Review
Breast specimen handling and reporting in the post-
neoadjuvant setting: challenges and advances
Miralem Mrkonjic,1,2 Hal K Berman,1,2 Susan J Done,1,2 Bruce Youngson,1,2
Anna Marie Mulligan1,2
1
Laboratory Medicine Program, Summary
University Health Network, Neoadjuvant systemic therapy is becoming more
Toronto, Ontario, Canada
2
Laboratory Medicine and commonly used in patients with earlier stages of breast
Pathobiology, University of cancer. To assess tumour response to neoadjuvant
Toronto, Toronto, Ontario, chemotherapy, pathological evaluation is the gold
Canada standard. Depending on the treatment response, the
pathological examination of these specimens can be
Correspondence to quite challenging. However, a uniform approach to
Dr Anna Marie Mulligan,
Laboratory Medicine Program, evaluate post-neoadjuvant-treated breast specimens has
University Health Network, been lacking. Furthermore, there is no single universally
Toronto, ON M5G 2C4, Canada; ​ accepted or endorsed classification system for assessing
annamarie.​mulligan@​uhn.​ca treatment response in this setting. Recent initiatives
have attempted to create a standardised protocol for
Received 27 November 2018
Accepted 28 November 2018 evaluation of post-neoadjuvant breast specimens.
This review outlines the necessary information that
should be collected prior to macroscopic examination
of these specimens, the recommended and most
pragmatic approach to tissue sampling for microscopic
examination, describes the macroscopic and microscopic
features of post-therapy breast specimens, summarises
two commonly used systems for classifying treatment
response and outlines the critical variables that should
be included in the final pathology report.
Introduction
Neoadjuvant therapy refers to the treatment of
patients before surgical removal of carcinoma.1
In patients with invasive breast carcinoma, this
is usually some combination of chemotherapy,
hormone receptor blockade and human epidermal
growth factor-2 (HER2) receptor monoclonal anti-
body, but may also include radiation therapy. Tradi-
tionally, neoadjuvant systemic therapy has been
used for either downsizing carcinomas to facilitate
►► http://​​dx.​​doi.​​org/​​10.​​1136/​ breast-conserving surgery or for downsizing previ-
jclinpath-​2018-​205592 ously unresectable locally advanced breast carci-
►► http://​​dx.​​doi.​​org/​​10.​1136/​ nomas.2 3 Supported by evidence from multiple
jclinpath-​2018-​205595 randomised trials showing comparable rates of
►► http://​​dx.​​doi.​​org/​​10.​1136/​
jclinpath-​2018-​205596 survival or overall disease progression between
►► http://​​dx.​​doi.​​org/​​10.​1136/​ neoadjuvant and adjuvant systemic chemotherapy
jclinpath-​2018-​205634 regimens, neoadjuvant therapies are increasingly
being offered as an alternative to adjuvant therapy,
particularly in women with early stage high-risk
breast cancer.4–10 While more frequent local recur-
© Author(s) (or their
employer(s)) 2019. No rence rates associated with neoadjuvant chemo-
commercial re-use. See rights therapy in the setting of breast-conserving surgery
and permissions. Published have been reported, this does not impact overall
by BMJ. survival.10 Furthermore, the neoadjuvant setting
To cite: Mrkonjic M, provides an opportunity to assess tumour response
Berman HK, Done SJ, to different systemic chemotherapeutic agents and
et al. J Clin Pathol provides an ideal setting to study biomarkers of
2019;72:120–132. responsiveness and resistance to novel therapeutic
120   Mrkonjic M, et al. J Clin Pathol 2019;72:120–132. doi:10.1136/jclinpath-2018-205598
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agents in the clinical trials setting.9 The United
States Food and Drug Administration (FDA) has
recommended complete pathological response as
an end-point for accelerated approval of new agents
for neoadjuvant treatment of high-risk early stage
breast cancer11 12; however, improved event-free
survival still remains the end-point for full FDA
approval.13
Response to neoadjuvant systemic therapy is
an excellent predictor of outcome,13 and achieve-
ment of pathological complete response (pCR) is
a prognostic predictor of long-term outcome with
significantly better disease-free survival and overall
survival.14 15 In addition, poor response to neoad-
juvant treatment provides opportunities to patients
for supplementary or alternative postsurgical ther-
apies.16 It is important to note that complete clin-
ical tumour regression does not correlate well with
complete pathological response. Between 60% and
80% of patients considered to have had a complete
clinical response have residual microscopic disease,
while 20% of patients with clinically suspected
residual disease have complete pathological
response.17 Therefore, thorough macroscopic and
microscopic assessment by the pathologist remains
the gold standard for determining complete treat-
ment response.
Responses to preoperative systemic therapies are
variable and assessment of these specimens pose
significant challenges to pathologists. Centralised
reviews of pathology reports reveal huge varia-
tion in handling and reporting between centres
resulting in substantial differences in the patho-
logical complete response rates.18–20 As such,
there is a need for a standardised and universally
accepted protocol for pathological evaluation and
reporting. A recent multidisciplinary initiative by
the Breast International Group–North American
Breast Cancer Group (BIG-NABCG) aimed to
produce standardised guidelines for evaluation and
reporting of post-neoadjuvant breast specimens.13
In this review, we will outline the challenges faced
by pathologists evaluating post-neoadjuvant breast
specimens, summarise the most practical guide-
lines for macroscopic and microscopic evaluation,
and present the most salient features for adequate
reporting of these specimens.
Prior to gross examination
Detailed clinical and radiological information is
essential for these specimens as the tumour site(s)
can be difficult to appreciate on macroscopic exam-
ination. Several initiatives have recommended
 Review

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Figure 1  Breast MRI with examples of radiological neoadjuvant treatment response. Patient before (A) and after (B) neoadjuvant therapy. Post-
therapy breast MRI demonstrates enhancement around the radiological clip site without evidence of residual carcinoma. Patient before (C) and after
(D) neoadjuvant therapy. Post-therapy breast MRI demonstrates minimal therapeutic response.

that all relevant clinical information accompany the specimen
requisition forms and have provided examples of requisition
templates.2 13 Alternatively, review of the documentation in the
electronic patient record is required. Multidisciplinary collabo-
ration and communication is essential as neoadjuvant therapy
creates challenges for all involved disciplines.16
Pathology
If the image-guided core-needle biopsy was performed at an
outside institution, and the slides are not available for review, the
clinical documents should contain the original pathology report
or a summary including the following: histological tumour
type, preliminary tumour grade, biomarker status and any other
parameters used to inform neoadjuvant treatment decisions.13
Similarly, original pathology reports for all fine-needle aspi-
rates of radiologically suspicious axillary lymph nodes should
be included.
