Mammary Neoplasia in Animals: Pathologic Aspects and the Effects of Contraceptive Steroids

  • H. W. Casey
  • R. C. Giles
  • R. P. Kwapien
Part of the Recent Results in Cancer Research / Fortschritte der Krebsforschung / Progrès dans les recherches sur le cancer book series (RECENTCANCER, volume 66)


The incidence of spontaneous tumors of the mammary gland varies greatly among the different mammalian species. Large domesticated animals have a very low frequency of the disease. Even though the cow has enormous mammary gland development and cows numbering in the millions are observed to an old age, less than 50 cases have been reported in the literature. Similarly, mammary tumors are equally rare in sheep, horses, pigs, and goats. In contrast, the incidence of mammary tumors in the dog exceeds that of women by a factor of 3 to 4, and the disease is common in the cat. Rats and mice have a high incidence of mammary tumors; however, they are less frequent in other species of small laboratory animals. Mammary neoplasms are apparently rare in the nonhuman primate, but interest in the disease in these animals remains high as they have a menstrual cycle comparable to women. This paper reviews some major aspects of spontaneous mammary tumors in mice, rats, cats, dogs, and nonhuman primates. Emphasis has been placed on the pathologic aspects of the neoplasms and the use of these species in the carcinogenic testing of contraceptive steroids. The literature contains a large number of excellent publications on mammary neoplasia in animals; only selected articles are cited. The reader is especially referred to the comprehensive review by Hamilton published in 1974 [32] and the review by STEWART published in 1976 [68] on the comparative pathology of animal neoplasia.


Mammary Gland Mouse Mammary Tumor Virus Tubular Adenocarcinoma Mammary Nodule Contraceptive Steroid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Allen, H. L.: Feline mammary hypertrophy. Vet. Pathol. 10, 501–508 (1973)PubMedCrossRefGoogle Scholar
  2. 2.
    Andersen, A. C.: Parameters of mammary gland tumors in aging beagles (abstract). JAVMA 147, 1653 (1965)Google Scholar
  3. 3.
    Appleby, E. C., Keymer, I. F., Hirne, J. M.: Three cases of suspected mammary neoplasia in nonhuman primates. J. Comp. Pathol. 84, 351–364 (1974)PubMedCrossRefGoogle Scholar
  4. 4.
    Berliner, V. R.: U.S. Food and Drug Administration requirements for toxicity testing of contraceptive products. In: Pharmacological Models in Contraceptive Development, WHO Symposium, Geneva: Bureau FDA, 1973, pp. 240–253Google Scholar
  5. 5.
    Bostock, D. E.: The prognosis following the surgical excision of canine mammary neoplasms. Eur. J. Cancer 11, 386–396 (1975)Google Scholar
  6. 6.
    Bradley, C. J., Kledzik, G. S., Meites, J.: Prolactin and estrogen dependency of rat mammary cancers at early and late stages of development. Cancer Res. 36, 319–324 (1976)PubMedGoogle Scholar
  7. 7.
    Brodey, R. S., Fidler, I. J., Howson, A. E.: The relationship of estrous irregularity, pseudopregnancy, and pregnancy to the development of canine mammary neoplasms. JAVMA 149, 1047–1049 (1966)PubMedGoogle Scholar
  8. 8.
    Cameron, A. M., Faulkin, L. J., Jr.: Hyperplastic and inflammatory nodules in the canine mammary gland. J. Natl. Cancer Inst. 47, 1277–1287 (1971)PubMedGoogle Scholar
  9. 9.
    Capel-Edwards, K., Hall, D. E., Fellowes, K. P., Vallance, D. K., Daview, M. J., Lamb, D., Robertson, W. B.: Long-term administration of progesterone to the female beagle dog. Toxicol. Appl. Pharmacol. 24, 474–488 (1973)PubMedCrossRefGoogle Scholar
  10. 10.
    Carcinogenicity Tests of Oral Contraceptives. A report by the Committee on Safety of Medicines. London: Her Majesty’s Stationery Office, 1972Google Scholar
  11. 11.
