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Drug Treatment of Breast Cancer

  • Practical Therapeutics
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Summary

Breast cancer is the most common malignancy of women in the United States, affecting one out of every 13 women at some time in their lives. Although only 10% of patients have demonstrable distant metastases at the time of diagnosis, a majority will eventually die of disseminated disease.

Chemotherapy was formerly considered to be the treatment of last resort in patients with breast cancer, reserved for those who had failed surgery, radiotherapy and hormonal manipulation. However, combination chemotherapy has now been shown to be highly effective. The most active drug combinations produce objective tumour regression in about 60% of patients with advanced disease. Parallel to the development of effective chemotherapy, there has been a renewal of interest in hormonal therapy. The ability to predict whether or not a patient will respond to hormonal therapy has been improved significantly by the clinical application of the oestrogen receptor assay.

The selection of a specific treatment for the patients with advanced breast cancer must be individualised. It should take into account a number of prognostic variables, including: sites of metastatic involvement; total extent of disease; disease free interval; menopausal status; and the presence or absence of oestrogen receptor in tumour tissue. The final decision regarding treatment should then be based not only on the probability of response, but also on the anticipated degree of toxicity.

Current efforts to improve the management of advanced breast cancer include the development of more effective drug regimens and the combination of chemotherapy with hormonal manipulation. For instance, it would appear that in premenopausal patients, the combination of chemotherapy with oophorectomy may yield results that are superior to those achieved with either treatment alone.

The most promising development in the management of early breast cancer has been the use of chemotherapy as an adjuvant treatment in patients with operable disease.

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References

  • Ahmann, D.L.; O’Connell, M.J.; Hahn, R.G.; Bisel, H.F.; Lee, R.A. and Edmonson, J.H.: An evaluation of early or delayed adjuvant chemotherapy in premenopausal patients with advanced breast cancer undergoing oophorectomy. New England Journal of Medicine 297: 356–360 (1977).

    PubMed  CAS  Google Scholar 

  • Anderson, D.E.: Familial and genetic predisposition; in Stoll (Ed) Risk Factors in Breast Cancer, volume 2, p.3–24 (Heinemann, London 1975).

    Google Scholar 

  • Ansfield, F.J.; Davis, H.L. Jr.; Ramirez, G.; Davis, T.E.; Borden, E.G.; Johnson, R.O. and Bryan, G.T.: Further clinical studies with megesterol acetate in advanced breast cancer. Cancer 38: 53–55 (1976).

    PubMed  CAS  Google Scholar 

  • Ansfield, F.; Klotz, J.; Nealon, T.; Ramirez, G.; Minton, J.; Hill, G.; Wilson, W.; Davis, H. and Cornell, G.: A phase II study comparing the clinical utility of four regimens of 5-fluorouracil: A preliminary report. Cancer 39: 34–40 (1977).

    PubMed  CAS  Google Scholar 

  • Axtell, L.M. and Myers, M.H.: Recent trends in survival of cancer patient 1960–1971; in End Results in Cancer Report No. 4 (US Department of Health, Education and Welfare, Washington, DC 1975).

    Google Scholar 

  • Band, P.R.; Tormey, D.C. and Bauer, M.: Induction chemotherapy and maintenance chemo-hormonotherapy in metastatic breast cancer. Proceedings of the American Association for Cancer Research 18: 228 (1977).

    Google Scholar 

  • Bender, R.A.; Zwelling, L.A.; Doroshow, J.H.; Gershon, Y.L.; Hande, K.R.; Murinson, D.S.; Cohen, M.; Myers, C.E. and Chabner, B.A.: Antineoplastic drugs: Clinical pharmacology and therapeutic use. Drugs 16: 46–87 (1978).

    PubMed  CAS  Google Scholar 

  • Benjamin, R.S.; Riggs, C.E. Jr. and Bachur, N.R.: Plasma pharmacokinetics of adriamycin and its metabolites in humans with normal hepatic and renal function. Cancer Research 37: 1416–1420 (1977).

    PubMed  CAS  Google Scholar 

  • Benjamin, R.S.; Wiernik, P.H. and Bachur, N.R.: Adriamycin chemotherapy — efficacy, safety, and pharmacologic basis of an intermittent high-dose schedule. Cancer 33: 19–27 (1974).

    PubMed  CAS  Google Scholar 

  • Bennett, A.H.: Cyclophosphamide and hemorrhagic cystitis. Journal of Urology 111: 603–606 (1974).

    PubMed  CAS  Google Scholar 

  • Bonadonna, G.; Brusamolino, E.; Valagussa, P.; Rossi, A.; Brugnatelli, L.; Brambilla, C.; DeLena, M.; Tancini, G.; Bajetta, E.; Musumeci, R. and Veronesi, U.: Combination chemotherapy as an adjuvant treatment in operable breast cancer. New England Journal of Medicine 234: 405–410 (1976).

