Breast Cancer

Primary carcinoma of the breast, the most common type of breast malignancy, usually begins as a neoplastic proliferation of epithelial cells lining the ducts or lobules of the breast. Histology is the primary method of diagnosis, while markers, such as ER/PR and HER2, can suggest prognosis. 

  • Key Points
  • Diagnosis
  • Screening
  • Monitoring
  • Pharmacogenetics
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos
American Society of Clinical Oncology 2016 Prognostic Marker Recommendations

Non-Panel Prognostic Markers






ER and PR status should be determined on all invasive breast cancers and breast cancer recurrences (ASCO, 2010)

ER positivity alone is a weak prognostic indicator; use in combination with PR


Two molecular subtypes – luminal A and luminal B; B has best prognosis


Positivity associated with improved prognosis when treated with anti-estrogen therapy (eg, tamoxifen)


(Human epidermal growth factor receptor 2)

HER2 status (HER2 negative or positive) should be determined in all patients with invasive (early stage or recurrence) breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive) (ASCO, 2013)


Graded scale

  • 0 and 1 – negative
  • 2 – equivocal
  • 3 – positive

Positivity occurs in 15-20% of breast cancer patients

Predominantly high-grade tumors

More common in

  • African Americans – significant number have BRCA1 gene mutation
  • Young age at onset
  • Premenopausal women

75% have basal-like gene expression (CK5/14+, EGFR+) – worst prognosis of all breast cancer subtypes

Worst prognosis for breast cancer


(Urokinase-type plasminogen activator/plasminogen-like activator inhibitor)

May be used in ER/PR-positive , HER2-negative (node-negative) women with early breast cancer to guide decisions on adjuvant therapy



(Immunohistochemistry 4)

Do not use in women who are ER/PR-positive, HER2-negative (node-negative or node-positive) for adjuvant decisions


Ki-67 (MIB-1)

(Cell proliferative-associated antigen)

Do not use to guide choice on adjuvant chemotherapy

Elevation associated with aggressive tumor behavior

Prognostic Panels




Prosigna Breast Cancer Prognostic Gene Signature assay*

May be used in ER/PR-positive, HER2-negative (node-negative) breast cancer in conjunction with other clinicopathologic variables to guide decisions on adjuvant systemic therapy

Do not use in the following

  • ER/PR-positive, HER2-negative (node-positive) breast cancer
  • HER2-positive breast cancer
  • Triple-negative (TN) breast cancer

Scores report risk as low, intermediate, or high based on

  • Molecular subtype of tumor
  • Proliferation status
  • Tumor size and node status

Does not provide information about which chemotherapy regimen should be given if at high risk for distant recurrence

Genomic Health Oncotype DX (NCI)*


May be used in ER/PR-positive, HER2-negative (node-negative) breast cancer to guide decisions on adjuvant systemic chemotherapy

Do not use in the following

  • ER/PR-positive, HER2-negative (node-positive) breast cancer
  • HER2-positive breast cancer
  • Triple-negative (TN) breast cancer

21 gene recurrence score

TAILORx (Trial for Assigning Individualized Options for Treatment [Rx]) – study of genes associated with recurrence risk for use in determining most effective treatment options

Helps to predict effectiveness of tamoxifen alone in postmenopausal women with node-negative, ER+, early stage breast cancer


May be used in ER/PR-positive, HER2-negative (node-negative) breast cancer to guide decisions on adjuvant systemic chemotherapy

Do not use in the following

  • ER/PR-positive, HER2-negative (node-positive) breast cancer
  • HER2-positive breast cancer
  • Triple-negative (TN) breast cancer

12 gene risk score

Breast Cancer Index*

May be used in ER/PR-positive, HER2-negative (node-negative) breast cancer to guide decisions on adjuvant systemic therapy

Do not use in the following

  • ER/PR-positive, HER2-negative (node-positive) breast cancer
  • HER2-positive breast cancer
  • Triple-negative (TN) breast cancer



Do not use in ER/PR positive, HER2 negative (node-positive or node-negative)

70 gene panel

*FDA approved for use in early stage (stage I-III), node-positive breast cancer, but not guideline recommended