    Chopra, H. C., Mason, M. M.: A new virus in a spontaneous mammary tumor of a rhesus monkey. Cancer Res. 30, 2081–2086 (1970)PubMedGoogle Scholar
  12. 12.
    Coleman, M. E., Murchison, T. E., Frank, D.: Mammary nodules in dogs receiving Depo-Provera and progesterones: An interim progress report. Toxicol. Appl. Pharmacol. 37, 181 (1976)Google Scholar
  13. 13.
    Cotchin, E.: Neoplasia in the cat. Vet. Rec. 69, 425–434 (1957)Google Scholar
  14. 14.
    Cotchin, E.: Mammary neoplasms of the bitch. J. Comp. Pathol. 68, 1–21 (1958)PubMedGoogle Scholar
  15. 15.
    Daniel, G. R.: Chlormadinone contraceptive withdrawn. Br. Med. J. 1, 303 (1970)PubMedCrossRefGoogle Scholar
  16. 16.
    De Vitta, J.: Mammary adenofibroma of the female dog. N. Am. Vet. 20, 53–55 (1939)Google Scholar
  17. 17.
    Dorn, C. R., Schneider, R.: Inbreeding and canine mammary cancer: A retrospective study. J. Natl. Cancer Inst. 57, 545–548 (1976)PubMedGoogle Scholar
  18. 18.
    Dorn, C. R., Taylor, D. O. N., Schneider, R., Hibbard, H. H., Klauber, M. R.: Survey of animal neoplasms in Alameda and Contra Costa counties, California. I. Cancer morbidity in dogs and cats from Alameda county. J. Natl. Cancer Inst. 40, 307–318 (1968)PubMedGoogle Scholar
  19. 19.
    Drill, V. A.: Experimental and clinical studies on relationship of estrogens and oral contraceptives to breast cancer. In: Experimental Model Systems in Toxicology and Their Significance in Man, Proceedings of the European Society for the Study of Drug Toxicity. Zurich: 1973, Vol. XV, pp. 200–214Google Scholar
  20. 20.
    Drill, V. A., Martin, D. P., Hart, E. R., McConnell, R. G.: Effect of oral contraceptives on the mammary glands of rhesus monkeys: A preliminary report. J. Natl. Cancer Inst. 52, 1655–1657 (1974)PubMedGoogle Scholar
  21. 21.
    Dunn, T. B.: Morphology of mammary tumors in mice. In: The Physiopathology of Cancer. Hamburger, F. (Ed.). New York: Harper (Hoeber), 1959, pp. 38–84Google Scholar
  22. 22.
    Durbin, P. W., Williams, M. H., Jeung, N., Arnold, J. S.: Development of spontaneous mammary tumors over the life-span of female Charles River (Sprague-Dawley) rats. The influence of ovariectomy, thyroidectomy and adrenalectomy-ovariectomy. Cancer Res. 26, 400–426 (1966)PubMedGoogle Scholar
  23. 23.
    Feldman, D. G., Gross, L.: Electron microscopic study of spontaneous mammary carcinomas in cats and dogs: Virus-like particles in cat mammary carcinomas. Cancer Res. 31, 1261–1267 (1971)PubMedGoogle Scholar
  24. 24.
    Fidler, J., Brodey, R. S.: A necropsy study of canine malignant mammary neoplasms. JAVMA 151, 710–715 (1967)PubMedGoogle Scholar
  25. 25.
    Fidler, I. J., Abt, D. A., Brodey, R. S.: The biological behavior of canine mammary neoplasms. JAVMA 151, 1311–1318 (1967)PubMedGoogle Scholar
  26. 26.
    Finkel, M. J., Berliner, V. R.: The extrapolation of experimental findings (animal to man): The dilemma of the systemically administered contraceptives. Presented at 62nd Annual Meeting of the IAP, Washington, D. C., pp. 13–18 (1973)Google Scholar
  27. 27.
    Foulds, L.: The histologic analysis of mammary tumors of mice. II. The histology of responsiveness and progression. The origins of tumors. J. Natl. Cancer Inst. 17, 713–752 (1956)Google Scholar
  28. 28.