    Google Scholar 

  • Bonadonna, G.; Rossi, A.; Valgussa, P.; Banfi, A. and Veronesi, U.: The CMF program for operable breast cancer with positive axillary nodes: Updated analysis of the disease-free interval, site of relpase and drug tolerance. Cancer 39: 2904–2915 (1977).

    PubMed  CAS  Google Scholar 

  • Brambilla, C.; DeLena, M.; Rossi, A.; Valagussa, P. and Bonadonna, G.: Response and survival in advanced breast cancer after two non-cross-resistant combinations. British Medical Journal 1: 801–804 (1976).

    PubMed  CAS  Google Scholar 

  • Brambilla, C.; Valagussa, P. and Bonadonna, G.: Sequential combination chemotherapy in advanced breast cancer. Proceedings of the American Association for Cancer Research. 18: 77 (1977).

    Google Scholar 

  • Broder, L.E. and Tormey, D.C.: Combination chemotherapy of carcinoma of the breast Cancer Treatment Reviews 1: 183–203 (1974).

    Google Scholar 

  • Bruce, J.; Carter, D.C. and Fraser, J.: Patterns of recurrent disease in breast cancer. Lancet 1: 433–435 (1970).

    PubMed  CAS  Google Scholar 

  • Brunner, K.W.; Sonntag, R.W.; Alberto, P.; Senn, H.J.; Martz, G.; Obrecht, P. and Maurice, P.: Combined chemo- and hormonal therapy in advanced breast cancer. Cancer 39: 2923–2933 (1977).

    PubMed  CAS  Google Scholar 

  • Bull, J.M.; Tormey, D.C.; Carbone, P.P.; Falkson, G.; Blom, J.; Perlin, E.; Li, S.H. and Simon, R.: A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy. Cancer 41: 1649–1657 (1978).

    PubMed  CAS  Google Scholar 

  • Canellos, G.P.; Pocock, S.J.; Taylor, S.G. III; Sears, M.E.; Klaassen, D.J.; and Band, P. R.: Combination chemotherapy for metastatic breast carcinoma: Prospective comparison of multiple drug therapy with L-phenylanine mustard. Cancer 38: 1882–1886 (1976).

    PubMed  CAS  Google Scholar 

  • Carter, S.K.: The chemical therapy of breast cancer. Seminars in Oncology 1: 131–144 (1974).

    PubMed  CAS  Google Scholar 

  • Carter, S.K.: Integration of chemotherapy into combined modality treatment of solid tumors: VII. Adenocarcinoma of the breast Cancer Treatment Reviews 3: 141–174 (1976).

    CAS  Google Scholar 

  • Chabner, B.A. and Johns, D.G.: Folate antagonists; in Becker (Ed) Cancer, volume 5, pp.363–377 (Plenum Press, New York and London 1977).

    Google Scholar 

  • Chabner, B.A. Myers, C.E. and Oliverio, V.T.: Clinical pharmacology of anticancer drugs. Seminars in Oncology 4: 165–191 (1977).

    PubMed  CAS  Google Scholar 

  • Clarysse, A.M.; Cathey, W.J.; Cartwright, G.E. and Wintrobe, M.M.: Pulmonary disease complicating intermittent therapy with methotrexate. Journal of the American Medical Association for Cancer Research 10: 15 (1969).

    Google Scholar 

  • Creasy, W.A.: Plant alkaloids; in Becker (Ed) Cancer, volume 5, pp.379–425 (Plenum Press, New York and London 1977).

    Google Scholar 

  • Creasy, W.A.; McIntosh, L.S.; Breseia, T.; Odujinrin, O.; Aspenes, G.T. and Murray, E.: Clinical effects and pharmacokinetics of different dosage schedules of adriamycin. Cancer Research 36: 216–221 (1976).

    Google Scholar 

  • Cutler, S.J.: Classification of extent of disease in breast cancer. Seminars in Oncology 1: 91–96 (1974).

    PubMed  CAS  Google Scholar 

  • Cutler, S.J.; Myers, M.H. and Green, S.B.: Trends in survival rates of patients with cancer. New England Journal of Medicine 233: 122–124 (1975).

    Google Scholar 

  • Cutler, S.J.; Scotto, J.; DeVesa, S.S. and Connelly, R.R.: Third national cancer survey — An overview of available information. Journal of the National Cancer Institute 53: 1565–1575 (1974).

    PubMed  CAS  Google Scholar 

  • Cvitkovic, E.; Cheng, E.; Whitmore, W.F. and Golbey, R.B.: Germ cell chemotherapy update. Proceedings of the American Society of Clinical Oncology 18: 324 (1977).

    Google Scholar 

  • Dahl, M.G.C.; Gregory, M.M. and Scheuer, P.J.: Liver damage due to methotrexate in patients with psoriasis. British Journal of Medicine 1: 625–630 (1971).

