Breast Cancer Differential Diagnoses

Author: Rachel Swart, MD, PhD; Chief Editor: Jules E Harris, MD more...

Updated: Nov 18, 2011

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Diagnostic Considerations

The differential diagnosis includes the following:

Circumscribed breast lesions: benign breast disease (eg, fibroadenomas, cysts), breast cancer, breast lymphoma, and metastasis to the breast from other primary sites
Skin thickening: inflammatory carcinoma and mastitis
Stellate lesions: breast cancer, traumatic fat necrosis, a radial scar, and a hyalinized fibroadenoma
Dilated ducts with or without nipple discharge: papilloma, ductal carcinoma, duct ectasia, and fibrocystic disease

Differential Diagnoses

Proceed to Workup

Contributor Information and Disclosures

Author

Rachel Swart, MD, PhD Assistant Professor of Medicine, Department of Hematology and Oncology, Arizona Cancer Center, University of Arizona

Rachel Swart, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society of Clinical Oncology, Arizona Medical Association, and Southwest Oncology Group

Disclosure: Roche Grant/research funds Other

Coauthor(s)

Leona Downey, MD Assistant Professor of Internal Medicine, Section of Oncology and Hematology, University of Arizona, Arizona Cancer Center

Leona Downey, MD is a member of the following medical societies: American Geriatrics Society, American Society of Clinical Oncology, and Southwest Oncology Group

Disclosure: Nothing to disclose.

Manjit Singh Gohel, MD, MRCS, MB, ChB Specialist Registrar, Division of Breast and Endocrine Surgery, Northwick Park Hospital

Disclosure: Nothing to disclose.

Kanchan Kaur, MBBS, MS (General Surgery), MRCS (Ed) Consulting Breast and Oncoplastic Surgeon, Medanta, The Medicity, India

Disclosure: Nothing to disclose.

Julie Lang, MD Assistant Professor of Surgery and the BIO5 Institute, Director of Breast Surgical Oncology, University of Arizona College of Medicine

Julie Lang, MD is a member of the following medical societies: American College of Surgeons, American Society of Breast Surgeons, American Society of Clinical Oncology, Association for Academic Surgery, and Society of Surgical Oncology

Disclosure: Genomic Health Grant/research funds Speaking and teaching; Agendia Grant/research funds Speaking and teaching; Surgical Tools Grant/research funds Research; Sysmex Grant/research funds Research

Robert B Livingston, MD Professor of Clinical Medicine and Director, Clinical Research Shared Services, Arizona Cancer Center

Robert B Livingston, MD is a member of the following medical societies: American Association for Cancer Research, American Federation for Clinical Research, and American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Hemant Singhal, MD, MBBS, FRCSE, FRCS(C) Senior Lecturer, Director of Breast Service, Department of Surgery, Imperial College School of Medicine; Consultant Surgeon, Northwick Park and St Marks Hospitals, UK

Hemant Singhal, MD, MBBS, FRCSE, FRCS(C) is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada and Royal College of Surgeons of Edinburgh

Disclosure: Nothing to disclose.

Alison T Stopeck, MD Associate Professor of Medicine, Arizona Cancer Center, University of Arizona Health Sciences Center; Director of Clinical Breast Cancer Program, Arizona Cancer Center; Medical Director of Coagulation Laboratory, University Medical Center; Director of Arizona Hemophilia and Thrombosis Center

Alison T Stopeck, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, Hemophilia and Thrombosis Research Society, and Southwest Oncology Group

Disclosure: Genentech Honoraria Speaking and teaching; AstraZeneca Honoraria Speaking and teaching; AstraZeneca Grant/research funds Other

Patricia A Thompson, PhD Assistant Professor, Department of Pathology, University of Arizona, Tucson

Disclosure: Nothing to disclose.

