San Antonio Breast Cancer Symposium 2006 Highlights Breast Surgery

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San Antonio Breast Cancer Symposium 2006
Highlights Breast Surgery

• Frederick M. Dirbas, M.D.
• Assistant Professor of Surgery
• Stanford Cancer Center

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Breast Conservation /- RT

• Abstract 29, Intergroup Study E5194 Local
  Excision Without Radiation for Selected Patients
  with DCIS
• Abstract 11, CALGB Study Tamoxifen /- RT in
  Women 70 with Breast Cancer

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Abstract 29, Intergroup Study E5194

• 711 women enrolled 1997 to 2002
• Grade 1 or 2 DCIS, 2.5 cm 580 pts
• Grade 3 DCIS, 1 cm 102 pts
• Ineligible 29 pts
• Mean age of eligible patients is 60 years
• 31 declared intent to take Tam
• Median f/u 4.96 years
• Post excision mammogram for residual
  microcalcifications, central path review

ECOG, NCCTG
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Abstract 29, Intergroup Study E5194

• Principle Outcome Measures
• Conclusions
• Low to intermediate grade DCIS has low recurrence
  rate w/o RT
• High grade DCIS has a high recurrence rate
  suggesting surgery alone is inadequate

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Abstract 29, Intergroup Study E5194

• Is this real?
• Dana Farber data demonstrates higher recurrence
  rates without RT, IBTR 12 at 5 years, with
  low/intermediate grade and margins gt 1 cm (TAM
  not allowed)
• Van Nuys data demonstrates low recurrence rates
  overall if margins gt 1 cm, IBTR 13.9, invasive
  IBTR 3.4 at 12 years
• higher recurrence rates with grade 3 DCIS

• J Clin Oncol (United States), Mar 1 2006, 24(7)
  p1031-6
• Am J Surg (United States), Oct 2006, 192(4)
  p420-2

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Abstract 29, Intergroup Study E5194

• Where does one go from here?
• RTOG 98-04 randomized study closed to accrual,
  results pending
• Favorable DCIS /- Tam /- RT
• Low to intermediate grade
• 3-9 mm margins vs 1 cm or greater
• lt 1 cm lesion vs 1 to 2.5 cm
• Age lt or gt 50
• TAM yes vs no

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Sentinel Node BiopsyITC (Nanomets) and Micromets

• Abstract 25, Axillary Lymph Node ITC
  (Nanometastases) are Prognostic Factors for
  Metastatic Relapse. These results support the
  inclusion of procedures for nanometastasis
  detection in TNM pathologic staging.
• National Cancer Institute, Milan, Italy
• Plenary session, 3, Micrometastases in the
  Sentinel Node One should not look too hard for
  micrometastases in the sentinel node.
• The Netherlands Cancer Institute, Amsterdam,
  Netherlands

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Abstract 25, Sentinel Node BiopsyITC (Nanomets)

• Compared with standard HE staining
• step sectioning increases sensitivity 10
• IHC increases sensitivity 10 further
• RT-PCT increases sensitivity 10 further still
• What is the value of these observations?
• Are these metastatic cells viable?
• Are these simply displaced cells?

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Abstract 25, Sentinel Node BiopsyITC (Nanomets)

• Abstract 25, Axillary Lymph Node ITC
  (Nanometastases) are Prognostic Factors
• 702 consecutive patients at the National Cancer
  Institute, Milan
• pN0
• Completion axillary dissections
• 8 years median f/u
• Outcomes
• Risk of first adverse event
• Crude cumulative incidence curves generated to
  estimate cumulative probability of occurrence of
  adverse events
• Distant relapse
• pN0(i) is a strong risk factor for event free
  survival (plt.0005) and for metastatic relapse in
  both univariate and multivariate analysis
  accounting for grading, T stage, and age

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Plenary Session 3, Sentinel Node BiopsyMicromets