    Fowler, E. H., Wilson, G. P., Koestner, A.: Biologic behavior of canine mammary neoplasms based on a histogenetic classification. Vet. Pathol. 77, 212–229 (1974)CrossRefGoogle Scholar
  29. 29.
    Frye, F. L., Dorn, C. R., Taylor, D. O. N., Hibbard, H. H., Klauber, M. R.: Characteristics of canine mammary gland tumor cases. Anim. Hospital 3, 1–12 (1967)Google Scholar
  30. 30.
    Geil, R. G., Lamar, J. K.: FDA studies of estrogen, progestogen and estrogen/progestogen. Inter. Res. & Develop. Corp., Mattawan, Michigan and the FDA, Rockville, Maryland. Presented at the Third Annual NCTR Res. Symp., Little Rock, Arkansas (1976)Google Scholar
  31. 31.
    Giles, R. C., Kwapien, R., Geil, R. G., Casey, H. W.: Mammary nodules in beagle dogs administered investigational oral contraceptive steroids. J. Natl. Cancer Inst. 60, 1351–1364 (1978)PubMedGoogle Scholar
  32. 32.
    Hamilton, J. M.: Comparative aspects of mammary tumors. Adv. Cancer Res. 19, 1–37 (1974)PubMedCrossRefGoogle Scholar
  33. 33.
    Hampe, J. F., Misdorp, W.: International histological classification of tumours of domestic animals. IX. Tumours and dysplasias of the mammary gland. Bull. WHO 50, 111–133 (1974)PubMedGoogle Scholar
  34. 34.
    Hayden, D. W., Nielsen, S. W.: Feline mammary tumours. J. Small Anim. Pract. 12, 687–697 (1971)PubMedCrossRefGoogle Scholar
  35. 35.
    Hayes, A.: Feline mammary gland tumors. Vet. Clin. N. Am. 7, 205–212 (1977)Google Scholar
  36. 36.
    Hernandez, F. J., Fernandez, B. B., Chertack, M., Gage, P. A.: Feline Pract., pp. 45–48 (1975)Google Scholar
  37. 37.
    Hill, R.: Pre-clinical toxicity of steroid hormones: Recent experiences with estrogens and progestogens in the dog. Adv. Steroid Biochem. Pharmacol. 3, 29–38 (1972)Google Scholar
  38. 38.
    Hill, R., Dumas, K.: The use of dogs for studies of toxicity of contraceptive hormones. Acta Endocrinol. [Suppl] (Kbh) 185, 74–84 (1974)Google Scholar
  39. 39.
    Howard, E. B., Nielsen, S. W.: Neoplasms of the boxer dog. Am. J. Vet. Res. 26, 114, 1121–1131 (1965)PubMedGoogle Scholar
  40. 40.
    Huggins, C., Briziarelli, G., Sutton, H.: Rapid induction of mammary carcinoma in the rat and the influence of hormones on the tumors. J. Exp. Med. 109, 25–42 (1958)CrossRefGoogle Scholar
  41. 41.
    Huggins, C., Grand, L. C., Brillantes, F. P.: Mammary cancer induced by a single feeding of polynuclear hydrocarbons and its suppression. Nature (London) 189, 204–207 (1961)CrossRefGoogle Scholar
  42. 42.
    Ihle, J. N., Arthur, L. O., Fine, D. L.: Autogenous immunity to mouse mammary tumor virus in mouse strains of high and low mammary tumor incidence. Cancer Res. 36, 2840–2844 (1976)PubMedGoogle Scholar
  43. 43.
    International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. Lyon, France, WHO Vol. VI, “Sex Hormones”, 1974Google Scholar
  44. 44.
    Kirschstein, R. L., Rabbon, A. S., Rusten, G. W.: Infiltrating duct carcinoma of the mammary gland of a rhesus monkey after administration of an oral contraceptive: A preliminary report. J. Natl. Cancer Inst. 48, 551–556 (1972)PubMedGoogle Scholar
  45. 45.