    CAS  Google Scholar 

  • D’Angio, G.J.; Evans, A.E.; Breslow, N.; Beckwith, B.; Bishop, H.; Feigl, P.; Goodwin, W.; Leape, L.L.; Sinks, L.F.; Sutow, W,; Tefft, M. and Wolff, J.: The treatment of Wilms’ tumor: Results of the National Wilms’ Tumor Study. Cancer 38: 633–646 (1976).

    PubMed  Google Scholar 

  • Dao, T.L. and Nemoto, T.: The clinical significance of skin recurrence after radical mastectomy in women with cancer of the breast Surgery Gynecology and Obstetrics 117: 447–453 (1963).

    CAS  Google Scholar 

  • Davis, H.L. Jr.; Ramirez, G. Ellerby, R.A. and Ansfield, F.J.: Five-drug therapy in advanced breast cancer: Factors influencing toxicity and response. Cancer 34: 239–245 (1974).

    PubMed  Google Scholar 

  • Deemarsky, L.Y. and Chernomordikova, M.F.: Combination chemotherapy in the management of breast cancer metastases. Cancer 26: 771–779 (1970).

    PubMed  CAS  Google Scholar 

  • DeVita, V.T. Jr.; Serpick, A.A. and Carbone, P.P.: Combination chemotherapy in the treatment of advanced Hodgkin’s disease. Annals of Internal Medicine 73: 881–895 (1970).

    PubMed  Google Scholar 

  • DeVita, V.T. Jr.; Young, R.C. and Canellos, G.P.: Combination versus single agent chemotherapy: A review of the basis for selection of drug treatment of cancer. Cancer 35: 98–110 (1975).

    PubMed  Google Scholar 

  • Eagen, R.T.; Ahmann, D.L.; Edmonson, J.H.; Hahn, R.G. and Bisel, H.F.: Controlled evaluation of adriamycin (NSC 123127), vincristine (NSC 67574), and methotrexate (NSC 740) in patients with disseminated breast cancer. Cancer Chemotherapy Reports (Part 3) 6: 339–342 (1975).

    Google Scholar 

  • Eastern Cooperative Group in Solid Tumor Chemotherapy: Comparison of antimetabolites in the treatment of breast and colon cancer. Journal of the American Medical Association 200: 770–778 (1967).

    Google Scholar 

  • Eastern Cooperative Oncology Group: Results of analyses of combination chemotherapy trials Unpublished data (1977).

  • Einhorn, L.H. and Donohue, J.: Cis-diamminedichloroplatinum, vinblastine and bleomycin combination chemotherapy in disseminated testicular cancer. Annals of Internal Medicine 87: 293–298 (1977).

    PubMed  CAS  Google Scholar 

  • Ezdinli, E.Z. and Stutzman, L.: Chlorambucil therapy for lymphomas and chronic lymphocytic leukemia. Journal of the American Medical Assoction 191: 444–450 (1965).

    CAS  Google Scholar 

  • Fairley, K.F.; Barrie, J.U. and Johnson, W.: Sterility and testicular atrophy related to cyclophosphamide therapy. Lancet 1: 568–569 (1972).

    PubMed  CAS  Google Scholar 

  • Fisher, B.: The surgical dilemma in the primary therapy of invasive breast cancer: A critical reappraisal. Current Problems in Surgery October: 1–53 (1970).

    Google Scholar 

  • Fisher, B.; Carbone, P.; Economou, S.G.; Frelick, R.; Glass, A.; Lerner, H.; Redmond, C.; Zellen, M.; Band, P.; Katrych, D.; Wolmark, N. and Fisher, E.R.: L-phenylalanine mutard (L-PAM) in the management of primary breast cancer: A report of early findings. New England Journal of Medicine 292: 117–122 (1975).

    PubMed  CAS  Google Scholar 

  • Fisher, B.; Glass, A.; Redmond, C.; Fisher, E.R.; Barton, B.; Such, E.; Carbone, P.; Economou, S.; Foster, R.; Frelick, R.; Lerner, H.; Levitt, M.; Margolese, R.; MacFarlane, J.; Plotkin, D.; Shibata, H. and Volk, H.: L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: An update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer 39: 2883–2903 (1977).

    PubMed  CAS  Google Scholar 

  • Fisher, B.; Ravdin, R.G. and Ausman, R.K.: Surgical adjuvant chemotherapy of the breast Results of a decade of cooperative investigation. Annlas of Surgery 168: 337–356 (1968).

    CAS  Google Scholar 

  • Fisher, B.; Slack, N.; Katrych, D. and Wolmark, N.: Ten year follow-up results of patients with carcinoma of the breast in a cooperative clinical trial evaluating surgical adjuvant therapy. Surgery Gynecology and Obstetrics 140: 528–534 (1975).

