Hazard of recurrence and adjuvant treatment effects over time in lymph node-negative breast cancer

Department of Health Studies, The University of Chicago, Chicago, IL 60637, USA.
Breast Cancer Research and Treatment (Impact Factor: 3.94). 11/2008; 116(3):595-602. DOI: 10.1007/s10549-008-0200-5
Source: PubMed


For patients with axillary lymph node-negative breast cancer, benefits from adjuvant therapy are smaller than in node-positive disease and thus more selective use is warranted, prompting development of risk profiling to identify those most likely to benefit. Examination of the magnitude and changes in the hazard of failure over time in node-negative breast cancer may also be informative in this regard.
Among 9,444 participants from five randomized trials (accrual 1982-1998) investigating chemotherapy and tamoxifen for node-negative breast cancer, we estimated recurrence hazards over time by tumor estrogen receptor (ER) status and adjuvant treatment.
In patients treated by surgery only, we observed the previously noted larger hazard peak followed by a rapid decrease in ER-negative patients and smaller but more persistent hazard in ER-positive patients. After approximately 48 months, the ER-positive hazard is greater. For adjuvant treatment, while tamoxifen decreases the early hazard in ER-positive patients to that of the chemotherapy-treated ER-negative group, in later follow-up (beyond 5 years) the hazard for ER-positive patients again exceeds that of ER-negative patients. Adding chemotherapy to tamoxifen in ER-positive patients results in large early hazard reduction, but in later follow-up the hazard converges with those of patients treated by surgery only or tamoxifen.
Recurrence hazards over time reveal changes in risk that may have biologic and therapeutic strategy relevance. In ER-negative tumors, a large early chemotherapy benefit is followed by a consistently low recurrence hazard over time. In ER-positive patients, the chemotherapy benefit appears concentrated mostly in earlier follow-up, and a greater recurrence risk remains.

Download full-text


Available from: Stewart J Anderson, Mar 20, 2014

Click to see the full-text of:

Article: Hazard of recurrence and adjuvant treatment effects over time in lymph node-negative breast cancer

791.26 KB

See full-text
  • Source
    • "This could explain why it is not significant for the complete follow-up period. The time-varying effect of the variable HR+ has also been pointed out in Dignam et al. (2009) and Hilsenbeck et al. (1998). This PHs assumption is satisfied when we divided the follow-up period into two periods: 0–5 years and 5–20 years. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Individuals may experience more than one type of recurrent event and a terminal event during the life course of a disease. Follow-up may be interrupted for several reasons, including the end of a study, or patients lost to follow-up, which are noninformative censoring events. Death could also stop the follow-up, hence, it is considered as a dependent terminal event. We propose a multivariate frailty model that jointly analyzes two types of recurrent events with a dependent terminal event. Two estimation methods are proposed: a semiparametrical approach using penalized likelihood estimation where baseline hazard functions are approximated by M-splines, and another one with piecewise constant baseline hazard functions. Finally, we derived martingale residuals to check the goodness-of-fit. We illustrate our proposals with a real dataset on breast cancer. The main objective was to model the dependency between the two types of recurrent events (locoregional and metastatic) and the terminal event (death) after a breast cancer.
    Biometrical Journal 11/2013; 55(6). DOI:10.1002/bimj.201200196 · 0.95 Impact Factor
  • Source
    • "Az emlőrák prognózisát és gyógyszeres kezelésének stratégiáját alapvetően a daganat biológiai tulajdonságai és kiterjedtsége határozzák meg [3] [4] [5] [6] [7] [8]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Healthy lifestyle, population-based screening mammography and modern medical-oncological treatment in specialized breast cancer centers are the basic elements of the fight against breast cancer mortality. Treatment plan for the individual patient should be recommended by multidisciplinary oncoteam before initiating definitive therapy. Strategy of the medical-oncological therapy of breast cancer is determined by the biological features and stage of the tumor. The most important biological features are endocrine sensitivity, Human Epidermal Growth Factor Receptor 2 status and proliferative capability of the tumor. In this review the strategy of medical-oncological treatment (chemotherapy, endocrine therapy, targeted biological therapy) of breast cancer is presented, based on receptor status and proliferative capability of the tumor in various stages of the disease.
    Orvosi Hetilap 01/2012; 153(2):56-65. DOI:10.1556/OH.2012.29257
  • Source
    • "The second later recurrence peak is, oppositely, higher for ERP and lower for ERN tumours. Thus the two hazard curves intersect at the third year, as observed by others [2,3]. Contrary to recurrence dynamics, however, the hazard rate pattern for mortality displays simpler dynamics, as death for ERP tumours is delayed compared to ERN tumours. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The study was designed to determine how tumour hormone receptor status affects the subsequent pattern over time (dynamics) of breast cancer recurrence and death following conservative primary breast cancer resection. Time span from primary resection until both first recurrence and death were considered among 2825 patients undergoing conservative surgery with or without breast radiotherapy. The hazard rates for ipsilateral breast tumour recurrence (IBTR), distant metastasis (DM) and mortality throughout 10 years of follow-up were assessed. DM dynamics displays the same bimodal pattern (first early peak at about 24 months, second late peak at the sixth-seventh year) for both estrogen receptor (ER) positive (P) and negative (N) tumours and for all local treatments and metastatic sites. The hazard rates for IBTR maintain the bimodal pattern for ERP and ERN tumours; however, each IBTR recurrence peak for ERP tumours is delayed in comparison to the corresponding timing of recurrence peaks for ERN tumours. Mortality dynamics is markedly different for ERP and ERN tumours with more early deaths among patients with ERN than among patients with ERP primary tumours. DM dynamics is not influenced by the extent of conservative primary tumour resection and is similar for both ER phenotypes across different metastatic sites, suggesting similar mechanisms for tumour development at distant sites despite apparently different microenvironments. The IBTR risk peak delay observed in ERP tumours is an exception to the common recurrence risk rhythm. This suggests that the microenvironment within the residual breast tissue may enforce more stringent constraints upon ERP breast tumour cell growth than other tissues, prolonging the latency of IBTR. This local environment is, however, apparently less constraining to ERN cells, as IBTR dynamics is similar to the corresponding recurrence dynamics among other distant tissues.
    BMC Cancer 11/2010; 10(1):656. DOI:10.1186/1471-2407-10-656 · 3.36 Impact Factor
Show more