    Kwapien, R. P., Giles, R. C., Geil, R. G., Casey, H. W.: Basaloid adenomas of the mammary gland in beagle dogs administered investigation contraceptive steroids. J. Natl. Cancer Inst. 59, 933–939 (1977)PubMedGoogle Scholar
  46. 46.
    Misdorp, W., Hart, A. A. M.: Prognostic factors in canine mammary cancer. J. Natl. Cancer Inst. 56, 779–786 (1976)PubMedGoogle Scholar
  47. 47.
    Misdorp, W., Cotchin, E., Hampe, J. F., Jabara, A. G., von Sandersleben, J.: Canine malignant mammary tumours. I. Sarcomas. Vet. Pathol. 8, 99–117 (1971)PubMedGoogle Scholar
  48. 48.
    Misdorp, W., Cotchin, E., Hampe, J. F., Jabara, A. G., von Sandersleben, J.: Canine malignant mammary tumours. II. Adenocarcinomas, solid carcinomas and spindle cell carcinomas. Vet. Pathol. 9, 447–470 (1972)Google Scholar
  49. 49.
    Misdorp, W., Cotchin, E., Hampe, J. F., Jabara, A. G., von Sandersleben, J.: Canine malignant mammary tumors. III. Special types of carcinomas, malignant mixed tumors. Vet. Pathol. 10, 241–256 (1973)PubMedCrossRefGoogle Scholar
  50. 50.
    Moore, D. H., Charney, J., Holben, J. A.: Titrations of various mouse mammary tumor viruses in different mouse strains. J. Natl. Cancer Inst. 52, 1757–1761 (1974)PubMedGoogle Scholar
  51. 51.
    Moore, D. H., Charney, J., Pullinger, B. D.: Mouse mammary tumor virus infectivity as a function of age at inoculation, breeding, and total lapsed time. J. Natl. Cancer Inst. 45, 561–565 (1970)PubMedGoogle Scholar
  52. 52.
    Moore, D. H., Holben, J. A., Charney, J.: Biologic characteristics of some mouse mammary tumor viruses. J. Natl. Cancer Inst. 57, 889–896 (1976)PubMedGoogle Scholar
  53. 53.
    Moulton, J. E.: Tumors in Domestic Animals. Berkeley: Univ. Calif. Press, 1961, pp. 179–189Google Scholar
  54. 54.
    Moulton, J. E., Taylor, D. O. N., Dorn, C. R., Andersen, A. C.: Canine mammary tumors. Pathol. Vet. 7, 289–320 (1970)PubMedCrossRefGoogle Scholar
  55. 55.
    Mulligan, R. M.: Neoplasms of the Dog. Baltimore: The Williams & Wilkins Company, 1949Google Scholar
  56. 56.
    Mulligan, R. M.: Comparative pathology of human and canine cancer. Ann. N.Y. Acad. Sci. 108, 642–690 (1963)PubMedCrossRefGoogle Scholar
  57. 57.
    Mulligan, R. M.: Mammary cancer in the dog: A study of 120 cases. Am. J. Vet. Res. 36, 1391–1396 (1975)PubMedGoogle Scholar
  58. 58.
    Nandi, S., McGrath, C. M.: Mammary neoplasia in mice. Adv. Cancer Res. 17, 353–414 (1973)CrossRefGoogle Scholar
  59. 59.
    Nelson, L. W., Shott, L. D.: Mammary nodular hyperplasia in intact rhesus monkeys. Vet. Pathol. 10, 130–134 (1973)PubMedCrossRefGoogle Scholar
  60. 60.
    Nelson, L. W., Carlton, W. W., Weikel, J. H., Jr.: Canine mammary neoplasms and progestogens. JAMA 219, 1601–1606 (1972)PubMedCrossRefGoogle Scholar
  61. 61.
    Nelson, L. W., Weikel, J. H., Jr., Reno, F. E.: Mammary nodules in dogs during four years treatment with megestrol acetate or Chlormadinone acetate. J. Natl. Cancer Inst. 51, 1303–1311 (1973)PubMedGoogle Scholar
  62. 62.
