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Diagnosis and Staging


Introduction

The 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.

Mammographic Findings and Breast Symptoms

Most breast cancers are diagnosed after suspicious findings from a screening mammography, although most mammographic findings are benign. The findings may include the presence of a soft tissue spiculated mass, or clusters of microcalcifications. Women with abnormal screening mammograms should always undergo further evaluation.1 2

A new mass or lump is the most frequent breast symptom of cancer. Cancerous masses most often have irregular borders and are immovable, painless, and hard. However, they may also be painful, soft, tender, or rounded, and the physical characteristics of the mass cannot reliably distinguish between a benign and malignant lesion. Other symptoms that require further screening include:3

  • swelling
  • skin irritation or dimpling
  • pain in breast or nipple
  • nipple retraction
  • redness, scaliness, or thickening of the breast or nipple skin
  • nipple discharge
  • swelling or lumps near the lymph nodes under the arm or around the collar bone
  • change in breast size or shape
Breast Cancer Diagnostic Algorithms for Primary Care Providers

To assist clinicians with the work-up of patients who present with breast symptoms or an abnormal breast finding, the Cancer Detection Section, California Department of Public Health has published the Breast Cancer Diagnostic Algorithms for Primary Care Providers (4th Ed.). The algorithms are not intended to replace clinical judgment in individual cases but are offered for use as an adjunct to clinical decision-making. Originally published in 1997, the most recent edition incorporates the latest research and guideline updates into a brief, user-friendly format. Flowcharts and key messages provide 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 table and, in the case of breast biopsy, an algorithm for the management of pathologic findings.4

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 changes over time, the provider should ask 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.4 Also important, the provider should ask about (or observe) any signs of emotional distress that may be related to the breast finding. The process of evaluation can be a difficult time for a patient and the provider can help by facilitating any needed emotional counseling or support.5

A complete physical examination should include a full pelvic and clinical breast exam. A visual and manual inspection of the breasts should search for the presence of lumps or masses; asymmetry; changes to the skin or nipples; and tenderness. Regional lymph nodes should 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.6  For more detailed information about clinical breast examination, please refer to the printable Core Competencies of Clinical Breast Examination guide for primary care providers involved in breast cancer screening published by the Cancer Detection Section of the California Department of Public Health.

The evaluation of suspected breast cancer requires the coordination of care among several specialists, including breast imagers and breast surgeons. An integrated, multidisciplinary approach is essential for minimizing unnecessary biopsies and diagnostic delays. Primary care records should contain all relevant imaging and biopsy results, documenting a thorough and timely follow-up.1 The Department of Health Care Services, Every Woman Counts program expects this complete follow-up of abnormal findings within 60 days.

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Imaging Tests

The two main imaging tests used for the evaluation of an abnormal breast finding are diagnostic mammogram and breast ultrasound.
The two main imaging tests used for the evaluation of an abnormal breast finding are diagnostic mammogram and breast ultrasound. Magnetic Resonance Imaging (MRI) and other imaging devices may be used along with one of the two main tests to improve diagnostic accuracy and to clarify indeterminate findings. A final BI-RADS (Breast Imaging Reporting and Data System) category, indicating the relative likelihood of a normal, benign, or malignant diagnosis, is assigned based on the results of all imaging procedures. Surgical decisions should not be made based on imaging findings alone. These findings should be confirmed with biopsy.

Mammogram
Mammogram. Source: Dr. Dwight Kaufman. National Cancer Institute. Adapted from NCI Visuals Online. AV-9402-4078.

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, a diagnostic mammogram may include lateromedial, mediolateral, and exaggerated craniocaudal views, as well as other special views, such as spot compression and magnification. Mammography is the imaging method of choice for investigating microcalcifications. Diagnostic mammograms are supervised by a radiologist, and the views obtained are specific to the targeted abnormality.7


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.

