be rewarding.
Keywords: Breast Cancer, Lymphocyte Count, Tumour Load, Systemic Recurrence, Total Lymphocyte Count
References
- 1.Baral E, Blomgren H, Petrini B, Wasserman J, Ogenstad S, Silversward C. Prognostic relevance of immunologic variables in breast carcinoma. Acta Radio Ther Phys Biol. 1977;16:417. doi: 10.3109/02841867709133963. [DOI] [PubMed] [Google Scholar]
- 2.Baum M. The curability of breast Cancer. Br Med J. 1976;1:439. doi: 10.1136/bmj.1.6007.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Bolton PM, Mander AM, Davidson JM, James SL, Newcombe RG, Hughes LE. Cellular immunity in cancer: comparison of delayed hypersensitivity skin tests in 3 common cancers. Br Med J. 1975;3:18. doi: 10.1136/bmj.3.5974.18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Donegan WL. Staging methods, primary treatment options and end results. In: Donegan WL, Spratt JS, editors. Cancer of the breast. Philadelphia: Saunders WB; 1979. p. 221. [PubMed] [Google Scholar]
- 5.Fisher B. Some thoughts concerning the primary therapy of breast cancer. Recent results. Cancer Res. 1976;57:150. doi: 10.1007/978-3-642-81043-5_13. [DOI] [PubMed] [Google Scholar]
- 6.Frank CR, Williams Y. Prognostic value of peripheral lymphocyte count in hormone therapy of advanced breast cancer. Br J Cancer. 1976;34:641. doi: 10.1038/bjc.1976.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Kopersztych S, Rezkallah MT, Miki SS, Naspitz CK, Mendes NF. Cell mediated immunity in patients with carcinoma. Correlation between clinical stage and immunocompetence. Cancer. 1976;37:724. doi: 10.1002/1097-0142(197609)38:3<1149::aid-cncr2820380316>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
- 8.Lee YTN, Sparks FC, Eilbar FR, Morton DL. Delayed cutaneous hypersensitivity and peripheral lymphocyte counts in patients with advanced cancer. Cancer. 1975;35:748. doi: 10.1002/1097-0142(197503)35:3<748::aid-cncr2820350330>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
- 9.Meyer JE. Thoracic effects of therapeutic irradiation for breast carcinoma. Am J Roentgenol. 1978;130:877. doi: 10.2214/ajr.130.5.877. [DOI] [PubMed] [Google Scholar]
- 10.Shukla HS, Whitehead RH, Hughes LE. A study and comparison of mechanism of T cell depression following radiotherapy or surgery in Stage III breast cancer. Clin Oncol. 1980;6:39. [PubMed] [Google Scholar]
- 11.Shukla HS, Hughes LE, Whitehead RH, Newcombe RG. Long-term (5–11 year) follow-up of general immune competence in breast cancer. 1. Pre treatment levels in reference to micrometastasis. Cancer Immunol Immunother. 1986;21:1. doi: 10.1007/BF00199369. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Simo-Camps E, Anguera A, Vick JMA, Vidal RA, Sola F, Sarrias R, Gumma J, Gri E, Puigdollers JMA. Immunologic impairment in patients with non lymphoid cancer. Correlation with the tumoral stage, response to treatment and survival. Cancer. 1976;37:724. doi: 10.1002/1097-0142(197602)37:2<724::aid-cncr2820370219>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
- 13.Steel GG. The cell cycle in tumours: An examination of data gained by technique of labelled mitoses. Cell Tissue Kinet. 1972;5:87. doi: 10.1111/j.1365-2184.1972.tb00358.x. [DOI] [PubMed] [Google Scholar]
- 14.Stein JA, Adler A, Efrain SB, Maor M. Immunocompetence, immunosuppression and human breast cancer. 1. An analysis of their relationship by known parameters of cell mediated immunity in well defined clinical stages of disease. Cancer. 1976;38:1171. doi: 10.1002/1097-0142(197609)38:3<1171::aid-cncr2820380319>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
- 15.Stjernsward J, Jondal M, Vankey F, Wigzell H, Sealy R. Lymphopenia and change in distribution of human B and T lymphocytes in peripheral blood induced by irradiation for mammary carcinoma. Lancet. 1972;I:1352. doi: 10.1016/s0140-6736(72)91091-4. [DOI] [PubMed] [Google Scholar]
- 16.Teasdale C, Hillyard JW, Webster DJT, Bolton PM, Hughes LE. Pre treatment general immune competence and prognosis in breast cancer. A prospective 2 year follow-up Eur J Cancer. 1979;15:975. doi: 10.1016/0014-2964(79)90281-0. [DOI] [PubMed] [Google Scholar]
- 17.Teasdale C, Hughes LE, Whitehead RH, Newcombe RG. Factors affecting pre treatment immune competence in cancer patients I. The effect of age, sex and ill health. II. The corrected effects of malignant disease. Cancer Immunol Immunother. 1979;6:89. [Google Scholar]
- 18.Wanebo HJ, Rosen PP, Thaler T, Urban JA, Oettgen HF. Immunobiology of operable breast cancer. An assessment of biologic risk by immuno parameters. Ann Surg. 1976;184:258. doi: 10.1097/00000658-197609000-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Whitehead RH, Thatcher J, Teasdale C, Roberts GP, Hughes LE. T and B lymphocytes in breast cancer — Stage relationship and abrogation of T lymphocyte depression by enzyme treatment in vitro. Lancet. 1976;I:330. doi: 10.1016/s0140-6736(76)90085-4. [DOI] [PubMed] [Google Scholar]