Correspondence

Chemotherapy in Older Women with Breast Cancer

N Engl J Med 2009; 361:1023-1024September 3, 2009

Article

To the Editor:

Muss et al. (May 14 issue)1 report that standard adjuvant chemotherapy is superior to capecitabine in older women with early-stage breast cancer. However, the authors neglect to mention that adjuvant radiotherapy in patients with positive axillary nodes affects relapse-free survival.2,3

The use of chest-wall and regional lymph-node irradiation after mastectomy and chemotherapy is recommended in women with four or more positive axillary lymph nodes, and it is recommended for strong consideration in women with one to three positive axillary lymph nodes.3,4 Prophylactic chest-wall irradiation in these patients substantially reduces the risk of local recurrence.5

Yue-Can Zeng, M.D.
Shengjing Hospital, Shenyang, China
wellyy2005@hotmail.com

5 References

1
Muss HB, Berry DA, Cirrincione CT, et al. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med 2009;360:2055-2065
Full Text | Web of Science | Medline

2
Truong PT, Olivotto IA, Kader HA, Panades M, Speers CH, Berthelet E. Selecting breast cancer patients with T1-T2 tumors and one to three positive axillary nodes at high postmastectomy locoregional recurrence risk for adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 2005;61:1337-1347
CrossRef | Web of Science | Medline

3
Ragaz J, Olivotto IA, Spinelli JJ, et al. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst 2005;97:116-126
CrossRef | Web of Science | Medline

4
Overgaard M, Nielsen HM, Overgaard J. Is the benefit of postmastectomy irradiation limited to patients with four or more positive nodes, as recommended in international consensus reports? A subgroup analysis of the DBCG 82 b&c randomized trials. Radiother Oncol 2007;82:247-253
CrossRef | Web of Science | Medline

5
Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;366:2087-2106
Web of Science | Medline

To the Editor:

Muss et al. found standard adjuvant chemotherapy (either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide plus doxorubicin) to be superior to capecitabine in terms of relapse-free survival and overall survival. An unplanned subgroup analysis revealed that the difference between treatment groups was significant in patients with hormone-receptor–negative tumors but not in patients with hormone-receptor–positive tumors. However, there is a smaller benefit from standard adjuvant chemotherapy in patients with hormone-receptor–positive tumors than in patients with hormone-receptor–negative tumors.1 Thus, to gain significance in this subgroup with a low-risk profile (mostly T1 or T2 tumors with zero to three positive lymph nodes), more patients are needed to observe the difference between treatment groups in a short follow-up time (2.4 years). Outcomes in patients with hormone-receptor–positive tumors require separate analyses.

Omer Dizdar, M.D.
Didem S. Dede, M.D.
Kadri Altundag, M.D.
Hacettepe University, Ankara, Turkey

1 References

1
Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365:1687-1717
CrossRef | Web of Science | Medline

Author/Editor Response

Zeng notes that radiation therapy after mastectomy in patients with positive lymph nodes improves survival. Indeed, we did “neglect” irradiation after mastectomy in our analysis. Such neglect is conventional in analyzing breast-cancer trials, and for good reason. Patients were not randomly assigned to irradiation or primary surgery. These doctor–patient choices are based at least in part on clinical characteristics. They might be considered as covariates in a multivariate analysis of treatment effect, but even this would be questionable because they are highly correlated with clinical characteristics that are already included in the analysis. Although it is true that some management issues may affect outcome, they are usually balanced across treatment groups — as is the case in our study. When they are not balanced, they are subsumed in the group's therapeutic strategy as part of an intention-to-treat analysis. Therefore, the conventional approach in medical research is to not consider patient treatment issues in comparisons of treatment groups.

We agree with Dizdar and colleagues that chemotherapy is associated with less benefit in hormone-receptor–positive breast cancer than in hormone-receptor–negative breast cancer. Indeed, an earlier analysis of our Cancer and Leukemia Group B (CALGB) data1 shows exactly this finding, and it led to our subgroup analysis in the present study. Moreover, these CALGB data show that chemotherapy's benefit occurs in the first few years after treatment. Regarding the “relatively short follow-up time” in our study, it is most unlikely that any difference will emerge in the hormone-receptor–positive subgroup with longer follow-up. Regarding the need for more patients, in view of the low relapse rate among patients with hormone-receptor–positive primary tumors, it would take thousands of patients to try to show a benefit, and any benefit would probably be very small. Such a large trial in this population would be almost impossible to complete. An adjuvant trial involving women 65 years of age or older that has just completed accrual of 1400 patients compares ibandronate with ibandronate and capecitabine.2

Hyman B. Muss, M.D.
University of North Carolina, Chapel Hill, NC
muss@med.unc.edu

Donald A. Berry, Ph.D.
M.D. Anderson Cancer Center, Houston, TX

Constance T. Cirrincione, M.S.
Cancer and Leukemia Group B Statistical Center, Durham, NC

2 References

1
Berry DA, Cirrincione C, Henderson IC, et al. Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 2006;295:1658-1667[Erratum, JAMA 2006;295:2356.]
CrossRef | Web of Science | Medline

2
ClinicalTrials.gov. Study in elderly patients with early breast cancer (ICE). (Accessed August 13, 2009, at http://clinicaltrials.gov/ct2/show/NCT00196859.)

Citing Articles (2)

Citing Articles

1
Amalia M Issa, Janis F Hutchinson, Waqas Tufail, Erica Fletcher, Roseline Ajike, Jose Tenorio. (2011) Provision of personalized genomic diagnostic technologies for breast and colorectal cancer: an analysis of patient needs, expectations and priorities. Personalized Medicine 8:4, 401-411
CrossRef
2
Nedal Arar, Sara J Knight, Stephen M Modell, Amalia M Issa. (2011) The Genome-based Knowledge Management in Cycles model: a complex adaptive systems framework for implementation of genomic applications. Personalized Medicine 8:2, 191-205
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