Diagnostic imaging
Pre-treatment imaging should be performed for clinical staging
at the time of diagnosis. A detailed description of the tumour
dimensions and location is required with an o’clock radius and
distance from the nipple being superior to the quadrant loca-
tion.13 This applies to all additional tumour foci as well as the
relationships between additional foci to the main tumour mass.
Clip placement at the time of diagnostic biopsy is strongly
recommended even if mastectomy is planned.21 Radiological
clips can subsequently be used to localise the tumour bed(s) in
cases with complete radiological response (figure 1). Presence of
calcifications associated with tumour should be noted as they can
be subsequently used to localise the lesion post-therapy.13
As the presence of nodal metastasis is a key prognostic indi-
cator and also plays a major role in treatment planning,22–25 the
axillary lymph nodes should be assessed and the report should
describe the number and dimensions of the most concerning

Figure 2  Spectrum of macroscopic changes observed in multiple post-neoadjuvant breast specimens. (A) Focal haemorrhagic area with no residual
tumour mass or tumour bed, (B) fibrous breast tissue without grossly visible tumour mass, (C) small focus of residual carcinoma within fibrous tumour
bed (black asterisk), (D) well-circumscribed firm solid mass (red circle) and (E) spiculated hard tumour mass.
Mrkonjic M, et al. J Clin Pathol 2019;72:120–132. doi:10.1136/jclinpath-2018-205598 121
 Review
Figure 3  Example of specimen mapping for microscopic evaluation. Lumpectomy specimen was sectioned into four slices, oriented from medial
to lateral. A firm fibrous mass was identified in tissue slices 2, 3 and focally in 4. Black frames indicate tissue sampled: full-face of the largest cross-
sectional area of mass with respective margins and skin in slice 3, additional sections of mass and margins in slice 2, adjacent areas with medial and
lateral margins in tissue slices 1 and 4, respectively. Orientation markers: S, superior; I, inferior; A, anterior; P, posterior.
lymph nodes. The National Comprehensive Cancer Network
guidelines recommend pathological confirmation of all clini-
cally palpable lymph nodes using ultrasound-guided sampling
methods.26 Axillary ultrasound combined with fine-needle aspi-
ration (FNA) of abnormal lymph nodes have high sensitivity and
specificity for detecting lymph node metastases.22 Response to
neoadjuvant therapy in the lymph nodes may be so pronounced
that any involved lymph node may appear unremarkable on
subsequent imaging. Therefore, if an axillary lymph node was
sampled by FNA, clip placement for future localisation of that
lymph node is strongly recommended as it improves accuracy of
sentinel lymph node biopsy.26 27
Post-treatment imaging should reflect the clinical response to
therapy as well as the dimensions of the tumour bed and the rela-
tionship to the radiological clip. Clinical response to therapy of
any abnormal axillary lymph node should also be noted. As clips
can migrate post-insertion, their position relative to the tumour
mass, tumour bed and positive lymph node should be reported.
Medical oncology
The type and duration of presurgical chemotherapy should be
available in the clinical record. Patient participation in clinical
trials should be highlighted and noted on the requisition form
especially if tissue sampling and processing requires modifica-
tions to the standard institutional protocol.
Surgery
Surgical resection is based on preoperative imaging, and all detect-
able residual disease should be excised with clear margins.28–30
The optimal margin width in the neoadjuvant setting is unknown
with a recent study demonstrating no difference in disease-free
survival and overall survival for margins <1 mm versus >1 mm.31
For cases with complete radiological response, the tumour bed
with radiological clip(s) should be removed. Any intraoperative
localisation techniques should be noted and careful specimen
orientation is imperative and applies to all additional speci-
mens, such as margin revisions. Sentinel lymph node biopsy is
the standard approach for axillary staging in patients with clini-
cally negative lymph nodes22 with recommended resection of at
least two sentinel lymph nodes.32 Completion of axillary lymph
node dissection is not required if the sentinel lymph nodes are
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negative for metastases.26 32 Removal of positive axillary lymph
node(s) with a sentinel lymph node biopsy before neoadjuvant
therapy is discouraged as it prevents the assessment of treatment
response in the lymph nodes. On the other hand, post-treatment
lymph node assessment is strongly recommended, as the treat-
ment response in the lymph nodes is a major prognostic vari-
able.33 Emerging evidence suggests that, in a neoadjuvant setting,
sentinel lymph node biopsy may be an appropriate alternative to
axillary node dissection in clinically node-positive patients.34–37
Previously clipped lymph nodes are identified as sentinel lymph
nodes in 75% of cases and intraoperative localisation or patho-
logical assessment is necessary to ensure that the clipped lymph
nodes have been resected.32 Removal of all sentinel lymph nodes
and clipped lymph nodes has been found to reduce the false
negative rates.27 Axillary lymph node dissection is recommended
if the clipped node has not been resected or if residual disease is
identified within the sentinel lymph node.32
Gross examination and sampling of resection
specimens
Lumpectomy and mastectomy specimens
Macroscopic examination of neoadjuvant surgical specimens and
identification of tumour bed can be particularly challenging for
pathologists. Tumour response to neoadjuvant therapy can be
very dramatic with residual tumour bed resembling unremark-
able fibrous breast tissue (figure 2). Accompanying calcifications,
fat necrosis or haemorrhage may be present. Prior needle core
biopsy reaction site, if present, is useful, to identify the loca-
tion of the tumour bed. Identification of radiological clips,
macroscopically or with specimen radiographs, is helpful and
may be essential. Clinical judgement should be used regarding
tissue collection for research in this setting. Regardless of spec-
imen size/type, careful mapping using specimen photography or
diagrams is necessary to allow reconstruction of the specimen
and to facilitate correlation of macroscopic and microscopic
findings (figure 3).18
Specimen preparation and processing protocols do not differ in
the neoadjuvant setting. Lumpectomy specimens are inked fresh
according to the institutional protocols and sliced at 3 mm to 5
mm intervals to ensure formalin penetration. Small specimens
(<5 cm in greatest diameter or <30 g) can be submitted in their
Mrkonjic M, et al. J Clin Pathol 2019;72:120–132. doi:10.1136/jclinpath-2018-205598
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Figure 4  Spectrum of microscopic changes in the breast post-neoadjuvant therapy. (A) Normal breast with atrophic terminal duct lobular unit
and stromal fibrosis. Note prominent myoepithelial cell layer and nuclear hyperchomasia of epithelial cells. (B) Fibrous tumour bed without residual
carcinoma and absence of normal breast parenchyma. Higher magnification of fibrous stroma (insert). (C) Tumour bed with chronic inflammation,
foamy macrophages, giant cells and cholesterol clefts without evidence of residual carcinoma. (D) Clip-reaction site in the tumour bed without
evidence of residual carcinoma. (E) Scattered small nests of tumour cells in tumour bed (black asterisk), representing a residual tumour cellularity of
approximately 1%. (F) The only focus of residual carcinoma is identified adjacent to a clip-site reaction (black asterisk) highlighting the importance of
identifying the radiological clip. Higher magnification (insert) demonstrates invasive carcinoma. (G) Heterogeneous response to neoadjuvant therapy.
