What is the recommended diagnostic workup for a postmenopausal woman with suspected early-stage, hormone receptor-positive breast cancer?

Diagnostic Workup for Postmenopausal Women with Suspected Early-Stage, Hormone Receptor-Positive Breast Cancer

For a postmenopausal woman with suspected early-stage, hormone receptor-positive breast cancer, the diagnostic workup must include bilateral mammography plus ultrasound of both breasts and regional lymph nodes, followed by core needle biopsy with complete biomarker assessment (ER, PR, HER2, Ki67), baseline blood work, and staging imaging only if stage IIb or higher disease is present. 1

Initial Clinical Assessment

Obtain a detailed history focusing on:

• Complete family history of breast and ovarian cancer in first- and second-degree relatives, including age at diagnosis and Ashkenazi Jewish ancestry 2
• Menopausal status confirmation (measure serum estradiol and FSH if uncertain) 1, 2
• Prior breast cancer treatments and timing 1

Physical examination must include:

• Bimanual palpation of both breasts and all regional lymph nodes 1, 2
• Assessment for hepatomegaly and bone tenderness 2

Baseline laboratory tests:

• Full blood count 1
• Liver and renal function tests 1
• Alkaline phosphatase and calcium 1
• Cardiac function tests if anthracycline/trastuzumab treatment is anticipated 1, 2

Imaging Protocol

Standard imaging (required for all patients):

• Bilateral diagnostic mammography 1
• Ultrasound of both breasts and regional lymph nodes 1
• Digital breast tomosynthesis or contrast-enhanced mammography may be considered as alternatives where available 1

Breast MRI is recommended in specific situations:

• Strong family history or known BRCA1/2 mutations 1, 2
• Lobular cancers 1
• Dense breasts 1
• Suspicion of multifocality/multicentricity 1
• Large discrepancies between conventional imaging and clinical examination 1
• Inconclusive findings on conventional imaging 1

Tissue Diagnosis

Core needle biopsy (preferably ultrasound or stereotactic-guided) must include: 1, 2

• Histological type and grade determination
• Estrogen receptor (ER) status
• Progesterone receptor (PR) status
• HER2 status
• Ki67 proliferation index
• Obtain minimum 2-3 cores during the procedure 2

If axillary lymph nodes appear suspicious on ultrasound, perform ultrasound-guided biopsy. 1

Staging and Metastatic Assessment

Assessment of distant metastases (bone, liver, lung) is recommended ONLY in: 1

• Stage IIb or higher disease (tumor >5 cm or ≥4 positive lymph nodes)
• Extensive lymph node involvement
• High risk of recurrence at first diagnosis
• Symptomatic patients (bone pain, constitutional symptoms, abnormal liver function tests)

If metastatic workup is indicated, obtain: 1, 2

• Chest imaging (chest X-ray or CT scan)
• Abdominal imaging (ultrasound or CT scan) to evaluate liver
• Bone scintigraphy or skeletal imaging
• Brain imaging (CT or MRI) only if neurological symptoms present 1

Additional Biomarker Testing

Gene expression assays (Oncotype DX, MammaPrint, Endopredict, PAM50, or BCI) should be considered in HR-positive, HER2-negative early breast cancer when there is uncertainty about adjuvant chemotherapy indications after considering all clinical and pathological factors. 1, 3

Germline BRCA1/2 testing and genetic counseling should be offered to patients who: 1

• Meet national criteria for hereditary cancer syndromes
• Are candidates for adjuvant olaparib therapy
• Have first-degree relative with breast cancer diagnosed before age 50 2
• Have multiple affected relatives or Ashkenazi Jewish heritage 2

Pathological Staging

Final disease staging must be performed according to: 1

• World Health Organization classification of tumors
• Eighth edition of the Union for International Cancer Control TNM staging system

Important Caveats

Do not routinely perform metastatic workup in stage I or IIA disease without symptoms or high-risk features, as this leads to unnecessary testing and potential false-positive results. 1 The 2024 ESMO guidelines specifically restrict staging imaging to stage IIb and higher to avoid overtreatment and patient anxiety from incidental findings.

PD-L1 expression levels should NOT be used to guide treatment decisions in early breast cancer. 1

Tumor-infiltrating lymphocytes (TILs) may provide prognostic information but have no distinct thresholds for treatment decisions in HR-positive disease. 1