Integrating Xeloda into primary systemic therapy of breast cancer: a surgeon’s perspective

1. Integrating Xeloda into primary systemic therapy of breast cancer: a surgeon’s perspective John Robertson Professor of SurgeryUniversity of NottinghamNottingham City HospitalUK

2. When is primary systemic therapy (PST) useful? • To make inoperable tumours operable • e.g. inflammatory cancer, fixed axillary LNs • To enable breast-conserving surgery in patients who were previously not suitable • To identify whether the tumour is sensitive to chemotherapy (CT) • if not, other CT can then be considered post-op • As part of a research study – e.g. biology of disease (HER2), drug development

3. Survival: neoadjuvantequivalent to adjuvant

4. Implications of PST: pCR and survival 1Bear HD, et al. J Clin Oncol 2003;21:4165–74 2Heys SD, et al. Clin Breast Cancer 2002;3(Suppl. 2):S69–74 3Ahn J-B, et al. Ann Oncol 2004;15(Suppl. 3):iii57 (Abst 215PD) 4Buzdar A, et al. Proc Am Soc Clin Oncol 2004;23 (Abst 520)

5. Implications of PST: pCR and BCR* ACSx or ACSxD vs ACDSx NSABP B-27: n=2411 CVAPx8 vs CVAPx4Dx4 Aberdeen: n=162 34 26.1 16 13.7 pCR (%) p<0.001 67 63.7 61.6 48 *BCR (%) p=0.33 *BCR = Breast conservation rates

6. NSABP B-18 disease-free and overall survival • No significant difference • DFS • DDFS • OS • OR 77% pCR 13% BCS 69 vs 60% • Local recurrence rate? Stratification (n~1500) Clinical tumour size Clinical nodal status AC x 4 + TAM if 50 years Operation AC x 4 + TAM if 50 years Operation 1Fisher B, et al. J Clin Oncol 1997;15:2483–93 2Fisher B. et al. J Clin Oncol 1998;16:2672–85

7. Relapse rate with pre- or post-surgical chemotherapy *p=0.04; MX = mastectomy; LX = lumpectomy

8. Implications of pCR for surgery • Surgical issues of increasing pCR • localisation of tumour bed • extent of excision • confidence in complete tumour removal • need for surgery?

9. Sentinel lymph node biopsy (SLNB) following PST • SLNB is a new option in the surgical managementof the axilla in patients with breast cancer • previous PST should not be considered an absolute contraindication1 • review of SLNB in patients with clinically node-negative disease following PST2 • Accuracy after PST is similar to that in patients receiving primary surgery alone3 • In one study, PST appeared to impair axillary evaluation; cautionadvised4 1Schwartz GF, Meltzer AJ. Breast J 2003;9:374–9 2Xing Y, et al. Asian J Surg 2004;27:262–7 3Reitsamer R, et al. J Surg Oncol 2003;84:63–7 4Vigario A, et al. Clin Nucl Med 2003;28:553–7

10. SLNB after PST: Cause for Caution?

11. Summary • PST offers similar outcomes to adjuvant therapy • Potential benefits of downsizing tumours to • enable surgery in previously inoperable tumours • increase rates of breast-conserving surgery • Docetaxel added to pre-op ‘anthracycline’ regimens •  ORR ( pCR) •  rate of breast-conserving surgery • effect on OS uncertain • Xeloda added to docetaxel achieves high pCR rate • SLNB remains an option after PST but has FN rate 10%