The latest options in diagnostic breast cancer testing

Approximately 1 in 8 women in the United States will be diagnosed with invasive breast cancer during her lifetime.¹ Although an individual patient’s risk, disease characteristics, and clinical course can vary considerably, access to the right diagnostic information at the right time can help inform decisions throughout the cancer care continuum.

Laboratory testing contributes information throughout their breast cancer journey that cannot be obtained from imaging or histopathology alone—from identifying hereditary risk and characterizing advanced disease to informing treatment decisions and evaluating the possibility of recurrence.

For primary care providers, understanding breast cancer testing options can support timely referrals, more informed patient conversations, and better coordination with oncology and genetic specialists.

In this article:

Clinical challenge | Why it matters | Ordering recommendations | Interpreting test results | Next steps | Supporting resources

Clinical challenge: Navigating expanding breast cancer blood test options

Primary care clinicians may encounter patients at several critical decision points in the breast cancer care continuum:

• Screening: A patient without cancer may exhibit risk factors such as dense breast tissue or have a concerning family history of breast cancer
• Diagnosis: A patient presenting with a breast lump or an abnormal screening mammogram may require diagnostic testing to confirm or rule out breast cancer
• Prognosis: A patient with advanced disease may undergo testing to identify potentially actionable biomarkers
• Treatment selection: A newly diagnosed patient may need testing to inform treatment and future risk management
• Monitoring: A survivor may return to primary care with questions about recurrence monitoring and the implications for family members

Each situation requires a different type of test. Distinguishing the right tests, particularly as the diagnostic landscape continually evolves, can present a clinical challenge for providers.

Germline testing to identify inherited cancer risk

Germline testing, or hereditary breast cancer panel testing, evaluates variants that are passed down from generation to generation, such as in the BRCA1 and BRCA2 genes. Results may affect the patient’s cancer management, future cancer risk, and biological relatives.

Testing for inherited germline mutations is different from testing for somatic mutations which are changes to tumor cells that have been acquired over an individual’s lifetime. Learn more about the difference between germline (hereditary cancer genetic testing) and somatic testing (tumor genetic testing).

Advanced molecular profiling with liquid biopsy

A blood-based comprehensive genomic profiling test, or liquid biopsy, evaluates genes and cancer-related genomic signatures in patients with solid tumors. To help characterize the tumor type and disease stage, it analyzes circulating tumor DNA released by cancer cells into the bloodstream and identifies biomarkers that may help focus on a treatment strategy.

Minimal residual disease testing for surveillance

Breast cancer blood tests for minimal (or molecular) residual disease focus on identifying tumor-derived DNA remaining in the blood after breast cancer treatment to help inform surveillance and follow-up care strategies.

These test types are not interchangeable. The appropriate choice depends on the clinical setting, inherited risk, disease stage, tumor subtype, professional guidelines, and how the result will be used. While advanced oncology testing is frequently ordered and interpreted by specialists, PCPs can help identify testing opportunities, collect a complete family history, explain why testing may be recommended, and ensure that patients receive appropriate follow-up.

Why it matters: Bringing clarity to a complex disease

Breast cancer is not one disease with a straightforward diagnostic and treatment plan. Its clinical presentation and response to treatment are influenced by inherited risk, tumor subtype, stage, and a range of molecular characteristics. That’s why laboratory testing is key to bringing clarity and helping clinicians determine the right test at the right time.

Ordering recommendations: Blood tests for breast cancer markers

From screening to survivorship, Quest offers several diagnostic blood tests that deliver breast cancer insights. But before ordering testing, first define what information is needed and how the result could affect patient management.

Recommended tests: Breast cancer blood tests

Guideline Based Hereditary Cancer Panel

Turn to this multi-gene panel to identify patients with a hereditary predisposition to cancer. The guideline-based panel tests for variants in 32 genes, many of which are associated with breast cancer as well as cancers of the colon, endometrium, stomach, urinary tract, ovary, pancreas, prostate, rectum, and other tissues.

• Test code: 38611
• CPT® code: 81432 

Components include APC [93797], ATM [38802], AXIN2, BARD1, BMPR1A, BRCA1 [91863], BRCA2 [91863], BRIP1, CDH1 [92568], CDK4, CDKN2A (p16, p14) [93939], CHEK2 [93940], EPCAM, GREM1, HOXB13 [38807], MLH1 [39782], MSH2 [70197], MSH3, MSH6 [16938], MUTYH [93944], NF1 [93941], NTHL1, PALB2 [92571], PMS2 [16997], POLD1, POLE, PTEN [90178], RAD51C, RAD51D, SMAD4, STK11 [92565], and TP53 [92560]

Note: Test codes are provided in brackets for components that are available for individual ordering.

LiquidSEQ™ comprehensive genomic profiling

Consider this liquid biopsy test for breast cancer treatment selection. As a precision medicine panel, LiquidSEQ™ evaluates 523 genes associated with a broad spectrum of solid tumor cancers and assesses the DNA for single nucleotide variants (SNVs), copy number variants (CNVs), and fusions, along with genomic signatures, microsatellite instability (MSI), and tumor mutation burden (TMB). As a result, it delivers personalized genomic information on a wide variety of cancer-related biomarkers including clinically actionable genes and genomic signatures for patients with solid tumors.

• Test code: 14308
• CPT code: 81464

Haystack MRD™ Baseline

Leverage this tumor-informed, personalized minimal residual disease (MRD) test after breast cancer is diagnosed to confidently find even the smallest evidence of cancer, such as residual disease after surgery or chemotherapy, for insights on treatment response and surveillance. It analyzes circulating tumor DNA (ctDNA) in the blood of patients with cancer or a previous diagnosis of cancer.

