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British Journal of Cancer logoLink to British Journal of Cancer
. 1992 Nov;66(5):951–957. doi: 10.1038/bjc.1992.391

Competing risks determining event-free survival in early breast cancer.

R Arriagada 1, L E Rutqvist 1, A Kramar 1, H Johansson 1
PMCID: PMC1977968  PMID: 1419642

Abstract

To evaluate the natural history of a disease and the effects of therapeutic interventions, it is important to determine which are the causes of treatment failure and to assess the extent to which each cause contributes to the total failure rate. The paper presents a new biostatistical technique to decompose the total event-free survival of a diseased population into cause-specific failure rates. The technique was based on a competing risk approach thereby avoiding biases related to assumptions of independence between different types of event. Such assumptions are inherent in the conventional Kaplan-Meier or actuarial methods. The competing risk method was used to analyse the pattern of failure among 2,850 pre- and postmenopausal patients with early-stage breast cancer and the results were compared to those obtained using conventional methods. The following events were analysed: loco-regional recurrence, distant metastasis, contralateral breast cancer, other new primary malignancies, and intercurrent deaths. The rate of new primary malignancies was found to be significantly higher in post- than in premenopausal patients (6% vs 3% at 10 years). In low-risk, node-negative postmenopausal patients the incidence of recurrences from breast cancer were found to be no greater than other types of events. This observation highlights the significance of the effect of different adjuvant therapies not only on the disease itself but also on the risk of second primary malignancies and other intercurrent diseases. In general, it was found that the conventional statistical methods tended to overestimate the event-specific rates. In conclusion, the method based on competing risks permits an unbiased analysis of all types of events determining the total event-free survival. It is thus useful for the description of the natural history of breast cancer as well as other diseases.