Simon Thomson, MB, BCh, MD, FRCS Specialist Registrar, Department of Breast and Endocrine Surgery, Northwick Park Hospital, UK

Simon Thomson, MB, BCh, MD, FRCS is a member of the following medical societies: British Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Robert C Shepard, MD, FACP Associate Professor of Medicine in Hematology and Oncology at University of North Carolina at Chapel Hill; Vice President of Scientific Affairs, Therapeutic Expertise, Oncology, at PRA International

Robert C Shepard, MD, FACP is a member of the following medical societies: American Association for Cancer Research, American College of Physician Executives, American College of Physicians, American Federation for Clinical Research, American Federation for Medical Research, American Medical Association, American Medical Informatics Association, American Society of Hematology, Association of Clinical Research Professionals, Eastern Cooperative Oncology Group, European Society for Medical Oncology, Massachusetts Medical Society, and Society for Biological Therapy

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Carl V Smith, MD The Distinguished Chris J and Marie A Olson Chair of Obstetrics and Gynecology, Professor, Department of Obstetrics and Gynecology, Senior Associate Dean for Clinical Affairs, University of Nebraska Medical Center

Carl V Smith, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, Council of University Chairs of Obstetrics and Gynecology, Nebraska Medical Association, and Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine; Consulting Staff, Arizona Cancer Center

Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research

Disclosure: GlobeImmune Salary Consulting

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Issam Makhoul, MD, Harold Harvey, MD, Wiley Souba, MD, and Hanan Makhoul, MD, to the development and writing of a source article.

References

Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. Sep-Oct 2010;60(5):277-300. [Medline]. [Full Text].
American Cancer Society. Breast Cancer Facts & Figures 2009-2010. Available at http://www5.cancer.org/downloads/STT/F861009_final%209-08-09.pdf. Accessed January 5, 2010.
Dawood S, Broglio K, Gonzalez-Angulo AM, Buzdar AU, Hortobagyi GN, Giordano SH. Trends in survival over the past two decades among white and black patients with newly diagnosed stage IV breast cancer. J Clin Oncol. Oct 20 2008;26(30):4891-8.
Taillefer R. The role of 99mTc-sestamibi and other conventional radiopharmaceuticals in breast cancer diagnosis. Semin Nucl Med. Jan 1999;29(1):16-40.
Weir L, Worsley D, Bernstein V. The value of FDG positron emission tomography in the management of patients with breast cancer. Breast J. May-Jun 2005;11(3):204-9.
[Guideline] National Comprehensive Cancer Network Practice Guidelines. Invasive Breast Cancer. 2009. (Registered Users Only). [Full Text].
[Guideline] Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. Jan 1 2007;25(1):118-45.
Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. Sep 16 1998;90(18):1371-88.
Bear HD, Anderson S, Smith RE, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer:National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. May 1 2006;24(13):2019-27. [Medline].
[Best Evidence] [Guideline] Visvanathan K, Chlebowski RT, Hurley P, Col NF, Ropka M, Collyar D, et al. American Society of Clinical Oncology clinical practice guideline update on the use of pharmacologic interventions including tamoxifen, raloxifene, and aromatase inhibition for breast cancer risk reduction. J Clin Oncol. Jul 1 2009;27(19):3235-58.
Cristofanilli M. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. Semin Oncol. Jun 2006;33(3 Suppl 9):S9-14.
Xeloda [package insert]. South San Francisco, Calif: Genentech; November 2009.
Ellence [package insert]. New York, NY: Pfizer; February 2007.
Herceptin [package insert]. South San Francisco, Calif: Genentech; October 2010.
Tykerb [package insert]. Research Triangle Park, NC: GlaxoSmithKline; January 2010.
Femara [package insert]. East Hanover, NJ: Novartis; April 2010.
Fareston [package insert]. Memphis, Tenn: GTX; December 2004.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Breast Cancer, v.2.2011. Available at http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed June 3 2011.
The U.S. Food and Drug Administration. FDA begins process to remove breast cancer indication from Avastin label. FDA NEWS RELEASE: Dec. 16, 2010. Available at http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm237172.htm. Accessed July 15, 2011.
The U.S. Food and Drug Administration. Postmarket Drug Safety Information: Avastin (bevacizumab) Information, Update, 6/29/2011. Available at http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm193900.htm. Accessed July 15, 2011.

Anatomy of the breast.

Intrinsic subtypes of breast cancer.

Breast cancer. Intraductal carcinoma, comedo type. Distended duct with intact basement membrane and central tumor necrosis.

Breast cancer. Intraductal carcinoma, noncomedo type. Distended duct with intact basement membrane, micropapillary, and early cribriform growth pattern.

Breast cancer. Lobular carcinoma in situ. Enlargement and expansion of lobule with monotonous population of neoplastic cells.

Breast cancer. Infiltrating ductal carcinoma. Low-grade carcinoma with well-developed glands invading the fibrous stroma.

