neoadjuvant chemotherapy for ca breast l.
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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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synonyms
Synonyms
  • Primary chemotherapy
  • Neoadjuvant chemotherapy
  • Induction chemotherapy
  • Preoperative chemotherapy
development
Development
  • Indications:
  • Inoperable Ca breast
  • Locally advanced Ca breast
  • Large operable Ca breast
  • ? All Biopsy confirmed invasive Ca breast
advantages
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
disadvantages
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
review
Review
  • Literature
  • Chemotherapy Regime
  • Treatment of axilla
response to chemotherapy
Response to chemotherapy
  • Classification
    • complete response ( 100%)
    • partial response (>50%)
    • static disease
    • disease progression (>25%)
predictors of response to primary chemotherapy
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

perioperative management
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
nsabp b18 j clin oncol 1998
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
results
Results

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

bordeaux study annals of oncology 1999
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
slide14
Results
    • Preop chemotherapy
      • BCT possible in 45%
      • More local recurrences
      • Similar survival
  • Limitation
    • Treatment arms not really balanced
milan trials j clin oncol 1998
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%
slide16
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
nsabp b 27 just closed
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
eortc 10902 j clin oncol 2001
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
chemotherapy regime
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
role of sentinel ln biopsy or axillary dissection
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.
slide21
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
conclusion
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