Breast Ultrasound (also called sonography) 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 of a simple cyst 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, and for evaluating the axillary lymph nodes for possible metastases. It is also useful in guiding interventional procedures.

Diagnostic breast ultrasound is highly operator-dependent, and there is significant inter-observer variability in the interpretation of solid breast masses.1

MRI
MRI. Source: Mitchell D. Schnall, M.D., Ph.D. University Of Pennsylvania. Adapted from NCI Visuals Online. AV-9402-4282.
Magnetic resonance image
(MRI) of individual breast,
demonstrating marked
enhancement (bright area)
which was confirmed to
be cancer.

Magnetic Resonance Imaging (MRI) uses magnets and radio waves to produce very detailed, cross-sectional images. Breast MRI is not recommended for routine diagnostic evaluation of suspected breast cancer. Although it is highly sensitive, it has a high rate of false-positives leading to an increase in the number of unnecessary medical procedures, including mastectomies.

The National Comprehensive Cancer Network considers breast MRI as a useful adjunct to diagnostic mammography in some specific situations, including:8

  • when the extent of the disease is larger than what can be viewed through mammography, particularly for women with dense breasts
  • for cancers that are invasive and adjacent to the chest wall to evaluate tumor extension and muscle involvement if that will help determine surgical approach or the benefit of neoadjuvant (pre-surgery) therapy
  • when the cancer has metastasized to the axillary nodes and the tumor is not visible on a mammogram or ultrasound to help identify patients who will benefit from surgery
  • for women with Paget’s disease of the breast who have negative physical examinations and mammograms to help define the extent of the cancer and plan for treatment
  • for women with locally advanced cancer being considered for neoadjuvant chemotherapy to define extent of disease and potential for breast conserving surgery
  • for women at high risk for developing breast cancer in the opposite breast or who are undergoing a prophylactic mastectomy in the other breast
  • for women who are undergoing extensive breast reconstruction
  • 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 an 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. Fluid from a nipple discharge might also be collected and examined under a microscope (nipple smear). Ductograms are technically challenging procedures, and the absence of a finding does not exclude a diagnosis of cancer. These tests can be useful, however, in locating a lesion which can assist surgeons in minimizing the amount of tissue removed during biopsy.9 

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. Still considered experimental by some experts, scintimammography is sometimes used as a supplemental imaging method for help with evaluating a breast abnormality in certain patients. Like MRI, it is most useful for women with dense breast tissue.10

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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.1 Biopsy removes 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: (1) Fine Needle Aspiration Biopsy (FNAB) and (2) Core Needle Biopsy (CNB).

Title: Needle Biopsy - Description: From NCI visuals online: https://visualsonline.cancer.gov/details.cfm?imageid=1973

Fine Needle Aspiration Biopsy (FNAB) is the least invasive method of breast biopsy. 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.11 FNAB can be conducted rapidly and easily, and quick smears can be used to assess the adequacy of the tissue sample. When FNAB is performed by highly experienced operators, its sensitivity can be as high as 98% and specificity as high as 97%.12 The primary disadvantages of FNAB are its inability to distinguish between in situ and invasive cancers and a high rate of non-diagnostic and false negative results when conducted by inexperienced operators.13

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. Because CNB removes more tissue than FNAB, CNB gives a more definitive diagnosis and is less likely to miss a cancer than FNAB, although false negatives are still possible with this method. CNB is also able to distinguish between in situ and invasive cancers. The vacuum-assisted CNB allows for the removal of a greater amount of tissue.13

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 provides the flexibility of real-time display while guiding the needle to the precise location.

A marker clip/localization device is usually placed to aid future identification of the area of a concern under stereotactic, ultrasound, or MRI guidance.13

Triple Test

  • clinical breast examination
  • breast imaging
  • biopsy

To increase diagnostic accuracy and eliminate as many false negative results as possible, the triple assessment principle is applied to the evaluation of a breast symptom or abnormal finding. 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 require additional follow-up to further investigate the abnormal findings from the CBE.2

Surgical Biopsy

Surgical Biopsy. Source: Linda Bartlett (photographer). Adapted from NCI Visuals Online. AV-8000-0507.

