1. Neoadjuvant Chemotherapy for Ca Breast CY Choi UCH

2. JHSGR Sep 2004 Synonyms Primary chemotherapy Primary chemotherapy Neoadjuvant chemotherapy Neoadjuvant chemotherapy Induction chemotherapy Induction chemotherapy Preoperative chemotherapy Preoperative chemotherapy

3. JHSGR Sep 2004 Development Indications: Indications: Inoperable Ca breast Inoperable Ca breast Locally advanced Ca breast Locally advanced Ca breast Large operable Ca breast Large operable Ca breast ? All Biopsy confirmed invasive Ca breast ? All Biopsy confirmed invasive Ca breast

4. JHSGR Sep 2004 Advantages 1.  tumour size and allow breast conservation 2. evaluate chemoresponsiveness of tumour 3.  effectiveness of systemic treatment for micrometastasis 4.  stimulation of metastatic cancer cell by tumour excision 5. May turn off surgically induced growth factors 6. Treat LN,  axillary dissection

5. JHSGR Sep 2004 Disadvantages 1. May treat in situ disease(if only FNA done) 2.  ability of pathology to act as prognostic indicator 3.  ability of surgical assessment of original tumour after chemotherapy 4.  ability to evaluate axillary LN status 5.  ability to evaluate biologic characteristics of tumour

6. JHSGR Sep 2004 Review Literature Literature Chemotherapy Regime Chemotherapy Regime Treatment of axilla Treatment of axilla

7. JHSGR Sep 2004 Response to chemotherapy Classification Classification  complete response (  100%)  partial response (  >50%)  static disease  disease progression (  >25%)

8. JHSGR Sep 2004 Predictors of response to primary chemotherapy pCR is good prognostic factor for disease free and overall survival pCR is good prognostic factor for disease free and overall survival pCR is predictive of complete axillary LN response pCR is predictive of complete axillary LN response pCR more seen in ER-, anaplastic, small size tumour pCR more seen in ER-, anaplastic, small size tumour Kuerer, McMasters. J Clin Oncol 1999

9. JHSGR Sep 2004 Perioperative management Mark the tumour before chemotherapy Mark the tumour before chemotherapy Monitor tumour response regularly Monitor tumour response regularly Residual mass in mammogram and USG may not be viable tissue, ?role of MRI (Cancer 1996) Residual mass in mammogram and USG may not be viable tissue, ?role of MRI (Cancer 1996) Well planned surgery Well planned surgery  Resection margin  Tumour/breast size ratio  Extent of microcalcifications

10. Evidence

11. JHSGR Sep 2004 NSABP-B18 J Clin Oncol 1998 RCT (Preop vs Postop chemotherapy) RCT (Preop vs Postop chemotherapy) doxorubicin/cyclophosphamide x 4 courses doxorubicin/cyclophosphamide x 4 courses 1523 F 1523 F Stage I/II/III Breast cancer (Tumour size 2-5cm 60%, >5cm 13%) Stage I/II/III Breast cancer (Tumour size 2-5cm 60%, >5cm 13%) FU 5yr FU 5yr

12. JHSGR Sep 2004 Results Chemotherapy regime PreopPostop Response* 80%  tumor size >50% pCR 10% Nodal response 89% BCT (>5cm) (>5cm)67.8% 22% 22%59.8% 8% 8% Ipsilateral recurrence Ipsilateral recurrence DFS DFS Overall survival (9y) Overall survival (9y)8%85.7%70%6%=70% *Multivariate analysis indicate that clinical tumour size, clinical nodal status were independent predictors of complete clinical response

13. JHSGR Sep 2004 Bordeaux Study Annals of Oncology 1999 RCT (single institution) RCT (single institution) MRM +/- adjuvant chemo vs MRM +/- adjuvant chemo vs Primary chemo+ surgery (mastectomy >2cm, BCT+RT 2cm, BCT+RT <2cm) Chemotherapy regime: Chemotherapy regime:  3 cycles of epirubicin, vincristine, methotrexate, then 3 cycles of mitomycin C, thiotepa, vindesine 272F 272F Clinical T>3cm Clinical T>3cm Median FU: 124months Median FU: 124months

14. JHSGR Sep 2004 Results Results  Preop chemotherapy  BCT possible in 45%  More local recurrences  Similar survival Limitation Limitation  Treatment arms not really balanced

