2000 NIH Consensus Development Conference on Adjuvant Therapy for Breast Cancer

Who Should Not Receive Chemotherapy?
International Databases

Jonas C. Bergh, M.D., Ph.D.

Adjuvant use of chemotherapy and tamoxifen probably saves more lives than any other medical therapy for cancer (Bergh, 2000; EBCTCG, 1998a; EBCTCG 1998b). Despite this major achievement, the principal problem in adjuvant therapy is selecting patient subgroups to receive any particular therapy. Data from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) demonstrate that a relatively large proportion of treated patients will relapse despite CMF or anthracycline-based adjuvant therapy with or without tamoxifen. In the future we hope to have a detailed bio-molecular "fingerprint" of each cancer that will allow us to tailor an optimal approach for each patient, combined with an appreciation of pharmacokinetic variation. Recent data using microarray technology strongly indicate that "fingerprints" have a very high degree of complexity (Perou, Ssrlie, Eisen, et al., 2000).

The most critical issue today is to find the optimal balance between patients who should be offered adjuvant therapy and those who are at a sufficiently low risk not to be offered such therapy. In addition, those selected should be given a specific and targeted therapy that avoids the problem of relapse. Cut-off levels and recommendations for adjuvant therapy vary from country to country and region to region, most likely reflecting medical, economic, or cultural differences.

Our goal is to identify women who are at sufficiently low risk of relapse that they need not be offered adjuvant chemotherapy. We will review data from population-based cancer registries in the Nordic countries, together with country-based and regional registries containing information on adjuvant therapy modalities, as well as information from the Swedish mammography program. This will be possible because the Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) have had population-based cancer registries for several decades. The broad coverage of these registries provides extensive data on the incidence of cancer and on mortality from the various kinds of cancer. Information on prognostic factors and on therapy, however, are not included in these national registries, except for those of Denmark and Sweden.

Beginning in 1977, the Danish Breast Cancer Group (DBCG) began to develop a population-based cancer registry (Mouridsen, personal communication). The registry contains the names of around 60,000 Danish women who have had breast cancer. The present annual incidence of breast cancer in Denmark is around 3,500. A retrospective analysis of 30,000 women with breast cancer made it possible to identify a group with a low risk of relapse (Mouridsen, personal communication). This group consists of approximately 20 percent of the patients in the registry. "Low-risk" is defined as a receptor-positive node-negative grade I (Bloom-Richardson) primary cancer less than 20 mm. The patients in this low-risk group were treated with mastectomy or breast-conserving surgery. Local radiotherapy was administered to the breast parenchyma remaining after breast-conserving surgery or to the scar area at the deep resection border in the case of nonradical surgery (Mouridsen, personal communication).

Using age-matched controls, it was found that the 5-year survival rate for all premenopausal Danish women (the control group) was 98 percent; the premenopausal low-risk group with breast cancer had the same 5-year survival rate of 98 percent (Mouridsen, personal communication). The corresponding figure for the entire postmenopausal group was 92 percent, and for the breast cancer cohort 91 percent (Mouridsen, personal communication). The team at DBCG is presently analyzing the 10-year figures.

The Stockholm (Sweden) Breast Cancer Group was established in 1976 and has a database containing the names of around 20,000 breast cancer patients (Rutqvist, personal communication). The annual incidence of new breast cancers in the Stockholm-Gotland region is from 1,200 to 1,300, from a population base of between 1.7 to 1.8 million. The registry covers between 85 and 90 percent of the women with breast cancer within that geographic region. There is also an Uppsala-.rebro breast cancer registry in Sweden that started operation on September 1, 1992. That registry listed 10,610 patients as of August 25, 2000 (Degerman, personal communication). The population base is around 1.9 million.

We will use these registries to identify low-risk groups with a sufficiently good prognosis that makes it unlikely that these women would benefit from adjuvant therapy, as suggested by DBCG data or using other criteria, with the assistance of Lars-Erik Rutqvist of Stockholm and Lars Holmberg of Uppsala, Sweden, and their collaborators. With the assistance of Lazlo Tabar of Falun, Sweden, we will also use mammography-based data to identify low-risk groups.

References

Bergh J. Where next with stem-cell-supported high-dose therapy for breast cancer? [comment]. Lancet 2000;355:944-5.

Danish Breast Cancer Group (DBCG). May 2000: Newsletter 32. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 1998;351:1451-67.

Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet 1998;352:930-42

Perou C, Sörlie T, Eisen M, et al. Molecular portraits of human breast tumours. Nature 2000;406:747-52.

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