Tumour area with near-complete treatment response (white asterisk) adjacent to an area with minimal treatment response (black asterisk). Overall,
this represents an average residual tumour cellularity of 30%. (H) Minimal response to neoadjuvant therapy with residual carcinoma within fibrotic
stroma and an average residual tumour cellularity of 50%. (I) Prominent retraction artefact surrounding the nests of tumour cells mimicking lymphatic
vascular invasion (LVI). (J) Residual invasive ductal carcinoma cells with foamy cytoplasm mimicking histiocytes. Insert demonstrates CAM 5.2
immunohistochemical staining in these cells, confirming their epithelial nature. (K) Single filing of residual invasive ductal carcinoma cells. (L) The only
residual carcinoma that can be identified is present as lymphovascular tumour emboli (LVI).

Mrkonjic M, et al. J Clin Pathol 2019;72:120–132. doi:10.1136/jclinpath-2018-205598 123

 Review

Figure 5  Spectrum of microscopic changes in axillary lymph nodes post-neoadjuvant therapy. (A) Atrophic lymph node demonstrating sinus J Clin Pathol: first published as 10.1136/jclinpath-2018-205598 on 22 January 2019. Downloaded from http://jcp.bmj.com/ on 23 January 2019 by guest. Protected by copyright.
histiocytosis and haemosiderin-laden macrophages with no evidence of metastatic carcinoma or scarring. (B) Lymph node with a small subcapsular
scar and no evidence of residual metastatic carcinoma. (C) Lymph node with a prominent fibrous scar and foamy macrophages. Fibrous scar extends
beyond the lymph node capsule suggesting pre-treatment extranodal extension or pre-treatment tissue sampling (fine-needle aspiration or core
biopsy). (D) Lymph node completely replaced by a fibrous scar and without evidence of residual carcinoma. Immunohistochemistry for keratins may
be useful to rule out isolated tumour cells. (E) Isolated tumour cells marked with a white asterisk identified in subcapsular metastatic tumour bed. (F)
Micrometastatic carcinoma (white asterisk) with minimal scarring. (G) Macrometastatic carcinoma with a background of fibrosis indicating partial
response of metastatic carcinoma to neoadjuvant therapy. (H) Macrometastatic carcinoma without any evidence of treatment response.

entirety.13 18 Residual tumour mass, tumour bed and radiolog-
ical clip site should be noted and measured. Tumour bed grossly
extending to the resection margins should be documented. With
larger lumpectomy specimens, targeted representative sections
are taken with careful and accurate representation of the tumour
bed, surrounding adjacent tissue and resection margins.
124
Neoadjuvant mastectomy specimens are inked fresh according
to the institutional protocols and sliced at 0.5 cm to 1.0 cm inter-
vals to ensure formalin penetration. Grossly identified tumour(s),
tumour bed(s) and clip site(s) should be documented. Sampling
should cover the pre-treatment size of the tumour and tissue just
beyond the visible lesion should be sampled for evaluation of
Mrkonjic M, et al. J Clin Pathol 2019;72:120–132. doi:10.1136/jclinpath-2018-205598

microscopic extent.13 In line with BIG-NABCG recommenda-
tion, when residual carcinoma is grossly identified, one full-face
cross-section of the slice with the largest tumour area should be
submitted for microscopic assessment. For large tumours, five
representative sections of such a full-face are submitted. Several
such full-face sections 1 cm apart may be submitted to deter-
mine the full extent of the tumour. This approach is sufficient to
assess the tumour size and cellularity for both the American Joint
Committee on Cancer (AJCC) staging and the residual cancer
burden (RCB) calculations.16 25 38–40
Residual tumour and tumour bed may be difficult to identify in
patients with a good response to neoadjuvant therapy. Correla-
tion with preoperative imaging should be used to help localise
the tumour site and, if possible, specimen radiographs should be
used to locate the clip site and/or calcifications, if known to be
associated with tumour prior to treatment. The pre-treatment
size of the tumour will determine the extent of the sampling.
A systematic approach is preferred over exhaustive sampling
of fibrotic areas or blind submission of an arbitrary number of
blocks. This is achieved by sampling of the correct area best
identified by careful clinical and radiological correlation.16
BIG-NABCG recommends the following approach when no
residual carcinoma is identified: one full-face (or five represen-
tative sections of a full-face for large tumours) of the cross-sec-
tion of the pre-treatment area of involvement per 1 cm (1–2 cm
for large tumours) of pre-treatment size up to a maximum of 25
blocks.13 16 Conversely, the US FDA recommends at least one
block per centimetre of the pre-treatment tumour size, or at least
10 blocks in total, whichever is greater.12 16 The Royal College of
Pathologists (UK), however, does not make any distinct recom-
mendations for specimen sampling in the neoadjuvant setting.41
In the case of multifocal disease, each tumour should be handled
in the same manner and sections documenting breast tissue in
between the tumours should be submitted. Additional sections
may have to be taken in cases where microscopic findings do not
correlate with the gross impression.
Axillary contents
As with breast specimens, preparation and processing protocols
for axillary contents/sentinel lymph nodes do not differ in the
neoadjuvant from the non-neoadjuvant setting. All identified
lymph nodes should be sectioned at 2 mm intervals in the long
axis of the lymph node and, in the absence of gross evidence of
disease, entirely submitted for microscopic examination. Serial
slicing at 2 mm intervals results in detection of most macro-
metastases.42 Care should be taken to identify and document
radiological clips placed following prior FNA procedures and
correlation with specimen radiographs may be helpful in these
cases.32 When no gross lymph nodes are identified, any tissue
that may represent a lymph node should be submitted for micro-
scopic examination.18 All grossly involved lymph nodes should
be documented along with grossly evident extranodal disease.
