Diagnosis
and Staging
Introduction
Evaluation of a breast symptom or abnormal
finding begins with a thorough medical history and
physical examination, followed by imaging tests. Breast
biopsy is used for subsequent investigation of suspicious
lesions and for definitive diagnosis. The process reflects
a gradually increasing degree of invasiveness so that
diagnosis is obtained with a minimum amount of patient
discomfort and cost. Abnormalities found to be cancer
are staged and further characterized in order to estimate
prognosis and determine appropriate treatment.
Medical
History and Physical Examination
The first step in the evaluation of a
patient with suspected breast cancer begins with a
complete medical history. In addition to obtaining
detailed information about the breast finding, including
any changes over time, the provider should inquire
about any new localized or constitutional symptoms;
take note of known breast cancer risk factors; and
elicit a detailed family history of cancer, with special
attention given to breast and ovarian cancers. Also
important, the provider should ask about or observe
any signs of emotional distress that may be related
to the discovery of the breast lesion. While most cases
will prove to be benign, the process of evaluation
can be a difficult time for a patient. The provider
can help by facilitating any needed emotional counseling
or support.1
In addition to a general exam, a complete
physical examination includes a full pelvic exam and
Pap smears. A visual and manual inspection of the breasts
will search for the presence of lumps or masses; asymmetry;
changes to the skin or to the nipples; and tenderness.
Regional lymph nodes will be palpated for swelling
or firmness. Other areas of the body will be checked
for obvious spread of breast cancer and to help evaluate
the general condition of the patient's health.2
The Breast
Cancer Diagnostic Algorithms for Primary Care Providers (Cancer
Detection Section, California Department of Health
Services, 2005) provides detailed guidance for
the work-up of a new palpable mass; abnormal screening
mammogram with normal CBE; spontaneous unilateral
nipple discharge; breast skin changes; and breast
pain. There is also a risk assessment algorithm,
and, in the case of breast biopsy, an algorithm for
the management of pathologic findings. The algorithms
have been developed by an expert panel of California
providers and are available for viewing on this web
site.
Primary care providers are responsible
for assessing a patient's risk for breast cancer, performing
CBE, recommending appropriate screening techniques,
and ensuring that the patient receives complete and
timely follow-up of any abnormal findings.
Primary care records should contain all relevant imaging
and biopsy results, documenting a complete and timely
follow-up. California's Cancer
Detection Programs: Every Woman Counts expects
this complete follow-up of abnormal findings within
60 days.
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Imaging
Tests
The
most common imaging tests used for the evaluation
of an abnormal breast finding are diagnostic
mammogram and breast ultrasound. |
The most common imaging tests used for
the evaluation of an abnormal breast finding are diagnostic
mammogram and breast ultrasound. Other imaging tests
may be used to improve diagnostic accuracy and to clarify
indeterminate findings. A final BI-RADS category should
be assigned based on the results of all imaging procedures.
|
Mammogram |
 |
Diagnostic Mammogram is
similar to a screening mammogram but includes additional
views focused on the area of concern. In addition to
the standard craniocaudal and mediolateral oblique
views, diagnostic mammogram may include lateromedial,
mediolateral, and exaggerated craniocaudal views, and
other special views, such as spot compression and magnification.
Mammography is the imaging method of choice for investigating
microcalcifications.
The additional views of a diagnostic
mammogram can be a source of concern for women who
are not properly informed about the procedure. The
primary care provider can help alleviate potential
anxiety by explaining that the need for additional
images does not imply that a malignancy has been found
on screening mammography. In fact, a majority of cases
where extra views are obtained do not result in recommendations
for biopsy.
Breast Ultrasound is
a common and indispensable adjunct to diagnostic mammography
Using high-frequency sound waves for examining tissues,
breast ultrasound is especially helpful for distinguishing
between a solid mass and a fluid filled cyst. Structures
with certain characteristics can be confidently diagnosed
as benign. Ultrasound is also used for evaluating masses
in women whose mammograms are difficult to interpret,
such as women with dense breast tissue.
|
MRI |
|
|
| Magnetic resonance image (MRI) of
individual breast, demonstrating marked enhancement (bright area) which
was confirmed to be cancer. |
Magnetic Resonance Imaging (MRI) may
be used for viewing palpable abnormalities that are
not visible with mammography or ultrasound. Using magnets
and radio waves to produce very detailed, cross-sectional
images, MRI is especially helpful for discriminating
between cancer and scar tissue. Like ultrasound, it
is also useful in evaluating dense breast tissue. Breast
MRI may also be used to help define the size and extent
of cancer within breast tissue and to help spot multifocal
disease. In known cases of breast cancer, MRI can be
used to scan other regions of the body for signs of
metastasis.
