Rosen's Breast Pathology Introduction
Transcript of Rosen's Breast Pathology Introduction
Authors: Rosen, Paul Peter
Title: Rosen's Breast Pathology, 3rd Edition
Copyright ©2009 Lippincott Williams & Wilkins
> Front of Book > Introduction
Introduction
The Pathologist as a Specialist in Breast Cancer Care
“The development and application of a concept of
localized pathology laid the groundwork for modern
specialism by providing a number of foci of interest in
the field of medicine. Each such focus of interest, that
is, a disease or the diseases of an organ or region of
the body, provided a nucleus around which could
gather the results of clinical and pathological
investigation.
On the technological side the influences represented
in specialization manifest themselves in the
multiplicity of technical skills, devices, and theories
applied to the achievement of human aims in the field
of medicine.”
--From The Specialization of Medicine by George
Rosen, M.D., 1944.
Impressive advances have been made in the past 50 years in the effort to
prevent, treat and cure breast cancer. Major milestones include the
development of mammography for early detection, the shift from
mastectomy to breast conservation therapy for many patients, advances in
chemotherapy for primary treatment and as an adjuvant modality, the
demonstration that antiestrogenic compounds can inhibit the development
and progression of breast cancer, and the introduction of sentinel lymph
node mapping for axillary staging. The growth of medical specialization in
the last half of the 20th century has had a profound influence on these
accomplishments by fostering multidisciplinary clinical practice and
research.
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Specialism in all aspects of medical care has revolutionized the role of the
surgical pathologist. Rather than fostering professional independence,
specialization in medicine has created circumstances in which the specialist
delivering a limited segment of medical care is increasingly dependent on the
assistance of colleagues who have acquired complimentary expertise. This
situation is epitomized by the multidisciplinary approach that is now
standard for treating breast diseases. Inherent in this circumstance is the
expectation that each member of the team is capable of delivering optimal
specialty care. A corollary effect is growing pressure for subspecialization in
diagnostic pathology, especially in academic centers. Breast pathology has
largely remained in the domain of generalists except for a few referral
centers. The formation of the International Society of Breast Pathology
heralds recognition of subspecialization in Breast Pathology. In 2000, a
European Society of Mastology position paper set forth guidelines for a
clinical program devoted to providing “high-quality specialist Breast Service”
included among the physicians “a lead pathologist plus usually not more than
one other nominated pathologist specializing in Breast Disease…(to be)…
responsible for all breast pathology and cytology” (1). The number of
pathologists needed to staff such a service will depend upon the number of
patients cared for. This process will be furthered by growing awareness on
the part of patients and patient advocacy organizations that accurate and
comprehensive pathology diagnosis is fundamental to effective treatment
and research in breast diseases.
Major advances that contributed to the role of the pathologist as a key
member of the breast cancer team include:
� widespread use of mammography which detects nonpalpable lesions;
� image-guided needle core biopsy procedures, which make it possible to
acquire samples from nonpalpable lesions;
� breast conservation therapy, which requires a more-detailed pathologic
assessment of breast specimens;
� the availability of histologically-based methods for detecting markers used
to assess prognosis and to plan therapy; and
� sentinel lymph node mapping and bone marrow sampling for
micrometastases.
Pathologists generate an important part of the information used for
therapeutic decisions. The complex multifactorial description of breast
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pathology now considered to be standard practice has expanded the
diagnostic report from a brief one- or two-line statement to a catalogue of
data that may be several pages in length. Immunohistochemistry makes it
possible to determine the presence of prognostic and therapeutic markers by
microscopic examination, and these observations are part of the pathologist's
report. This technology is also essential for detecting micrometastases in
sentinel lymph nodes.
The expanded role of pathologists in the management of breast diseases
requires their active participation with the clinical care team. Pathologists
who diagnose breast specimens need to be aware of how various components
of their reports are relevant to treatment decisions. Optimally, there should
be a procedure for correlating imaging studies with biopsy results in regard
to nonpalpable lesions detected by mammography, ultrasound or MRI (1).
Coincidental with these medical developments has been the growing
involvement of patients in making decisions about their treatment. This, in
turn, has led to a greater public awareness of the importance of information
contained in pathology reports. For the untrained layperson to read and
interpret a pathology report, it is necessary to learn and understand a new
vocabulary. This is a daunting task—one that is even more difficult for the
patient whose name appears on the document.
