Clinical features, diagnosis, and staging of newly diagnosed breast cancer

Official reprint from UpToDate® www.uptodate.com

©2024 UpToDate®

Clinical features, diagnosis, and staging of newly

diagnosed breast cancer
Author: Bonnie N Joe, MD, PhD
Section Editor: Harold J Burstein, MD, PhD
Deputy Editor: Sadhna R Vora, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Sep 2024. | This topic last updated: Oct 02, 2023.

INTRODUCTION

Globally, breast cancer is the most frequently diagnosed malignancy, accounting for over
two million cases each year [1]. It is also the leading cause of cancer death in women
worldwide. In the United States, breast cancer is the most common female cancer, and the
second most common cause of cancer death in women [2].

Once a diagnosis of breast cancer is established, it is important to accurately define the

initial extent of disease since this information will affect treatment recommendations. This
topic will review the clinical manifestations, differential diagnosis, and staging following a
diagnosis of breast cancer.

The factors that modify breast cancer risk, the treatment approach to in situ and invasive
breast cancer, and the use of prognostic and predictive factors when making adjuvant
treatment decisions are reviewed as separate topics.
● (See "Factors that modify breast cancer risk in women".)
● (See "Ductal carcinoma in situ: Treatment and prognosis".)
● (See "Overview of the treatment of newly diagnosed, invasive, non-metastatic breast
cancer".)
● (See "Overview of the approach to metastatic breast cancer".)
● (See "Prognostic and predictive factors in early, non-metastatic breast cancer".)

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Clinical features, diagnosis, and staging of newly diagnosed breast cancer

EPIDEMIOLOGY

Breast cancer is the most commonly diagnosed cancer worldwide, including low- and
middle-income countries [3]. The incidence rates are highest in North America,
Australia/New Zealand, and in western and northern Europe and lowest in Asia and sub-
Saharan Africa [4]. These international differences are likely related to societal changes as
a result of industrialization (eg, changes in fat intake, body weight, age at menarche,
and/or lactation, and reproductive patterns such as fewer pregnancies and later age at
first birth). Studies of migration patterns to the United States are consistent with the
importance of cultural and/or environmental changes [5]. In general, incidence rates of
breast cancer are greater in second-generation migrants and increase further in third- and
fourth-generation migrants.

In the United States, breast cancer accounts for approximately 300,000 cases each year
and is responsible for over 40,000 deaths [2]. The incidence rates decreased from 1999 to
2007 by 1.8 percent per year [6]. This decline in incidence reflects the end of the prevalence
peak of screening. When women are screened for the first time, there is a "prevalence
peak" that is due to cancers that have been building up in the population added to the
cancers that are detected early due to the screening. An extended prevalence peak was
seen with the gradual uptake of screening in the United States from the mid-1980s to
1999. The drop in incidence starting in 1999 reflected the end of the prevalence peak when
participation in screening plateaued and, as expected, breast cancer incidence began to
fall back to baseline. Discontinuation of hormone replacement therapy (HRT) had
previously been touted as the major reason for this decline, although subsequent results
from the Women's Health Initiative indicate HRT is safe in many postmenopausal women
[7-12]. (See "Menopausal hormone therapy: Benefits and risks", section on 'Breast cancer'.)

Breast cancer mortality rates have been decreasing since the 1970s [13]. This decrease in
mortality is due to improved breast cancer screening and improvements in adjuvant
therapy [14,15]. Therapy saves lives when breast cancers are treated earlier, as
demonstrated in a landmark article in which women age 40 to 69 years who participated in
organized mammography screening had a 60 percent lower risk of dying from breast
cancer within 10 years of diagnosis and a 47 percent lower risk of dying from breast cancer
within 20 years of diagnosis compared with women who did not participate in screening
[16].

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Clinical features, diagnosis, and staging of newly diagnosed breast cancer

Additional risk factors for breast cancer development and models to predict risk are
reviewed separately. (See "Factors that modify breast cancer risk in women" and
"Screening for breast cancer: Strategies and recommendations", section on 'Breast cancer
risk determination'.)