Indications for Testing

  • Malignant histology compatible with breast cancer


  • Therapeutic decisions are made using combination of the following tumor features
    • Histologic grade – includes nuclear probe and mitotic index
    • Estrogen receptor (ER) and progesterone receptor (PR) status
    • HER2 (ERBB2) status
      • Methods for initial HER2 determination – immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), or dual in situ hybridization (ISH)
        • Concordance between IHC and dual ISH/FISH may vary due to subjective interpretation
        • Dual ISH includes fluorescence or Bright-field assays; most current dual ISH assays consist of two differentially labeled probes, one for HER2 and one for chromosome 17 centromere
          • IHC or dual ISH/FISH may be used in initial evaluation for HER2 status
        • Equivocal results should be resolved with alternate test (ASCO/College of American Pathologists [CAP], 2013; National Comprehensive Cancer Network [NCCN], 2016)
          • Equivocal (2+) IHC – dual ISH/FISH recommended follow-up test
          • Equivocal dual ISH/FISH – follow-up testing options
            • Repeat dual ISH/FISH on same specimen using an alternative control probe
            • IHC for HER2 expression status using the same block or a different block from the same specimen, if not already performed
            • Repeat testing (dual ISH/FISH or IHC) on a different specimen from patient’s tumor
    • For metastatic disease – ASCO (2016) recommends retesting available tumor tissue for ER, PR, and HER2 status
  • Other immunohistochemical staining
    • Immunoreactivity of normal breast epithelium
      • Luminal: CK 7, CK 8, CK 18, CK 19
      • Basal cells: CK 5/6, CK 14, CK 17
      • Myoepithelial cells: CK 5, CK 14, CK 17, SMA, calponin, p63
    • IHC staining may be used to differentiate ductal versus lobular carcinoma
      • E-cadherin
        • Ductal (+)
        • Lobular (-)
      • CK 5/6 – sometimes used to differentiate usual ductal hyperplasia (UDH) from atypical ductal hyperplasias (ADH)/low-grade ductal carcinoma in situ (LG-DCIS)
        • Ductal (-)
        • Lobular (+)


  • ASCO 2016 prognostic marker recommendations – refer to Key Points section
  • Other markers
    • p53
      • Positivity may be associated with worse prognosis
    • Aneuploid and high S-phase tumors
      • Associated with worse prognosis in node-negative cancers
      • Low S-phase and diploid DNA content associated with better prognosis​
    • PIK3CA gene mutation
      • Associated with shorter breast cancer-specific and disease-free survival
    • FGFR2 gene mutation
      • ~1% of breast cancers show copy number gains in the FGFR2 gene
      • Reported in triple-negative breast cancers (negative for ER, PR, and HER2 expression)
      • Patients whose tumors demonstrate FGFR2 gene amplification may benefit from FGFR2-targeting antibodies or FGFR-specific tyrosine kinase inhibitors
  • Minimally invasive disease detection helps determine risk or presence of metastatic disease and includes measures of tumor cells in
    • Bone marrow
    • Axillary nodes/sentinel nodes
    • Systemically (circulating tumor cells [CTCs])
      • Most helpful in prognosis of advanced disease
      • Should not be used for diagnosis or treatment decisions

Screening recommendations (mammogram, clinical breast exam, breast self-exam) for women of average risk



Clinical Breast Exam (CBE)

Breast Self-Exam (BSE)

AAFP (2016)

<50 yrs – should be evaluated on individual basis

50-74 yrs – every 2 yrs

Insufficient evidence to assess harms or benefits

Recommend against teaching BSE

ACS (2015)

40-44 yrs – may choose to start annual screening

45-54 – annual screening

≥55 – every 2 years, as long as woman is in good health and is expected to live ≥10 yrs

Not recommended due to lack of evidence

ACOG (2017)

Offer starting at 40 yrs; initiate at 40-49 yrs after counseling and if patient desires

Recommend by no later than 50 yrs

Screen every 1-2 yrs based on shared decision making

May be offered after shared decision making

  • Every 1-3 yrs for women 25-39 yrs
  • Annually for women ≥40 yrs

Not recommended in average-risk women

AGS (2008*)

Stop screening healthy women ≥85 yrs; ≥75 yrs consider life expectancy and quality of life when screening

USPSTF (2016)