Books and literature provided by medical and lay societies or associations are
helpful, as is the bottomless well of information that appears on the
Internet. The surgeon, oncologist, and radiotherapist are experts at
interpreting pathology reports for their patients and at explaining the
significance of the data. Nonetheless, a substantial number of patients with
breast diseases want an explanation from the pathologist who issued the
report or they seek out another pathologist, often with specialized expertise,
for a second opinion review. Many more patients are aware that a pathology
consultant is involved in their case. In this way, pathologists increasingly
participate in direct patient care and patient education, a vital public
service.
Consultations and Second Opinions in Breast PathologySurgical pathologists in general practice provide accurate diagnoses for the
great majority of the breast specimens they encounter without the assistance
of intramural or extramural consultation. Nonetheless, pathology
departments should have a built-in mechanism for obtaining second opinions
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internally through conferencing or other quality assurance programs. In this
setting, the individual pathologist or the pathology group in a department
may seek an extramural opinion from an expert consultant. This typically
occurs when there is a difference of interpretation among pathologists in an
institution or the diagnosis is uncertain after internal review. Consultation
may also be obtained when the probable diagnosis is one with which there is
little or no experience. Another category of consultation results from
uncertainty about the diagnosis engendered by a limited or unrepresentative
sample, poor histologic preparation, or a pathologic change that appears to
be on the borderline between two or more diagnoses. As noted by Leslie et
al., “Second opinions in anatomic pathology are an integral part of quality
practice…frequent consultation between pathologists should be fostered in
all practice settings and documented as part of the quality assurance
process” (2).
Several studies have demonstrated the important contribution to patient
care of second opinion pathology consultations, generally in the context of
referrals seen at academic centers. A very positive aspect of this practice is
the high degree to which the primary diagnosis has been confirmed by the
consultant. Epstein et al. reported concordant diagnoses (cancer vs.
noncancer) in 98.7% of 535 prostatic needle biopsies diagnosed as cancer (3).
Nonetheless, the 6 diagnoses not sustained as cancer were critically
important for the 1.3% of patients. A cost analysis of these results suggested
that the saving in medical expenses for the 6 patients who did not undergo
surgery substantially exceeded the cost of reviewing all 535 biopsies. A
higher rate of discrepancies was found by Abt et al. (4) who compared the
original and second opinion diagnoses in a broad range of pathology among
777 patients referred to an academic center. Forty-five diagnostic
disagreements (6%) were regarded as clinically significant, and overall the
level of agreement was 92.1%. Perkins et al. (5) estimated that diagnoses
were inaccurate in 2% to 4% of breast cancer cases, including mistaking
benign for malignant disease or vice versa, over- or underdiagnoses of
invasive carcinoma, or misinterpretation of prognostic markers such as
HER2/neu.
It is unlikely that complete microscopic pathology samples will be routinely
converted to electronic images in the foreseeable future given the time and
cost of this undertaking and the fact that much of the information will be a
record of “normal” or nonlesional tissue. Consequently, the need to ship
glass slides for consultation is likely to be with us for some time to come.
Within the United States, several factors have contributed to the growing
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number of pathology consultations. Much of the increase is generated by
patients who seek multiple clinical opinions from different physicians and
institutions. Some patients are primarily concerned with confirmation of
their diagnosis, and one or more consultations may be obtained directly from
pathologists for this reason alone. Most of the remainder of consultations are
initiated by pathologists seeking opinions from their colleagues. Surgeons,
medical oncologists, and other physicians generate some second opinion
reviews. The review of “outside” pathology slides should be mandatory
whenever a patient is referred to a physician for consultation or treatment at
an institution other than the one where the primary diagnosis was rendered
(6).
Slides sent for consultation, regardless of the reason, must be accompanied
by documents that: (a) confirm the identity of the specimen with the
patient, (b) explain why the material has been sent, (c) provide complete
information about who should receive the report, and (d) designate who will
pay for the consultation and how billing should be submitted. The
correspondence may take many forms, but it is essential that the information
cited above be provided. This must include a copy of the pathology/cytology
report for each specimen represented, clearly displaying the name of the
patient and the accession number corresponding to the slides and paraffin
blocks enclosed. It is unacceptable and substandard practice to withhold the
pathology report previously obtained from a consultant or second opinion
institution so as not to “bias” the second review.