Representative sections of grossly involved lymph nodes demon-
strating the largest focus of metastatic carcinoma and extranodal
extension are appropriate.16
Microscopic examination
Breast tissue specimens
Chemotherapy-induced changes in normal breast tissue are well
documented. These include significant atrophy of the terminal
ductal lobular units (TDLUs).43 44 Lobular acini appear reduced
with attenuation of lobular/ductal epithelium, intralobular
sclerosis and, as a result, the myoepithelial cell layer becomes
Mrkonjic M, et al. J Clin Pathol 2019;72:120–132. doi:10.1136/jclinpath-2018-205598
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more prominent (figure 4). Occasional atypical epithelial cells
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with large hyperchromatic nuclei, visible nucleoli and vacuo-
lated cytoplasm may be seen and should not be mistaken for
non-treatment-related significant epithelial atypia.
Chemotherapy-induced changes in breast carcinoma result
in stromal fibrosis, oedema and fibromyxoid changes with
chronic inflammatory infiltrate, haemosiderin-laden macro-
phages, foreign body giant cells, and cholesterol clefts with
a total absence of normal breast ducts and TDLUs (figure 4).
Haemosiderin-laden macrophages, foreign body giant cells and
fat necrosis are also present in biopsy site reactions and should
not be confused with treatment response. Tumour response to
preoperative systemic therapy is highly variable with hetero-
geneous change in tumour size and cellularity ranging from
complete resolution, concentric contraction, scattered patterns
of residual disease, to minimal response. Even in the absence of a
significant decrease in tumour size, carcinomas are typically less
cellular post-chemotherapy and the distribution of cells varies
from uniform to haphazard.1 Residual cancer cells, if present, are
seen as infiltrating cords, nests and singly dispersed individual
cells resembling lobular carcinoma or histiocytes (figure 4).43
Difficult cases may require immunohistochemistry to distinguish
between residual tumour cells and histiocytes (figure 4). Most
common cytomorphological changes induced by chemotherapy
include nuclear hyperchromasia, nuclear pleomorphism, abun-
dant hypereosinophilic cytoplasm and cytoplasmic vacuolisation.
Apart from decreased cellularity, most carcinomas do not change
in appearance and overall histological grade.1 Some tumours
may appear to be of higher nuclear grade because of cytomor-
phological changes induced by chemotherapy17 45 46; however,
this is usually offset by decreased tumour cell mitotic activity.
Nevertheless, actual change in tumour histological grade can
only be assessed by comparison of the post-treatment tumour
to the pre-treatment tumour in the needle core biopsy, if one is
available. Even then, tumour heterogeneity has to be considered.
Change in the histological grade of cancers post-chemotherapy
has not been correlated with clinical outcome and its prognostic
significance is unknown.1 It is important to note that pre-treat-
ment and post-treatment tumour histological grade, tumour size
and lymphovascular invasion (LVI) are correlated with distant
disease-free survival.45
Ductal carcinoma in situ (DCIS) and lymphovascular
tumour emboli are relatively resistant to treatment compared
with carcinoma invading the stroma and may represent the
only residual disease (figure 4).46 Residual tumour nests
may show marked retraction artefact in the fibrous stroma
mimicking lymphovascular invasion and immunohistochem-
istry may be useful to distinguish the two (figure 4). DCIS can
show a variable response to therapy from minimal alteration
to reduced distension and replacement of neoplastic cells by
macrophages.47 In some cases, only ducts with rare residual
neoplastic cells with marked nuclear atypia remain after treat-
ment. In these cases, it can be particularly challenging to
distinguish foci of residual DCIS from benign ducts with treat-
ment artefact.
Margins can be difficult to evaluate in the post-neoadjuvant
setting when there has been marked treatment response. In such
cases, the extent of the tumour bed can be difficult to appreciate
on radiological imaging, intraoperatively by the surgeon and even
macroscopically by the pathologist, and it may not be possible to
obtain an excision of the entire tumour bed surrounded by a
rim of normal tissue.1 In patients with a pCR, the significance
of tumour bed at the margin is unclear. However, in cases with
scattered residual foci of invasive carcinoma, presence of tumour
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bed at the resection margin in breast-conserving specimens may

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Table 1  Summary elements to be included in the post-neoadjuvant
predict for residual carcinoma in the breast.1
pathology report
Breast specimen
Axillary lymph nodes
Gross examination Comments
Axillary lymph nodes may become small and atrophic following
1. Time and date of tissue excision, placement Fixation and cold ischaemic
neoadjuvant therapy with depletion of lymphocytes and with
of tissue in formalin and duration of fixation in time are important if biomarker
prominent sinus histiocytosis (figure 5).43 Lymph node metastases formalin testing needs to be reported
with complete response to neoadjuvant therapy show hyaline 2. Procedure type
stromal scars, mucin pools, aggregates of histiocytes and haemo-
3. Tissue labelling, orientation by the surgeon and
siderin without viable tumour cells (figure 5). In some cases, a subsequent painting of the resection margins
diagnosis of pCR in lymph nodes cannot be definitively made as 4. Specimen dimensions: breast tissue, skin, nipple Depends on the procedure type
metastases can resolve without a scar or with minimal scarring and areola
(figure 5).1 Changes related to previous FNA can be identical 5. Description of any grossly visible lesion with Appearance, texture,
to regressed metastasis and cannot be reliably distinguished.48 dimensions and distances to the resection margins demarcation, relationship to
Partial response to therapy, on the other hand, is character- other lesions if present
ised by small clusters and individual tumour cells set in hyaline 6. If no visible gross lesion, description of fibrous
stromal fibrosis (figure 5). It is important to note any treatment parenchyma, radiological clip or biopsy site
effect in positive lymph nodes as these patients have better reaction
disease-free survival and lower relapse rates than patients with 7. Description of the uninvolved breast tissue Fatty or fibrous
positive lymph nodes without any treatment effects (figure 5).1 49 8. Specimen photography or diagrams of the
It is also recommended to report any histological findings in the sectioned breast tissue with gross lesion(s)
lymph nodes containing radiological clips.32 Overall, the pres- 9. Note if specimen X-rays were performed and
ence of residual lymph node disease confers a worse prognosis reported
regardless of the tumour response in the breast.50 A summary of 10. Mapping of all tissue sections submitted for With the aid of photograph or
microscopic examination diagram
all elements to be included in the post-neoadjuvant pathology
Microscopic examination Comments
report is provided in table 1.