    CAS  Google Scholar 

  • Fisher, E.R.: Pathology of breast cancer; in McGuire (Ed) Breast Cancer, volume 1, pp.43–123 (Plenum, New York and London, 1977).

    Google Scholar 

  • Fletcher, G.H.: Reflections on breast cancer. International Journal of Radiation Oncology Biology Physics 1: 769–779 (1976).

    CAS  Google Scholar 

  • Forrest, A.P.M.: Primary cancer of the breast — indications for therapy; in Atkins (Ed) The Treatment of Breast Cancer, pp.9–58 (University Park Press, Baltimore 1974).

    Google Scholar 

  • Frei, E.III; Freireich, E.J.; Gehan, E.; Pinkel, D.; Holland, J.F.; Selawry, O.; Haurani, F.; Spurr, C.L.; Hayes, D.M.; James, G.W.; Rothberg, H.; Sodee, D.B.; Rundles, R.W.; Schroeder, L.R.; Hoogstraten, B.; Wolman, I.J.; Traggis, D.G.; Cooper, T.; Gendel, B.R.; Ebaugh. F. and Taylor, R. (Acute Leukemia Cooperative Group B): Studies of sequential and combination antimetabolite therapy in acute leukemia — 6-mercaptopurine and methotrexate. Blood 18: 431–454 (1961).

    Google Scholar 

  • Gerber, N.L. and Steinberg, A.D.: Clinical use of immunosuppressive drugs: Part I. Drugs 11: 14–35 (1976).

    PubMed  CAS  Google Scholar 

  • Goldberg, I.H.; Beerman, T.A. and Poon, R.: Antibiotics: Nucleic acids as targets in chemotherapy; in Becker (Ed) Cancer, volume 5, pp.427–456 (Plenum Press, New York and London 1977).

  • Goldenberg, I.S.; Sedransk, N.; Volk, H.; Segaloff, A.; Kelley, R.M. and Haines, C.R.: Combined androgen and antimetabolite therapy of advanced female breast cancer. Cancer 36: 308–310 (1975).

    PubMed  CAS  Google Scholar 

  • Goldin, A.; Greenspan, E.M. and Schoenbach, E.B.: Studies on the mechanism of action of chemotherapeutic agents in cancer: VI. Synergistic (additive) action of drugs on a transplantable leukemia in mice. Cancer 5: 153–160 (1952).

    PubMed  CAS  Google Scholar 

  • Gordon, I. and McArthur, J.: Thiotepa and cyclophosphamide in the treatment of advanced mammary cancer. Scottish Medical Journal 10: 27–33 (1965).

    PubMed  CAS  Google Scholar 

  • Gottlieb, J.A.; Rivkin, S.E.; Spigel, S.C.; Hoogstraten, B.; O’Bryan, R.M.; Delaney, F.C. and Singhakowinta, A.: Superiority of adriamycin over oral nitrosoureas in patients with advanced breast carcinoma. Cancer 33: 519–526 (1974).

    PubMed  CAS  Google Scholar 

  • Greco, F.A.; Brereton, H.D.; Kent, H.; Zimbler, H.; Merrill, J. and Johnson, R.E.: Adriamycin and enhanced radiation reaction in normal esophagus and skin. Annals of Internal Medicine 85: 294–298 (1976).

    PubMed  CAS  Google Scholar 

  • Greenspan, E.: Combination cytotoxic chemotherapy in advanced disseminated breast cancer. Journal of the Mt. Sinai Hospital 33: 1–27 (1966).

    CAS  Google Scholar 

  • Greenspan, E.M.; Fieber, M.; Lesnick, G. and Edelman, S.: Response of advanced breast carcinoma to the combination of the antimetabolite, methotrexate, and the alkylating agent, thio-TEPA. Journal of the Mt. Sinai Hospoital 30: 246–267 (1963).

    CAS  Google Scholar 

  • Gutterman, J.U.; Cardenas, J.O.; Blumenschein, G.R.; Hortobagyi, G.; Burgess, M.A.; Livingston, R.B.; Mavligit, G.M.; Freireich, E.J.; Gottlieb, J.A. and Hersh, E.M.: Chemoimmunotherapy of advanced breast cancer: Prolongation of remission and survival with BCG. British Medical Journal 2: 1222–1225 (1976).

    PubMed  CAS  Google Scholar 

  • Hayward, J.L.; Rubens, R.D.; Carbone, P.P.; Heuson, J.C.; Kumaoka, S.; and Segaloff, A.: Assessment of response to therapy in advanced breast cancer. British Journal of Cancer 35: 292–298 (1977).

    PubMed  CAS  Google Scholar 

  • Heel, R.C.; Brogden, R.N.; Speight, T.M. and Avery, G.S.: Tamoxifen: A review of its pharmacological properties and therapeutic use in the treatment of breast cancer. Drugs 16: 1–24 (1978).

