pathological response post neo-adjuvant chemotherapy in ......sign guidance. treatment of primary...
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Pathological response post
neo-adjuvant chemotherapy in
breast excision specimens
Mubashar Ahmed ST-1, RVI
Supervisor: Yvonne Bury,
Consultant Histopathologist, RVI
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Introduction
Most centres offer neoadjuvant chemotherapy(NACT).
Aims of pathological assessment
◦ evaluation of treatment effects
◦ responsiveness to chemotherapy
◦ tumour down staging
Snapshot of our current practice
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NHSBSP 2014 guidance
Tumour response:
◦ Complete pathological response
◦ Partial response to therapy
◦ No evidence of response to therapy.
Nodal response:
◦ No evidence of metastatic disease
No changes in the lymph nodes.
Response/’down-staging’, e.g. fibrosis.
◦ Metastatic disease present
Evidence of response
No response to therapy.
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Aim and Objectives
To assess current practice in context of neo-adjuvant chemotherapy
To Assess
◦ current types of specimens
◦ number of blocks sampled and use of large tissue blocks
◦ frequency of local pathological complete response
◦ status quo in view of the 2014 NHS BSP guidelines regarding reporting of tumour characteristics and predictive factors
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Audit Standards
100 % reporting of prognostic and predictive in Pre-
NACT cores
histological grade and sub-type
ER
HER-2 status should have been determined in the
majority of core biopsies during the audit period.
Lymph node status should be assessed 100% by imaging
of the axilla and pathological evaluation (FNA or core
biopsy) if indicated
(pCR) should be similar to the rates reported in the
literature (12.1-25.8%)
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Sampling & Data collection
All breast excision specimens from
patients received NACT.
Oct 2012-Feb 2015.
Data collected from APEX and Pathosys
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Findings
Total Number of cases =20
45% 55%
Specimen Type
Mastectomy Wide Local Excision
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Blocks
Average 28 blocks per case
0
2
4
6
8
10
12
Yes No unknown
Large tissue blocks used
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Histological Evidence of Tumour
Present
75%
Absent
25%
5% 5%
90%
Tumour type pre-treatment
Mixed Lobular Ductal NST
Evidence of Tumour
post treatment
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Residual Tumour Size
0.11 1.2 2 3 9 9
24 25 25 28
36
45 45
73
90
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Residual tumour size (mm)
Residual tumour size (mm)
Most of these tumours were
large at time of diagnosis
Difficult to assess ER,PR and
HER 2 on small tumours
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Pre-treatment assessment
92%
93%
94%
95%
96%
97%
98%
99%
100%
101%
PR not routinely assessed
unless ER is negative; therefore PR has not been
included into the audit.
SOP change in July 2013: HER-2 status was assessed on
excision specimens.
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Tumour Grade
0
2
4
6
8
10
12
14
Grade 1 Garde 2 Grade 3 No Invasive
tumour
Pre-NACT
Post NACT
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HER2 and ER Pre and Post NACT
0
2
4
6
8
10
12
14
ER
Pre NACT
Post NACT
0%
20%
40%
60%
80%
100%
HER 2
Post NACT
Pre-NACT
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PCR rate in audit population
Study Complete pathological response (pCR) of primary tumour
RVI Audit (NHSBSP-G) 25%
Chevalier 14.3%
Sataloff 25.8%
Mazouni Total 12.1%
pCR 3.4% (RVI 5%)
pCR with DCIS 8.6% (RVI 20%)
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PCR according to Chevallier et al.
1. Disappearance of all tumors both on
macroscopic and microscopic assessment.
2. In situ carcinoma present but no residual
invasive tumor and no metastatic lymph
nodes.
3. Invasive carcinoma present with stromal
changes(sclerosis, fibrosis).
4. Few modifications of the
appearance of the tumor.
1 10%
2 15%
3 55%
4 20%
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PCR according to Sataloff et al.
A: total or near total therapeutic effect (in the
latter case: scattered cells accounting for >5%
of the tumor surface).
B: subjectively >50% therapeutic effect but less
than total or near total.
C: >50% therapeutic effect.
D: no therapeutic effect evident
25%
30% 25%
20%
Type
A B C D
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Lymph nodes according to Sataloff
N-A: evidence of therapeutic effect, no
metastatic disease.
N-B: no nodal metastasis or therapeutic effect.
N-C: evidence of therapeutic effect but nodal
metastasis still present.
N-D: viable metastatic
disease, no therapeutic effect.
55%
5%
15%
10%
15%
A B C D X
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Histological Response to NACT
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Areas of good practice
100% pathology reporting of histological grade,
histological sub-type, ER and lymph node stage
95%- 100 % reporting of HER 2 on pre-
treatment cores.
pCR rates largely in keeping with international
levels (around 25%)
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Areas of good practice
Partial response was seen in 55% of cases
100% reporting of prognostic and predictive
factors Post NACT
The average number of blocks taken per
case was 28 blocks (SD 9)
Reporting of these cases by only 2
pathologists encourages less inter-observer
variability
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Areas for improvement:
Terminology for pathological response should
be brought in line with 2014 NHS BSP
guidelines
Increase the use of large blocks
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Areas for improvement:
Reporting of ER and HER-2 status in excision
specimens post NACT appears variable and
clarification of oncologic requirements should
be discussed.
Not all cases may have been identified on
Pathosys and greater awareness in marking
these cases as neo-adjuvant should be
encouraged among pathologists.
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Recommendations
Standardised terminology of reporting of pathological tumour response as recommend by 2014 NHS BSP guidelines.
Clarify with oncologists the requirements for re-testing ER and HER-2 on excision specimens following neo-adjuvant chemotherapy and recording these requirements in SOP on q-pulse.
Re-audit after 2 years in view of increasing numbers of patients receiving neo-adjuvant chemotherapy and oncoplastic surgery.
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References 1. 2014 NHS BSP guidelines (circulated as finalised draft version via QARC)
2. Marchiò C, Sapino A. The Pathologic Complete Response Open Question in Primary Therapy, Journal of the National Cancer Institute Monographs, No. 43, 2011, Oxford University Press
3. Mazouni et al. Inclusion of taxane, particularly weekly paclitaxel, in preoperative chemotherapy improved pathologic complete response rate in estrogen receptor-positive breast cancers. Annuals of Oncology 18: 874-880,2007
4. SIGN Guidance. Treatment of primary breast cancer . Neoadjuvant systemic therapy, 2009
5. Mazouni et al. Residual Ductal Carcinoma In Situ in Patients With Complete Eradication of Invasive Breast Cancer After Neo-adjuvant Chemotherapy Does Not Adversely Affect Patient Outcome. Journal of clinical oncology VOLUME 25 _ NUMBER 19 _ JULY 1 2007
6. Chevallier B, Roche H, Olivier JP et al. Inflammatory breast cancer. Pilot study of intensive induction chemotherapy (FEC-HD) results in a high histologic response rate. Am. J. Clin. Oncol. 1993; 16; 223–228.
7. Sataloff DM, Mason BA, Prestipino AJ et al. Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: a determinant of outcome. J. Am. Coll. Surg. 1995; 180; 297–306.
8. Pinder et al. Laboratory handling and histology reporting of breast specimens from patients who have received neoadjuvant chemotherapy. Histopathology 2007, 50, 409–417.
9. MD Anderson website http://www3.mdanderson.org/app/medcalc/index.cfm?pagename=jsconvert3