In addition to confirming the anatomic source and patient identity of the
slides, the pathology report provides essential information such as an index
of the specific location(s) of the specimen(s) in individual slides, a
description of the gross appearance of the specimen(s), clinical information
provided with the specimen, frozen section interpretations, and details of
the pathologist's diagnosis that should be evaluated. The pathology report
must be included even if the final diagnosis has not been reached and will
depend upon the consultation. When the slides are sent directly from one
laboratory to another in relation to a clinical consultation at the recipient
institution, the correspondence should include the pathology report, the
name of the clinical physician who is being consulted, and detailed billing
instructions. When more than one consultant is involved, it is vital that all
consultants examine the same or equivalent material.
Progress and Uncertainty in Breast Pathology
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Extraordinary progress has been made in linking anatomic pathology, the
study of normal and diseased tissues, to patient care throughout the
spectrum of human ailments. The 20th century has been marked by great
advances in defining the pathology of breast diseases and in relating these
observations to the development of more effective therapy tailored to the
specific type and extent of disease in the individual patient.
The stage was set in the latter half of the 19th century and first decades of
the 20th century with the flowering of classical pathology based largely on
postmortem examination of the gross and microscopic changes found in
diseased tissues. The principle objectives of these investigations were to
describe and catalogue diseases in an effort to detect clues to their
pathogenesis and to better understand their clinical manifestations. Surgical
pathology, the study of tissues from the living, emerged from classical
anatomic pathology as advances in surgery, made possible by effective
anesthesia and antisepsis, focused greater attention on a pathologic diagnosis
as a critical element in the treatment of many diseases. The study of breast
pathology has been a model of interdisciplinary investigation involving
clinical and laboratory science. Pathologists are in a unique position to meet
the challenge of developing and adapting innovative laboratory methods to
better understand and to improve the treatment of breast diseases.
Despite the perceptions of the public and some medical colleagues that
diagnostic pathology lacks ambiguity and subtlety, pathologists are
repeatedly faced with the need to deal with uncertainty. The usually blunt,
seemingly “black and white” recitation of a final pathology report actually
represents a synthesis of possibilities that constitute the “differential
diagnosis.” Pathologists strive to reduce uncertainty by constant study,
leading to the development and application of new insights or improved
techniques. Yet, each advance brings with it a new horizon of uncertainty-a
new confidence interval. One manifestation of uncertainty in the study of
breast cancer and precancerous breast disease is our limited ability to
separate “the drivers from the hitchhikers,” that is “to distinguish between
silent alterations acquired by the malignant cell and those that truly
contribute to the malignant phenotype” (7).
In the clinical arena, the phenomenon of advances creating new uncertainty
is illustrated by the procedure for axillary lymph node staging by sentinel
lymph node mapping. The coincidence of improved surgical techniques to
localize the lymph node or nodes most likely to harbor metastatic carcinoma
and the application of immunohistochemistry to the lymph nodes by the
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pathologist makes it possible to determine whether axillary lymph nodes
harbor metastases by examining selected lymph nodes without the need for
more extensive axillary dissection. Sentinel lymph node staging results in
reliable information about axillary nodal status with less morbidity than
conventional axillary dissection. Nonetheless, the procedure has raised new
questions about the prognostic significance of the micrometastases so
elegantly uncovered, and uncertainty about the need for therapy based on
this finding.
Pathologists have unique opportunities in breast cancer research. Technical
advances now make it possible to apply the extraordinarily powerful
techniques of molecular and genetic analysis directly to tissues visualized
with the microscope. This is truly the intersection of the classical
microscopic pathology of the 19th and 20th centuries with the molecular
science of the 21st century. Using microdissection, the pathologist can select
small groups of cells and even individual cells from normal and abnormal
tissues that are identified and diagnosed with the microscope. DNA extracted
from these minute samples can be amplified and studied for molecular
alterations by a variety of techniques. This approach holds great promise for
furthering our understanding of precancerous and cancerous breast diseases
and for finding clues to improved prevention and therapeutic strategies.
Currently, microdissection is too costly and laborious for widespread clinical
application. It is possible that pathologists will employ microdissection and
molecular analysis in the diagnosis of breast tissues in the next 10 to 20
years. The development of robotic instrumentation will contribute
substantially to making this a clinically feasible enterprise. The ability of
pathologists to distinguish between structurally normal and abnormal tissues
will remain a fundamental step in diagnosis in the foreseeable future, but
technological advances will require greater sophistication on the part of
pathologists and continue to foster the subspeciality of Breast Pathology.