While the AJCC 8th edition guidelines remain the same 1. Specimen, procedure and neoadjuvant setting
for assessing the metastatic involvement of the lymph nodes 2. Type of residual carcinoma If present
regardless of the treatment status, it is imperative to note that 3. Histological grade of residual tumour
the significance of lymph node metastases drastically changes 4. Dimensions:
post-chemotherapy. Post-treatment isolated tumour cells (ITCs) ►► Size of largest contiguous focus of invasive
carcinoma for AJCC staging (include span and
and micrometastases predict worse survival compared with the
focality of residual carcinoma)
same findings in the non-neoadjuvant setting.17 Furthermore, ►► Size of largest cross section of residual invasive
survival in patients with lymph node metastases measuring <1 carcinoma (“residual tumour bed”) in 2
mm and <2 mm (micrometastases) is similar to that of patients dimensions for RCB score
with macrometastases in the post-neoadjuvant setting.17 5. Tumour cellularity (%) Average cellularity across the
Molecular assays for assessment of sentinel lymph nodes are largest cross-section containing
discouraged by the BIG-NABCG as they do not allow evaluation residual carcinoma (including
of treatment response in the lymph node and the assays have not invasive and in situ disease)
been calibrated for detection of ITCs.18 51 6. Percentage of cancer within tumour bed that
represents in situ disease
7. Lymphovascular invasion
Complete pathological response and residual 8. Confluent tumour necrosis
disease classification systems 9. Distance to closest margins Include tumour bed at margins
Until recently, various definitions for complete pathological 10. Treatment effect Describe presence of treatment
response have been applied in neoadjuvant clinical trials in breast effect, biopsy site reaction, clip-
cancer, which hindered any cross-trial data interpretation.12 18 site reaction
The US FDA defines pCR as ypT ypN0 and ypTis ypN0.12 52 11. Other findings Including calcifications
Similarly, the AJCC 8th edition states that any residual inva- 12. Biomarker status If required
sive carcinoma in the breast or lymph nodes precludes classi-
Axillary lymph nodes
fication as pCR.40 This includes the presence of tumour within
lymphatic or vascular spaces (LVI) as well as isolated tumour Gross examination Comments
cells in lymph nodes.25 Conversely, the presence of in situ carci- 1. Tissue labelling, orientation by the surgeon and Proper precautions and disposal
localisation technique of radioactive material
noma after treatment (DCIS or LCIS) in the absence of residual
2. Specimen dimensions: for the overall specimen, Note any grossly identified
invasive disease constitutes a pCR.25 Mounting data with a
for each lymph node identified, and for the extranodal extension
strong consensus exists to include absence of invasive disease greatest metastatic focus identified
in the breast and the lymph nodes as a standard definition of
3. Description of lymph nodes Appearance of sectioned lymph
pCR.52–60 Patients with residual carcinoma that is present only in nodes
the lymph nodes have considerably inferior prognoses.52–60 On 4. Presence or absence of clip(s) Correlate with specimen X-ray
the other hand, the significance of in situ carcinoma is unclear Microscopic examination Comment
and patients with ypTis ypN0 have comparable survival with
1.Type of lymph nodes examined: sentinel and
ypT0 ypN0 patients.52 61
non-sentinel
Depending on the type and duration of neoadjuvant chemo-
therapy, different rates of pCR have been reported between breast Continued

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Table 1  Continued
Axillary lymph nodes
2. Number of lymph nodes identified and involved
by the metastatic carcinoma
3. Dimensions:
►► Size of single largest continuous metastatic
focus for AJCC staging
►► Size of the largest extent of lymph node
involvement by tumour cells including
intervening fibrosis for RCB score
4. Presence of extranodal extension
5. Treatment effect: number of lymph nodes with Including FNA/biopsy site
possible treatment effect including negative lymph reaction and clip-site reaction
nodes
AJCC, American Joint Committee on Cancer; FNA, fine-needle aspiration; RCB,
residual cancer burden.
cancer subtypes (table 2).45 52 62–67 However, consistent patterns
have emerged to demonstrate highest pCR rates among patients
with HER2-positive tumours, followed by those with triple-neg-
ative tumours and finally, patients with hormone receptor–posi-
tive tumours.45 52 62–67 Even though hormone receptor–positive
tumours are relatively chemoresistant, they do have the best
prognosis in the absence of chemotherapy and pCR rates cannot
be used reliably to predict recurrence-free survival.62
Pathological response (ie, reduction in pT and/or pN category)
that is less than a complete response is labelled a partial patho-
logical response (pPR), while no apparent change in the T or N
categories compared with pre-treatment assignment, or increase
in the T or N category indicates no response (NR) to treatment.25
Alternatively, some systems use a reduction in tumour cellularity,
as compared with pre-treatment tumour cellularity, to define a
pPR to therapy.2 68–70
Many studies have attempted to provide criteria for evalu-
ating pathological response after treatment. A limited list of such
studies with their proposed classification categories is provided
in table 3.
Merits of each classification system are beyond the scope of this
review; however, they collectively demonstrate that the degree
of response to treatment correlates with survival. Different clas-
sification systems also yield different estimates of future risk.13 60
The two most widely used systems to measure residual disease
are the AJCC system, currently in its 8th edition, and the RCB
calculator (table 4).25 38
Of note, when clearly separate tumours are identified grossly
that are confirmed microscopically to have intervening areas
of normal breast tissue and when these presented as multifocal
disease pre-treatment, the dimension of the largest focus is used
for staging using AJCC (with use of the (m) modifier, repre-
senting multiple foci of residual disease) and for determining the
tumour bed dimensions for the purpose of calculating the RCB
(see below).
Table 2  pCR rates across breast cancer subtypes
HR+/HER2− HR+/HER2+
pCR rates 4.4%–9% 17.3%–33%
Comments Best prognosis without Best survival, pCR less critical for
chemotherapy outcome
Lymph node conversion rates 13.1%–21% 36.6%
Ranges reflect different chemotherapy regimens, accrual methods and duration of therapy across trials. Increased pCR rates in HER2-amplified cancers were observed following
addition of trastuzumab or pertuzumab therapy, which are reflected in wide ranges of pCR rates.45 52 62–67
pCR, pathological complete response.