    PubMed  CAS  Google Scholar 

  • Heuson, J.C.: Current overview of EORTC clinical trials with tamoxifen. Cancer Treatment Reports 60: 1463–1466 (1976).

    PubMed  CAS  Google Scholar 

  • Hirayama, T. and Wynder, E.L.: A study of the epidemiology of cancer of the breast II. The influence of hysterectomy. Cancer 15: 28–41 (1962).

    Google Scholar 

  • Hoge, A.F.; Bottomry, R.H.; Shaw, M.T. and Assal, N.R.: Adrenalectomy and oophorectomy plus limited-term chemotherapy in the treatment of breast cancer. Cancer Treatment Reports 60: 857–865 (1976).

    PubMed  CAS  Google Scholar 

  • Hoogstraten, B.; George, S.L.; Samal, B.; Rivkin, S.E.; Costanzi, J.J.; Bonnet, J.D.; Thigpen, T. and Braine, H.: Combination chemotherapy and adriamycin in patients with advanced breast cancer: A Southwest Oncology Group study. Cancer 38: 13–20 (1976).

    PubMed  CAS  Google Scholar 

  • Hurley, J.D.; Ellison, E.H.; Riesch, J. and Schulte, W.: Chemotherapy of solid carcinoma: Indications, agents and results. Journal of the American Medical Association 174: 1696–1701 (1960).

    PubMed  CAS  Google Scholar 

  • Hutter, A.M.; Bauman, A.W. and Frank, I.N.: Cyclophosphamide and severe hemmorrhagic cystitis. New York State Journal of Medicine 69: 305–309 (1969).

    PubMed  Google Scholar 

  • Ingle, J.N.; Tormey, D.C.; Bull, J.M. and Simon, R.M.: Bone marrow involvement in breast cancer: Effect on response and tolerance to combination chemotherapy. Cancer 39: 104–111 (1977).

    PubMed  CAS  Google Scholar 

  • Jacobs, S.A.; Stoller, R.G.; Chabner, B.A. and Johns, D.G.: 7-Hydroxymethotrexate as a urinary metabolite in human subjects and rhesus monkeys receiving high-dose methotrexate. Journal of Clinical Investigation 57: 534–538 (1976).

    PubMed  CAS  Google Scholar 

  • Jaffe, N.; Traggis, D.; Cassady, J.R.; Filler, R.M.; Watts, H. and Frei, E. III: The role of high-dose methotrexate with citrovorum factor “rescue” in the treatment of osteogenic sarcoma. Radiation Oncology Biology Physics 2: 261–266 (1977).

    CAS  Google Scholar 

  • Johnson, W.W. and Meadows, D.C.: Urinary-bladder fibrosis and telangiectasia associated with long-term cyclophosphamide therapy. New England Journal of Medicine 284: 230–234 (1971).

    Google Scholar 

  • Jones, S.E.; Durie, B.G.M. and Salmon, S.E.: Combination chemotherapy with adriamycin and cyclophosphamide for advanced breast cancer. Cancer 36: 90–97 (1975).

    PubMed  CAS  Google Scholar 

  • Keiser, L.W. and Capizzi, R.L.: Principles of combination chemotherapy in Becker (Ed) Cancer,volume 5, pp.163–190 (Plenum Press, New York and London 1977).

    Google Scholar 

  • Kennedy, B.J.: Hormonal therapies in breast cancer. Seminars in Oncology 1: 119–130 (1974).

    PubMed  CAS  Google Scholar 

  • Kennedy, B.J.; and Kiang, D.T.: The effects of short-term cyclophosphamide on estrogen therapy in metastatic breast cancer. Medical and Pediatric Oncology 1: 265–270 (1975).

    PubMed  CAS  Google Scholar 

  • Koyama, H.; Wada, T.; Nishizawa, Y.; Iwanaga, T.; Aoki, Y.; Terasawa, T.; Kosaki, G.; Yamamoto, T. and Wada, A.: Cyclophosphamide-induced ovarian failure and its therapeutic significance in patients with breast cancer. Cancer 39: 1403–1409 (1977).

    PubMed  CAS  Google Scholar 

  • Lawley, P.D.: Effects of some chemical mutagens and carcinogens on nucleic acids. Progress in Nucleic Acid Research and Molecular Biology 5: 89–131 (1966).

    PubMed  CAS  Google Scholar 

  • Lawley, P.D. and Brookes, O.: Further studies on the alkylation of nucleic acids and their constituent nucleotides. Biochemical Journal 89: 127–138 (1963).

    PubMed  CAS  Google Scholar 

  • Legha, S.S.; Davis, H.L. Jr. and Muggia, F.M.: Hormonal therapy of breast cancer: New approaches and concepts. Annals of Internal Medicine 88: 69–77 (1978).