Tissue Microarrays, Gene Expression Profiles, and Breast PathologyIt is widely accepted that altered gene expression is fundamental to the
neoplastic process. The “devil is in the details” of how the exceedingly
complex system of gene actions becomes disrupted, resulting in the
phenotypic changes in cells and tissues employed by pathologists for
diagnosis and estimating prognosis. Interest in exploring and understanding
the molecular basis of breast cancer pathology has been propelled forward in
the past decade by technological advances that make it possible to
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efficiently investigate very small samples from large numbers of tumors.
These studies have relied on two methodologies: high-throughput tissue
microarrays and microarray gene expression profiling. The former employs
histologic sections of small samples of multiple tumors and the latter uses
RNA extracted from diagnostic tumor tissue samples. It can be reasonably
predicted that these and related technologies will eventually have a
significant impact on the role of pathologists in breast cancer diagnosis and
treatment. The following discussion provides illustrations from the current
literature of how these studies are being used. Although largely
investigational, a few procedures, such as a recurrence score (RS) based on a
21-gene RT-PCR assay, are being employed in clinical practice for selected
patients (8,9).
Tissue MicroarraysIn 2003, Callagy et al. (10) described a classification of breast carcinoma
based on the expression of protein biomarkers detected by
immunohistochemistry in tissue microarray preparations. The inherent
efficiency of tissue microarray technology made it possible for these
investigators to study 13 biomarkers in 107 cases with only 39 histologic
slides. The authors estimated that 1,391 slides would have been needed to
obtain the same data from “conventional sections.” Two patterns of
biomarker expression were described: estrogen receptor (ER)-related (ER,
PR, bcl2, cyclin-D, p27, cytokeratin 8/18, c-myc) and proliferation-related
(Mcm2, MIB1, cyclin-E, p53, c-erbB2, cytokeratin 5/6). There was a
statistically significant association between the biomarker expression group
and the conventional prognostic markers. Tumors in the ER-related group
were more likely to have a low histologic grade and negative lymph nodes,
whereas tumors expressing proliferation-related markers were more likely to
be high grade and have nodal metastases.
A more-complex tissue microarray study published in 2005 examined the
immunohistochemical expression of 25 biomarkers in 1076 previously
characterized breast carcinomas (11). Six groups of protein expression were
found, representing 0.4% to 31.2% of the tumors. The biomarker-defined
groups were significantly related to tumor grade, tumor size, nodal status,
patient age, and prognosis. Multivariate analysis revealed that biomarker
clustering was a prognostically significant independently of grade, size, and
nodal status.
Gene Expression Profiling
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In contrast to tissue microarray technology that describes gene activity in
terms of protein products that can be detected in tissue sections by
immunohistochemistry, gene expression profiling examines large numbers of
genes directly using RNA extracted from tumor tissue with the reverse
transcriptase polymerase chain reaction (RT-PCR) in DNA microarrays. These
studies have been done with frozen (12,13) or paraffin embedded (14) tissue
samples, including needle core biopsy specimens (15,16). Needle core biopsy
samples provide satisfactory material for gene expression profile analysis in
the majority of cases. Zanetti-Dallenbach et al. (17) reported 82%
concordance in the expression profiles for 60 genes obtained from core
biopsies and subsequent surgical excision biopsy specimens from 22 patients.
In four cases where gene expression profiles for the two specimens differed,
the surgical biopsy specimens exhibited a higher expression of genes
associated with tissue injury and repair that were probably activated by the
core biopsy procedure. Rody et al. (18) found greater than 90% concordance
in the gene expression profiles for estrogen and progesterone receptors and
for Her2/neu in core biopsy samples from patients undergoing neoadjuvant
chemotherapy when compared to immunostains of the same samples.
Gene profiles that were associated with prognosis, response to
chemotherapy, and patterns of metastases have been described. For
example, a recurrence score (RS) indicative of the risk of recurrence after 10
years of follow-up in node-negative, estrogen receptor-positive patients
treated with tamoxifen was based on a 21-gene RT-PCR expression profile
(19). Analysis of the 21-gene profile resulted in a quantitative assessment of
recurrence risk after treatment in this selected group of patients. Three
recurrence risk categories were defined: low risk (RS<18%), intermediate risk
(RS 19%–30%), and high risk (RS ≥ 31%). It was found that after 10 years of
follow-up, patients in the high-risk group derived a significant reduction in
recurrence from combined treatment with chemotherapy and tamoxifen (11%
recurrence) when compared to women treated with tamoxifen alone (38.3%
recurrence). Patients in the low recurrence group did not experience a
significant reduction in recurrence when chemotherapy was added to
tamoxifen (tamoxifen, 3.7% recurrence; tamoxifen plus chemotherapy, 5%
recurrence). There was a small benefit from chemotherapy in the
intermediate-risk group (tamoxifen, 17.8% recurrence; tamoxifen plus
chemotherapy, 10.1% recurrence). Histologic grade was significantly related
to RS but, when graded by more than one pathologist, 5% to 12% of
histologically low-grade tumors had a high RS and 19% to 36% of histologically
poorly differentiated carcinomas had a low RS. Lyman et al. (9) estimated a
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net savings of $2,256 per patient treated when the choice between
tamoxifen alone and tamoxifen plus chemotherapy was based on the RS
derived from the 21-gene RT-PCR assay. The clinical management of a
patient whose tumor grade is at odds with the RS is an issue that needs
further investigation.