Women age 40-49 yrs – decision to screen should be an individual one

Women age 50-74 – screen every 2 years

Women ≥75 yrs – no recommendation due to insufficient evidence

No recommendation

Recommend against teaching BSE

*Cited in AFP, 2008

USPSTF = U.S. Preventive Services Task Force; ACS = American Cancer Society; AAFP = American Academy of Family Physicians; AGS = American Geriatrics Society; ACOG = American Congress of Obstetricians and Gynecologists

  • ​Breast cytology screening (eg, using ductal lavage) not yet recommended, but may be useful in high-risk patients
  • No tumor markers recommended in screening (ASCO, 2007)
    • All markers have low sensitivity and specificity when used in a screening setting
  • Hereditary breast and ovarian cancer (HBOC) genetic testing (National Cancer Institute)

Indications for testing in women with any of the following

Based on family history only (in asymptomatic patient)

  • Individuals with a family history of a known pathogenic mutation previously identified in a relative – perform targeted mutation testing

Hereditary gene mutations

  • Annual mammography
    • Most organizations (ACS, NCI, AMA, AGS) recommend annual screening beginning at 50 years (see table in Screening section)
  • Annual gynecological examination for patients receiving tamoxifen therapy due to increased risk of endometrial cancer
    • Endometrial ultrasound and biopsy indicated in patients with abnormal vaginal bleeding or atypical endometrial cells on a PAP smear
  • Cancer markers
    • CA 15-3 and CA 27.29
      • May be used to monitor advanced disease in conjunction with diagnostic imaging, history, physical (NCCN, 2016)
      • Cannot be used singly for monitoring breast cancer patients
        • Serial measurements are most useful, using the same marker sequentially
    • Carcinogenic embryonic antigen – use in conjunction with imaging, history, physical for monitoring therapy in metastatic disease (NCCN, 2016)
    • Circulating tumor cell count – use to determine prognosis, assess treatment efficacy, and aid in treatment decisions for patients with metastatic breast cancer
    • HER2 (serum) – preliminary evidence suggests potential value in monitoring trastuzumab therapy in advanced disease
  • Tamoxifen is an anti-estrogen drug used in treatment of ER+ breast cancer
    • Tamoxifen metabolites, particularly endoxifen and 4-hydroxy-tamoxifen, bind the estrogen receptors and suppress breast cancer cell proliferation
  • Cytochrome P450 2D6 (CYP2D6) and tamoxifen
    • Metabolism of tamoxifen to endoxifen depends on a CYP2D6-mediated reaction
    • Decreased metabolite production (due to nonfunctional or poorly functional CYP2D6) could put patients at risk for recurrence of breast cancer
    • CYP2D6 genotype is associated with the following phenotypes
      • Poor metabolizer – little or no metabolism; alternate drug recommended
      • Intermediate metabolizer – possible impaired metabolism
      • Ultrarapid metabolizer – faster-than-normal metabolism; implications for tamoxifen therapy not well-characterized
    • NCCN (2015), ASCO (2016) do not recommend routine CYP2D6 genotyping to determine optimal adjuvant endocrine strategy
  • Cytochrome P450 2C19 (CYP2C19) and tamoxifen
    • Metabolism of tamoxifen to 4-hydroxy-tamoxifen can be accelerated by the presence of the CYP2C19*17 allele that confers an ultrarapid metabolizer phenotype
  • Tamoxifen metabolism is also affected by concomitant administration of selective serotonin reuptake inhibitors (SSRIs) and other strong inhibitors of CYP2D6
    • Strong inhibitors of CYP2D6 should be avoided in patients taking tamoxifen


  • Incidence – ~235,000 new cases of breast cancer diagnosed in U.S. per year (NCCN, 2016)
    • BRCA1 or BRCA2 mutation
      • 1:500 – individuals from general population
      • 1:40 – Ashkenazi Jewish population
  • Prevalence – increases with age
    • Sporadic breast cancer usually occurs after age 50
    • Breast cancer commonly occurs before age 50 in BRCA1 and BRCA2 mutation carriers
  • Median age at diagnosis – 61 years (SEER, 2014)
  • Sex – most common cancer in females
    • Rare in males (~2,000/year in U.S.) (SEER, 2014)

