Annual Hazard Rates of Recurrence for Breast Cancer During 24 Years of Follow-Up: Results From the International Breast Cancer Study Group Trials I to V.

PURPOSE Predicting the pattern of recurrence can aid in the development of targeted surveillance and treatment strategies. We identified patient populations that remain at risk for an event at a median follow-up of 24 years from the diagnosis of operable breast cancer. PATIENTS AND METHODS International Breast Cancer Study Group clinical trials I to V randomly assigned 4,105 patients between 1978 and 1985. Annualized hazards were estimated for breast cancer-free interval (primary end point), disease-free survival, and overall survival. RESULTS For the entire group, the annualized hazard of recurrence was highest during the first 5 years (10.4%), with a peak between years 1 and 2 (15.2%). During the first 5 years, patients with estrogen receptor (ER)--positive disease had a lower annualized hazard compared with those with ER-negative disease (9.9% v 11.5%; P = .01). However, beyond 5 years, patients with ER-positive disease had higher hazards (5 to 10 years: 5.4% v 3.3%; 10 to 15 years: 2.9% v 1.3%; 15 to 20 years: 2.8% v 1.2%; and 20 to 25 years: 1.3% v 1.4%; P < .001). Among patients with ER-positive disease, annualized hazards of recurrence remained elevated and fairly stable beyond 10 years, even for those with no axillary involvement (2.0%, 2.1%, and 1.1% for years 10 to 15, 15 to 20, and 20 to 25, respectively) and for those with one to three positive nodes (3.0%, 3.5%, and 1.5%, respectively). CONCLUSION Patients with ER-positive breast cancer maintain a significant recurrence rate during extended follow up. Strategies for follow up and treatments to prevent recurrences may be most efficiently applied and studied in patients with ER-positive disease followed for a long period of time.

[1]  K. Gelmon,et al.  Comparison of breast cancer recurrence and outcome patterns between patients treated from 1986 to 1992 and from 2004 to 2008. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  R. Peto,et al.  Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials , 2014, The Lancet.

[3]  EBCTCG (Early Breast Cancer Trialists' Collaborati Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials , 2014, The Lancet.

[4]  R. Greil,et al.  Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone. , 2014, Annals of oncology : official journal of the European Society for Medical Oncology.

[5]  B. Haffty Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials: EBCTCG (Early Breast Cancer Trialists' Collaborative Group) () Lancet 383:2127-2135, 2014§ , 2014 .

[6]  R. Schiff,et al.  Metastasis Dormancy in Estrogen Receptor–Positive Breast Cancer , 2013, Clinical Cancer Research.

[7]  Jack Cuzick,et al.  Factors Predicting Late Recurrence for Estrogen Receptor–Positive Breast Cancer , 2013, Journal of the National Cancer Institute.

[8]  R. Gelber,et al.  Patterns of Recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from international breast cancer study group trials VIII and IX. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  C. Perou,et al.  Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013 , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[10]  I. Henderson,et al.  Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100 000 women in 123 randomised trials: Early Breast Cancer Trialists' Collaborative Group (EBCTCG) (Clinical Trial Service Unit (CTSU), Oxford, UK) Lancet 379:432-444, 2012§ , 2013 .

[11]  E. Winer,et al.  The natural history of hormone receptor-positive breast cancer. , 2012, Oncology.

[12]  Ryung S. Kim,et al.  Dormancy Signatures and Metastasis in Estrogen Receptor Positive and Negative Breast Cancer , 2012, PloS one.

[13]  R. Peto,et al.  Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. , 2012, Lancet.

[14]  R Peto,et al.  Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials , 2011, The Lancet.

[15]  Early Breast Cancer Trialists' Collaborative Group Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials , 2011, The Lancet.

[16]  Jong-Hyeon Jeong,et al.  Breast cancer adjuvant therapy: time to consider its time-dependent effects. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  M. Coleman,et al.  'Cure' from breast cancer among two populations of women followed for 23 years after diagnosis. , 2009, Annals of oncology : official journal of the European Society for Medical Oncology.

[18]  A. Melville,et al.  Guidance on cancer services : improving outcomes in breast cancer - manual update. , 2009 .

[19]  R. Gelber,et al.  Patterns of recurrence of early breast cancer according to estrogen receptor status: a therapeutic target for a quarter of a century , 2009, Breast Cancer Research and Treatment.

[20]  J. Dixon,et al.  Extended follow-up of breast cancer patients in clinic wastes time for both patients and doctors: the case for , 2008, Breast Cancer Research.

[21]  R. Demicheli,et al.  Dormancy and surgery‐driven escape from dormancy help explain some clinical features of breast cancer   , 2008, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[22]  B. Quesnel Tumor dormancy and immunoescape   , 2008, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[23]  R. Vessella,et al.  Cancer micrometastasis and tumour dormancy   , 2008, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[24]  Thomas J. Smith,et al.  American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  Y Wang,et al.  Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials , 2005, The Lancet.

[26]  G. Bonadonna,et al.  30 years' follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study , 2005, BMJ : British Medical Journal.

[27]  S. Koscielny,et al.  Natural history of human breast cancer: Recent data and clinical implications , 1991, Breast Cancer Research and Treatment.

[28]  Hermann Brenner,et al.  Are patients diagnosed with breast cancer before age 50 years ever cured? , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  S. Green Do estimates of long-term survival tell us whether patients diagnosed with breast cancer before age 50 years are ever cured? , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  A parametric model for long‐term follow‐up data from phase III breast cancer clinical trials , 2003, Statistics in medicine.

[31]  Robert Gray,et al.  A Proportional Hazards Model for the Subdistribution of a Competing Risk , 1999 .

[32]  R. Gray,et al.  Annual hazard rates of recurrence for breast cancer after primary therapy. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[33]  J. Forbes,et al.  The International (Ludwig) Breast Cancer Study Group Trials I-IV: 15 years follow-up. , 1994, Annals of oncology : official journal of the European Society for Medical Oncology.

[34]  G Marini,et al.  Effect of systemic adjuvant treatment on first sites of breast cancer relapse , 1994, The Lancet.

[35]  M. Zelen,et al.  Prolonged disease-free survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer. , 1989, The New England journal of medicine.

[36]  R. Gray A Class of $K$-Sample Tests for Comparing the Cumulative Incidence of a Competing Risk , 1988 .

[37]  V. Jordan,et al.  Reliability of steroid hormone receptor assays: an international study. , 1983, European journal of cancer & clinical oncology.

[38]  J. Meakin,et al.  Ovarian irradiation and prednisone following surgery and radiotherapy for carcinoma of the breast. , 1979, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.