    PubMed  CAS  Google Scholar 

  • Lenaz, L. and Page, J.A.: Cardiotoxicity of adriamycin and related, anthracyclines. Cancer Treatment Reviews 3: 111420 (1976).

    Google Scholar 

  • Lewison, E.F.: Castration in the treatment of advanced breast cancer. Cancer 18: 1558–1562 (1965).

    PubMed  CAS  Google Scholar 

  • Li, M.C.; Whitmore, W.F. Jr.; Golbey, R. and Grabstald, H.: Effects of combined drug therapy on metastatic cancer of the testis. Journal of the American Medical Association 174: 1291–1299 (1960).

    PubMed  CAS  Google Scholar 

  • Lloyd, R.E.; Salmon, S.E.; Jones, S.E. and Jackson, R.A.: Randomized trial of low-dose adriamycin and cyclophosphamide ± calusterone for advanced breast cancer. Proceedings of the American Association for Cancer Research 17: 126 (1976).

    Google Scholar 

  • Ludlum, D.B.: Alkylating agents and the nitrosoureas; in Becker (Ed) Cancer, volume 5, pp.285–307 (Plenum Press, New York and London 1977).

    Google Scholar 

  • McGuire, W.L.; Carbone, P.P.; Sears, M.E. and Escher, G.C.: Estrogen receptors in human breast cancer: An overview; in McGuire, Carbone and Vollmer (Eds) Estrogen Receptors in Human Breast Cancer, pp.1–7 (Raven Press, New York1975).

    Google Scholar 

  • MacMahon, B.; Cole, P.; Lin, T.M.; Lowe, C.R.; Mirra, A.P.; Ravnihar, B.; Salber, E.J.; Valaoras, V.G. and Yuasa, S.: Age at first birth and breast cancer risk. Bulletin of the World Health Oraganization 43: 209–221 (1970).

    CAS  Google Scholar 

  • Maley, F.: Pyrimidine antagonists; in Becker (Ed) Cancer, volume 5, pp.327–361 (Plenum Press, New York and London 1977).

    Google Scholar 

  • Manalo, F.B.; Marks, A. and Davis, H.L. Jr.: Doxorubicin toxicity: Onycholysis, plantar callus formation, and epidermolysis. Journal of the American Medical Association 233: 56–57 (1975).

    PubMed  CAS  Google Scholar 

  • Minow, R.A.; Benjamin, R.S.; Lee, E.T. and Gottlieb, J.A.: Adriamycin cardiomyopathy — risk factors, Cancer 39: 1397–1402 (1977).

    PubMed  CAS  Google Scholar 

  • Moertel, C.G.: Therapy with fluorinated pyrimidines; in Moertel and Reitemeier (Eds) Advanced Gastrointestinal Cancer: Clinical Management and Chemotherapy, p.96 (Harper and Row, New York 1969).

    Google Scholar 

  • Moore, F.D.; Van Devanter, S.B.; Boyden, C.M.; Lokich, J. and Wilson, E.; Adrenalectomy with chemotherapy in the treatment of advanced breast cancer: Objective and subjective response rates; duration and quality of life. Surgery 76: 376–388 (1974).

    PubMed  CAS  Google Scholar 

  • Moore, G.; Bross, I.D.J.; Ausman, R.; Nadler, S.; Jones, R. Jr.; Slack, N. and Rimm, A.A.: Effects of chlorambucil (NSC 3088) in 374 patients with advanced cancer. Cancer Chemotherapy Reports 52: 661–666 (1968).

    CAS  Google Scholar 

  • Nemoto, T.; Horton, J.; Cunningham, T.; Sponzo, R.; Rosner, D.; Diaz, R. and Dao, T.L.: Update report: A comparison of combination chemotherapy (FCP) vs. Adriamycin (ADM) vs. adrenalectomy (ADX) in breast cancer Proceedings of the American Association for Cancer Research 16: 46 (1975).

    Google Scholar 

  • Olson, C.E.; Ansfield, F.J.; Richards, M.J.S.; Ramirez, G. and Davis, H.L.: Review of local soft tissue recurrence of breast cancer irradiated with and without actinomycin-D. Cancer 39: 1981–1983 (1977).

    PubMed  CAS  Google Scholar 

  • Papaioannou, A.N.: Etiologic factors in cancer of the breast in humans. Surgery Gynecology and Obstetrics 138: 257–287 (1974).

    CAS  Google Scholar 

  • Pomeroy, T.C. and Johnson, R.E.: Combined modality therapy of Ewing’s sarcoma. Cancer 35: 36–47 (1975).

    PubMed  CAS  Google Scholar 

  • Ramirez G.; Klotz, J.; Strawitz, J.G.; Wilson, W.L.; Cornell, G.N.; Madden, R.E.; Minton, J.P. and the Central Oncology Group: Combination chemotherapy in breast cancer: A randomized study of 4 versus 5 drugs. Oncology 32: 101–108 (1975).