    Nielsen, S. W.: The malignancy of mammary tumors in cats. N. Am. Vet. April, 245–252 (1952)Google Scholar
  63. 63.
    Pulley, L.: Ultrastructural and histochemical demonstration of myoepithelium in mixed tumors of the canine mammary gland. Am. J. Vet. Res. 34, 1513–1522 (1973)PubMedGoogle Scholar
  64. 64.
    Riser, W. H.: Surgical removal of the mammary gland of the bitch. JAVMA 110, 86–90 (1947)PubMedGoogle Scholar
  65. 65.
    Schneider, R., Dorn, C. R., Taylor, D. O. N.: Factors influencing canine mammary cancer development and postsurgical survival. J. Natl. Cancer Inst. 43, 1249–1261 (1969)PubMedGoogle Scholar
  66. 66.
    Segaloff, A.: The role of the ovary in estrogen production of mammary cancer in the rat. Cancer Res. 34, 2708–2710 (1974)PubMedGoogle Scholar
  67. 67.
    Sher, S. P.: Mammary tumors in control rats: Literature tabulation. Toxicol. Appl. Pharmacol. 22, 562–588 (1972)Google Scholar
  68. 68.
    Stewart, H. L.: Comparative aspects of certain cancers. In: Cancer. Becker, F. F. (Ed.). New York: Plenum Publishing Corporation, 1976, Vol. IV, pp. 303–374Google Scholar
  69. 69.
    Uberreiter, O.: Neubildungen bei Tieren. Wien. Tieraerztl. Mschr. 47, 805–832 (1960)Google Scholar
  70. 70.
    Vallance, D. K., Capel-Edwards, K.: Chlormadinone and mammary nodules. Br. Med. J. 2, 221–222 (1971)PubMedCrossRefGoogle Scholar
  71. 71.
    van Ebbenhorst Tengbergen, W. J. P. R.: Morphological classification of mammary tumours in the mouse. Pathol. Eur. 5, 260–272 (1970)PubMedGoogle Scholar
  72. 72.
    van Nie, R., Dux, A.: Biological and morphological characteristics of mammary tumors in gr mice. J. Natl. Cancer Inst. 46, 885–897 (1971)PubMedGoogle Scholar
  73. 73.
    Warner, M. R.: Age incidence and site distribution of mammary dysplasias in young beagle bitches. J. Natl. Cancer Inst. 57, 57–61 (1976)PubMedGoogle Scholar
  74. 74.
    Wazeter, F. X., Geil, R. G., Berliner, V. R., Lamar, J. K.: Studies of tumorigenic and diabetogenic potential of certain oral contraceptive steroids in female dogs and monkeys. Toxicol. Appl. Pharmacol. 25, 498 (1973)Google Scholar
  75. 75.
    Weijer, K., Head, K. W., Misdorp, W., Hampe, J. F.: Feline malignant mammary tumors. I. Morphology and biology: Some comparisons with human and canine mammary carcinomas. J. Natl. Cancer Inst. 49, 1697–1704 (1972)PubMedGoogle Scholar
  76. 76.
    Welsch, C. W.: Interaction of estrogen and prolactin in spontaneous mammary tumorigenesis of the mouse. J. Toxicol. Environ. Health [Suppl.] 1, 161–175 (1976)Google Scholar
  77. 77.
    Young, S., Hallowes, R. C.: Tumours of the mammary gland. In: Pathology of Tumours in Laboratory Animals. Vol. I. Tumours of the Rat. Turusov, V. S. (Ed.). Int. Agency for Res. on Cancer, Lyons, France: IARC Scientific Publication, No. 5, 1973, pp. 31–55Google Scholar
  78. 78.
    Young, S., Cowan, D. M., Sutherland, L. E.: The histology of induced mammary tumours in rats. J. Pathol. Bacteriol. 85, 331–340 (1963)PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1979

Authors and Affiliations

  • H. W. Casey
  • R. C. Giles
  • R. P. Kwapien

There are no affiliations available

Personalised recommendations