Ductogram (also
called a galactogram) is a type of contrast enhanced
mammography used for helping to determine the cause
of abnormal nipple discharge. The procedure involves
the insertion of a cannula (a very fine plastic tube)
into the breast duct into which a small amount of contrast
medium (dye) is injected. The breast is then imaged
with mammography. A ductogram may be valuable for diagnosing
benign tumors, such as papillomas, and for evaluating
suspected cancer, such as ductal carcinoma in situ.
Fluid from a nipple discharge might also be collected
and examined under a microscope (nipple smear).
Scintimammography is
a nuclear medicine imaging test that uses a radioactive
tracer (Tc 99m Sestamibi) to help detect breast cancer.
The procedure involves injecting small amounts of slightly
radioactive substances into the body. Most generally,
malignancies show increased uptake of the radioactive
tracer as compared to benign lesions. Although considered
still experimental by some experts, scintimammography
is sometimes used as a supplemental imaging method
for certain patients. Like MRI, it is most useful for
women with dense breast tissue and for women with breast
implants. It is also useful with large, palpable abnormalities
that cannot be imaged well with mammography or ultrasound,
and for detecting axillary involvement.
|
PET |
 |
Positron Emission
Tomography (PET) is another type of nuclear
medicine imaging that may play a role in determining
whether a breast mass is cancerous. As with scintimammography,
PET imaging requires an injection of a small amount
of radioactive substance into the body. A series
of detailed computer images record metabolic activity
that help distinguish normal cells from cancer. Higher
metabolic rates suggest cancer. An NCI-sponsored
clinical trial is evaluating the usefulness of PET
scans in women with breast cancer compared with other
imaging techniques. This trial is also studying the
effectiveness of PET scans in tracking the response
of a tumor to treatment.
Electrical Impedance
Imaging (also known as Transscan, or T-scan)
consists of a hand-held probe that scans the breast
for electrical conductivity, sending two-dimensional
images of breast tissue to a computer screen. Because
breast cancer cells tend to have lower electrical
impedance causing them to appear different (bright
white) from normal cells, electrical impedance imaging
can help evaluate tumors detected by mammography.
While the device is not approved as a screening method,
it does have FDA approval for use as a diagnostic
aid. According to the National Cancer Institute (NCI),
electrical impedence imaging may reduce the number
of biopsies needed to determine whether a breast
mass is cancerous and also improve the identification
of women for whom a biopsy is appropriate.3
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Breast
Biopsy
The
only definitive method for diagnosing breast
cancer is with a breast biopsy. |
In some cases, breast imaging can determine
that an abnormality is not cancer, however, imaging
tests alone cannot prove that a lesion is malignant.
The only definitive method for diagnosing breast cancer
is with a breast biopsy. Biopsy involves the removal
of tissue or cells for microscopic examination. The
specimen can be obtained from a symptomatic area or
from an area identified with breast imaging. There
are several different types of breast biopsies.
Needle Biopsy
Two types of needle biopsies are used
to diagnose breast cancer. The most common is core
needle biopsy. A less commonly used needle procedure
is fine needle aspiration biopsy.
Fine
Needle Aspiration Biopsy (FNAB) is the least
invasive method of breast biopsy. However, the method
is reliable
only when performed by extremely experienced
clinicians, specifically, by fellowship trained cytopathologists.
With FNAB, a thin, hollow needle is inserted into
the breast to withdraw cells from the suspicious
lesion. The cells are then submitted to a lab for
analysis.
Core Needle Biopsy
(CNB) uses a larger needle than FNAB and instead
of cells, CNB removes a small cylinder of tissue
(a core) about the size of a grain of rice. About
3 to 5 cores are usually removed, although more may
be taken. The core tissue samples are then analyzed
by a pathologist for malignant cells.