CLINICAL FEATURES

The diagnosis of breast cancer requires histologic evaluation. The typical features of
invasive breast cancer are reviewed below.

Signs and symptoms — In countries with established breast cancer screening programs,
most patients present due to an abnormal mammogram. However, up to 15 percent of
women are diagnosed with breast cancer due to the presence of a breast mass that is not
detected on mammogram (mammographically occult disease), and another 30 percent
present with a breast mass in the interval between mammograms (interval cancers) [17]. In
addition, women without access to screening mammograms and younger women under
40 years who may not be undergoing routine screening mammograms may present with a
breast or axillary mass with or without skin changes.

Breast mass — The "classic" characteristics of a cancerous lesion include a hard,

immovable, single dominant lesion with irregular borders. However, these features cannot
reliably distinguish a benign from a malignant tumor. (See "Clinical manifestations,
differential diagnosis, and clinical evaluation of a palpable breast mass" and "Diagnostic
evaluation of suspected breast cancer".)

Locally advanced disease — The signs of more advanced locoregional disease include
axillary adenopathy (suggesting locoregional disease) or skin findings such as erythema,
thickening, or dimpling of the overlying skin (peau d'orange), suggesting inflammatory
breast cancer. (See "Overview of the treatment of newly diagnosed, invasive, non-
metastatic breast cancer", section on 'Locally advanced breast cancer' and "Inflammatory
breast cancer: Clinical features and treatment".)

Metastatic disease — Symptoms of metastatic breast cancer depend on the organs

involved, with the most common sites of involvement being the bone (eg, back or leg pain),
liver (abdominal pain, nausea, jaundice), and lungs (eg, shortness of breath or cough). (See
"Overview of long-term complications of therapy in breast cancer survivors and patterns of
relapse", section on 'Metastatic disease'.)
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Clinical features, diagnosis, and staging of newly diagnosed breast cancer

Imaging findings — Classic mammographic findings of breast cancer include the

presence of a soft tissue mass or density ( image 1) and suspicious microcalcifications.
The most specific feature is a spiculated, high-density mass, with nearly 90 percent
representing an invasive cancer. A more detailed discussion on the mammographic
presentation of breast cancer is covered separately. (See "Diagnostic evaluation of
suspected breast cancer", section on 'Mammographic features of breast cancer'.)

Breast ultrasound is often used to distinguish a benign versus malignant lesion.

Sonographic features of malignancy include hypoechogenicity; internal calcifications;
shadowing; a lesion taller than it is wide; and spiculated, indistinct, or angular margins
[18]. A typical ultrasound of early breast cancer is depicted here ( image 2). (See
"Diagnostic evaluation of suspected breast cancer", section on 'Ultrasonography'.)

Magnetic resonance imaging (MRI) is typically used to screen women at high risk for breast
cancer. Although nearly all invasive breast cancers enhance on gadolinium contrast-
enhanced MRI, MRI is not specific enough to obviate the need for biopsy. MRI features of
breast cancer include irregular or spiculated mass margins, heterogeneous internal
enhancement, and rim enhancement ( image 3) [19]. Nonmass enhancement on
contrast-enhanced MRI may also increase suspicion of an invasive lesion, particularly if the
enhancement is associated with a mass or exhibits segmental distribution [19,20]. (See
"MRI of the breast and emerging technologies", section on 'Screening high-risk women'
and "Diagnostic evaluation of suspected breast cancer", section on 'Breast MRI'.)

DIAGNOSIS

The diagnosis of breast cancer is defined by the presence of malignant epithelial cells
(carcinoma) on biopsy [21].

PATHOLOGY

There are various histologic types of breast carcinoma that differ in microscopic
appearance and biologic behavior. (See "Pathology of breast cancer".)

The most common histologic types of epithelial breast carcinoma are described below.