Mrkonjic M, et al. J Clin Pathol 2019;72:120–132. doi:10.1136/jclinpath-2018-205598
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The AJCC ypT category is based on the largest contiguous
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focus of residual invasive carcinoma (figure 6). Treatment-re-
lated fibrosis adjacent to residual disease is not included when
measuring the maximum dimension of the tumour. Cases with
scattered tumour nests that were part of a single tumour mass
before treatment will result in systemic artificial downstaging by
this system.13 For this reason, AJCC also recommends a descrip-
tion of the extent of residual carcinoma to be included in the
pathology report as this may assist the clinician in estimating
the extent of residual disease. Where possible, inclusion of the
pre-treatment clinical tumour stage (cT) category should be docu-
mented. When the only residual cancer in the breast is present
as lymphovascular tumour emboli (LVI), the tumour is classified
as ypT0; however, as noted above, pCR cannot be assigned in
these cases. Similarly, the largest contiguous tumour focus in the
lymph nodes is used for ypN classification and adjacent treat-
ment-related fibrosis is not included in the measurements. While
ITCs after chemotherapy is still considered ypN0(i+), it cannot
be regarded as a pCR. If a cancer is categorised clinical or patho-
logical M1 prior to therapy, it remains classified as M1 regardless
of the observed response to therapy.25 40 The post-neoadjuvant
yAJCC 7th edition classification has been shown to have prog-
nostic value.62 71
The RCB system calculates a prognostic score based on (1) a
two-dimensional measurement of the tumour bed demarcated
by residual carcinoma (figure 6), (2) the average residual tumour
cellularity (invasive and in situ disease), (3) the percentage of
residual disease that represents in situ disease, (4) the number
of positive lymph nodes and (5) the diameter of the largest
metastatic focus, inclusive of intervening treatment-related
fibrosis.38 A mathematical formula combines these variables into
a continuous index to define four RCB categories; RCB-0 for
pCR and RCB-1–3 represent progressively greater extents of
residual cancer. A web-based calculator and detailed instructions
are publicly available to calculate the RCB scores (http://www.​
mdanderson.​org/​breastcancer_​RCB).
There are some pitfalls to be aware of when calculating the
RCB (summarised in Bossuyt, Surgical Pathology Clinics, March
2018).16 The residual tumour bed may differ in size from the
microscopic ‘fibrous’ tumour bed as well as from the grossly
identified tumour bed. The perimeter of the residual tumour
bed is defined by residual cancer cells, even if these are widely
scattered and separated by treatment-induced fibrosis. There-
fore, this measurement is determined following microscopic
evaluation and it may be smaller or larger than the gross tumour
bed measurement. Determining the dimensions of the residual
tumour bed can be aided by dotting the cancer perimeter in
each slide and reconstructing the three-dimensional extent of
the disease with the help of a block diagram. Based on this, the
two largest dimensions can be measured and recorded (figure 6).
Within the dotted perimeter of the largest cross-sectional area,
the percentage tumour cellularity should be assessed in each
HR−/HER2+ HR−/HER2−
36.4%–50.3% 31.1%–36.8%
Prognosis poor if pCR not achieved pCR associated with excellent
prognosis
46.8%–64.7% 46.4%–49.4%
127
Review
Table 3  Systems for categorising neoadjuvant treatment response
System Categories
Feldman98 Group A: No macroscopic evidence of cancer in
1986 mastectomy or axillary contents
Group B: Macroscopic evidence of cancer in
mastectomy specimen
Bonadonna68 Grade 1: No overall reduction in tumour cells
1990 compared with pre-treatment core biopsy
Grade 2: Mild loss of invasive cells
Grade 3: Considerable, up to 90%, reduction in
tumour cells
Grade 4: Marked reduction of tumour cells, only
clusters of dispersed cells detected
Grade 5: No invasive carcinoma, DCIS only
Sinn99 0: No effect
1994 1: Resorption and tumour sclerosis
2: Minimal residual invasive tumour (<0.5 cm)
3: Residual non-invasive tumour only
4: No tumour detectable
6
Chevallier Class 1: Disappearance of all tumour, microscopically
1993 or macroscopically
Class 2: DCIS only, no invasive tumour and negative
lymph nodes
Class 3: Presence of invasive carcinoma with stromal
alterations
Class 4: Few modifications in tumour appearance
Sataloff100 Tumour
1995 T-A: total or near total therapeutic effect; <5%
tumour surface
T-B: >50% therapeutic effect but less than T-A
T-C: <50% therapeutic effect
T-D: no therapeutic effect
Nodes
N-A: no metastatic disease with evidence of
therapeutic effect
N-B: no nodal metastases or therapeutic effect
N-C: metastases present with therapeutic effect
N-D: metastases present without therapeutic effect
Honkoop101 pCR: no residual cancer in mastectomy or axillary
1998 lymph nodes
MPR: microscopic disease (scattered foci) with normal
macroscopic examination
MRD: gross residual disease with macroscopic tumour
or diffuse tumour infiltration microscopically
Kuerer102 1. No evidence of residual tumour
1998 2. <1 cm3 of residual tumour macroscopically,
residual microscopic tumour foci
3. >1 cm3 of residual tumour macroscopically
Pinder2 Tumour
2007 1. pCR: (i) no residual carcinoma or (ii) DCIS only
2. Partial response: (i) <10% tumour cellularity,
(ii) 10%–50% tumour cellularity, >50% tumour
cellularity compared with pre-treatment biopsy
3. No response to therapy
Nodes
1. No metastasis and no therapy changes
2. No metastasis but evidence of response
3. Metastasis with evidence of response
4. Metastasis without response
NSABP B-1817 pCR: no invasive tumour cells present
2002 pPR: scattered individual or small clusters of tumour
cells in a desmoplastic/hyalinised stroma
pNR: tumour lacking changes in pCR and pPR
Miller-Payne System69 Grade 1: no reduction in overall cellularity
2003 Grade 2: minor loss of tumour cells (<30%)
Grade 3: 30%–90% reduction in tumour cells
Grade 4: >90% loss of tumour cells
Grade 5: no invasive cells present, DCIS may be
present
Smith70 Tumour
2002 1. No reduction in overall cellularity
2. Mild reduction in tumour cells
3. Up to 90% reduction in cellularity
4. Marked disappearance with only small clusters
remaining
5. No invasive tumour, DCIS remaining
Nodes
1. True negative: no metastasis and no changes
2. Metastasis with no changes
3. Metastasis with changes
4. No metastasis, but changes
Residual Cancer Burden RCB-0: no carcinoma in breast and lymph node
(RCB)38 RCB-I: partial response (minimal residual disease)
2007 RCB-II: partial response (moderate residual disease)
RCB-III: chemoresistant (extensive residual disease)
128
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Table 3  Continued
Comments System Categories Comments
By macroscopic Clinical-Pathological Based on combined clinical stage (0–2 marks), HER2 status included
examination only Stage–Oestrogen/Grade pathological stage (0–2 marks), ER negative status (1 in new Neo-Bioscore
(CPS-OG) 84
mark) and high nuclear tumour grade (1 mark) system85
2011
Requires comparison to Neoadjuvant Response Pre-treatment clinical stage by MRI minus post-
pre-treatment biopsy Index (NRI)83 treatment ypT stage with additional points for near-
specimen 2010 pCR (1 point) or pCR (2 points)
0=no response to therapy and 1=pCR
Residual Disease in Residual tumour size (cm)×0.2+index of positive Based on modified
Breast and Nodes lymph nodes (0–3: none, 1–4, 5–7 and >7)+tumour Nottingham Prognostic
(RDBN)82 grade Index
2008 Level 1: pCR
Requires comparison to Level 2: 0.1–2.9
pre-treatment biopsy Level 3: 3.0–4.3
specimen Level 4: >4.4
yAJCC 8th edition25 pCR: no invasive carcinoma in breast and lymph node, Anatomical stage
2017 no LVI and no ITCs (ypT0 N0, ypTis pN0) groupings based on the
Developed for pPR: reduction in T and/or N stage TNM staging system
inflammatory carcinoma NR: no change or increase in the T or N stage
DCIS, ductal carcinoma in situ; ITC, isolated tumour cell; LVI, lymphatic vascular invasion; NR, no response; pCR,
pathological complete response; pPR, partial pathological response.