Surgical biopsy, also called open biopsy, is not used as the primary diagnostic tool unless previous needle biopsies were inadequate or the lesion is not accessible by needle biopsy. There are two types of surgical biopsy: incisional and excisional.13

Incisional biopsy removes a small portion of the lesion. It is used to confirm a diagnosis when a needle biopsy diagnosis is not definitive and if the mass is too large to remove without extensive cosmetic damage.11

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. Excisional biopsy is indicated in the following situations:13

  • when the CNB results are non-diagnostic, not concordant with imaging, or suggest a malignancy or high risk abnormality such as atypical hyperplasia, radial scar, papilloma, or lobular carcinoma in-situ (LCIS)
  • for complex cysts not amenable to CNB
  • with aspirated cysts that do not resolve completely
  • when follow-up imaging after CNB shows an increase in size of the mass or suspicious changes

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. One or more imaging procedures may be used to help screen for evidence of cancer spread, including chest x-ray, bone scan, computed tomography (CT) scan, MRI, and/or positron emission tomography (PET) scan.

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Pathology and Prognostic Factors

Once the breast biopsy identifies cancer, the cancer is then classified according to its biologic features. This provides information about the likely outcome (prognosis) of the disease and which course of treatment may be effective. Biologic features examined include tumor morphology, histologic grade, hormone receptor status (estrogen and progesterone), HER-2/neu (also known as HER2) expression, patterns of gene expression, molecular subtypes, and peritumoral lymphovascular invasion.

Tumor Morphology

Non-invasive breast cancers include lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS).

The most common type of invasive breast cancer is invasive ductal carcinoma, accounting for more than 70% of invasive breast cancers, followed by lobular ductal carcinoma, comprising approximately 10% of invasive breast cancers. Rarer subtypes of invasive breast cancer include tubular, papillary, mucinous, medullary, and adenoid cystic carcinoma.2 The many variations of ductal and lobular carcinoma have differing implications for prognosis.

Histologic Grade

According to the National Comprehensive Cancer Network, all invasive breast cancers should be graded. The recommended grading system is the Nottingham combined histologic grade (Elston-Ellis modification of Scarff-Bloom-Richardson grading system).14 The tumor grade is determined by 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 slower-growing cancer and more favorable prognosis.11

Estrogen Receptor Assay
Estrogen Receptor Assay. Source: Linda Bartlett (photographer). Adapted from NCI Visuals Online. AV-8000-0394.

Tissue Markers

In 2007, the American Society of Clinical Oncology updated its recommendations for the use of tumor markers as prognostic factors. Markers of clinical utility include: CA 15-3, CA 27.29, carcinoembryonic antigen, estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, urokinase plasminogen activator, plasminogen activator inhibitor 1, and certain multiparameter gene expression assays. Several categories are not recommended for routine use: DNA/ploidy by flow cytometry, p53, cathepsin D, cyclin E, proteomics, certain multiparameter assays, detection of bone marrow micrometastases, and circulating tumor cells.15

The major tissue markers: hormone receptors (estrogen and progesterone) and human epidermal growth factor receptor-2 (HER2) are discussed below.

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 have at least one of these receptors.11 Hormone receptive positive breast cancers predict response to hormone therapy (e.g., tamoxifen, aromatase inhibitors). The rate of recurrence is higher in the first five years for ER-negative cancers; this effect, however, recedes with time.16 It is unclear whether PR expression is prognostic independently of ER, but some studies suggest that women with ER-positive and PR-negative cancers have a worse prognosis than when both receptors are positive.17