As a leading-edge diagnostic innovation, Haystack MRD has patented error-correction technology. With zero false-positive results, Haystack MRD boasts analytical specificity of 100%, which is underscored by published clinical data.

• Test code: 13682
• CPT code: 0560U

Related breast cancer tests

Quest offers additional breast cancer blood testing for multiple stages of the breast cancer journey.

Comprehensive Hereditary Cancer Panel

• Test code: 38600
• CPT code: 81432 

Components include APC [93797], ATM [38802], AXIN2, BAP1 [39872], BARD1, BLM [38804], BMPR1A, BRCA1 [91863], BRCA2 [91863], BRIP1, CDH1 [92568], CDK4, CDKN1B, CDKN2A (p16, p14) [93939], CHEK2 [93940], DICER1, EGFR [94718], EPCAM, FANCA, FANCC, FANCM, FH [94877], FLCN [38806], GALNT12, GREM1, HOXB13 [38807], MAX, MEN1 [93942], MET, MITF [38808], MLH1 [39782], MRE11 (MRE11A), MSH2 [70197], MSH3, MSH6 [16938], MUTYH [93944], NBN, NF1 [93941], NTHL1, PALB2 [92571], PMS2 [16997], POLD1, POLE, POT1, PTCH1,

PTEN [90178], RAD50, RAD51C, RAD51D, RECQL, RET [93796], SDHA, SDHAF2, SDHB, SDHC, SDHD, SMAD4, SMARCA4 [38809], STK11 [92565], SUFU, TMEM127, TP53 [92560], TSC1 [38661], TSC2 [38661], VHL [93943], and XRCC2.

Note: Test codes are provided in brackets for components that are available for individual ordering.

AmeriPath® pathology services

PD-L1, IHC with Interpretation

• Test code: 94007
• CPT code: 88360

HER-2, IHC with Interpretation

• Test code: 30316
• CPT code: 88360

ER/PR, Paraffin Block

• Test code: 7037
• CPT code: 88360 (x2)

Ki-67, IHC with Interpretation

• Test code: 29914
• CPT code: 88360

Interpreting results: Blood tests for breast cancer biomarkers

No single result of a breast cancer blood test can be evaluated in isolation. Interpret results alongside personal and family history, pathology, disease stage, prior treatment, and other clinical findings.

Hereditary cancer panel results

A hereditary cancer panel may return any of the following 3 results:

Pathogenic or likely pathogenic variant is a positive result indicating an inherited cancer predisposition. It is important to note that this positive result does not mean that an individual has breast cancer—it means they have an increased risk of developing certain types of cancer in their lifetime.

When no pathogenic or likely pathogenic variant is detected, the result is considered negative; however, it does not eliminate an increased risk of cancer or a hereditary risk. The family may carry a variant not detectable by the assay, a variant in a gene not included on the panel, or a hereditary risk factor not yet uncovered. Families also share other risk factors such as lifestyle, diet, and environment, which can contribute to risk.

Variant of uncertain significance (VUS) means that the variant has not been previously described in medical literature or that the clinical significance is unclear based upon currently available evidence. Care decisions should be based on personal and family history.

LiquidSEQ results

The comprehensive genomic profiling report from a LiquidSEQ biopsy delivers personalized genomic information such as

• Genomic alterations with an approved therapy in the relevant cancer type
• Alterations associated with therapies approved in another tumor type
• Potential clinical trial opportunities
• Genomic signatures or biomarkers relevant to treatment planning
• Alterations without an established therapeutic implication

The significance of an identified alteration depends on the tumor type, disease setting, variant classification, strength of evidence, drug indication, previous treatments, and the patient’s overall health.

A result of no actionable alteration is not necessarily a normal result as several technical and biologic factors may limit detection.

Haystack MRD results

MRD detected results indicate the presence of residual cancer in the body. Following a Haystack MRD Baseline test, subsequent Haystack MRD Monitoring tests can be ordered to track whether the amount of ctDNA increases or decreases in response to treatment over time.

MRD not detected results indicate a lack of ctDNA detection at the time of the blood draw, which may point to the absence of residual cancer but does not definitively exclude the possibility of residual disease in the patient. Subsequent Haystack MRD Monitoring tests can be ordered to track whether residual disease remains undetectable over time.

The timing of Haystack MRD specimen collection relative to surgery and chemotherapy should be considered. In fact, trends over a series of test samples may be more informative than a single result.

Next steps: Breast cancer guidance from the primary care setting

Primary care clinicians remain important members of the care team before, during, and after breast cancer diagnosis and treatment. Following laboratory testing, primary care can help translate results into coordinated, longitudinal care.

Key actions may include

• Close the referral loop: Confirm that patients with hereditary findings or complex family histories receive genetic counseling and oncology specialty follow-up
• Update the medical and family history: Record the specific gene and variant, tumor biomarkers, and relevant molecular findings
• Support secondary risk assessments: Work with oncology and genetics to coordinate screening for second primary cancers or other gene-associated malignancies when indicated
• Encourage family communication: Help patients with a pathogenic germline variant to understand which relatives could benefit from counseling and targeted testing
• Manage comorbidities and treatment effects: Guide patients through any potential issues with cardiovascular risk, bone health, metabolic conditions, mental health, menopausal symptoms, and medication interactions that may impact their treatment success
• Evaluate new symptoms promptly: Remain vigilant for new focal pain, neurologic changes, respiratory symptoms, unexplained weight loss, or other persistent concerns that may warrant further evaluation
• Recommend ongoing preventive care: Continue age- and risk-appropriate preventive services while coordinating breast cancer surveillance with the patient’s oncology team

Supporting resources