slide and the average cellularity calculated to include all fields
that fall within the tumour bed perimeter, even those with very
low cellularity or no disease. Tools are freely available at http://
www.​mdanderson.​org/​breastcancer_​RCB that provide a visual
aid in estimating the percentage of residual tumour cellularity.
RCB measurements are based on the largest residual tumour
bed. If smaller foci demonstrate higher cellularity, calculating
separate RCBs for these foci is worthwhile as these may yield
pCR and MPR are higher RCB scores.
regarded as one group
The RCB system has been shown to be reproducible.72 It
provides prognostic value independent of the yAJCC stage for
patients with stage II and III disease and across all phenotypic
subgroups of breast cancer.38 73 This has been shown to be the
case in multiple different institutional cohorts and with long-
term follow-up.45 60 62 74–76
Requires comparison A recent study compared the RCB and the AJCC staging
with pre-treatment
biopsy specimen
systems using the I-SPY 1 trial dataset.62 This study used the
seventh edition of yAJCC staging system; however, this should
not have impacted the anatomical TNM tumour staging based on
the eighth edition. Both systems identify patients with interme-
diate (4-fold) risk of relapse (RCB-1–2 and yAJCC1–2) and high
(11-fold) risk of relapse (RCB-3 and yAJCC3).62 Both systems
show the strongest association with recurrence-free survival in
triple-negative breast cancers, while hormone receptor positive
cancers have relatively low recurrence rates regardless of RCB
or yAJCC class.62 Patients who are RCB-3 or yAJCC3 and have
Requires comparison
with pre-treatment triple negative or HER2+ tumours have a higher risk of relapse
biopsy specimen
than all other patients.62 The study also found that in 34% of
cases, RCB and yAJCC staging systems are discrepant and this
is attributed to unequal weighting of positive lymph nodes
Modification of the
Miller-Payne System to
and the weighting of tumour cellularity in RCB. In discrepant
include lymph nodes cases, however, if one classification system identifies a patient as
having a high risk of recurrence, then that patient tends to have
an increased rate of recurrence regardless of the other system’s
ranking.62 Therefore, there is benefit to computing both scores
for patients in order to identify those with the highest risk of
relapse.
With rising interest in immunotherapeutic strategies, eval-
Based on an online uation of tumour-infiltrating lymphocytes (TILs) has garnered
calculator
considerable research interest. Emerging evidence indicates
that TIL density may be predictive for response to neoadju-
Continued vant therapy.77 A recent study indicates that high pre-therapy
TIL levels may be predictive of pCR for HER2-amplified breast
cancers.78 Furthermore, high TILs in post-neoadjuvant residual
Mrkonjic M, et al. J Clin Pathol 2019;72:120–132. doi:10.1136/jclinpath-2018-205598
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Table 4  Comparison of the AJCC 8th edition and RCB system
AJCC 8th edition RCB
Pathological complete response (pCR) No evidence of invasive carcinoma in the breast and axillary lymph No evidence of invasive carcinoma in the breast and axillary
nodes (ypT0 ypN0 or ypTis ypN0) lymph nodes
Tumour size Largest contiguous focus of residual invasive carcinoma for ypT stage Two dimensions of the largest cross-section of residual
carcinoma defines residual tumour bed
Tumour cellularity Not applicable Average cellularity of residual carcinoma
Tumour focality Multiple separate foci of residual invasive carcinoma designated as Calculate RCB for largest tumour focus±smaller foci if these
mypT stage show higher cellularity
LVI identified only Considered ypT0, but not pCR Area of the breast involved by LVI only determines the
residual tumour bed (in two dimensions)
Direct extension beyond breast Stage as for non-neoadjuvant setting Not applicable
Lymph nodes Size of largest contiguous metastatic focus for ypN staging Size of the largest extent of lymph node involvement by the
tumour cells including intervening fibrosis
No of lymph nodes involved Determines ypN stage, ITCs still considered ypN0(i+) All positive lymph nodes included
Location of lymph nodes involved Influences ypN2, ypN3 and ypN4 stages All positive lymph nodes included
Pathological partial response (pPR) Reduction in T and/or N stage Determined by the formula: RCB-I or RCB-II
No response (NR) No apparent change in the T or N categories or an increase in the T or Determined by the formula: RCB-III
N category
AJCC, American Joint Committee on Cancer; ITC, isolated tumour cell; LVI, lymphatic vascular invasion; RCB, residual cancer burden.

cancers may be an important predictor of survival in triple-neg-
ative breast cancers.79 80 The International Immuno-Oncology
Biomarker Working Group on Breast Cancer has recently
published recommendations to assess TILs in residual tumours
following neoadjuvant therapy.77 Initiatives to include TILs in
future classifications of neoadjuvant treatment response are in
progress.77
More complex staging systems that combine clinical and patho-
logical stage, tumour histological grade, proliferation index,
biomarker status and/or molecular testing are continuously

Figure 6  Illustration contrasting AJCC and RCB measuring techniques. (A) In the breast tissue, measurement of the single largest tumour focus
(black oval) is used to determine AJCC ypT stage (blue arrow). Measurements of the residual tumour bed for RCB (red arrows) is determined by the
span of residual invasive carcinoma (black circles) within a fibrous scar (pink star) and measured in two dimensions as outlined by the red rectangle.