Human Epidermal Growth Factor Receptor- 2 (HER2) expression refers to a type of cell surface receptor that functions to regulate cell growth. Testing for HER2 is of clinical value in assessing prognosis and choice of treatment. While HER2 overexpression is generally associated with an adverse prognosis, it also predicts response to the monoclonal antibody, trastuzumab (Herceptin) and the kinase inhibitor, lapatinib (Tykerb). HER2 overexpression affects approximately 20% of breast cancer patients.11

Genomic Profiles

Molecular subtypes group breast cancers according to their molecular features, rather than according to the tumor’s microscopic appearance. Four molecular subtypes have been identified:2 18

Luminal A and Luminal B types are ER-positive tumors that have gene expression patterns similar to the normal cells lining the inside (lumen) of the ducts and glands. Luminal A cancers make up 40% of all breast cancers, typically have high expression of ER-related genes and low expression of the HER2 gene cluster. They are low grade, grow slowly, and have the most favorable prognosis.

Luminal B cancers make up approximately 20% of all breast cancers, have a lower expression of ER-related genes, and a variable expression of the HER2 cluster. Luminal B cancers grow somewhat faster and the prognosis is not as positive.

HER-2 type cancers are often hormone receptor negative. Only half of clinical HER2-positive breast cancers are HER2 enriched on molecular profiling. The other half are usually made up of HER2-positive luminal subtypes. HER2 type cancers make up 10-15% of breast cancers, are high grade, tend to grow quickly, and have a poorer prognosis. They can often be effectively treated with targeted therapies such as trastuzumab (Herceptin) and lapatinib (Tykerb) which are usually given along with chemotherapy.

Basal type tumors usually fall into the category of triple-negative cancers because they are ER, PR and HER2 negative. The gene expression patterns of these tumors are similar to those in the deeper basal layers of the ducts and glands. These cancers are high grade, grow quickly, and have a poor prognosis. They are more common among women with BRCA1 mutations and among younger and African-American women.

Gene Expression Profiles

Tests of gene patterns are used to predict the likelihood that an early-stage breast cancer will recur after initial treatment. The three most commonly used tests are: the Oncotype Dx, the MammaPrint, and the PAM50.

Gene Expression Profiling Tests
Test Score # Genes Analyzed Cancer Classes Utility

Oncotype Dx

Recurrence Score (RS) 1-100

21

Node negative, ER positive cancers

Likelihood of response to chemotherapy

MammaPrint

Amsterdam 70 gene profile

70

Any

Prognosis stratification: Poor or Good

PAM50

Risk of Recurrence (ROR)

50

Node negative, ER positive cancers

Recurrence risk: low, medium, or high and molecular subtyping

The Oncotype Dx generates a Recurrence Score (RS) from 1-100 based on the expression of 21 genes. It is useful for women with node-negative, ER-positive breast cancer and can be helpful in deciding whether or not treatment with chemotherapy post-surgery will be beneficial. Women with lower scores are less likely to benefit from chemotherapy.16 18

The MammaPrint, one of the first gene expression tests, generates the “Amsterdam 70-gene profile” based on the analysis of 70 different genes. The MammaPrint can now be used on both live and frozen tissue. Unlike the Oncotype Dx, the MammaPrint can be used for all women, regardless of hormone-receptor status. This test stratifies patients as having a poor or good prognosis. Its clinical utility in guiding treatment decisions is unclear but continues to be studied.16 18

The Predictor Analysis of Microarray 50 (PAM50) analyzes 50 genes and characterizes tumors by molecular subtype. This test generates a Risk of Recurrence Score (ROR) which classifies patients with ER-positive breast cancer into low, medium, and high risk of recurrence groups. The ROR has been found to be highly predictive of prognosis among patients with node-negative breast cancer. It is not, however, available for use in the United States.16 18

Other genetic assays include the Genomic grade index (CGI), the Breast cancer index (BCI), and the Immunohistochemical 4 (IHC4).16

Peritumoral Lymphovascular Invasion (PLVI)

The presence of lymphovascular invasion, in which the cancer has spread to the blood vessels or lymphatics, indicates a poorer prognosis, especially in high grade tumors. The clinical utility of this measure, however, is not yet known.19

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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 for comparing outcomes in cancer research.