Risk Factors

  • Associated with only a minority of cases
  • Gene mutations – BRCA1, BRCA2 most common; several other genes likely involved (see Screening section)
    • BRCA1 and BRCA2 mutations believed to cause 20-60% of all hereditary breast cancers
    • 5-10% of all breast cancer and 10-15% of ovarian cancers are caused by BRCA1 or BRCA2 mutations
    • BRCA mutation database (University of Utah Huntsman Cancer Institute (HCI), WHO International Agency for Research on Cancer (IARC), University of Utah Department of Pathology and ARUP Laboratories)
  • Early menarche
  • Late menopause
  • First childbirth at >30 years
  • Menopausal hormonal replacement therapy
  • Chest radiation at <30 years
  • Moderate alcohol intake
  • Family history of breast cancer
  • Previous exposure to chest radiation
  • See the National Cancer Institute for the Breast Cancer Risk Assessment Tool  (based on the GAIL model) to further estimate breast cancer risk


  • Tumors are usually epithelial cell in origin
    • Other rare tumors include phyllodes tumors, Paget disease of the breast, inflammatory breast cancer
    • Sarcoma or lymphoma (B cell and T/NK cell) is rare
  • Noninvasive forms may be present alone or in association with invasive carcinoma

Clinical Presentation

  • Breast mass
  • Nipple discharge
  • Breast asymmetry
  • Retraction of nipple, skin changes
  • Redness or tenderness – inflammatory breast cancer
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Estrogen/Progesterone Receptor with Interpretation by Immunohistochemistry 0049210
Method: Immunohistochemistry


For paraffin-embedded, formalin-fixed tissue

ERBB2 (HER2/neu) (HercepTest) by Immunohistochemistry, Tissue with Reflex to FISH if 2+ 0049178
Method: Immunohistochemistry

ERBB2 (HER2/neu) (HercepTest) with Interpretation by Immunohistochemistry, Tissue 0049174
Method: Immunohistochemistry

ERBB2 (HER2) (HercepTest) by Immunohistochemistry 2007332
Method: Immunohistochemistry

ERBB2 (HER2/neu) Gene Amplification by FISH, Tissue 2008603
Method: Fluorescence in situ Hybridization


FDA approved for formalin-fixed tissue only

HER2/neu Quantitative by ELISA 2004672
Method: Quantitative Enzyme-Linked Immunosorbent Assay


Positive results are reliable; however, this serum assay has a 30% false-negative rate

Colon Cancer Gene Panel, Somatic 2011616
Method: Mass Spectrometry


Limit of detection – ~10% mutant alleles

Oncogenic mutations outside of codons tested will not be detected

p53 with Interpretation by Immunohistochemistry 0049250
Method: Immunohistochemistry

Ki-67 with Interpretation by Immunohistochemistry 2007182
Method: Immunohistochemistry

Cytology, Non-Gynecologic 2000623
Method: Microscopy


Known false negatives and false positives

Breast and Ovarian Hereditary Cancer Panel, Sequencing and Deletion/Duplication, 20 Genes 2012026
Method: Massively Parallel Sequencing/Exonic Oligonucleotide-based CGH Microarray


Deep intronic and regulatory mutations, breakpoints for large deletions/duplications, sequence changes in EPCAM, exons 11-15 of CHEK2 will not be evaluated with the exception of the c.1100delC mutation, and deletions/duplications (exon 1 in CDH1, MSH2, and RAD51D; exons 4,6, 7 in STK11; exon 8 in PTEN; exon 12 in ATM) will not be determined or evaluated

Small deletions or insertions may not be detected

Diagnostic errors can occur due to rare sequence variations


Breast and Ovarian Hereditary Cancer Syndrome (BRCA1 and BRCA2) Sequencing and Deletion/Duplication 2011949
Method: Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification


Rare diagnostic errors can occur due to primer or probe site mutations

Regulatory region mutations and deep intronic mutations will not be detected

Genes causing HBOC syndrome, other than BRCA1 and BRCA2, are not tested

Deletion/duplication breakpoints will not be determined

Prosigna Breast Cancer Prognostic Gene Signature 2010248
Method: Hybridization/gene expression


Minimum 10% tumor required

Test is intended for women with hormone receptor-positive breast cancer only

Not intended to provide information about what chemotherapy regimen should be given if at high risk for distant recurrence