    PubMed  CAS  Google Scholar 

  • Ravitch, M.M.: Carcinoma of the breast: The place for the Halsted radical mastectomy. Johns Hopkins Medical Journal 129: 202–211 (1971).

    PubMed  CAS  Google Scholar 

  • Reilly, J.J.; Neufield, J.P. and Rosenberg, S.A.: Clinical course and management of accidental adriamycin extravasation. Cancer 40: 2053–2056 (1977).

    PubMed  CAS  Google Scholar 

  • Romsdahl, M.M.; Sears, M.E. and Eckles, N.E.: Post treatment evaluation of breast cancer; in M.D. Anderson Hospital (Ed) Breast Cancer: Early and Late, p.291–299 (Year Book, Chicago 1970).

    Google Scholar 

  • Rose, D.P. and Davis, T.E.: Ovarian function in patients receiving adjuvant chemotherapy for breast cancer. Lancet 1: 1174–1176 (1977).

    PubMed  CAS  Google Scholar 

  • Rosen, G.; Wollner, N.; Tan, C.; Wu, J.; Hajdu, S.I.; Cham, W.; D’Angio, G.J. and Murphy, M.L.: Disease-free survival in children with Ewing’s sarcoma treated with radiation therapy and adjuvant four-drug sequential chemotherapy. Cancer 33: 384–393 (1974).

    PubMed  CAS  Google Scholar 

  • Sadee, W. and Wong, C.G.: Pharmacokinetics of 5-fiuorouracil: Inter-relationship with biochemical kinetics in monitoring therapy. Clinical Pharmacokinetics 2: 437–450 (1978).

    Google Scholar 

  • Schabel, F.M. Jr.: Concepts for systemic treatment of micrometastases. Cancer 35: 15–24 (1975).

    PubMed  CAS  Google Scholar 

  • Shapiro, S.; Strax, P.; Venet, L. and Fink, R.: The search for risk factors in breast cancer. American Journal of Public Health 58: 820–835 (1968).

    PubMed  CAS  Google Scholar 

  • Shen, D.D. and Azarnoff, D.L.: Clinical Pharmacokinetics of methotrexate. Clinical Pharmacokinetics 3: 1–13 (1978).

    PubMed  CAS  Google Scholar 

  • Sherins, R.J. and De Vita, V.T. Jr.: Effect of drug treatment for lymphoma on male reproductive capacity: Studies on men in remission after therapy. Annals of Internal Medicine 79: 216–220 (1973).

    PubMed  CAS  Google Scholar 

  • Silverberg, E.: Cancer statistics, 1977. Ca-A Journal For Clinicians 27: 26–41 (1977).

    CAS  Google Scholar 

  • Simone, J.V.; Aur, R.J.A.; Hustu, H.O.; Verzosa, M. and Pinkel, D.: Combined modality therapy of actue lymphocytic leukemia. Cancer: 35: 25–53 (1975).

    PubMed  CAS  Google Scholar 

  • Skipper, H.E.: Cellular kinetics associated with “curability” of experimental leukemias; in Dameshek and Dutcher (Eds) Perspectives in Leukemia, pp.187–216 (Grune and Stratton, New York and London 1968).

    Google Scholar 

  • Skipper, H.E.; Chapman, J.B. and Bell, M.: The antileukemia action of combinations of certain known antileukemic agents. Cancer Research 11: 103–112 (1951).

    Google Scholar 

  • Smalley, R.V.; Carpenter, J.; Bartolucci, A.; Vogel, C. and Krauss, S.: A comparison of cyclophosphamide, adriamycin, 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone (CMFVP) in patients with metastatic breast cancer: A Southeastern Cancer Study Group project. Cancer 40: 625–632 (1977).

    PubMed  CAS  Google Scholar 

  • Steinberg, A.D.; Plotz, P.H.; Wolff, S.M.; Wong, V.G.; Agus, S.G. and Decker, J.L.: Cytotoxic drugs in treatment of non-malignant diseases. Annals of Internal Medicine 76: 619–642 (1972).

    Google Scholar 

  • Stoller, R.G.; Hande, K.R.; Jacobs, S.A.; Rosenberg, S.A. and Chabner, B.A.: Use of plasma pharmacokinetics to predict and prevent methotrexate toxicity. New England Journal of Medicine 297: 630–634 (1977).

    PubMed  CAS  Google Scholar 

  • Stott, P.B.; Zelkowitz, L. and Tucker, W.G.: Combination chemo-hormonal therapy for disseminated breast carcinoma. Cancer Chemotherapy Reports 57: 106: (1973).

    Google Scholar 

  • Takanashi, S. and Bachur, N.P.: Adriamycin metabolism in man. Drug Metabolism and Disposition 4: 79–87 (1976).