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 and pathological staging.

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. Information for both clinical and pathological staging is gathered during the period prior to the first course of therapy.20

TNM System

Anatomic Stage/Prognostic Groups
Stage 0 Tis N0 M0
Stage IA T1 N0 M0
Stage IB T0 N1mi M0
T1 N1mi M0
Stage IIA T0 N1 M0
T1 N1 M0
T2 N0 M0
Stage IIB T2 N1 M0
T3 N0 M0
Stage IIIA T0 N2 M0
T1 N2 M0
T2 N2 M0
T3 N1 M0
T3 N2 M0
Stage IIIB T4 N0 M0
T4 N1 M0
T4 N2 M0
Stage IIIC Any T N3 M0
Stage IV Any T Any N M1
Source: American Joint Committee on
Cancer. Breast cancer staging, 7th edition.
(2009) Retrieved from:
https://cancerstaging.org/references-
tools/quickreferences/pages/default.aspx

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 TNM stand for tumor (T), lymph nodes (N), and metastasis (M). Each letter is followed by a number and sometimes additional letters that describe what is known about the growth and extent of disease at diagnosis. For example, T1a, N0, M0 indicates a tumor greater than 1 mm but less than 5 mm and no regional node involvement or distant metastasis. The T component designates the size and invasiveness of the primary tumor, with the numeric value increasing with tumor size and extent of invasiveness.20 21

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. Imaging tests such as Position Emission Tomography (PET), CT-Scan, and MRI may be used to assess whether or not the breast cancer has metastasized.20 21

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 I, II, and III are further refined into subsets, represented by capital letters (IA, IIB, IIC, etc.). In practice, most clinicians simply use Stages 0-IV.20 21

Further information about TNM definitions and AJCC stage groupings is available on the National Cancer Institute website. Additionally, the American Joint Committee on Cancer website offers a variety of publications and other staging resources for healthcare professionals. 

5-Year Survival Rates

5-Year Relative Survival Rate
by Stage:
Stage 0 100%
Stage I 100%
Stage II 93%
Stage III 72%
Stage IV 22%

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. The figures are derived from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Data Base as reported by the American Cancer Society.22

As with all averages, 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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Notes

1Esserman, L. J., &  Joe, B. N. (2013, April 25). Diagnostic evaluation of women with suspected breast cancer. Retrieved from the Up to Date website: http://www.uptodate.com/contents/diagnostic-evaluation-of-women-with-breast-cancer

2Esserman, L. J., &  Joe, B. N. (2013, May 20). Clinical features, diagnosis, and staging of newly diagnosed breast cancers. Retrieved from the Up to Date website: http://www.uptodate.com/contents/clinical-features-diagnosis-and-staging-of-newly-diagnosed-breast-cancer

3American Cancer Society. (2013, October 24). Signs and symptoms of breast cancer. Retrieved from: http://www.cancer.org/cancer/breastcancer/moreinformation/breastcancerearlydetection/breast-cancer-early-detection-signs-symptoms-br-ca

4California Department of Public Health, Cancer Detection Section, Breast Expert Workgroup. (2011, June). Breast cancer diagnostic algorithms for primary care providers. Retrieved from: http://qap.sdsu.edu/resources/tools/diagnosticalgorithms.html

5National Cancer Institute. (2013, October 4). Adjustment to cancer: anxiety and distress (PDQ). Retrieved from:  http://www.cancer.gov/cancertopics/pdq/supportivecare/adjustment/Patient/

6Sabel, M. S. (2013, November 13). Clinical manifestations and diagnosis of a palpable breast mass. Retrieved from the Up to Date website: http://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-a-palpable-breast-mass

7Venkataramann, S., & Slanetz, P. J. (2013, June 11). Breast imaging: mammography and ultrasonography. Retrieved from the Up to Date website: http://www.uptodate.com/contents/breast-imaging-mammography-and-ultrasonography