Infiltrating ductal carcinoma — Infiltrating ductal carcinomas are the most common type
of invasive breast cancer, accounting for 70 to 80 percent of invasive lesions. These lesions
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Clinical features, diagnosis, and staging of newly diagnosed breast cancer

are characterized by cords and nests of cells with varying amounts of gland formation and
cytologic features that range from bland to highly malignant.

Infiltrating lobular carcinoma — Infiltrating lobular carcinomas comprise about 8

percent of invasive breast cancers. Microscopically, they are characterized by small cells
that insidiously infiltrate the mammary stroma and adipose tissue individually and in a
single-file pattern.

Mixed ductal/lobular carcinoma — A mixed histologic appearance comprising both

ductal and lobular characteristics is defined as a mixed invasive carcinoma. These comprise
7 percent of invasive breast cancers.

Other histologic types of breast cancer include metaplastic, mucinous, tubular, medullary,
and papillary carcinomas. Together they account for less than 5 percent of invasive
cancers. (See "Pathology of breast cancer".)

DIFFERENTIAL DIAGNOSIS

Breast cancers are heterogeneous in origin. The differential diagnosis of breast cancer
includes malignancies that develop from epithelial, mesothelial, adenomyoepithelium,
luminal progenitor, and basal stem cells [22].

The differential of a breast mass is reviewed separately. (See "Overview of benign breast
diseases" and "Clinical manifestations, differential diagnosis, and clinical evaluation of a
palpable breast mass" and "Atypia and lobular carcinoma in situ: High-risk lesions of the
breast".)

For women who undergo a biopsy, the pathologic differential diagnosis must include other
breast lesions beyond invasive breast cancer. Given the heterogeneity in the presentation
and pathologic features of invasive breast cancer, expertise in breast pathology is often
required to distinguish invasive carcinoma from other breast lesions. Breast lesions that
should be considered in the review of pathology include:
● Ductal carcinoma in situ (DCIS) represents a heterogeneous spectrum of
precancerous lesions confined to the breast ducts and lobules and is potentially a
precursor lesion to invasive breast cancer. DCIS is characterized by the size of the
lesion, nuclear grade, presence and extent of comedo necrosis, and architectural
pattern. (See "Breast ductal carcinoma in situ: Epidemiology, clinical manifestations,

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Clinical features, diagnosis, and staging of newly diagnosed breast cancer

and diagnosis".)
● Microinvasive breast cancer (or DCIS with microinvasion) typically presents as a
palpable mass. On pathologic examination, it is an invasive carcinoma of the breast
where the largest focus is no more than 1 mm. It tends to be associated with high-
grade DCIS and comedo-type necrosis. (See "Microinvasive breast carcinoma".)
● Other cancers – The breast can give rise to other invasive malignancies separate
from primary breast cancer. These rare tumors include sarcoma, Paget disease,
malignant phyllodes tumor, and lymphoma. A biopsy is required to distinguish these
tumors from primary breast cancer.

• Breast sarcoma – Breast sarcomas are rare, histologically homogenous tumors

that arise from the connective tissue within the breast. They can arise de novo,
following radiation therapy, or in the context of lymphedema. (See "Breast
sarcoma: Epidemiology, risk factors, clinical presentation, diagnosis, and staging".)

• Paget disease – Paget disease of the breast typically presents as a raw, scaly,
vesicular, or ulcerated lesion that begins on the nipple and spreads to the areola.
Over 80 percent of cases are associated with an underlying breast cancer and are
usually human epidermal growth factor 2 positive. (See "Paget disease of the
breast (PDB)".)

• Phyllodes tumors – Phyllodes tumors are uncommon fibroepithelial breast tumors

that can behave in variable fashion and are classified as benign, borderline, or
malignant based on histologic criteria (cellular atypia, mitotic activity, margins,
and stromal overgrowth). (See "Phyllodes tumors of the breast".)

