Abstract
Purpose. To gather information on the natural history of breast cancer from the time-distribution of deaths of patients undergoing mastectomy alone.
Patients and methods. A total of 1173 patients, who entered controlled clinical trials carried out at the Milan Cancer Institute and underwent radical or modified radical mastectomy without any adjuvant therapy for operable breast cancer, were examined. The risk of death at a given time after surgery was studied utilizing the death-specific hazard rate. The risk distribution was assessed relative to tumor size, axillary lymph node involvement, and menopausal status.
Results. The hazard rate for death presented an early peak at about the 3rd–4th year after surgery and a second late peak near the 8th year. The double-peaked pattern was almost completely generated by N+ patients, while N− patients did not show relevant structures. Pre-menopausal patients showed an initial mortality wave covering about 6 years, with maximum height at the 4th year, followed by a peak 8 years after surgery, while post-menopausal patients showed an early high mortality surge peaking at the 3rd year, followed by a modest increase at the 8th year. Detailed analysis revealed that post-menopausal patients with early mortality had significantly larger tumors and higher nodal involvement, while no special trait characterized the corresponding pre-menopausal patients. Moreover, patients of the late mortality peak were more likely to have suffered early local-regional or contra-lateral recurrence or to be pre-menopausal patients recurring anywhere at the second recurrence peak.
Conclusion. The double-peaked hazard curve confirmed the occurrence of discontinuous features in the natural history of breast cancer for patients undergoing mastectomy. Indeed, the mortality pattern maintained definite signs of the previous double-peaked structure of recurrences. However, death events did not parallel the corresponding recurrence events and, moreover, pre and post-menopausal patients revealed dissimilar survival after recurrence, at least for early deaths. These findings, showing disconnection of mortality pattern from recurrence pattern for subsets of patients, suggest that parameters other than those influencing the recurrence risk may determine the survival of recurred patients.
Similar content being viewed by others
References
Demicheli R, Abbatista A, Miceli R, Valagussa P, Bonadonna G: Time distribution of the recurrence risk for breast can-cer patients undergoing mastectomy: further support about the concept of tumor dormancy. Breast Cancer Res Treat 41: 177–185, 1996
Demicheli R, Miceli R, Brambilla C, Ferrari L, Moliterni A, Zambetti M, Valagussa P, Bonadonna G: Comparative analysis of breast cancer recurrence risk for patients receiving adjuvant Cyclophosphamide, Methotrexate, Fluorouracil (CMF). Data supporting the occurrence of 'cures'. Breast Cancer Res Treat 53: 209–215, 1999
Fortin A, Larochelle M, Laverdiere J, Lavertu S, Tremblay D: Local failure is responsible for the decrease in survival for pa-tients with breast cancer treated with conservative surgery and postoperative radiotherapy. J Clin Oncol 1: 101–109, 1999
Demicheli R, Retsky MW, Swartzendruber DE, Bonadonna G: Proposal for a new model of breast cancer metastatic development. Ann Oncol 8: 1075–1080, 1997
Retsky MW, Demicheli R, Swartzendruber DE, Bame PD, Wardwell RH, Bonadonna G, Speer JF, Valagussa P: Computer simulation of a breast cancer metastasis model. Breast Cancer Res Treat 45: 193–202, 1997
Karrison TG, Ferguson DJ, Meier P: Dormancy of mammary carcinoma after mastectomy. J Natl Cancer Inst 91: 80–85, 1999
Demicheli R, Miceli R, Valagussa P, Bonadonna G: Re: Dormancy of mammary carcinoma after mastectomy. J Natl Cancer Inst 92: 347–348, 2000
Statistical Sciences: S-PLUS Guide to Statistical and Mathematical Analysis. Version 3.3, StatSci a Division of MathSoft, Seattle, 1995
Ramlau-Hansen H: Smoothing counting process intensities by means of Kernel functions. Ann Stat 11: 453–466, 1983
Adami HO, Malker B, Holmberg L, Persson I, Stone B: The relation between survival and age at diagnosis in breast cancer. N Engl J Med 315: 559–563, 1986
Sant M, Gatta G, Micheli A, Verdecchia A, Capocaccia R, Crosignani P, Berrino F: Survival and age at diagnosis of breast cancer in a population-based cancer registry. Eur J Cancer 27: 981–984, 1991
Recht A, Hayes DG, Eberlein TJ, Sadowsky NL: Local-regional recurrence after mastectomy or breast conserving therapy. In: Harris JR, Lippman ME, Morrow M, Hellman S (eds), Diseases of the Breast. Lippincott-Raven Publishers, Philadelphia, 1996, pp. 649–667
Retsky M, Demicheli R, Hrushesky W: Premenopausal status accelerates relapse in node positive breast cancer: hypothesis links angiogenesis, screening controversy. Breast Cancer Res Treat 65: 217–224, 2001
Greenberg PAC, Hortobagyi GN, Smith TL, Ziegler LD, Frye DK, Buzdar AU: Long term follow-up of patients with complete remission following combination chemother-apy for metastatic breast cancer. J Clin Oncol 14: 2197–2205, 1996
Perez JE, Machiavelli M, Leone BA, Romero A, Rabinovich MG, Vallejo CT, Bianco A, Rodriguez R, Cuevas MA, Alvarez LA: Bone-only versus visceral-only metastatic pattern in breast cancer: analysis of 150 patients. Am J Clin Oncol 13: 294–298, 1990
Cocconi G: The natural history of operable breast cancer after primary treatment. Ann Oncol 6(suppl 2): S11–S21, 1995
Biganzoli E, Boracchi P, Daidone MG, Gion M, Marubini E: Flexible modelling in survival analysis. Structuring biological complexity from the information provided by tumor markers. Int J Biol Markers 13: 107–123, 1998
Sauerbrei W, Royston P, Bojar H, Schmoor C, Schumacher M and the German Breast Cancer Study Group (GBCSG): Modelling the effects of standard prognostic factors in node-positive breast cancer. Br J Cancer 79: 1752–1760, 1999
Hilsenbeck SG, Ravdin PM, de Moor CA, Chamness GC, Osborne CK, Clark GM: Time-dependence of hazard ratios for prognostic factors in primary breast cancer. Breast Cancer Res Treat 52: 227–237, 1998
Yoshimoto M, Sakamoto G, Ohashi Y: Time dependency of the influence of prognostic factors on relapse in breast cancer. Cancer 72: 2993–3001, 1993
Gilchrist KW, Gray R, Fowble B, Tormey DC, Taylor SG: Tumor necrosis is a prognostic predictor for early recurrence and death in lymph node positive breast cancer: a 10-year follow-up study of 728 Eastern Cooperative Oncology Group patients. J Clin Oncol 11: 1929–1935, 1993
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Demicheli, R., Valagussa, P. & Bonadonna, G. Double-Peaked Time Distribution of Mortality for Breast Cancer Patients Undergoing Mastectomy. Breast Cancer Res Treat 75, 127–134 (2002). https://doi.org/10.1023/A:1019659925311
Issue Date:
DOI: https://doi.org/10.1023/A:1019659925311