Gene expression profiling has also been applied to breast carcinoma
prognosis in other patient groups. Espinosa et al. (12) investigated a 70 gene
profile in 96 stage I and II patients. A patient was classified as having a poor
prognosis in this study if the tumor expressed more than 47% of the
previously determined poor prognosis “signature,” which featured up-
regulation of genes involved in the cell cycle, invasion and metastasis,
angiogenesis, and signal transduction (20,21). The gene profile used in this
study was significantly related to overall and relapse-free survival for the
entire group of patients, but not when patients were stratified by nodal
status.
Foekens et al. (22) used a previously validated (23) 76-gene signature to
assess prognosis in node negative patients who had not received
chemotherapy. Patients were classified as having a low or high risk for
developing a systemic recurrence. Ten-year recurrence-free survivals were
94% and 65%, respectively, in the low- and high-recurrence risk groups as
determined by the 76-gene signature. In a multivariate analysis with age at
diagnosis, tumor size, grade, and menopausal status, the 76-gene signature
was the only significant predictor of distant recurrence-free survival.
Predicting response to chemotherapy is likely to be an important application
of gene expression profiling. Mina et al. (15) identified a 22-gene signature
that significantly correlated with a pathologic complete response to
chemotherapy (doxorubicin and docetaxel) in 45 evaluable patients treated
for locally advanced breast carcinoma. Signature genes were of three types:
angiogenesis-related, proliferation-related, and invasion-related. In this
study, the expression of estrogen receptor-related genes and the RS
determined from the previously discussed 21-gene RT-PCR assay did not
correlate with a pathologic complete response. Gianni et al. (16) reported
that the expression of 86 genes correlated significantly with achieving a
pathologic complete response in women with locally advanced carcinoma
who received neoadjuvant paclitaxel and doxorubicin. A pathologic complete
response was significantly associated with a higher expression of
proliferation-related and immune-related genes and with lower expression of
estrogen receptor-related genes. A pathologic complete response was
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achieved significantly more often with tumors that had a high RS based on
the 21-gene RT-PCR assay.
Gene expression profiling has also been investigated as a method for
predicting response to neoadjuvant chemotherapy in women with primary
operable breast carcinoma. One such study involved 100 women with T2-4,
N0-2, M0 breast carcinoma treated with gemcitabine, epirubicin, and
docetaxel (24). A signature of genes associated with a pathologic complete
response included prominent representation from the following categories:
TGF-β signaling, RAS-related, apoptosis-related, and DNA damage response-
related genes. Ayers et al. (25) reported that a gene expression profile had
78% predictive accuracy for identifying women who achieved a complete
pathologic response to multiagent neoadjuvant chemotherapy when
compared to a 28% overall expected response rate. Using a different gene
profile, Iwao-Koizumi et al. (26) reported 80% accuracy in predicting clinical
response to docetaxel. In a trial that compared doxorubicin-
cyclophosphamide to doxorubicin-docetaxel treatment in patients with
locally advanced carcinoma, Hammerman et al. (27) found changes in gene
expression profiles determined before and after neoadjuvant chemotherapy
in responders but not in nonresponders. However, no gene expression profile
was predictive of response to either treatment.