• Lymphoma – Lymphoma of the breast typically presents as a painless unilateral

breast mass in an older woman. The vast majority are non-Hodgkin lymphomas,
most commonly of B-cell lineage. (See "Overview of the pathobiology of the non-
Hodgkin lymphomas", section on 'B cell lymphoma'.)

POSTDIAGNOSIS EVALUATION

If cancer is identified, hormone receptor status is determined. (See 'Breast cancer receptor
testing' below.)

In addition, patients should proceed with an appropriate staging work-up to determine

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Clinical features, diagnosis, and staging of newly diagnosed breast cancer

local and distant extent of disease. Women presenting with signs or symptoms of
metastatic breast cancer should undergo additional imaging; in addition, a biopsy should
be done of at least one metastatic lesion to confirm the diagnosis of metastatic breast
cancer. (See 'Role of imaging' below and 'Staging' below and 'Assessing the extent of local
disease' below.)

Breast cancer receptor testing — Newly diagnosed breast cancers must be tested for
estrogen (ER) and progesterone (PR) receptor expression and for overexpression of human
epidermal growth factor 2 (HER2) receptors. This information is critical for both prognostic
and therapeutic purposes. (See "Prognostic and predictive factors in early, non-metastatic
breast cancer" and "Overview of the treatment of newly diagnosed, invasive, non-
metastatic breast cancer".)

ER and PR — Estrogen receptor (ER) and progesterone receptor (PR) are prognostic
factors for invasive breast cancer. In addition, patients with cancers that are ER and/or PR
positive are treated with adjuvant endocrine therapy. ER-positivity is defined by
immunohistochemistry (IHC) for ER and PR in more than 1 percent of tumor cells. More
discussion on the use of ER/PR in breast cancer is covered separately. (See "Hormone
receptors in breast cancer: Clinical utility and guideline recommendations to improve test
accuracy" and "Prognostic and predictive factors in early, non-metastatic breast cancer".)

HER2 — Human epidermal growth factor receptor 2 (HER2) overexpression is present in

15 to 20 percent of patients and predicts those who will benefit from HER2-directed
therapy. HER2 overexpression is detected by uniform intense membrane staining of >10
percent of invasive tumor cells (IHC 3+) or the presence of HER2 gene amplification by
fluorescence in situ hybridization defined as a ratio of HER2/CEP17 (centromeric probe to
chromosome 17) ratio ≥2.0, with the HER2 copy number signals/cell being ≥4. Other
criteria for defining HER2-positivity also exist and are discussed elsewhere. (See "HER2 and
predicting response to therapy in breast cancer", section on 'Testing for HER2 expression'
and "Prognostic and predictive factors in early, non-metastatic breast cancer".)

Frequency of subtypes — Breast cancer can be characterized into different subtypes by

whether or not they express ER, PR, and HER2 [23,24]. The proportions of breast cancers
with different receptor phenotypes were evaluated in one study of 61,309 cases diagnosed
between 1999 and 2004 [23]:
● Hormone receptor (ER and/or PR) positive cancers comprised the majority of cases (n
= 48,851 cases, 80 percent).
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Clinical features, diagnosis, and staging of newly diagnosed breast cancer
● HER2 was overexpressed in 23 percent (n = 13,921). Of these, 67 and 32 percent were
hormone receptor-positive and negative, respectively.
● ER, PR, and HER2-negative (triple negative) cancers comprised 13 percent (n = 8022).

However, the frequency of subtypes also varies according to race. As an example, in the
Carolina Breast Cancer Study, compared with White American women (n = 631), African
American women (n = 518) were less likely to have hormone receptor (ER/PR)-positive,
HER2-negative disease (48 versus 64 percent, respectively) and more likely to have
ER/PR/HER2-negative disease (22 versus 11 percent, respectively) [24].

Role of imaging — Our approach to imaging is as follows.

● Most patients with asymptomatic stage 1 or 2 cancers do not require imaging beyond
the breast. (See 'Assessing the extent of local disease' below.)