Image Guided Biopsy is
often used to facilitate the sampling of cells or tissue
from abnormalities
that can be seen on one or more imaging tests but cannot
be felt. If an abnormality is better seen on a mammogram,
guidance with mammography is usually preferred. If
better seen by ultrasound, then the method of choice
may be ultrasound. Similarly, MRI may be used for enabling
the biopsy of a lesion that cannot be seen by either
mammogram or ultrasound. The mammogram guided technique,
called stereotactic needle biopsy, creates pairs of
x-ray images of the breast biopsy path from two slightly
angled directions to help guide the needle. Ultrasound,
which does not use x-ray, provides the flexibility
of real-time display while guiding the needle to the
precise location. A marker clip is usually placed to
aid in future identification of the area biopsied.
To increase diagnostic accuracy and eliminate
as many false-negative results as possible, the triple
assessment principle is applied. Also known as triple
test, this refers to the correlation of findings from
1) clinical breast examination, 2) breast imaging,
and 3) biopsy. The triple test seeks concordance of
findings using different screening and diagnostic techniques
and ensures comprehensive follow-up of abnormal findings.
For example, abnormal clinical breast exam (CBE) findings
with a normal mammography result requires additional
follow-up to further investigate the abnormal findings
from the CBE.
Surgical Biopsy
Surgical biopsy, also called open biopsy,
may be used for a lesion that is not accessible by
needle biopsy. There are two types of surgical biopsy:
incisional and excisional. Incisional biopsy removes
a small portion of the lesion. Excisional biopsy
removes the entire lesion as well as a surrounding
margin of normal appearing breast tissue. If the lesion
is nonpalpable, or otherwise difficult to locate, a
wire localization technique may be used to direct the
surgeon to its precise location.
As with needle biopsy, tissue removed
by surgical biopsy is sent to a pathology lab for microscopic
examination. In the case of positive findings, blood
tests will be taken and one or more imaging procedures
may be used for helping to screen for evidence of
cancer spread, including chest chest x-ray, bone scan,
CT-scan, MRI and/or PET.
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Staging of Breast
Cancer
Staging is the process of determining
the growth and extent of cancer in the body. The
stage of cancer is one of the most important factors
for planning treatment and offers insight into prognosis.
Staging also provides a standardized means by which
medical providers may communicate with one another
about an individual case and a method by which cancer
researchers may compare case outcomes.
|
The stage of a patient's cancer
is determined by information gathered from tests
on tumor tissue, lymph nodes, and distant organs. |
The stage of a breast cancer is determined
by information gathered from tests on tumor tissue,
lymph nodes, and distant organs. There are two assessment
points. Clinical staging occurs prior to surgery and
is based upon information obtained from physical examination
and imaging tests. Pathological staging occurs after
biopsy, and includes both clinical information and
findings from microscopically examined tissue. The
latter is the more definitive for planning treatment
and estimating prognosis.
TNM System
The system most widely used for breast
cancer staging is the TNM system. This system has been
accepted by the American Joint Committee on Cancer
(AJCC) and is the main method used by most medical
facilities for cancer reporting. The letters stand
for tumor (T), lymph nodes (N), and metastasis (M).