8National Comprehensive Cancer Network. (2013, December 18). NCCN Guidelines Version 1.2014. Staging breast cancer. Retrieved from: http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf

9Golshan, M., & Iglehart, D. (2013, June 6). Nipple Discharge. Retrieved from the Up to Date website: http://www.uptodate.com/contents/nipple-discharge

10American Cancer Society. (2013, December 31). What's new in breast cancer research and treatment? Retrieved from: www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-new-research

11American Cancer Society. (2013, October 24). How is breast cancer diagnosed? Retrieved from: http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-diagnosis

12Ljung, B. M., Dreject, A., Chiammpi, N., Jeffrey, J., Goodson, W. H., Chew, K.,... Miller, T. R. (2001). Diagnostic accuracy of fine-needle aspiration biopsy is determined by physician training in sampling technique. Cancer, 93(4), 263-268. doi: 10.1002/cncr.9040

13Esserman, L. J., & Joe, B. N. (2013, November 20). Breast biopsy. Retrieved from: http://www.uptodate.com/contents/breast-biopsy

14National Comprehensive Cancer Network.(2013, December 18). NCCN guidelines Version 1.2014. Staging breast cancer. Retrieved from: http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf

15Harris, L., Fritsche, H., Mennel, R., Norton, L., Ravdin, P., Taube, S.,... Bast, R. C., Jr. (2007). American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. Journal of Clinical Oncology, 25(33), 5287-5312. doi: 10.1200/jco.2007.14.2364

16Foukakis, T., & Bergh, J. (2013, September 25). Prognostic and predictive factors in early, non-metastatic breast cancer. Retrieved from the Up to Date website: http://www.uptodate.com/contents/prognostic-and-predictive-factors-in-early-non-metastatic-breast-cancer

17Hammond, M. E. H. (2013, December 9). Hormone receptors in breast cancer: clinical utility and guideline recommendations to improve test accuracy. Retrieved from the Up to Date website: http://www.uptodate.com/contents/hormone-receptors-in-breast-cancer-clinical-utility-and-guideline-recommendations-to-improve-test-accuracy

18American Cancer Society. (2013, December 31). Breast cancer detailed guide. Retrieved from:  http://www.cancer.org/acs/groups/cid/documents/webcontent/003037-pdf.pdf

19Ejlertsen, B., Jensen, M. B., Rank, F., Rasmussen, B. B., Christiansen, P., Kroman, N.,... Mouridesn, H. T. on behalf of the Danish Breast Cancer Cooperative Group. Population-based study of peritumoral lymphovascular invasion and outcome among patients with operable breast cancer. Journal of the National Cancer Institute, 101, 729-735. doi: 10.1093/jnci/djp090

20American Cancer Society. (2013, October 24). How is breast cancer staged? Retrieved from: http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-staging

21Hayes, D. F. (2013, June 26). Tumor node metastasis (TNM) staging classification for breast cancer. Retrieved from the Up to Date website: http://www.uptodate.com/contents/tumor-node-metastasis-tnm-staging-classification-for-breast-cancer

22American Cancer Society.(2013, October 24). Breast cancer survival rates by stage. Retrieved from: http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-survival-by-stage


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Last updated: February 10, 2014

The Breast Cancer Review is sponsored by the Department of Health Care Services (DHCS), Every Woman Counts (EWC) program, with the goal of providing healthcare professionals a general reference for breast cancer screening,diagnosis, and treatment. The Breast Cancer Review is not anexpression of medical opinion, diagnosis, prognosis or treatment recommendation for any particular patient. It should be used for informational purposes only. EWC does not dispense clinical advice or patient care consultation. Links to other web resources are offered as a courtesy; no endorsement is made or implied. While every care has been taken in their selection, EWC makes no claims as to the validity, quality, or viability of their content.

 

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