For women with newly diagnosed breast cancer, we reserve imaging to evaluate for
advanced or metastatic disease in the following situations:
● For patients with localized bone pain or an elevated alkaline phosphatase, we obtain
a bone scan. If the bone scan is negative and clinical suspicion warrants further
evaluation, magnetic resonance imaging (MRI) should be performed localized to the
symptomatic area.
● For patients with abnormal liver function tests, an elevated alkaline phosphatase,
abdominal pain, or an abnormal abdominal or pelvic examination, we obtain a
computed tomography (CT) scan of the abdomen and pelvis. Abdominal MRI or
ultrasound would be reasonable alternatives depending on the specific symptom to
be evaluated. Positron emission tomography-CT (PET-CT) would be reasonable if
whole-body screening for metastatic disease is also desired.
● For patients presenting with pulmonary complaints (ie, cough or hemoptysis), we
obtain a chest CT scan, although chest radiograph would be a reasonable alternative.
● For patients with stage IIIA or higher disease, regardless of whether symptoms are
present or not, we obtain a whole-body PET-CT or, alternatively, a bone scan as well
as a CT scan of the chest, abdomen, and pelvis (CT C/A/P). Patients with inflammatory
breast cancer, regardless of stage, should also undergo imaging evaluation. (See
"Inflammatory breast cancer: Clinical features and treatment", section on 'Staging
and pretreatment evaluation'.)

In a randomized trial in 369 patients with stage III or IIb (T3N0, but not T2N1)
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Clinical features, diagnosis, and staging of newly diagnosed breast cancer

• breast cancer, 23 percent of patients assigned to staging with PET-CT were

upstaged to stage IV compared with 11 percent assigned to conventional staging
with CT C/A/P and bone scan (absolute difference, 12.3 percent [95% CI 3.9-19.9])
[25]. As such, fewer patients in the PET-CT group received combined modality
therapy (81 versus 89 percent, absolute difference 8.2 [95% CI 0.1-15.4]).

• A novel PET methodology, using fluoroestradiol F-18 as the radioactive diagnostic

agent, is approved by the US Food and Drug Administration for the detection of
ER-positive lesions, as an adjunct to biopsy, in patients with recurrent or
metastatic breast cancer [26]. However, it does not as yet have a defined role in
routine management of assessment of early breast cancer. This agent is being
evaluated in clinical trials to determine clinical utility for predicting endocrine
therapy response and to provide prognostic information [27-29]. (See "MRI of the
breast and emerging technologies", section on 'Positron emission tomography
scanning'.)

This approach is consistent with National Comprehensive Cancer Network guidelines [30]
and is based on multiple studies that have shown extensive imaging has little yield for
most patients with newly diagnosed breast cancer [31-33]. In one of the largest reports,
516 consecutive patients seen at one institution for newly diagnosed breast cancer were
retrospectively evaluated to determine the impact of staging [33]. Major findings were:
● A bone scan detected bony metastases in 26 of 412 patients (6 percent). The
prevalence of a positive bone scan for women with preimaging stage I, II, and III
breast cancer was 5, 6, and 14 percent, respectively.
● Liver ultrasound detected hepatic metastases in 3 of 412 patients (0.7 percent). No
patients with stage I or II breast cancer had liver metastases. For patients with stage
III breast cancer, the prevalence of a positive liver ultrasound was 6 percent.
● Chest radiograph detected lung metastases in 4 of 428 patients (0.9 percent). No
patients with stage I or II breast cancer had pulmonary metastases. The prevalence
of a positive chest radiograph among women with stage III disease was 7 percent.