Each letter is followed by a number, or additional
letters, that describes what is known about the growth
and extent of disease at diagnosis. (Both information
for clinical and pathological staging is gathered during
the period prior to first course of therapy.) The T
component designates the size and invasiveness of the
primary tumor, with the numeric value increasing with
tumor size and extent of invasiveness. The N component
designates the presence or absence of regional node
involvement, with the numeric value based on the number
or location of involved lymph nodes. The M component
identifies the presence or absence of distant metastasis,
including lymph nodes that are not regional. Once the
values for the T, N, and M components have been determined,
the information is grouped and expressed as one of
five possible stages, represented by Roman numerals
from Stage 0 (carcinoma in situ) to Stage IV (distant
metastasis). Stages II and III are further refined
into subsets, represented by capital letters (IIB,
IIC, etc.). In practice, most clinicians simply use
Stages 0-IV. See Table I.4
Table I
| Stage |
TNM |
Description |
| 0 |
Tis,N0,M0 |
Carcinoma in situ (Tis) with
no positive lymph nodes (N0) and no known distant
metastasis (M0). |
| I |
T1,N0,M0 |
Tumor is 2 cm or
less in diameter (T1) with no positive lymph nodes
(N0) and no known distant metastasis (M0). |
| IIA |
T0,N1,M0 |
No tumor is
found in the breast (T0) but in 1-3 axillary
lymph nodes (N1) with no known distant metastasis
(M0), or |
| |
T1,N1,M0 |
Tumor is 2 cm
or less (T1) and has spread to 1-3 axillary lymph
nodes or found by sentinel node biopsy as microscopic
disease in internal mammary nodes but not on
imaging studies or by clinical exam (N1) with
no known distant metastasis (M0), or |
| |
T2,N0,M0 |
Tumor is larger than 2 cm
but less than 5 cm in diameter (T2) with no positive
lymph nodes (N0) and no known distant metastasis
(M0). |
| IIB |
T2,N1,M0 |
Tumor is larger
than 2 cm but less than 5 cm (T2) and has spread
to 1-3 axillary lymph nodes or found by sentinel
node biopsy as microscopic disease in internal
mammary nodes but not on imaging studies or by
clinical exam (N1) with no known distant metastasis
(M0), or |
| |
T3,N0,M0 |
Tumor is larger than 5 cm
and does not grow into the chest wall or skin (T3)
with no positive lymph nodes (N0) and no known
distant metastasis (M0). |
| IIIA |
T0-2,N2,MO |
Tumor is smaller
than 5 cm in diameter (T0-2) and has spread to
4 to 9 axillary lymph nodes on the same side as
the breast cancer or to internal mammary nodes
found by imaging studies or clinical exam (N2)
but with no known distant metastasis (M0), or |
| |
T3,N1-2,MO |
Tumor is larger than 5 cm
(T3) and as spread to 1- 9 axillary nodes on the
same side as the breast cancer or to internal mammary
nodes found by imaging studies or clinical exam
(N1-2) but with no known distant metastasis (M0). |
| IIIB |
T4,N0-2,M0 |
Tumor
has grown into the chest wall or skin (T4) and
may or may not have spread to lymph nodes (up
to 9) or may or may not have spread to internal
mammary nodes (N0-2). There is no known distant
metastasis (M0). |
| IIIC |
T0-4,N3,M0 |
Tumor
is any size (T0-4) and has spread to 10 or more
nodes in the axilla or to 1 or more infraclavicular
or supraclavicular lymph nodes or to internal
mammary lymph nodes, which are enlarged because
of the cancer - all on the same side as the breast
cancer (N3). There is no known distant metastasis
(M0). |
| IV |
T0-4,N0-3,M1 |
Tumor is any
size (T0-4) with known distant metastasis to
organs (most often the bones, lungs, liver, or
brain), or to lymph nodes distant from the breast
(M1). |
Further information about TNM Definitions
and AJCC Stage Groupings
is available on the National
Cancer Institute web site.
Additionally, the American
Joint Committee on Cancer web
site offers a variety of publications and other staging
resources for healthcare professionals.
5-Year Survival Rates
Five-year survival rates refer to the
percentage of patients who live at least 5 years from
diagnosis. Relative survival compares the observed
survival of people with breast cancer with that expected
for people without breast cancer. (Mortality due to
others causes is excluded from the rate.) The following
is an approximate 5-year relative survival rate for
each stage of breast cancer based on data from patients
diagnosed from 1995 to 1998. Current survival rates
may be higher due to improvements in treatment and
modifications to the TNM staging system made in 2002.
The figures are derived from the American College of
Surgeons National Cancer Data Base, as reported by
the American Cancer Society.5
5-Year Relative Survival Rate by Stage:
| Stage 0 |
100% |
| Stage I |
100% |
| Stage IIA |
92% |
| Stage IIB |
81% |
| Stage IIIA |
67% |
| Stage IIIB |
54% |
| Stage IIIC |
rate not available |
| Stage IV |
20% |
After seven years, the relative survival
rates decrease for each stage. As with all averages, however,
it should be noted that individual outcomes may vary
depending upon a woman's personal characteristics,
such as age, general health and menopausal status,
and upon additional prognostic factors related to tumor
features.