Evidence that gene expression profiling might detect signatures associated
with patterns of metastases has started to emerge. A study of primary tumor
tissue from 107 patients with node negative breast carcinoma identified a
panel of 69 genes that were “differentially expressed” when patients with
metastases in bone were compared to those with non-osseous metastases
(13). The genes for thyroid transcription factor 1 (TTF1) and TTF3 were found
to be most highly expressed in the 69-gene signature associated with bone
metastases. Other categories of genes associated with bone metastases were
related to cell adhesion, signaling pathways, and cell organization. Others
have also investigated gene profiles associated with breast carcinoma
metastases in bone (28,29), the lungs (30), and locoregional recurrence after
mastectomy (31). The mechanisms by which these gene profiles predisposed
to patterns of recurrence and the roles of particular genes or groups of genes
in this process have not been elucidated. Nonetheless, the ability to predict
likely sites of distant metastases could provide an opportunity to selectively
offer adjuvant therapy designed to inhibit site-specific recurrence such as
bisphosphonates for bone metastases (32) and radiotherapy for local
recurrences.
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Contradictory results have been reported in attempts to find gene profiles
predictive of low and high risk for axillary nodal metastases. Weigelt et al.
(33) did not find a gene signature associated with axillary lymph node
metastases in a study of 295 tumors. In a considerably smaller series of
cases, West et al. (34) reported that gene expression profiling was predictive
of axillary nodal status. The use of gene profiling as a tool to predict the risk
for axillary lymph node metastases and to identify the genes involved in this
process, which is fundamental to breast carcinoma staging, has not yet
received the attention warranted by the clinical importance of this aspect of
the disease.
Gene expression profiles may be influenced by mutations associated with
hereditary breast carcinoma. Hedenfalk et al. (35) described a panel of 176
genes that had different expression patterns in tumors with BRCA1- and
BRCA2-associated mutations. The gene expression patterns of the BRCA-
associated carcinomas also differed from those found in sporadic carcinomas.
The strength of these results is limited by the small numbers of cases
studied.
The Future of Tissue Microarray and Gene Expression Profiling in Breast CancerThe foregoing examples offer an insight into the promise and complexity of
tissue microarray and gene expression profiling in breast carcinoma. Many
issues remain to be addressed before these techniques can be introduced
into general clinical practice. There are important technical problems
related to the use of formalin-fixed paraffin embedded tissue and the limited
availability of unfixed frozen tissue. Most breast carcinoma gene expression
profiling studies have had significant limitations that include small numbers
of tumors and/or patients, heterogeneous patient groups, and
nonstandardized treatment. There does not appear to have been an a priori
basis for selecting genes for study, and there is little understanding of how
the genes that form a particular signature are related to the outcome under
investigation (e.g., site of metastases, response to therapy or to the
histomorphology of breast proliferative lesions and carcinomas). It has been
reported that analysis of data from two different studies (21,23) identifying
prognostic gene profiles consisting, respectively, of 70 and 76 genes had only
3 genes in common (36). Disparities of a similar magnitude between other
gene signatures have also been noted (37). The predictability of gene
expression profiles can be substantially reduced when they are cross-tested
from one series of tumors to another (36,37). On the other hand, clustering
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of tumor subtypes (e.g., basal, luminal, erb-b2) was reported in an analysis
of three studies (38). A re-analysis of data from a study (21) that reported a
specific 70-gene signature revealed that this gene set was not unique and
that other gene signatures also present in the data set correlated with
outcome (37).
No single gene profile has proven to be applicable to breast carcinoma
generally. At present, the 21-gene RT-PCR assay has been used clinically in
the limited subset of patients with estrogen receptor positive, lymph node-
negative tumors under treatment with tamoxifen to estimate the benefit
that would be obtained from adding chemotherapy. It is likely that other
clinically useful gene signatures will be found by analyzing subsets of
patients which are defined by established markers (e.g., ER, erb-b2) and
clinicopathologic parameters (e.g., age at diagnosis, hereditary breast
carcinoma, tumor grade). To develop assays that can be standardized for
clinical practice, larger groups of tumors need to be evaluated and gene
profiles in defined patient groups need to be cross-tested. As more studies
are performed, gene signatures associated with particular end-points can be
developed and modified when new information becomes available.
Gene expression profiling and tissue microarrays offer great promise as tools
that may revolutionize the treatment of breast carcinoma. Nonetheless, we
are certainly not on the verge of abandoning conventional prognostic
markers, and there is reason to believe that they will continue to play an
important clinical role in the foreseeable future, as suggested by Eden et al.
(39) in a provocative study titled “Good old' clinical markers have similar
power in breast cancer prognosis as microarray gene expression profiles.”
The extent to which the pathology community adapts to this new era and
incorporates these technologies into clinical practice in the pathology
laboratory will be an important factor in determining the continued primary
role of pathology in cancer classification and diagnosis.
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