Assessing the extent of local disease — Mammographic assessment of the extent of

ductal carcinoma in situ (DCIS) and early invasive carcinoma begins during diagnostic
mammography and continues through the biopsy, specimen management, and the
postexcision mammogram [34]. Mammography of both breasts is particularly important in
the patient with DCIS or invasive cancer who is considering breast conservation.
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Clinical features, diagnosis, and staging of newly diagnosed breast cancer

Preoperative diagnostic mammography can help to define the extent of disease and may
identify multifocal or multicentric cancer that could preclude breast conservation or signal
a potential difficulty in achieving clear surgical margins. Multifocal disease is usually
defined as involvement of several areas within a breast quadrant, probably representing
disease along an entire duct. By contrast, multicentric disease involves multiple areas
within different quadrants, probably representing involvement of multiple ducts.

Although the extent of mammographic nonlinear branching microcalcifications frequently

underestimates the pathologic extent of the malignancy, the discrepancy is less than 2 cm
in 80 to 85 percent of cases [35]. Several groups of microcalcifications separated by
normal-appearing tissue should not be interpreted as multifocal or multicentric disease.
Often, these represent areas of contiguous tumor that is only partially calcified within a
ductal lobule [35,36].

The combination of a mass and associated calcifications often indicates the presence of an
extensive intraductal component (EIC). EIC is defined pathologically as DCIS found adjacent
to an invasive carcinoma, accounting for more than 25 percent of the volume of disease.
This finding can be a predictor for more widespread residual tumor (usually DCIS)
following gross excision of the lesion [37]. (See "Breast ductal carcinoma in situ:
Epidemiology, clinical manifestations, and diagnosis".)

Postoperative mammograms to look for residual calcifications after surgical resection

should be considered when the microcalcifications are not clearly or completely
documented on the specimen radiograph, or when margins are close or positive [38,39]. If
a re-excision is to be recommended based on residual calcifications, care should be taken
to ensure that the calcifications are associated with malignancy on histopathology and not
benign tissue. Multifocal disease is not necessarily a contraindication to breast
conservation but is one of the factors that should be taken into consideration along with
breast size relative to the extent of disease on imaging. (See "Breast-conserving therapy"
and "Breast ductal carcinoma in situ: Epidemiology, clinical manifestations, and
diagnosis".)

A significant limitation of mammographic assessment of disease extent is the obscuring of

the borders or extent of the primary tumor by dense overlying tissue. Dense breasts can
limit the sensitivity of mammography both for detection of breast cancers and for
delineating disease extent [40-42]. In this setting, contrast-enhanced breast MRI may
complement mammographic staging. If the clinical extent of disease is larger than what

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Clinical features, diagnosis, and staging of newly diagnosed breast cancer

can be appreciated by mammography, MRI may be considered. (See "Diagnostic evaluation

of suspected breast cancer", section on 'Breast MRI'.)

Contrast enhanced mammography is a new technology that approaches accuracy of MRI

for pre-operative staging and may be considered in patients unable to obtain breast MRI
[43].

Mammographic assessment of tumor size for the staging of multifocal disease presents a
unique dilemma. Most staging classifications require that the largest tumor mass be
utilized for T staging, even in cases where multifocal disease is suspected. However, others
suggest that the total surface area, volume, or aggregate measurements are a better
indicator of prognosis [44-46]. Accurate delineation of the extent of odd-shaped, irregular,
or multifocal tumors is important for treatment planning. (See "Tumor, node, metastasis
(TNM) staging classification for breast cancer".)

For invasive cancers that are contiguous to the chest wall and not completely included on
mammographic projections, ancillary imaging techniques such as MRI may be necessary to
assess posterior tumor extension and pectoralis fascia or muscle involvement if that will
determine a change in surgical approach or the use of neoadjuvant therapy [47]. Breast
MRI may also be useful for evaluating response to neoadjuvant therapy in locally advanced
breast cancers and can provide prognostic information. In a multicenter trial of
neoadjuvant chemotherapy, functional tumor volume at MRI was a stronger predictor of
recurrence-free survival than pathologic complete response [48]. (See "General principles
of neoadjuvant management of breast cancer", section on 'Clinical assessment and
indications for imaging'.)