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Additional
Prognostic Factors
In addition to those described for TNM
staging, factors that affect prognosis include type
of cancer, tumor grade, hormone receptor status (estrogen
and progesterone), HER-2/neu expression, DNA content
(ploidy) and cell proliferation rate (S-phase fraction).
Type of cancer may
be in situ or invasive, ductal or lobular, or a rarer
form, such a Phylloides tumor which develops in the
breast stroma. The many variations of ductal and lobular
carcinoma have differing implications for prognosis. (For
more information, please see Anatomy
and Pathology: Types of Breast Cancer )
Tumor grade classifies
breast cancer cells on the basis of three features:
rate of cell division (mitotic rate), percent of cancer
composed of tubular structures (tubule formation),
and change in cell size and uniformity (nuclear grade).
Each feature is assigned a score ranging from 1 to
3, based upon microscopic observations of the cells.
The three scores are then added together for a final
sum that ranges from 3 to 9. Generally,
a lower total number is associated with a more favorable
prognosis. One of the most popular grading systems
in the United States is the modified Scarff-Bloom-Richardson
grading scale.
Hormone receptor status refers
to the estrogen and progesterone receptors on the surface
of cells that bind to circulating hormones. Tumors
that contain estrogen and progesterone receptors are
referred to as ER-positive and PR-positive, or hormone
receptive positive. About two-thirds of breast cancers
are ER-positive, with the likelihood of ER-positivity
increasing with age. Hormone receptive positive breast
cancers predict response to hormone therapy (e.g.,
tamoxifen, aromatase inhibitors) and their prognosis
is generally more favorable than cancers without this
feature. However, recent research has shown that advances
in chemotherapy have resulted in improved outcomes
for patients with ER-negative tumors, with prognoses
approaching that of patients with optimally treated
ER-positive disease.6
HER-2/neu expression refers
to a type of cell surface receptor that functions to
regulate cell growth. Testing for HER-2/neu is of clinical
value in assessing prognosis and choice of treatment.
While HER-2/neu overexpression is generally associated
with an adverse prognosis, it also predicts response
to the monoclonal antibody, trastuzumab (Herceptin). HER-2/neu
overexpression affects approximately 20% to 30% of
breast cancer patients.
DNA content (ploidy) and cell
proliferation rate (S-phase fraction) are
measured by flow cytometry, which is a technique
that separates, classifies and quantifies cell types.
The ploidy of cancer cells refers to the amount of
DNA they contain which has prognostic implications.
Tumors with a normal amount of DNA are described
as diploid; those with an abnormal amount are described
as aneuploid. The prognosis is usually worse for
breast cancers with a greater degree of cellular
aneuploidy. Cell proliferation rate, or S-phase
fraction, refers to the rate at which cells divide
and grow. High values indicate faster rates of growth
and less favorable disease outcomes than low values.
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Notes
1Edge
SB, Hurd TC. Best Practice
of Medicine: Breast Cancer (Mar., 2003.) Merck
Medicus. Retrieved Jun. 8, 2006 at: http://merck.micromedex.com/index.asp?page=bpm_brief&article
_id=BPM01ON03
2See
note 1.
3National
Cancer Institute. Improving
Methods for Breast Cancer Detection and Diagnosis (updated,
Apr. 26, 2002). Retrieved Jun. 8, 2006 at: http://www.cancer.gov/cancertopics/factsheet
/Detection/breast-cancer
4Table
content was compiled from information published on
the American Cancer Society (ACS) web page: How
is Breast Cancer Staged? (revised, Sep. 2, 2005).
Retrieved May 28, 2006 at: http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_breast_cancer_staged
_5.asp? sitearea=CRI
5See
note 4.
6OncoLink
Cancer News. Prognosis
similar in estrogen positive and negative breast cancer (Apr.
12, 2006). Retrieved Jun. 7, 2006 at: http://www.oncolink.com/resources/article.cfm?c=3&s=
8&ss=23&id=13051&month=04&year=2006
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Revised: November 21, 2007. |