15. JHSGR Sep 2004 Milan trials J Clin Oncol 1998 Prospective (nonRCT) Prospective (nonRCT) Chemotherapy regime Chemotherapy regime  3-4 cycles of CMF / FAC / FEC / FNC / adriamycin 536F 536F T>2.5cm T>2.5cm Median age 49 Median age 49 Median FU 65 months Median FU 65 months Results Results  Overall response 76% - cCR 16% - pCR 3% - pCR 3% - PR 60% - PR 60%  Stable disease 5%  Minor response(<50% reduction) 16%  Progressive disease 5%

16. JHSGR Sep 2004  BCT possible in 85%(in 62% patients with tumour >5cm)  Local relapse after BCT 6.8%  Response  in receptor –ve tumour, unrelated to age, menopausal status, chemo regimen  Multivariate analysis showed response to primary chemo and axillary LN involvement correlate with disease free survival

17. JHSGR Sep 2004 NSABP-B 27 Just closed Randomised to preop chemotherapy Randomised to preop chemotherapy  Gp 1 AC+ TAM -> surgery  Gp 2 AC+ TAM -> taxotere -> surgery  Gp 3 AC+ TAM -> surgery-> taxotere cT1-3, N0-1 cT1-3, N0-1 2411F 2411F Results: Results:  no difference in BCT (60%)  Gp 2 increase pCR(26.1 vs 13.7%) Pending 5 yr survival 2005 Pending 5 yr survival 2005

18. JHSGR Sep 2004 EORTC 10902 J Clin Oncol 2001 RCT (Preop vs Postop chemotherapy) RCT (Preop vs Postop chemotherapy) 4 cycles of 5FU, Epirubicin, cyclophosphamide 4 cycles of 5FU, Epirubicin, cyclophosphamide 698F (Yr 1991-1999) 698F (Yr 1991-1999) (T1c, T2, 3, 5b, N0, 1 and M0) (T1c, T2, 3, 5b, N0, 1 and M0) Median FU 56mos Median FU 56mos Results: Results:  No difference in OS, PFS, LRR  23% downstaged

19. JHSGR Sep 2004 Chemotherapy Regime Which has  Response Rate ? Which has  Response Rate ?  Primary chemotherapy with doxorubicin and docetaxel is well tolerated and highly active  Taxane to  pCR comparing with FAC  Sequential treatment schedule is a little more active than combination therapy, but a higher toxicity

20. JHSGR Sep 2004 Role of Sentinel LN biopsy or axillary dissection Incidence of histological negative axillary LN 37% greater - NSABP B-18 Incidence of histological negative axillary LN 37% greater - NSABP B-18 23% has histological conversion from + to – (MD Anderson) 23% has histological conversion from + to – (MD Anderson) Can axillary irradiation replace ALND in patients downstaged from node + to – ? Can axillary irradiation replace ALND in patients downstaged from node + to – ?  Axillary irradiation without axillary LN dissection may provide adequate local control in patients with at least a partial response. Lenert JT. Ann Surg Oncol 99 Buzdar AU, J Clin Oncol 99.

21. JHSGR Sep 2004 SLN Small sample size, Variable results for SLN identification and FN finding(1-11%) Small sample size, Variable results for SLN identification and FN finding(1-11%) SLNB is reliable for accurate staging of axilla in advanced Ca breast Haid A. Cancer 2001 SLNB is reliable for accurate staging of axilla in advanced Ca breast Haid A. Cancer 2001 SLN accurately predict axillary LN status in 96% patients(325/340) ASCO Annual meeting 2002 SLN accurately predict axillary LN status in 96% patients(325/340) ASCO Annual meeting 2002 FN rate FN rate  9% NSABP B27  4.3% MD Anderson CC

22. JHSGR Sep 2004 Conclusion Neoadjuvant chemotherapy Neoadjuvant chemotherapy   breast conservation  survival benefit Recommended for Stage II, III Ca breast Recommended for Stage II, III Ca breast ?extrapolate to early Ca breast ?extrapolate to early Ca breast Prognostic value of axillary LN Prognostic value of axillary LN Accuracy of SLNB not affected Accuracy of SLNB not affected Study on QOL Study on QOL