• Meta-analysis of 25 studies, gt 8,687 published
  patients who had neg SN bx
• 3 years mean f/u
• 31 relapses, axillary recurrence only .36 (.8
  to 2.3 reported for ALND)
• Compare this with false negative rate after
  upfront ALND, which ranges from 2 to 11 in the
  literature
• Conclusion not all histologic findings of
  residual disease represent viable tumor
• Iatrogenic tumor cell displacement recognized,
  papillary lesions, DCIS (Bleiweiss JCO, 2006)
• What does this mean for micrometastases?
• Should they be ignored?
• Can micrometastases predict non-SN metastasis,
  whether additional micrometastases or
  macrometastases?
• Prognostically, may not add much information
  above and beyond tumor size and grade
• Conclusions
• ITC can be ignored
• Micrometastases should be treated with completion
  ALND or systemic therapy
• If completion ALND, and other nodes are negative,
  treatment should be based on the characteristics
  of the primary tumor, not the presence of the
  micrometastasis

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Sentinel Node BiopsyMicromets

• Are these findings real?
• Are nanometastases prognostic?
• Should micrometastases be ignored?

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Sentinel Node BiopsySignificance of ITC and
Micromets

• Where does one go from here?
• Data from randomized studies pending
• NSABP B-32
• ACOSOG Z10
• IBCSG 230-1 focused specifically on micromets
• New randomized studies incorporate gene signature
  patterns as prognostic tools
• Trial Assigning IndividuaLized Options for
  Treatment (Rx), or TAILORx
• MINDACT (MIcroarray for Node negative Disease may
  Avoid ChemoTherapy).
• Will micrometastases be as/more/less prognostic
  than a gene signature?

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Intraoperative SN Evaluation

• Abstract 26, Sentinel Node Biopsy in Invasive
  Ductal Carcinoma, Invasive Lobular Carcinoma,
  Favorable Histologic Subtypes
• Abstract 28, Multiplex Molecular Assay Has
  Improved Sensitivity over Histologic
  Intraoperative Nodal Metastases Tests

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Abstract 26Sentinel Node Biopsy in IDC, ILC, and
Favorable Subtypes

• Single institution, 5,298 consecutive patients
  with T1-3 invasive carcinoma, 1996 to 2004
• SLN bx with frozen section (FS)
• For IDC and ILC, but not Fav, yield increased
  with Tumor Size
• Sensitivity and yield of FS were higher with
  patients lt 50, increasing tumor size, and AL
  invasion.
• Yield of FS was lt 10 for all patients with ID/IL
  tumors lt 1 cm in size who were older than age 60.

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Abstract 26Sentinel Node Biopsy in IDC, ILC, and
Favorable Subtypes

• Conclusion for ID and IL, overall sensitivity is
  gt 50
• For any individual with age gt 60, T1a or b tumor
  of any histology, yield lt 10
• Intraoperative FS is not worthwhile for this low
  yield subset.

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Abstract 28, Multiplex Molecular Assay

• Standard HE processing of axillary node samples
  2 to 5, and will miss 10 to 15 of nodal
  metastases
• Intraoperative evaluation even less sensitive

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Abstract 28, Multiplex Molecular Assay

• RT-PCR kit for intraoperative SN evaluation
• GeneSearch BLN Assay
• Markers
• Mammoglobin (breast)
• Cytokeratin 19 (epithelial)
• Closed tube system
• If either or both are positive, node is
  positive
• Approximately ½ hour to perform test
• Does not require a pathologist
• Price not set

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Abstract 28, Multiplex Molecular Assay

• RT-PCR kit for intraoperative SN evaluation
• Approximately 1,000 cells in a .2 mm micromet
• Assay designed to report lt 1,000 cells as
  negative
• Therefore, will detect metastases gt .2 mm and
  give a positive result
• Clinical trial design
• Half of lymph node sent for standard SN
  processing
• Half of lymph node sent for RT-PCR

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Abstract 28, Multiplex Molecular Assay

• FS used at 11 sites testing 319 patients
• TP used for 29 subjects

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Abstract 28, Multiplex Molecular Assay

