Neoadjuvant chemotherapy for ca breast
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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 l.jpg

NeoadjuvantChemotherapyfor Ca Breast

CY Choi

UCH


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Synonyms

  • Primary chemotherapy

  • Neoadjuvant chemotherapy

  • Induction chemotherapy

  • Preoperative chemotherapy


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Development

  • Indications:

  • Inoperable Ca breast

  • Locally advanced Ca breast

  • Large operable Ca breast

  • ? All Biopsy confirmed invasive Ca breast


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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


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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


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Review

  • Literature

  • Chemotherapy Regime

  • Treatment of axilla


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Response to chemotherapy

  • Classification

    • complete response ( 100%)

    • partial response (>50%)

    • static disease

    • disease progression (>25%)


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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


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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



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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


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Results

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


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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


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  • Results

    • Preop chemotherapy

      • BCT possible in 45%

      • More local recurrences

      • Similar survival

  • Limitation

    • Treatment arms not really balanced


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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%


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  • 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


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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


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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


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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


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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.


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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


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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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