The residual tumour bed can be smaller or larger than the fibrous scar. Average tumour cellularity is estimated within the residual tumour bed taking
into account the invasive and in situ (pink circles) carcinoma. (B) A similar approach is taken to measure metastatic carcinoma in the lymph node.
Measurement of the single largest metastatic focus (black oval) is used to determine AJCC ypN stage (blue arrow). Measurement for the RCB (red
arrow) is determined by the span of metastatic carcinoma (black circles) inclusive of intervening fibrosis (pink oval). Distant metastatic foci or ITCs
(black circles outside pink oval) are not included in the measurement. (C) When more than one focus of invasive carcinoma within distinct tumour
beds are identified and separated by normal breast tissue, then each focus is measured separately. The dimension of the largest ‘dominant’ focus
(blue arrow) is used for ypT AJCC classification and the (m) modifier is applied. Tumour bed dimensions (red arrows and red rectangle) and cellularity
are calculated for the largest focus using RCB methods. If the additional focus demonstrates different residual tumour cellularity, then RCB can be
calculated for the second focus as it may yield different RCB classification. Note that when the tumour demonstrates concentric shrinkage, the yAJCC
and RCB maximum dimensions are equivalent. (D) When a single focus of metastatic carcinoma is identified in the tumour bed, the ypN AJCC and
RCB dimensions are also equivalent. AJCC, American Joint Committee on Cancer; ITC, isolated tumour cell; RCB, residual cancer burden.
Mrkonjic M, et al. J Clin Pathol 2019;72:120–132. doi:10.1136/jclinpath-2018-205598 129
 Review
emerging. The Nottingham Prognostic Index was one of the first
systems to combine tumour size, histological grade and lymph
node status.81 While this system was not developed for use in the
neoadjuvant setting, it forms the basis of the Residual Disease in
Breast and Nodes system.82 The Neoadjuvant Response Index is
based on pre-treatment clinical/radiological measurements and
post-treatment pathological measurements.83 Clinical-patho-
logical stage–oestrogen/grade (CPS-OG) combines pathological
stage post-therapy with clinical stage pre-therapy, tumour nuclear
grade and ER status.84 CPS-EG was subsequently modified to
incorporate the tumour HER2 amplification status in a system
called Neo-Bioscore.85 Post-treatment Ki-67 indices have been
correlated with long-term outcome for neoadjuvant endocrine
therapy and chemotherapy.86–88 Ki-67 index is increasingly being
used as a component of newer multivariate prediction models in
the post-neoadjuvant setting such as the Preoperative Endocrine
Prognostic Index and Residual Proliferative Cancer Burden,
the latter representing a modification to the RCB system that
combines post-therapy Ki-67 index with the RCB.75 86 Finally, as
the latest AJCC 8th edition of breast cancer staging includes new
parameters for prognostic staging that combine anatomic TNM
factors, tumour grade, biomarker status and multigene panel
testing,25 it seems probable that such a system will eventually
expand into the post-therapy yAJCC staging. Currently, there
are limited data on the use of multigene panel testing, such as
Oncotype DX, in the neoadjuvant setting.89 90
Biomarkers status post-systemic therapy
There is no consensus on reassessment of hormone receptor and
HER2 status in residual cancer post-neoadjuvant therapy.18 In
general, tumour markers do not change before and after chemo-
therapy in the majority of cases18 91–93; however, discordant
results have been reported for ER (13%–18%), PR (26%–32%)
and HER2 (6%–9%) before and after chemotherapy with various
causes for the discordances being described.94 95 In some cases,
change in tumour marker expression may be related to the type
of neoadjuvant chemotherapy.1 96 Loss of HER2 amplification
following neoadjuvant trastuzumab has been reported and also
found to be associated with a worse outcome.97 Biomarkers must
be reassessed in cases where retesting for biomarkers is required
by the clinical trial protocol and in cases where the biomarker
status was previously unknown.18 Reassessment of biomarkers
should be considered for negative or equivocal results on
pre-treatment core biopsy, in cases where biopsies had insuffi-
cient invasive carcinoma for accurate assessment, where biopsies
were performed and biomarkers assessed at other institutions, in
post-treatment tumours demonstrating heterogeneous morphol-
ogies or in cases where the tumour did not demonstrate any
response to therapy.18 Routine biomarker reassessment is not
recommended for triple-positive breast cancers.18
Summary
As neoadjuvant systemic therapies are becoming increasingly
used in patients with breast cancer, a standardised approach to
the evaluation of post-neoadjuvant systemic therapy specimens is
essential. Pathological evaluation of tumour response to neoad-
juvant chemotherapy remains the gold standard for judging
the effectiveness of the therapy. As novel classification systems
for treatment responses are continuously developed, patholo-
gists will remain at the forefront to drive the development of
this field. Recent evidence demonstrates benefits of using more
than one staging system to identify patients at the highest risk
of relapse. Therefore, the pathology reports should provide the
130
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Take home messages
►► A multidisciplinary approach when handling neoadjuvant
breast specimens is imperative with review of previous
pathology and clinical documentation prior to specimen
examination.
►► Correlation of macroscopic findings and diagnostic imaging
is essential.
►► A standardised and systematic approach to tissue sampling
yields the most useful microscopic results.
►► Mindfulness of potential pitfalls and understanding the
limitations of applied classification system can help avoid
misclassification of patients.
►► Standardisation in reporting of neoadjuvant specimens
will provide the most useful information to the clinicians
regarding patient outcomes.
►► Recent evidence indicates possible benefits to reporting
additional classification system to the yAJCC 8th edition in
assessing treatment response to help identify patients at
highest risk of relapse.
most updated yAJCC staging system and, if no other classifi-
cation systems are routinely reported, it is recommended that
sufficient information be provided so that other classification
systems, like the RCB, can be applied if needed.
Handling editor  Runjan Chetty.
Contributors  All authors listed contributed to this manuscript.
Funding  The authors have not declared a specific grant for this research from any
funding agency in the public, commercial or not-for-profit sectors.
Competing interests  None declared.
Patient consent for publication  Not required.
Provenance and peer review  Commissioned; internally peer reviewed.
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