Breast cancer. Colloid (mucinous) carcinoma. Nests of tumor cells in pool of extracellular mucin.

Breast cancer. Papillary carcinoma. Solid papillary growth pattern with early cribriform and well-developed thin papillary fronds.

Table 1. Ductal Carcinoma in Situ Subtypes

DCIS Characteristic	Comedo	Noncomedo
Nuclear grade	High	Low
Estrogen receptor	Negative	Positive
HER2 overexpression	Present	Absent
Distribution	Continuous	Multifocal
Necrosis	Present	Absent
Local recurrence	High	Low
Prognosis	Worse	Better

Table 2, below, summarizes the accuracy of various techniques used in breast imaging. In nonfatty breasts, ultrasonography and MRI are more sensitive than mammography for invasive cancer but may overestimate tumor extent. Combined mammography, clinical examination, and MRI are more sensitive than any other individual test or combination of tests. Table 2. Accuracy of Breast Imaging Modalities

Modality	Sensitivity	Specificity	Positive predictive value	Indications
Mammography	63-95% (>95% palpable, 50% impalpable, 83-92% in women older than 50 y) (decreases to 35% in dense breasts)	14-90% (90% palpable)	10-50% (94% palpable)	Initial investigation for symptomatic breast in women older than 35 years and for screening; investigation of choice for microcalcification
Ultrasonography	68-97% (palpable)	74-94% (palpable)	92% (palpable)	Initial investigation for palpable lesions in women younger than 35 years
MRI	86-100%	21-97% (< 40% primary cancer)	52%	Scarred breast, implants, multifocal lesions, and borderline lesions for breast conservation; may be useful in screening high-risk women
Scintigraphy	76-95% (palpable) 52-91% (impalpable)	62-94% (94% impalpable)	70-83% (83% palpable, 79% impalpable)	Lesions larger than 1 cm and axilla assessment; may help predict drug resistance
PET scanning	96% (90% axillary metastases)	100%		Axilla assessment, scarred breast, and multifocal lesions

Table 3. Grading System in Invasive Breast Cancer (Modified Bloom and Richardson)

	Score
	1	2	3
A. Tubule formation	>75%	10-75%	< 10%
B. Mitotic count per high-power field (microscope- and field-dependent)	< 7	7-12	>12
C. Nuclear size and pleomorphism	Near normal Little variation	Slightly enlarged Moderate variation	Markedly enlarged Marked variation
Grade I cancer if the total score (A + B + C) is 3-5
Grade II cancer if the total score (A + B + C) is 6 or 7
Grade III cancer if the total score (A + B + C) is 8 or 9

Table 4. Ductal Carcinoma in Situ Subtypes

DCIS Characteristic	Comedo	Noncomedo
Nuclear grade	High	Low
Estrogen receptor	Negative	Positive
HER2 overexpression	Present	Absent
Distribution	Continuous	Multifocal
Necrosis	Present	Absent
Local recurrence	High	Low
Prognosis	Worse	Better

Table 5. TNM Staging System for Breast Cancer

Stage	Tumor	Node	Metastases
Stage 0	Tis	N0	M0
Stage I	T1	N0	M0
Stage IIA	T0 T1 T2	N1 N1 N0	M0 M0 M0
Stage IIB	T2 T3	N1 N0	M0 M0
Stage IIIA	T0 T1 T2 T3	N2 N2 N2 N1-2	M0 M0 M0 M0
Stage IIIB	T4 T4 T4	N0 N1 N2	M0 M0 M0
Stage IIIC	Any T	N3	M0
Stage IV	Any T	Any N	M1

Table 6. Follow-up Recommendations for Breast Cancer Survivors per NCCN Guidelines

Intervention^*	Year 1	Year 2	Year 3-5	Year 6+
History and physical examination	q3-4 mo	q4 mo	q6 mo	Annually
Mammography	Annually (or 6 mo after post-BCS irradiation)	Annually	Annually	Annually
Chest x-ray	NR	NR	NR	NR
Pelvic examination^†	Annually	Annually	Annually	Annually
Bone density^‡	q1-2 y
BCS = breast-conserving surgery; NR = not recommended.
^* Bone scan, blood counts, LFTs, and tumor markers are not routinely recommended and should be performed if clinically indicated. ^† For patients with an intact uterus on tamoxifen.
^‡ For patients at risk for osteoporosis.

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