What is the recommended workup for a patient with a new onset breast mass, night sweats, and weight loss, especially with a family history of breast cancer?

Workup for New Onset Breast Mass with Constitutional Symptoms and Family History

This patient requires urgent triple assessment (clinical examination, imaging, and tissue diagnosis) with expanded metastatic workup given the concerning constitutional symptoms of night sweats and weight loss, which suggest possible advanced or systemic disease. 1

Immediate Clinical Assessment

Obtain detailed history focusing on:

• Complete family history of breast/ovarian cancer in first- and second-degree relatives, including age at diagnosis and Ashkenazi Jewish ancestry 1
• Menopausal status (measure serum estradiol and FSH if uncertain) 1
• Duration and progression of constitutional symptoms (night sweats, weight loss)
• Cardiac and renal function baseline (relevant for potential anthracycline/trastuzumab treatment) 1

Physical examination must include:

• Bimanual palpation of both breasts and all regional lymph nodes (axillary, supraclavicular, infraclavicular) 1
• Assessment for hepatomegaly and bone tenderness 1
• Full blood count, liver function tests, renal function, alkaline phosphatase, and calcium 1

Imaging Protocol

Primary breast imaging (age-dependent approach):

• Age ≥30 years: Bilateral diagnostic mammography PLUS breast ultrasound of both breasts and regional lymph nodes 1
• Age <30 years: Start with breast ultrasound; proceed to diagnostic mammography if ultrasound shows suspicious findings 1, 2

Given family history, strongly consider adding breast MRI (with and without IV contrast) because:

• Family history qualifies this patient as potentially high-risk 1
• MRI detects disease at more favorable stages in familial breast cancer (70% lower risk of stage II or higher diagnosis) 1
• Annual MRI plus mammography is recommended for strong familial history regardless of proven BRCA mutations 1, 3

Tissue Diagnosis - Mandatory Before Any Treatment

Core needle biopsy (preferably ultrasound or stereotactic-guided) is mandatory and must include:

• Histology and grade determination 1
• Estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki67 status 1
• Minimum 2-3 cores should be obtained 1

If ultrasound-guided biopsy of suspicious axillary lymph nodes is indicated based on imaging findings 1

Expanded Metastatic Workup - Critical Given Constitutional Symptoms

The presence of night sweats and weight loss mandates assessment for metastatic disease, which is NOT routinely recommended in early breast cancer but IS indicated when:

• High tumor burden is suspected 1
• Aggressive biology is present 1
• Symptoms suggestive of metastases are present 1

This patient meets the symptomatic criteria, therefore obtain:

• Chest imaging (chest X-ray or CT) 1
• Bone scan or skeletal imaging if bone pain or elevated alkaline phosphatase 1
• Abdominal imaging (ultrasound or CT) to evaluate liver 1
• Neurological examination only if neurological symptoms present 1

Critical Pitfalls to Avoid

Do not rely on negative mammography alone - the false-negative rate of individual diagnostic methods necessitates triple assessment (clinical exam + imaging + biopsy) to reduce missed cancer risk to 1% 4

Do not delay biopsy for "probably benign" imaging findings in the setting of a palpable mass, family history, and constitutional symptoms 1, 4

Do not dismiss constitutional symptoms as unrelated - while breast cancer typically presents as a localized mass, night sweats and weight loss may indicate:

• Advanced/metastatic breast cancer 1
• Aggressive biology requiring immediate systemic therapy 1
• Alternative diagnosis (e.g., lymphoma, which can present with breast masses and constitutional symptoms) 5

Genetic Risk Assessment

Refer for genetic counseling if:

• First-degree relative with breast cancer diagnosed before age 50 1
• Multiple affected relatives 1, 3
• Ashkenazi Jewish heritage 1, 3
• Any relative with ovarian cancer 1

High-risk women (≥20% lifetime risk or BRCA mutations) require annual MRI plus mammography starting at age 25-30 3, 6

Timeline for Action

All imaging and biopsy should be completed within 1-2 weeks given the combination of palpable mass, constitutional symptoms, and family history suggesting potentially aggressive disease requiring prompt diagnosis and treatment initiation 1