Significance of intramammary lymph nodes — Intramammary lymph nodes are

detected in 1 to 28 percent of patients with breast cancer [49-53]. Benign nodes can often
be distinguished from metastatic or infiltrated intramammary lymph nodes by their
mammographic or sonographic appearance, but definitive assessment often requires
histopathologic study [54]. The presence of intramammary lymph node metastases
appears to confer a worse prognosis, both in women who otherwise have stage I breast
cancer based upon tumor size and axillary nodal status and in those with higher stage
disease [49]. Isolated clinically detected intramammary lymph node metastases are
considered to represent stage III disease, even if the axillary nodes are uninvolved. (See
"Tumor, node, metastasis (TNM) staging classification for breast cancer".)

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Clinical features, diagnosis, and staging of newly diagnosed breast cancer

GENETIC COUNSELING

Some patients with a diagnosis of breast cancer may be appropriate candidates for genetic
evaluation to determine their own and family members' risk for future breast cancers and
other malignancies. This is discussed in detail elsewhere. (See "Genetic testing and
management of individuals at risk of hereditary breast and ovarian cancer syndromes",
section on 'Criteria for genetic risk evaluation'.)

In addition, patients with triple-negative breast cancer (at any age) or those with high-risk
disease who would be candidates for adjuvant olaparib if they were found to have a BRCA
mutation should be offered genetic counseling and testing. Criteria for adjuvant olaparib
among BRCA carriers with high-risk early breast cancer are discussed elsewhere. (See
"Selection and administration of adjuvant chemotherapy for HER2-negative breast cancer",
section on 'Patient selection for adjuvant PARP inhibitors' and "Genetic testing and
management of individuals at risk of hereditary breast and ovarian cancer syndromes".)

STAGING

Breast cancer is staged using the American Joint Committee on Cancer and the
International Union for Cancer Control classification system for Tumor, Nodes, and
Metastases (TNM). The eighth edition of the TNM staging system, which was effective as of
January 1, 2018, includes anatomic stage groups ( table 1) as well as prognostic stage
groups, which incorporate biomarker testing ( table 2 and table 3). (See "Tumor, node,
metastasis (TNM) staging classification for breast cancer".)

In the TNM system, patients are assigned a clinical stage (cTNM) preoperatively. Following
surgery, the pathologic stage (pTNM) is then determined. For patients who undergo
neoadjuvant treatment, the final pathologic stage is designated by the letter y (ypTNM).
(See "Diagnostic evaluation of suspected breast cancer" and "General principles of
neoadjuvant management of breast cancer", section on 'Pathologic assessment'.)

Primary tumor — Clinical tumor (T) stage is assessed by clinical examination and/or
imaging. While the majority of breast cancers are associated with abnormal
mammographic findings, breast ultrasound and/or magnetic resonance imaging may be
required to accurately assess tumor size, particularly in patients presenting with a breast
mass that is not identified on mammography. (See "Diagnostic evaluation of suspected
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Clinical features, diagnosis, and staging of newly diagnosed breast cancer

breast cancer", section on 'Mammography and digital breast tomosynthesis' and

"Diagnostic evaluation of suspected breast cancer", section on 'Ultrasonography' and
"Diagnostic evaluation of suspected breast cancer", section on 'Breast MRI'.)

Lymph nodes — The status of the regional lymph nodes is one of the most important
prognostic factors in early-stage breast cancer. Physical examination is neither a sensitive
nor a reliable method to ascertain the status of the axillary lymph nodes because
metastatic lymph nodes are often not palpable and reactive lymph nodes may be mistaken
for metastases. The positive predictive value of clinical palpation ranges from 61 to 84
percent, while the negative predictive value is only 50 to 60 percent [55-57].

Given these findings, axillary staging should be performed. The assessment and
management of the regional lymph nodes in breast cancer are discussed separately. (See
"Overview of management of the regional lymph nodes in breast cancer".)

