What are doctors and scientists doing to learn more about adjuvant and neoadjuvant therapy for breast cancer?

Doctors and scientists are conducting research studies called clinical trials to learn how to treat breast cancer more effectively. In these studies, researchers compare two or more groups of patients who receive different treatments. Clinical trials allow researchers to examine the effectiveness of new treatments in comparison with standard ones, as well as to compare the side effects of the treatments.

Researchers are also investigating whether molecular information obtained from a woman’s tumor can be used to decide if the woman would benefit from adjuvant therapy. Two large clinical trials sponsored by NCI, a part of the National Institutes of Health, are currently under way in this area of research.

The Trial Assigning Individualized Options for Treatment (TAILORx) is examining whether molecular markers that are frequently associated with risk of recurrence among women who have early-stage breast cancer can be used to assign patients to the most appropriate and effective treatment. TAILORx is using a test called Oncotype DX™, which calculates the risk of recurrence based on the levels of expression of 21 genes in breast tumors, in over 10,000 women recruited at 900 sites in the United States and Canada. Based on their risk of recurrence, women will be assigned to one of three different treatment groups: women with a high risk of recurrence will receive chemotherapy plus hormonal therapy; women with a low risk of recurrence will receive hormonal therapy alone; and women with an intermediate risk of recurrence will be randomly assigned to receive adjuvant hormonal therapy, with or without chemotherapy. Because the degree of benefit of chemotherapy for women with an intermediate risk of recurrence is unknown, TAILORx seeks to determine whether the Oncotype DX test will be helpful in future treatment planning for this group.

In the Microarray In Node-negative Disease may Avoid Chemotherapy Trial (MINDACT), investigators are studying genomic profiling compared with clinical assessment to determine the need for chemotherapy in women with node-negative breast cancer (cancer that has not spread to the axillary lymph nodes). The investigators will use both a 70-gene signature test and clinical assessment to determine the women’s risk of recurrence. Women eligible to receive chemotherapy who have a high risk of recurrence according to the clinical criteria and a low risk of recurrence according to the 70-gene signature, or have a low risk of recurrence according to the clinical criteria and a high risk of recurrence according to the 70-gene signature, will be randomly assigned to receive treatment based on either the genetic or clinical criteria to determine which better predicts the need for chemotherapy. 

Women with breast cancer who are interested in taking part in a clinical trial should talk with their doctor. Complete listings of current clinical trials testing adjuvant and neoadjuvant therapies for female breast cancer are available from NCI’s website:

Trials of adjuvant therapy for female breast cancer

Trials of neoadjuvant therapy for female breast cancer

Additional information about clinical trials can be found on NCI’s website. NCI’s Cancer Information Service (CIS) can also provide information about clinical trials and help with clinical trial searches. Call the CIS at 1–800–4–CANCER (1–800–422–6237).

Selected References

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2. International Breast Cancer Study Group.Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13–93. Journal of Clinical Oncology 2006; 24(9):1332–1341.

3. Coates AS, Keshaviah A, Thürlimann B, et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1–98. Journal of Clinical Oncology 2007; 25(5):486–492.

4. The Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists’ Group. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC Trial. Lancet Oncology 2008; 9(1):45–53.

5. Coombes RC, Kilburn LS, Snowdon CF, et al. Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet 2007; 369(9561):559–570. Erratum in: Lancet 2007; 369(9565):906. 

6. Boccardo F, Rubagotti A, Guglielmini P, et al. Switching to anastrozole versus continued tamoxifen treatment of early breast cancer. Updated results of the Italian Tamoxifen Anastrozole (ITA) Trial. Annals of Oncology 2006; 17(Suppl 7):vii10–vii14.

7. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. New England Journal of Medicine 2005; 353(16):1659–1672.

8. Smith I, Procter M, Gelber RD, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007; 369(9555):29–36.

9. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. New England Journal of Medicine 2005; 353(16):1673–1684.

10. Goldhirsch A, Glick JH, Gelber RD, et al. Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. Annals of Oncology 2005; 16(10):1569–1583.

11. Lonning PE. Breast cancer prognostication and prediction: are we making progress? Annals of Oncology 2007; 18(Suppl 8):viii3–7.

12. Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. Journal of Clinical Oncology 1998; 16(8):2672–2685.

13. van der Hage JA, van de Velde CJ, Julien JP, et al. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer Trial 10902. Journal of Clinical Oncology 2001; 19(22):4224–4237.

14. Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. Journal of the National Cancer Institute 2005; 97(3):188–194.

Source: National Cancer Institute