• Are these results real?
• RT-PCR has been used for evaluation of axillary
  nodes previously, not novel
• Prior difficulty has been false positive findings
  and complexity of performing assay in real time
• Addition of real time evaluation of nodal
  material, and quantitative assessment of RT-PCR
  findings is novel
• No other publications for direct comparison

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Abstract 28, Multiplex Molecular Assay

• Where do we go from here?
• Additional data forthcoming from company
  regarding cost
• Weigh cost of assay versus cost of return trip to
  OR for completion ALND
• Long term
• Where will SNB fit compared to gene signature
  assays, such as Mammaprint, Oncotype DX?
• Will SNB become obsolete?

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Abstract 27, The RACS/SNAC Trial

• 32 Sites in Australia/New Zealand
• SNB ALND (RAC), 544 patients
• SNB /- Delayed ALND if SN (SNBM), 544 patients
• Surgeon accreditation required
• Lymphoscintigraphy and blue dye
• Outcomes measures
• To assess performance of SNB
• To assess morbidity of SNB vs ALND in first 12
  mos
• Subjective symptoms
• Objective findings
• Complication rates

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Abstract 27, The RACS/SNAC Trial

• Patient characteristics
• 1,088 patients
• Mean age 60
• Identification
• Screening 58
• Mean tumor size 1.6 cm
• Breast conservation 87
• Mapping technique
• Tracer 89
• Blue dye 99
• Blue dye alone 11
• Mean number of SN, 1.7 nodes
• Mean number of SN in RAC 14.6 nodes /- 7

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Abstract 27, The RACS/SNAC Trial

• Results
• SNB performance
• Conclusions
• SNB is accurate
• SNB has lower morbidity
• Should dysfunction in SNBM group decreased over
  time
• Arm swelling in RCA group increased over time

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Abstract 27, The RACS/SNAC Trial

• Are these findings real?
• SB accuracy rate comparable to that seen in other
  randomized trials
• Lymphedema rate for SNB alone arm higher than
  originally expected, but lower than that seen in
  other trials
• NSABP B32
• Z10
• Almanac

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Abstract 27, The RACS/SNAC Trial

• Where does one go from here?
• SNB alone remains attractive from a quality of
  life perspective
• Still SNB alone is not without significant
  symptoms
• Is SNB oncologically safe?
• Survival data lacking from this study
• Question remains unanswered
• NSABP B32 pending
• Z10 pending

27
CALGB Study C9343 Update

• Clinical T1N0, ER , age 70
• 636 women enrolled 1994 to 1999
• Tam RT 317
• Tam No RT 319
• Previous report 5 year f/u
• Current update 7.9 year f/u

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CALGB Study C9343 Update

• Principle Outcome Measures
• IBTR
• Frequency of mastectomy
• Time to distant metastases
• Breast cancer specific mortality
• All cause mortality

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CALGB Study C9343 Update

• Principle Outcome Measures
• Conclusions
• WB-XRT reduces IBTR 5.3 for women 70, clinical
  T1N0, ER pos
• WB-XRT reduction in mastectomy 1 vs 3, pNS at
  7.9 years f/u
• Breast cancer specific mortality identical at 2
  at 7.9 years f/u
• All cause mortality 26 for both w or w/o RT at
  7.9 years f/u

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CALGB Study C9343 Update

• Is this real? Probably so.
• NSABP B-21
• Fyles subset analysis
• Milan III
• This study just proves point
• IBTR is less likely as patients age

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CALGB Study C9343 Update

• Where does one go from here?
• Arimidex replacing Tamoxifen
• Arim reduces IBTR compared with Tam
• Arim alone even more compelling in women 70
• However, APBI will replace WB-XRT
• APBI easier on patients, better tolerated, than
  WB-XRT
• Will effectiveness of lower morbidity of APBI
  diminish arguments against WB-XRT in terms of
  time, cost, complications?
• NSABP B39 in progress