Chemotherapy for older women with node-positive breast cancer
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* David Ginsburg

In their recent guideline on adjuvant systemic therapy for node-positive breast cancer, Mark Levine and colleagues state that postmenopausal women with estrogen receptor (ER)-positive tumours gain additional benefit from taking chemotherapy in addition to tamoxifen.1 I have some concerns about this statement, based on my own analysis of the studies they cite in its support.

In the NSABP B-16 trial 20% of the patients had ER-negative tumours.2,3 The results may therefore have been influenced in favour of the combined therapy, because these patients would not be expected to derive any benefit from tamoxifen therapy alone.4,5 A preliminary report of another study showed overall benefit when chemotherapy was added to tamoxifen therapy, but only for ER-negative patients.6 The Ludwig study also combined patients with ER-positive and ER-negative status and thus had similar limitations.7 

About 33% of the patients in a study using epirubicin in the chemotherapy arm had ER-negative tumours.8 Surprisingly, there was no interaction between treatment effect and receptor status (or age). The authors suggested that for the chemotherapy arm to be effective, an anthracycline should be included. 

A review of randomized trials showed diminishing benefit with age when postmenopausal women with ER-positive tumours were treated with combination chemotherapy and tamoxifen.9 Very few patients over 70 years of age have been studied, and they seem to have been adversely affected by combined therapy.

The report by the International Breast Cancer Study Group appears to support the recommendations of Levine and colleagues, but there were small numbers of patients in the relevant study arms and the study included patients who received delayed chemotherapy.10

The Intergroup study appears to be the most significant to date that might justify a recommendation for chemo-endocrine therapy in postmenopausal patients with ER-positive tumours.11 Unfortunately the full report has not yet been published. It would be useful to know whether there were differential benefits in this study in women aged 50–59, 60–69 and more than 69 years, for making decisions concerning the adjuvant treatment of otherwise healthy people at risk of iatrogenic disease but also at varying risk of developing metastatic disease if not optimally treated.

I should appreciate the authors' views on the use of chemotherapy, particularly in older women with ER- positive tumours, in light of these comments. 

## References

1.  1. Levine M, for the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. Clinical practice guidelines for the care and treatment of breast cancer: adjuvant systemic therapy for node-positive breast cancer (summary of the 2001 update). CMAJ 2001;164(5):644-6.
    
    [FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czo5OiIxNjQvNS82NDQiO3M6NDoiYXRvbSI7czoyMjoiL2NtYWovMTY1LzUvNTI1LjMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

2.  2. Fisher B, Redmond C, Fisher E, Wolmark N. Systemic adjuvant therapy in treatment of primary operable breast cancer: National Surgical Adjuvant Breast and Bowel Project experience. J Natl Cancer Inst Monogr 1986;1:35-43.
    
    

3.  3. Fisher B, Redmond C, Legault-Poisson S, Dimitrov NV, Brown AM, Wickerham DL, et al. Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. J Clin Oncol 1990;8:1005-18.
    
    [Abstract](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjg6IjgvNi8xMDA1IjtzOjQ6ImF0b20iO3M6MjI6Ii9jbWFqLzE2NS81LzUyNS4zLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

4.  4. Huq AU, Huq MB. Hormonal versus chemohormonal adjuvant therapy in node-positive postmenopausal patients [letter]. J Clin Oncol 1990;8:1922.
    
    [FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6MzoiUERGIjtzOjExOiJqb3VybmFsQ29kZSI7czozOiJqY28iO3M6NToicmVzaWQiO3M6MTE6IjgvMTEvMTkyMi9hIjtzOjQ6ImF0b20iO3M6MjI6Ii9jbWFqLzE2NS81LzUyNS4zLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

5.  5. Fisher B, Redmond C, and Brown A. Hormonal versus chemohormonal adjuvant therapy in node-positive postmenopausal patients [letter]. J Clin Oncol 1990; 8:1925-6.
    
    

6.  6. Castiglione-Gertsch M, Price KN, Nasi ML. Is the addition of adjuvant chemotherapy always necessary in node negative (N–) postmenopausal patients who receive tamoxifen (TAM): first results of IBCSG Trial IX. Proc Am Clin Oncol 2000;19:73a. 
    
    

7.  7. Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metasatsis. Lancet 1990; 335:1099-100. 
    
    

8.  8. Wils JA, Bliss JM, Marty M, Coombes G, Fontaine C, Morvan F, et al. Epirubicin plus tamoxifen versus tamoxifen alone in node-positive postmenopausal patients with breast cancer: a randomized trial of the International Collaborative Cancer Group. J Clin Oncol 1999;17(7): 1988-98. 
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjk6IjE3LzcvMTk4OCI7czo0OiJhdG9tIjtzOjIyOiIvY21hai8xNjUvNS81MjUuMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

9.  9. Early Breast Cancer Trialists' Collaborative Group. Polychemotherapy for early breast cancer: an overview ot the randomized trials. Lancet 1998;352:930-42. 
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1016/S0140-6736(98)03301-7&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=9752815&link_type=MED&atom=%2Fcmaj%2F165%2F5%2F525.3.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000076002200008&link_type=ISI) 

10. 10. International Breast Cancer Study Group. Effectiveness of adjuvant chemotherapy in combination with tamoxifen for node-positive postmenopausal breast cancer patients. J Clin Oncol 1997;15:1385-94. 
    
    [Abstract](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjk6IjE1LzQvMTM4NSI7czo0OiJhdG9tIjtzOjIyOiIvY21hai8xNjUvNS81MjUuMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

11. 11. Albain K, Green K, Osborne C. Tamoxifen (T) versus cyclophosphamide, adriamycin and 5-FU plus either concurrent or sequential T in postmenopausal receptor (+) node (+) breast cancer: a Southwest Oncology Group Phase III Intergroup trial (SWOG- 8814, INT-0100) [abstract]. Proc Am Soc Oncol 1997;16:128a.