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Neoadjuvant Chemotherapy for Ca Breast

Neoadjuvant Chemotherapy for Ca Breast. CY Choi UCH. Synonyms. Primary chemotherapy Neoadjuvant chemotherapy Induction chemotherapy Preoperative chemotherapy. Development. Indications : Inoperable Ca breast Locally advanced Ca breast Large operable Ca breast

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Neoadjuvant Chemotherapy for Ca Breast

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  1. NeoadjuvantChemotherapyfor Ca Breast CY Choi UCH

  2. Synonyms • Primary chemotherapy • Neoadjuvant chemotherapy • Induction chemotherapy • Preoperative chemotherapy

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

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

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

  6. Review • Literature • Chemotherapy Regime • Treatment of axilla

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

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

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

  10. Evidence

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

  12. Results *Multivariate analysis indicate that clinical tumour size, clinical nodal status were independent predictors of complete clinical response

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

  14. Results • Preop chemotherapy • BCT possible in 45% • More local recurrences • Similar survival • Limitation • Treatment arms not really balanced

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

  16. 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. NSABP-B 27 Just closed • 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 • 2411F • Results: • no difference in BCT (60%) • Gp 2 increase pCR(26.1 vs 13.7%) • Pending 5 yr survival 2005

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

  19. Chemotherapy Regime • 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. Role of Sentinel LN biopsy or axillary dissection • Incidence of histological negative axillary LN 37% greater - NSABP B-18 • 23% has histological conversion from + to – (MD Anderson) • 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. SLN • 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 • SLN accurately predict axillary LN status in 96% patients(325/340) ASCO Annual meeting 2002 • FN rate • 9% NSABP B27 • 4.3% MD Anderson CC

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

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