Circulating Tumor Cell Count 0093399
Method: Immunomagnetic Separation/Immunofluorescent Stain/Computer Assisted Analysis


CTC is not as accurate as imaging in assessing whether a patient has progressive disease

Doxorubicin therapy patients – allow at least 7 days following administration of dose before testing

Not detected – CTCs that do not express EpCAM; CTCs that express EpCAM but not cytokeratins 8, 18, and 19

Serial CTCs should be performed in the same laboratory

E-Cadherin by Immunohistochemistry 2003869
Method: Immunohistochemistry

PAX8 by Immunohistochemistry 2010787
Method: Immunohistochemistry

GATA3 by Immunohistochemistry 2012558
Method: Immunohistochemistry

Cytochrome P450 2D6 (CYP2D6) 15 Variants and Gene Duplication 2014547
Method: Polymerase Chain Reaction/Fluorescence Monitoring


Only the targeted CYP2D6 variants will be detected by this panel

Diagnostic errors can occur due to rare sequence variations

Risk of therapeutic failure or adverse reactions with CYP2D6 substrates may be affected by genetic and nongenetic factors that are not detected by this test

This result does not replace the need for therapeutic drug or clinical monitoring

Cytochrome P450 2C19, CYP2C19 - 9 Variants 2012769
Method: Polymerase Chain Reaction/Fluorescence Monitoring


Only the targeted CYP2C19 mutations will be detected

Diagnostic errors can occur due to rare sequence variations

Risk of therapeutic failure or adverse reactions with CYP2C19 substrates may be affected by genetic and nongenetic factors that are not detected by this test

This result does not replace the need for therapeutic drug or clinical monitoring


Albert RH, Clark MM. Cancer Screening in the Older Patient. Am Fam Physician. Leawood, KS [Accessed: Dec2016]

American College of Obstetricians-Gynecologists. Practice bulletin no. 122: Breast cancer screening. Obstet Gynecol. 2011; 118(2 Pt 1): 372-82. PubMed

Clinical Preventive Service Recommendation - Breast Cancer. Am Fam Physician. Leawood, KS [Accessed: Dec 2016]

Hammond EH, Hayes DF, Dowsett M, Allred C, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne K, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams B, Wittliff JL, Wolff AC, American Society of Clinical Oncology, College of American Pathologists. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med. 2010; 134(7): e48-72. PubMed

Hammond EH. ASCO-CAP guidelines for breast predictive factor testing: an update. Appl Immunohistochem Mol Morphol. 2011; 19(6): 499-500. PubMed

Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL, Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2015; 17(1): 70-87. PubMed

Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, Somerfield MR, Hayes DF, Bast RC, American Society of Clinical Oncology. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007; 25(33): 5287-312. PubMed

Harris LN, Ismaila N, McShane LM, Andre F, Collyar DE, Gonzalez-Angulo AM, Hammond EH, Kuderer NM, Liu MC, Mennel RG, Van Poznak C, Bast RC, Hayes DF. Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016; 34(10): 1134-50. PubMed

NCCN Clinical Practice Guidelines in Oncology, Breast Cancer. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Apr 2017]

NCCN Clinical Practice Guidelines in Oncology: Breast and Ovarian Cancer Genetic/Familial High-Risk Assessment: Breast and Ovarian. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Nov 2017]

Oeffinger KC, Fontham ET, Etzioni R, Herzig A, Michaelson JS, Shih YT, Walter LC, Church TR, Flowers CR, LaMonte SJ, Wolf AM, DeSantis C, Lortet-Tieulent J, Andrews K, Manassaram-Baptiste D, Saslow D, Smith RA, Brawley OW, Wender R, American Cancer Society. Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update From the American Cancer Society. JAMA. 2015; 314(15): 1599-614. PubMed

Protocol for the Examination of Specimens from Patients with Ductal Carcinoma In Situ (DCIS) of the Breast. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: December 2013. College of American Pathologists (CAP). Northfield, IL [Revised : Dec 2013; Accessed: Dec 2016]

Protocol for the Examination of Specimens from Patients with Invasive Carcinoma of the Breast. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Jan 2016. College of American Pathologists (CAP). Northfield, IL [Revised : Jan 2016; Accessed: Dec2016]

