Neoadjuvant Chemotherapy for Breast Cancer

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Neo-adjuvant Chemotherapy for Breast Cancer

• Shiuh-Wen Luoh MD PhD
• Portland VA Medical Center
• Oregon Health Sciences University

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Neoadjuvant Treatment of Primary BC Improve
Surgical Options Obtain Information on
Response Obtain Long Term Disease Free Control
JCO Vol 24, pp 1940-, 2006.
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Neoadjuvant Treatment of Primary BC An increase
in the pCR rate as the result of a Superior
Treatment has not been proven to consistently
translate into an Improved Long Term
Outcome. Caution on Future Trial Design!
JCO Vol 24, pp 1940-, 2006.
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Recurrence Score in Predicting Response to
Chemotherapy Recurrence Score (RS) from
Genomic Health -- L Gianni JCO 237265-,
2005 Pre-OP AP/P -- S Paik JCO
243726-,2006 Adjuvant CMF -- J Chang ASCO
2006, abs 538 Pre-OP Taxotere Third is the
charm for RS? Publication Bias? ASCO 2006,
Abs 538
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Predicting Residual Tumor Size is Difficult! M D
Anderson Experience
Annals of Surgery Vol. 243, pp 257- , 2006.
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doxorubicin 50 mg/m2 plus docetaxel 75 mg/m2 each
on day 1 every 14 days for 4 cycles with
granulocyte colony-stimulating factor support
(ADOC) versus doxorubicin 60 mg/m2 plus
cyclophosphamide 600 mg/m2 on day 1 every 21 days
followed by docetaxel 100 mg/m2 every 21 days for
4 cycles (AC-DOC).
Factors associated with a significantly higher
breast-conserving surgery rate pre-chemotherapy
tumor size lt 40 mm, non-lobular histological
characteristics, treatment with AC-DOC, clinical
response, post-chemotherapy tumor size lt 20 mm,
and treatment in a larger center (gt10 enrolled
patients).
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Neo!Adjuvant
Cancer 2006 107145966.
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A total of 143 neoadjuvant and 170 surgery-first
patients were studied. Patients treated with
neoadjuvant chemotherapy were significantly more
likely to have fewer than 10 lymph nodes
retrieved at ALND than were the surgery-first
patients (19/143 or 13 vs. 6/170 or 4, P003).
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Cancer 20029568195.
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Neoadjuvant versus Adjuvant - A Meta-analysis
JNCI Vol 97, pp 188-, 2005.
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Neoadjuvant versus Adjuvant - A Meta-analysis
JNCI Vol 97, pp 188-, 2005.
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Neoadjuvant versus Adjuvant - A
Meta-analysis Equivalent in Survival and Overall
Disease Progression. Statistically Significant
Increased Risk of Loco-Regional Relapse if RT
without Surgery. Trend Towards Increased Local
Recurrence in B18! (Multi-centric or Multi-focal
Disease)
JNCI Vol 97, pp 188-, 2005.
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Breast Cancer Vol. 13 No. 3. 2006
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Evolving Role of Surgery and Radiationin the
Pre-operative Systemic Therapy Setting- Morrow,
Giuliano, Harris Expert Opinions Ultrasound and
FNA before Neoadjuvant therapy to assess Axillary
LN status FNA ()-- Axillary Clearance after
Chemotherapy Pitfalls 10-20 Error rate even in
Best Hands Dr. Morrow Recommends Sentinel
Mapping pre-Chemo. Radiation Planning based on
pre-treatment tumor features. ASCO 2006
Ticketed Session
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Evolving Role of Surgery and Radiation in the
Pre-operative Systemic Therapy Setting- Morrow,
Giuliano, Harris Surgical Options if Residual
Tumor Present--- Dr. Morrow Recommends If
Uni-focal tumor found with Negative
Margin Minimal Margin of 2 mm. If Multi-focal
tumor found with Negative Margin Further Surgery
to Achieve as Wide Margin as Possible. ASCO
2006 Ticketed Session
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• Sentinel Node Mapping post Neo-adjuvant Chemo
• NSABP B-27 Experience
• ID rate 85 False (-) 10.7 Only Node ()
  56.

