Treatment of locally advanced breast cancer
===========================================

* Deepu Mirchandani
* Kamal Haider
* Haji Chalchal

*   © 2004 Canadian Medical Association or its licensors

We would like to raise another issue related to adjuvant chemotherapy for the treatment of women with locally advanced breast cancer.1 For adjuvant therapy of patients with node-positive, operable breast cancer, cross-trial comparison over similar follow-up periods has indicated a greater risk of acute leukemia with more anthracyclines and alkylators. Specifically, among patients treated with 4 cycles of adriamycin and cyclophosphamide (AC) followed by 4 cycles of paclitaxel, the incidence of acute leukemia ranged from 0.25% over a 69-month follow-up period2 to 0.18% over a 36-month follow-up period.3 For regimes of 6 cycles of anthracyclines and alkylating agents, the risk of acute leukemia was much greater: 1.42% over 59 months with cyclophosphamide, epirubicin and fluorouracil (CEF)4 and 1.17% over 48 months with epirubicin and cyclophosphamide.5 Even as therapy with AC followed by paclitaxel is being compared with a CEF regimen in the randomized phase III MA.21 trial (being conducted by the Clinical Trials Group of the National Cancer Institute of Canada), this side effect profile should not be ignored in discussions of adjuvant chemotherapy. 

Given these data, the use of taxanes should be covered in clinical guideline development. 

**Deepu Mirchandani** **Kamal Haider** **Haji Chalchal** Saskatoon Cancer Center Allan Blair Cancer Center Saskatoon, Sask.

## Footnotes

*   *Competing interests:* None declared.

## References

1.  1. Shenkier T, Weir L, Levine M, Olivetto I, Whelan T, Reyno L; 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: 15. Treatment for women with stage III or locally advanced breast cancer. CMAJ 2004; 170 (6):983-94. 
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czo5OiIxNzAvNi85ODMiO3M6NDoiYXRvbSI7czoyMjoiL2NtYWovMTcxLzMvMjE5LjIuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

2.  2. Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, et al. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol 2003;21(6):976-83.
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjg6IjIxLzYvOTc2IjtzOjQ6ImF0b20iO3M6MjI6Ii9jbWFqLzE3MS8zLzIxOS4yLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

3.  3. Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 2003;21(8):1431-9.
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjk6IjIxLzgvMTQzMSI7czo0OiJhdG9tIjtzOjIyOiIvY21hai8xNzEvMy8yMTkuMi5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

4.  4. Levine MN, Bramwell VH, Pritchard KI, Norris BD, Shepherd LE, Abu-Zahra H, et al. Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1998;16:2651-8.
    
    [Abstract](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjk6IjE2LzgvMjY1MSI7czo0OiJhdG9tIjtzOjIyOiIvY21hai8xNzEvMy8yMTkuMi5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

5.  5. Piccart MJ, Di Leo A, Beauduin M, Vindevoghel A, Michel J, Focan C, et al. Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer. J Clin Oncol 2001;19(12):3103-10.
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjEwOiIxOS8xMi8zMTAzIjtzOjQ6ImF0b20iO3M6MjI6Ii9jbWFqLzE3MS8zLzIxOS4yLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==)