    PubMed  CAS  Google Scholar 

  • Talley, R.W.; Vaitkevicius, V.K. and Leighton, G.A.: Comparison of cyclophosphamide and 5-fluorouracil in the treatment of patients with metastatic breast cancer, Clinical Pharmacology and Therapeutics 6: 740–748 (1965).

    PubMed  CAS  Google Scholar 

  • Taylor, S.G. III; Pocock, S.J.; Shnider, B.I.; Colsky, J. and Hall, T.C.: Clinical Studies of 5-fluorouracil + premarin in the treatment of breast cancer. Medical and Pediatric Oncology 1: 113–121 (1975).

    PubMed  Google Scholar 

  • Tormey, D.C.: Combined chemotherapy and surgery in breast cancer: A review. Cancer 36: 881–892 (1975a).

    PubMed  CAS  Google Scholar 

  • Tormey, D.C.: Adriamycin in breast cancer: An overview of studies. Cancer Chemotherapy Reports (Part 3) 6: 319–327 (1975b).

    Google Scholar 

  • Tormey, D.C.; Falkson, H.; Falkson, G. and Davis, T.E.: Evaluation of chemotherapy ± tamoxifen in breast cancer. Proceedings of the American Association for Cancer Research 19: 34 (1978).

    Google Scholar 

  • Tormey, D.C. and Neifeld, J.P.: Chemotherapeutic approaches to disseminated disease-, in Stoll (Ed) Breast Cancer Management — Early and Late, pp.117–131 (London 1977).

    Google Scholar 

  • Tormey, D.C.; Simon, R.; Falkson, G.; Bull, J.; Band, P.; Perlin, E. and Blom, J.: Evaluation of adriamycin and dibromodulcitol in metastatic breast carcinoma. Cancer Research 37: 529–534 (1977).

    PubMed  CAS  Google Scholar 

  • Trichopoulos, D.; MacMahon, B. and Cole, P.: Menopause and breast cancer risk. Journal of the National Cancer Institute 48: 605–613 (1972).

    PubMed  CAS  Google Scholar 

  • Uldall, P.R.; Kerr, D.N.S. and Tacchi, D.: Sterility and cyclphosphamide. Lancet 1: 693–694 (1972).

    PubMed  CAS  Google Scholar 

  • Urban, J.A. and Marjani, M.A.: Significance of internal mammary lymph node metastases in breast cancer. American Journal of Roentgenology 111: 130–136 (1971).

    CAS  Google Scholar 

  • van Dyk, J.J. and Falkson, G.: Extended survival and remission rates in metastatic breast cancer. Cancer 27: 300–303 (1971).

    PubMed  Google Scholar 

  • Van Theil, D.H.; Sherins, R.J.; Myers, G.H. Jr. and DeVita, V.T. Jr.: Evidence for a specific seminiferous tubular factor affecting follicle-stimulating hormone secretion in man. Journal of Clinical Investigation 51: 1009–1019 (1972).

    Google Scholar 

  • Warne, G.L.; Fairley, K.F.; Hobbs, J.B. and Martin, F.I.R.: Cyclophosphamide-induced ovarian failure. New England Journal of Medicine 289: 1159–1172 (1973).

    PubMed  CAS  Google Scholar 

  • Wasserman, T.H.; Slavik, M. and Carter, S.K.: Review of CCNU in clinical cancer therapy. Cancer Treatment Reviews 1: 131–151 (1974).

    Google Scholar 

  • Weiss, H.D.; Walker, M.D. and Wiernik, P.H.: Neurotoxicity of commonly used antineoplastic agents (second of two parts). New England Journal of Medicine 291: 127–133 (1974).

    PubMed  CAS  Google Scholar 

  • Wilcox, W.S.: The last surviving cancer cell: The chances of killing it. Cancer Chemotherapy Reports 50: 541–542 (1966).

    CAS  Google Scholar 

  • Wood, S. Jr.: Pathogenesis of metastasis formation observed in vivo in the rabbit ear chamber. AMA Archives of Pathology 66: 550–568 (1958).

    PubMed  Google Scholar 

  • Zubrod, C.G.; Schneiderman, M., Frei, E. III; Brindley, C.; Gold, G.L.; Shnider, B.; Oviedo, R.; Gorman, J.; Jones, R. Jr.; Jonsson, U.; Colsky, J.; Chalmers, T.; Ferguson, B.; Dederick, M.; Holland, J.; Selawry, O.; Regelson, W.; Lasagna, L. and Owens, A.H. Jr.: Appraisal of methods for the study of chemotherapy of cancer in man: Comparative therapeutic trial of nitrogen mustard and triethylene thiophospharmide. Journal of Chronic Diseases 11: 7–53 (1976).

    Google Scholar 

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Davis, T.E., Carbone, P.P. Drug Treatment of Breast Cancer. Drugs 16, 441–464 (1978). https://doi.org/10.2165/00003495-197816050-00004

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