JCO Vol. 23, pp 2694- , 2005.
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Neoadjuvant Treatment of Primary BC An increase
in the pCR rate as the result of a Superior
Treatment has not been proven to consistently
translate into an Improved Long Term
Outcome. Caution on Future Trial Design!
JCO Vol 24, pp 1940-, 2006.
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Nodal Status post Neo-adjuvant Chemo is a
Powerful Prognostic Factor - NSABP B-27 Experience
JCO Vol. 24, pp 2019- , 2006.
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Pathologic CR (pCR) post Neo-adjuvant Chemo is a
Powerful Prognostic Factor - NSABP B-27 Experience
JCO Vol. 24, pp 2019- , 2006.
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Residual Cancer Burden (RCB) Measurement of
Primary Tumor (size and cellularity) and Nodal
Met (Number and Size) RCB-0 (pCR) to
RCB-3 Prognosis RCB-0 RCB-1 gt RCB-2 gt RCB-3
ASCO 2006 Abs 536.
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In vivo Sensitivity Directed Neoadjuvant Therapy
-The Aberdeen Trial Locally Advanced or Large
Primary (gt 3 cM). 162 Patients Completed 4 Cycles
of CVAP 52 Responders to get 4 More Cycles of
CVAP (Group 1), 52 Responders to get 4 Cycles of
Taxetere (Group 2), 55 Non-Responders to get 4
Cycles of Taxotere (Group 3). pCR 16 (Gr 1)
34 (Gr 2) 2 (Gr 3). Improved BCS and 3 year
Survival for Group 2.
JCO Vol 20, pp 1456-, 2002.
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In vivo Sensitivity Directed Neoadjuvant Therapy
- The Gepartrio Trial TAC x2 to Select for
Responders- gt50 Size Reduction Responders to
Complete TAC x6. Non-responders randomized to TAX
x4 or NX x4. pCR in Responders after TAC x6
22.6 pCR in Non-responders after TAC
x6 7.3 pCR in Non-responders after NX
x4 3.1. More Effective Treatments Needed for
Non-responders
Annals Oncology Vol 16, pp 56- , 2005.
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In vivo Sensitivity Directed Adjuvant Therapy -
The M.D. Anderson Experience
JCO Vol 22, pp 2294- , 2004.
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In vivo Sensitivity Directed Adjuvant Therapy -
The M.D. Anderson Experience
JCO Vol 22, pp 2294- , 2004.
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In vivo Sensitivity Directed Adjuvant Therapy -
The M.D. Anderson Experience
What to do When There is Residual Disease?
JCO Vol 22, pp 2294- , 2004.
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Neo-adjuvant Chemotherapy Negative Receptor
Status Predicts Higher pCR
JCO Vol 24, pp 1940-, 2006.
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ILC Patients 122 (12) vs IDC Patients 912
(88). Invasive Lobular Carcinoma (vs
Ductal) Older (53 y vs 47 y) More HR () (92
vs 62) Lower Nuclear Grade and Higher Stage at
Diagnosis. Less Likely to have pCR (3 vs
15). Less Breast Conservation Surgery (16 vs
29). Longer Recurrence Free and Overall
Survival!!!
JCO Vol. 23, pp 41- , 2005.
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Invasive Lobular Carcinoma and Response to
Neo-adjuvant Chemotherapy Single Institution
1990-2002. Pure ILC (n118, 14), Pure IDC
(n742, 86). Lobular Histology- Older (53 y vs
49.6 y) Lower Grade Larger Primary (T3 38.1
vs 21.4) More N0 More HR() (89 vs 60).
Mastectomy Rate 70 (ILC) vs 52 (IDC). pCR 1
(ILC) vs 9 (IDC). DFS at 60 month 76.5 (ILC)
vs 60.8 (IDC). OS at 60 month 91.7 (ILC) vs
79.3 (IDC).
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Neo-adjuvant Endocrine Therapy Trials
JCO Vol 24, pp 1940-, 2006.
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Neoadjuvant Treatment of Primary BC Candidate
Selections as in Adjuvant Therapy -Avoid
Over-treating. Endocrine Tx. for menopausal women
unfit for chemo. Low pCR (1-8) with Endocrine
Tx. Higher pCR with HR(-) than HR(). A Trial
shows Endocrine and chemo comparable. Optimal
Regimen or Duration not Established. -- 3-4
Month of Endocrine Tx. or 4 Cycles of
Chemo. Sentinel Node Mapping after Tx. Might be
Reasonable. Marker Studies pre- and post- Tx.
JCO Vol 24, pp 1940-, 2006.
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SWOG 0012 Locally Advanced and Inflammatory
Breast Cancer A60C600 q3w x 5 cycles vs. A24qw
oral C60qd G x 15w Followed by Taxol 80 qw x
12w. 372 Patients Enrolled, 265 evaluable. All
Received MRM. FN 1.8 and 0.6. No Grade V
Toxicity. More Hand Foot and Stomatitis with
Continuous Chemo. pCR plus N0 is 26 versus 13
P0.02. Highest PCR rate reported for LABC and
IBC. SWOG 0221 is companion Adjuvant Trial S0012
and S0221 both closed due to poor
accrual. ASCO 2006 LBA 537
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Neo-adjuvant Dose Dense AC-Taxol A60C600 X
4cycles q2W followed by Taxol175 (N34) or
Taxotere90-100 (N8) q2W. 42 Patients (6IIA,
12IIB, 10IIIA, 5IIIB, 9IIIC). Grade III 19, ER()
18, HER-2() 8, Clinically N() 26. cCR plus cPR
gt 95. pCR 33(14/42) -- pCR 52.4 (HR-) versus
17.6 (HR). Dose Dense AC-Taxol Safe, Efficient
and High pCR Rate.
SABC 2005 Abst 5062.
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Docetaxel/Xeloda versus Adria/Cytoxan
Neo-adjuvant Chemo for Stage II/III BC Mature
Result from a Randomized Phase III
Trial. Positive Axillary Nodes by PET or
FNA. A60C600 q3W X4 versus D75X(1000bid d1-14)
q3W X4. 209 Patients (Aug 02-April 05). Primary
Tumor pCR DX (23) versus AC (8) p0.0059. More
Hand-Foot Syndrome, Skin ? Mucositis with DX .
SABC 2005 Abst 5052.
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Breast Cancer Vol. 13 No. 3. 2006