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Selected References

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  1. Arriagada R., Kramar A., Le Chevalier T., De Cremoux H. Competing events determining relapse-free survival in limited small-cell lung carcinoma. The French Cancer Centers' Lung Group. J Clin Oncol. 1992 Mar;10(3):447–451. doi: 10.1200/JCO.1992.10.3.447. [DOI] [PubMed] [Google Scholar]
  2. Arriagada R., Rutqvist L. E. Adjuvant chemotherapy in early breast cancer and incidence of new primary malignancies. Lancet. 1991 Aug 31;338(8766):535–538. doi: 10.1016/0140-6736(91)91100-9. [DOI] [PubMed] [Google Scholar]
  3. BORELL U., FERNSTROM I. Arteriovenous fistulae of the uterus and adnexa; an arteriographic study. Acta radiol. 1958 Jan;49(1):1–16. doi: 10.3109/00016925809170973. [DOI] [PubMed] [Google Scholar]
  4. Bagshawe K. D., Dent J., Webb J. Hydatidiform mole in England and Wales 1973-83. Lancet. 1986 Sep 20;2(8508):673–677. doi: 10.1016/s0140-6736(86)90179-0. [DOI] [PubMed] [Google Scholar]
  5. Bagshawe K. D. Risk and prognostic factors in trophoblastic neoplasia. Cancer. 1976 Sep;38(3):1373–1385. doi: 10.1002/1097-0142(197609)38:3<1373::aid-cncr2820380342>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  6. Bonadonna G., Brusamolino E., Valagussa P., Rossi A., Brugnatelli L., Brambilla C., De Lena M., Tancini G., Bajetta E., Musumeci R. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976 Feb 19;294(8):405–410. doi: 10.1056/NEJM197602192940801. [DOI] [PubMed] [Google Scholar]
  7. Brewis R. A., Bagshawe K. D. Pelvic arteriography in invasive trophoblastic neoplasia. Br J Radiol. 1968 Jul;41(487):481–495. doi: 10.1259/0007-1285-41-487-481. [DOI] [PubMed] [Google Scholar]
  8. Castiglione M., Gelber R. D., Goldhirsch A. Adjuvant systemic therapy for breast cancer in the elderly: competing causes of mortality. International Breast Cancer Study Group. J Clin Oncol. 1990 Mar;8(3):519–526. doi: 10.1200/JCO.1990.8.3.519. [DOI] [PubMed] [Google Scholar]
  9. Eckstein R. P., Paradinas F. J., Bagshawe K. D. Placental site trophoblastic tumour (trophoblastic pseudotumour): a study of four cases requiring hysterectomy including one fatal case. Histopathology. 1982 Mar;6(2):211–226. doi: 10.1111/j.1365-2559.1982.tb02716.x. [DOI] [PubMed] [Google Scholar]
  10. Elston C. W. The histopathology of trophoblastic tumours. J Clin Pathol Suppl (R Coll Pathol) 1976;10:111–131. [PMC free article] [PubMed] [Google Scholar]
  11. Fornander T., Rutqvist L. E., Cedermark B., Glas U., Mattsson A., Silfverswärd C., Skoog L., Somell A., Theve T., Wilking N. Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers. Lancet. 1989 Jan 21;1(8630):117–120. doi: 10.1016/s0140-6736(89)91141-0. [DOI] [PubMed] [Google Scholar]
  12. Gelman R., Gelber R., Henderson I. C., Coleman C. N., Harris J. R. Improved methodology for analyzing local and distant recurrence. J Clin Oncol. 1990 Mar;8(3):548–555. doi: 10.1200/JCO.1990.8.3.548. [DOI] [PubMed] [Google Scholar]
  13. Kardana A., Bagshawe K. D. A rapid, sensitive and specific radioimmunoassay for human chorionic gonadotrophin. J Immunol Methods. 1976;9(3-4):297–305. doi: 10.1016/0022-1759(76)90204-0. [DOI] [PubMed] [Google Scholar]
  14. Kramar A., Pejovic M. H., Chassagne D. A method of analysis taking into account competing events: application to the study of digestive complications following irradiation for cervical cancer. Stat Med. 1987 Oct-Nov;6(7):785–794. doi: 10.1002/sim.4780060709. [DOI] [PubMed] [Google Scholar]
  15. Leopold G. R. Diagnostic ultrasound in the detection of molar pregnancy. Radiology. 1971 Jan;98(1):171–176. doi: 10.1148/98.1.171. [DOI] [PubMed] [Google Scholar]
  16. Long M. G., Boultbee J. E., Begent R. H., Bagshawe K. D. Ultrasonic morphology of the uterus and ovaries after treatment of invasive mole and gestational choriocarcinoma. Br J Radiol. 1990 Dec;63(756):942–945. doi: 10.1259/0007-1285-63-756-942. [DOI] [PubMed] [Google Scholar]
  17. Long M. G., Boultbee J. E., Begent R. H., Hanson M. E., Bagshawe K. D. Preliminary Doppler studies on the uterine artery and myometrium in trophoblastic tumours requiring chemotherapy. Br J Obstet Gynaecol. 1990 Aug;97(8):686–689. doi: 10.1111/j.1471-0528.1990.tb16239.x. [DOI] [PubMed] [Google Scholar]
  18. Long M. G., Boultbee J. E., Hanson M. E., Begent R. H. Doppler time velocity waveform studies of the uterine artery and uterus. Br J Obstet Gynaecol. 1989 May;96(5):588–593. doi: 10.1111/j.1471-0528.1989.tb03261.x. [DOI] [PubMed] [Google Scholar]
  19. Newlands E. S., Bagshawe K. D., Begent R. H., Rustin G. J., Holden L., Dent J. Developments in chemotherapy for medium- and high-risk patients with gestational trophoblastic tumours (1979-1984). Br J Obstet Gynaecol. 1986 Jan;93(1):63–69. doi: 10.1111/j.1471-0528.1986.tb07815.x. [DOI] [PubMed] [Google Scholar]
  20. Pijnenborg R., Bland J. M., Robertson W. B., Brosens I. Uteroplacental arterial changes related to interstitial trophoblast migration in early human pregnancy. Placenta. 1983 Oct-Dec;4(4):397–413. doi: 10.1016/s0143-4004(83)80043-5. [DOI] [PubMed] [Google Scholar]
  21. Rutqvist L. E., Cedermark B., Glas U., Johansson H., Nordenskjöld B., Skoog L., Somell A., Theve T., Friberg S., Askergren J. The Stockholm trial on adjuvant tamoxifen in early breast cancer. Correlation between estrogen receptor level and treatment effect. Breast Cancer Res Treat. 1987 Dec;10(3):255–266. doi: 10.1007/BF01805762. [DOI] [PubMed] [Google Scholar]
  22. Rutqvist L. E., Cedermark B., Glas U., Johansson H., Rotstein S., Skoog L., Somell A., Theve T., Askergren J., Friberg S. Radiotherapy, chemotherapy, and tamoxifen as adjuncts to surgery in early breast cancer: a summary of three randomized trials. Int J Radiat Oncol Biol Phys. 1989 Mar;16(3):629–639. doi: 10.1016/0360-3016(89)90478-1. [DOI] [PubMed] [Google Scholar]
  23. Scully R. E., Young R. H. Trophoblastic pseudotumor: a reappraisal. Am J Surg Pathol. 1981 Jan;5(1):75–76. doi: 10.1097/00000478-198101000-00010. [DOI] [PubMed] [Google Scholar]
  24. Skidmore R., Woodcock J. P. Physiological interpretation of Doppler-shift waveforms--I. Theoretical considerations. Ultrasound Med Biol. 1980;6(1):7–10. doi: 10.1016/0301-5629(80)90057-5. [DOI] [PubMed] [Google Scholar]
  25. Woo J. S., Wong L. C., Ma H. K. Sonographic patterns of pelvic and hepatic lesions in persistent trophoblastic disease. J Ultrasound Med. 1985 Apr;4(4):189–198. doi: 10.7863/jum.1985.4.4.189. [DOI] [PubMed] [Google Scholar]

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