Siu AL, U.S. Preventive Services Task Force. Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016; 164(4): 279-96. PubMed

Van Poznak C, Somerfield MR, Bast RC, Cristofanilli M, Goetz MP, Gonzalez-Angulo AM, Hicks DG, Hill EG, Liu MC, Lucas W, Mayer IA, Mennel RG, Symmans WF, Hayes DF, Harris LN. Use of Biomarkers to Guide Decisions on Systemic Therapy for Women With Metastatic Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2015; 33(24): 2695-704. PubMed

Wolff AC, Hammond EH, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF, American Society of Clinical Oncology, College of American Pathologists. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013; 31(31): 3997-4013. PubMed

General References

Breast Cancer Risk Assessment Tool. National Cancer Institute. Bethesda, MD [Accessed: Nov 2017]

Dooley WC, Ljung BM, Veronesi U, Cazzaniga M, Elledge RM, O'Shaughnessy JA, Kuerer HM, Hung DT, Khan SA, Phillips RF, Ganz PA, Euhus DM, Esserman LJ, Haffty BG, King BL, Kelley MC, Anderson MM, Schmit PJ, Clark RR, Kass FC, Anderson BO, Troyan SL, Arias RD, Quiring JN, Love SM, Page DL, King EB. Ductal lavage for detection of cellular atypia in women at high risk for breast cancer. J Natl Cancer Inst. 2001; 93(21): 1624-32. PubMed

Duffy MJ, Evoy D, McDermott EW. CA 15-3: uses and limitation as a biomarker for breast cancer. Clin Chim Acta. 2010; 411(23-24): 1869-74. PubMed

Duffy MJ, Walsh S, McDermott EW, Crown J. Biomarkers in Breast Cancer: Where Are We and Where Are We Going Adv Clin Chem. 2015; 71: 1-23. PubMed

Gutierrez C, Schiff R. HER2: biology, detection, and clinical implications. Arch Pathol Lab Med. 2011; 135(1): 55-62. PubMed

Lalloo F, Evans DG. Familial breast cancer. Clin Genet. 2012; 82(2): 105-14. PubMed

López-Muñoz E, Méndez-Montes M. Markers of circulating breast cancer cells. Adv Clin Chem. 2013; 61: 175-224. PubMed

Nofech-Mozes S, Vella ET, Dhesy-Thind S, Hagerty KL, Mangu PB, Temin S, Hanna WM. Systematic review on hormone receptor testing in breast cancer. Appl Immunohistochem Mol Morphol. 2012; 20(3): 214-63. PubMed

Ramsey SD, Henry L, Gralow JR, Mirick DK, Barlow W, Etzioni R, Mummy D, Thariani R, Veenstra DL. Tumor marker usage and medical care costs among older early-stage breast cancer survivors. J Clin Oncol. 2015; 33(2): 149-55. PubMed

Walsh T, Casadei S, Lee MK, Pennil CC, Nord AS, Thornton AM, Roeb W, Agnew KJ, Stray SM, Wickramanayake A, Norquist B, Pennington KP, Garcia RL, King M, Swisher EM. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci U S A. 2011; 108(44): 18032-7. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

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Bastien R, Lewis TB, Hawkes JE, Quackenbush JF, Robbins TC, Palazzo J, Perou CM, Bernard PS. High-throughput amplicon scanning of the TP53 gene in breast cancer using high-resolution fluorescent melting curve analyses and automatic mutation calling. Hum Mutat. 2008; 29(5): 757-64. PubMed

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Carey LA, Rugo HS, Marcom K, Mayer EL, Esteva FJ, Ma CX, Liu MC, Storniolo AM, Rimawi MF, Forero-Torres A, Wolff AC, Hobday TJ, Ivanova A, Chiu W, Ferraro M, Burrows E, Bernard PS, Hoadley KA, Perou CM, Winer EP. TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. J Clin Oncol. 2012; 30(21): 2615-23. PubMed

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Medical Reviewers

Bayrak-Toydemir, Pinar, MD, PhD, Medical Director, Molecular Genetics and Genomics at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Bernard, Philip S., MD, Medical Director, Molecular Oncology at ARUP Laboratories; Associate Professor of Anatomic Pathology, University of Utah