Metastases — Most patients presenting with breast cancer have disease confined to the
breast (stage I to II) with no or limited (ie, less than three) nodes involved. We do not
routinely stage such patients in the absence of signs or symptoms suspicious for
metastatic disease. We restrict further work-up to patients who present with locally
advanced (T3 or greater, N2 or N3, M0) or inflammatory breast cancer and those with signs
or symptoms suspicious for metastatic disease. Specific indications for imaging are
discussed above. (See 'Role of imaging' above.)

Management of patients with metastatic disease is discussed above. (See "Overview of the
approach to metastatic breast cancer" and "Epidemiology, clinical presentation, and
diagnosis of bone metastasis in adults".)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and

regions around the world are provided separately. (See "Society guideline links: Breast
cancer".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
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Clinical features, diagnosis, and staging of newly diagnosed breast cancer

grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview
and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces
are longer, more sophisticated, and more detailed. These articles are written at the 10th to
12th grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Breast cancer (The Basics)")
● Beyond the Basics topics (see "Patient education: Breast cancer guide to diagnosis
and treatment (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

● Introduction – Breast cancer is the most common malignancy diagnosed worldwide.

Breast cancer mortality rates have been decreasing due to improved breast cancer
screening and improvements in adjuvant therapy. (See 'Epidemiology' above.)
● Presentation – In countries with established breast cancer screening programs, most
patients present due to an abnormal mammogram. However, women with advanced
cases of breast cancer may present with skin changes (also known as peau d'orange)
or axillary adenopathy. Less than 5 percent of patients present with signs or
symptoms of metastatic breast cancer. (See 'Signs and symptoms' above.)
● Evaluation

• Women who present with abnormal imaging findings alone should undergo
biopsy guided by mammogram (stereotactic biopsy), ultrasound, or breast
magnetic resonance imaging. (See "Breast biopsy".)

• Women presenting with a suspicious palpable breast mass should undergo

diagnostic imaging evaluation followed by a fine needle aspiration or core needle
biopsy. (See "Breast biopsy", section on 'Core needle biopsy' and "Breast biopsy",
section on 'Fine needle aspiration'.)

• In addition to a biopsy of the breast, women presenting with signs of

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inflammatory breast cancer (eg, rapidly progressing, tender, firm, and enlarged
breast with thickening of the underlying skin) require full-thickness skin biopsies.
The presence of dermal lymphatic invasion is pathognomonic for inflammatory
breast cancer. (See "Breast biopsy", section on 'Skin punch biopsy'.)
● Diagnosis and pathology

• The diagnosis of breast cancer is defined by the presence of malignant epithelial

cells (carcinoma) showing evidence of stromal invasion. (See 'Diagnosis' above.)

• Most breast malignancies are carcinomas that arise from epithelial elements.
However, there are various histologic types of breast carcinomas, such as
sarcomas, that differ in microscopic appearance and biologic behavior. (See
'Differential diagnosis' above.)
● Classification

• Breast cancer can be categorized based on expression of estrogen (ER),

progesterone, and human epidermal growth factor (HER2) receptors. Each of
these factors influence prognosis for patients with invasive breast cancer and is
used to individualize treatment options. (See 'Pathology' above and 'Postdiagnosis
evaluation' above.)
● Staging – Breast cancer is classified according to the American Joint Committee on
Cancer and the International Union for Cancer Control for tumor, nodes, and
metastases (TNM; ( table 1 and table 2 and table 3)). In the TNM system,
patients are assigned a clinical stage (cTNM) preoperatively. Following surgery, the
pathologic stage (pTNM) can be assigned. For patients who undergo neoadjuvant
treatment, the final pathologic stage is designated by the letter y (ypTNM). (See
'Staging' above.)

ACKNOWLEDGMENT

The editorial staff at UpToDate acknowledge Laura J Esserman, MD, MBA, who contributed
to an earlier version of this topic review.

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