Preoperative Therapy: an OverviewFAC-CMF 174 87% 26%/10y Hortobagyi AV-CMF 277 23%/10y Valagussa...
Transcript of Preoperative Therapy: an OverviewFAC-CMF 174 87% 26%/10y Hortobagyi AV-CMF 277 23%/10y Valagussa...
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Preoperative Rx
Preoperative Therapy:an Overview
William C. Wood, MD
Department of Surgery
Emory University School of Medicine
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Preoperative Rx
Terminology*
• Adjuvant therapy
• Neo-adjuvant chemotherapy Frei
• Basal chemotherapy Dunphy
• Induction chemotherapy Holland
• Primary chemotherapy DeVita
• Preoperative therapy Anon.*Wood WC. Neoadjuvant Therapy, in Adjuvant Therapy of Breast Cancer,
Henderson IC, Ed. Kluwer Academic Pub, 1992.
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Preoperative Rx
Origin of Preoperative Therapy
•To shrink inoperable cancers to allow surgical extirpation
•Endocrine therapy used initially
•Then cytotoxic chemo
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Preoperative Rx
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Preoperative Rx
Preoperative Rx for Locally Advanced
Agents N %Resp Surv Author
FAC-CMF 174 87% 26%/10y Hortobagyi
AV-CMF 277 23%/10y Valagussa
AC-MLF 75 91% 73%/3y Ragaz
VTMFAP 98 91% 77%/3y Jacquillat
CAFV 170 48% Namer
Wood WC, Neoadjuvant chemotherapy in Adjuvant Therapy of Breast Ca, Henderson IC Ed., Kluwer Academic, 1992
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Preoperative Rx
Preoperative Therapy for Locally Advanced and Inflammatory Breast Cancer
• Never prospectively compared to other methods
• 25% and more survivals at 10 years far superior to historical experience in this population
• Response directly related to survival in these series
• Outcome of response vs. selecting biologically more favorable tumors for both response and survival?
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Preoperative Rx
Original Rationale for Preoperative Therapy In Stage II BC
• Bonadonna introduced preoperative therapy for Stage II breast cancer to allow BCT
• Second putative advantage was to hasten treatment of micro-metastases, eliminating them prior to the growth spurt after removal of the primary, described in experimental tumor systems
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Preoperative Rx
Results of Surgery and Cyclophosphamide on Rat Shay Chloroleukemia
Treatment Remaining
Free of Disease
Surgery only 10%
Cyclophosphamide only 30%
CycloP Post-op days 0 & 1 50%
CycloP Pre-op days -8 & -7 90%
Brock N. Strahlentherapie 1959;41:347-354.
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Preoperative Rx
Downstaging Operable Breast Cancer
National Tumor Institute of Milan
Gianni Bonadonna
94 with resectable tumors >3cm diameter
Treated with CMF or CAF preoperatively
Converted 87% to BCT
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Preoperative Rx
Bonadonna’s Observation
• Response to preoperative chemotherapy predicted prognosis [also Jacquillat, Namer, and Hortobagyi]
• Cause, or biologic staging?
• Only randomized trials would answer
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Preoperative Rx
NSABP Protocol BNSABP Protocol B--1818Operable Breast Cancer
StratificationAgeClinical Tumor SizeClinical Nodal Status
AC x 4+ TAM if > 50 yrs
Operation
OperationAC x 4
+ TAM if > 50 yrs
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Preoperative Rx
NSABP B-18: Overall SurvivalNine Year Update
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9
Years from study entry
% S
urvi
val
Postop Preop
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Preoperative Rx
Lessons of B-18
• No survival advantage from preoperative timing of chemotherapy
• No survival disadvantage from leaving tumor in place with preoperative chemotherapy
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Preoperative Rx
EORTC 10902
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Preoperative Rx
Lessons from EBCTCG Overview*
11 Randomized trials 1983-91, 4675 women
• Preoperative arm 18% fewer mastectomies
• Preoperative arm 3% more in-breast recurrences, yr 5
• No significant difference in any recurrence, breast cancer mortality, or death by year 10
*Oxford, September 7, 2006, NOT FINAL DATA, TENTATIVE RESULTS
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Preoperative Rx
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Preoperative Rx
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Preoperative Rx
Goals for Breast Cancer Therapy
• No recurrence of the cancer
• No evidence of having had breast cancer
• No evidence of having had treatment for breast cancer
• No acute toxicity of the therapy
• No late sequelae of the therapy
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Preoperative Rx
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Preoperative Rx
Clinical Breast Tumor Response to PreopChemo
(N=685 pts)36%
17%
43%
3%
Partial Response(296 pts)
CompleteResponse(249 pts)
StableDisease(118 pts)
Progressive Disease(22 pts)
79%
B-18
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Preoperative Rx
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Preoperative Rx
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Preoperative Rx
Timing of Systemic Therapy
• Surgery first is an accident of medical history
• Preoperative therapy allows:
Reduction of tumor volume- cosmesis
Identification of tumors resistant to Rx- for trials of other therapies
Trials of biological and other agents- to hasten development of these
Favors tailored therapy- new generation of trials
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Preoperative Rx
Who To Get Preoperative Rx?
Anyone who will require the systemic therapy in question with
certainty…
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Preoperative Rx
No more “One size fits all…”
Finis