Chadwick, Barbara E., MD, Medical Director, Cytology, and Staff Pathologist, Surgical Pathology at ARUP Laboratories; Assistant Professor of Anatomic Pathology, University of Utah

Factor, Rachel E., MD, MHS, Medical Director, Anatomic Pathology and Cytology; Assistant Professor of Pathology, Director of Breast Pathology, Co-Director of the Cytopathology Fellowship Prgoram, University of Utah

Lyon, Elaine, PhD, FACMG, Medical Director, Molecular Genetics and Genomics, Medical Director, Pharmacogenomics at ARUP Laboratories; Professor of Clinical Pathology, University of Utah

Mao, Rong, MD, FACMG, Section Chief, Molecular Genetics and Genomics, at ARUP Laboratories; Professor of Clinical Pathology, Adjunct Associate Professor, Pediatrics, and Co-Director, Clinical Molecular Genetics Fellowship Program, University of Utah

McMillin, Gwendolyn A., PhD, Medical Director, Toxicology, and Medical Director, Pharmacogenetics, at ARUP Laboratories; Professor of Clinical Pathology, University of Utah

Salama, Mohamed E., MD, Laboratory Section Chief, Hematopathology, at ARUP Laboratories; Professor of Clinical Pathology, Chief of Hematopathology, and Director of the Hematopathology Fellowship Program, University of Utah

Atypical Lesions: To Excise or Not To Excise? - H. Evin Gulbahce, MD (FREE CME credit) (50 min)
Breast Predictive Factor Update - Elizabeth H.Hammond, MD, FCAP (FREE CME credit) (37 min)
Clinical Next-Gen Sequencing for Solid Tumors: What, How, Why, and When? - Christopher Corless, MD, PhD (FREE CME credit) (48 min)
Hereditary Breast and Ovarian Cancer and Genetic Testing - Rong Mao, MD, and Gwendolyn A. McMillin, PhD, DABCC (CC, TC) (FREE CME credit) (23 min)
Intraductal Proliferative Lesions of the Breast - Juan Rosai, MD (FREE CME credit) (48 min)
Laboratory Testing for HER2 Status in Breast Cancer - Katherine Geiersbach, MD, FCAP, FACMG (FREE CME credit) (38 min)
Molecular Oncology: The Role of Next-Generation, Sequencing-Based Gene Panels in Solid Tumors - Allie Grossmann, MD, PhD (60 min)
Molecular Testing and Cytopathology: Downsizing Precision Medicine but not Precision - Georgios Deftereos, MD, FCAP, FASCP (FREE CME credit) (50 min)
Molecular Testing in Breast Cancer: An Oncologist’s Perspective - Adam Cohen, MD (no credit) (52 min)
Next Generation Sequencing for Solid Tumors Diagnostics: Current Practice and New Developments - Larissa V. Furtado, MD (FREE CME credit) (62 min)
Pharmacogenetics of CYP-Mediated Drug Metabolism - Gwendolyn A. McMillin, PhD (FREE CME credit) (25 min)
Prognostic Gene Expression Tests for Early Stage Breast Cancer - Philip S. Bernard, MD (FREE CME credit) (22 min)
Risk Mitigation in Breast Predictive Factor Testing - Elizabeth H. Hammond, MD, FCAP (FREE CME credit) (34 min)
Spindle Cell Lesions of the Breast - Erinn Downs-Kelly, DO, MS (no credit) (60 min)
Spotlight on Testing: Genetic Testing for Hereditary Breast and Ovarian Cancer Syndrome - Hunter Best, PhD (4 min)
Spotlight on Testing: HER2 Testing in Gastroesophageal Adenocarcinoma - Lori Lanphere (8 min)
Surprise! Breast Tumors with Unexpected Final Pathology - Rachel E. Factor, MD, MHS (FREE CME credit) (36 min)
Updates in Margin Status and Lymph Node Dissection - Leigh Neumayer, MD, MS, FACS (no credit) (44 min)
Utility of Whole Genome Arrays for the Detection of Clinically Relevant Imbalances and Homozygosity in the Constitutional and Hematologic Malignancies Setting - Sarah South, PhD, FACMG (50 min)

Last Update: December 2017