Breast Cancer Diagnostics

Histologic or Cytologic Tests  

Breast tissue biopsy is recommended if mammogram and/or ultrasound findings are suspicious or highly suggestive of malignancy. Fine needle aspiration (FNA) biopsy, core needle biopsy, or surgical (excisional) biopsy are types of needle biopsies used in diagnosing breast carcinoma. Documentation of metastasis or recurrence using biopsy is recommended especially if to be assessed for the first time.  

Fine Needle Aspiration (FNA) Cytology  

FNA cytology is a diagnostic option for the pathological evaluation of palpable breast lumps. It is usually done in clinically positive axillary lymph nodes, especially in large breast tumors, ≥3 suspicious nodes on imaging, or when preoperative systemic therapy is being considered but suspicious lymph nodes are present. Ultrasound-guided FNA can be performed in nonpalpable lesions.  

It is a minimally invasive method with low cost; however, it needs a pathologist with specific expertise in test result interpretation and performing a follow-up tissue biopsy when atypia or malignancy is seen. It may be replaced by core needle biopsy for highly suspicious lesions.  

Core Needle Biopsy  

Core needle biopsy is also called percutaneous core breast biopsy, with image-detectable clips or markers, and can be performed under imaging guidance. It may also be done under vacuum assistance which collects adequate tissue from a breast lesion without the need for multiple needle insertions.  

It is the preferred method of tissue biopsy if there is a suspicious or indeterminate solid lesion detected by ultrasound, ≥3 suspicious nodes on imaging, or when preoperative systemic therapy is being considered but suspicious lymph nodes are present. It has higher accuracy over FNA when the mass is nonpalpable and has the capability to obtain sufficient tissue sample sizes which eliminates the need for a follow-up biopsy to confirm a malignancy.  

Surgical or Excisional Biopsy  

Surgical or excisional biopsy remains to be the gold standard of diagnosis with almost 100% sensitivity.  It is recommended following diagnosis by core biopsy of an indeterminate lesion, atypical hyperplasia, lobular neoplasia, lobular carcinoma in situ, or a benign and image-discordant lesion. It provides larger tissue samples but is a more invasive method than a core needle biopsy and requires needle localization in a nonpalpable mass.  

Sentinel Lymph Node Biopsy  

A sentinel lymph node biopsy is the preferred method of axillary lymph node staging in early, clinically node-negative breast cancer or in patients with ≤2 suspicious nodes on imaging or ≤2 positive nodes confirmed by needle biopsy if there is an experienced sentinel node team and if the patient is an appropriate candidate for sentinel lymph node biopsy.  

Please see Histologic Diagnosis under Classification for further information.  

Other Tests  

Complete blood count (CBC), liver and renal function tests, alkaline phosphatase, calcium, liver ultrasound, hepatitis B virus (HBV) testing, and chest X-ray are recommended especially in patients with invasive breast carcinoma or advanced breast cancer.  

Germline Testing  

Consider using genomic tests as a guide for management decisions and predicting the prognosis (eg EndoPredict^®, Mammostrat test, MammaPrint, Prosigna^®, Oncotype Dx^®)¹. Comprehensive germline and somatic profiling in patients with recurrent or metastatic disease may be considered to identify candidates for additional targeted therapies.  

Germline testing includes tests for hormone receptors (HR) (eg estrogen receptor [ER], progesterone receptor [PR]) and HER2/neu. Perform HER2 testing on all newly diagnosed patients with primary or metastatic breast cancer using either immunohistochemistry (IHC) assay or in situ hybridization (ISH) assay to help guide decisions regarding HER2-targeted therapy. This helps in accurately identifying patients who would benefit from HER2-targeted treatment and thereby preventing unnecessary side effects and cost of therapy. It helps differentiate recurrent disease from the new primary disease.  

For recurrent or stage IV disease, assess for PIK3CA mutation for possible Alpelisib therapy, germline BRCA1 or 2 testing for patients with HER2-negative tumors being considered for chemotherapy, programmed cell death ligand 1 (PD-L1) biomarker status on tumor-infiltrating immune cells to test if a patient with triple-negative breast cancer will be responsive to immune checkpoint inhibitors.  

Testing for ER gene ligand-binding domain (ESR1) mutation is recommended in patients with breast cancer recurrence or progression in patients with ER-positive, HER2-negative metastatic breast cancer despite endocrine therapy with or without CDK4/6 inhibitor.  

¹Not all tests mentioned are available in all countries.  

Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)  

Consider a 21-gene RT-PCR assay for estimating the probability of tumor recurrence.  

RT-PCR is recommended in the following patients with HR-positive, HER2-negative tumors:

• Premenopausal with tumor >0.5 cm and stage pN0
• Postmenopausal with tumor >0.5 cm or stage pN1Mi or pN1
• Candidates for chemotherapy

 

Mammography  

Mammography (done bilaterally) detects clinically occult breast lesions and is the recommended screening method for women ≥40 years old annually. It is not done routinely as a screening method in low- and moderate-risk women aged <40 years but should not be denied in women who would like to undergo the procedure. It is the preferred initial evaluation for high-risk women starting at the age of ≥30 years. Screening with both mammography and magnetic resonance imaging (MRI) provides more sensitivity than mammography alone. Further evaluation is necessary after bilateral mammography.  

Ultrasound  

Ultrasound is the preferred initial test for women aged <30 years and may be useful in patients under 35 years old with focal breast disease. It is used as an adjunct to mammography. It determines the nature of the mass, whether fluid-filled or solid tissue and assesses regional lymph nodes.  

Magnetic Resonance Imaging (MRI)  

An MRI may be used in patients with metastatic deposits in the axilla or axillary lymph nodes where primary cancer has not been identified. It may help identify otherwise clinically occult disease in patients with axillary node metastases (cT0, cN+), with Paget disease, or with invasive lobular carcinoma that is poorly or inadequately defined on physical examination, mammography, or ultrasound.  

MRI should be considered in cases where other imaging procedures have been inconclusive or unreliable such as invasive lobular cancer, suspicion of multicentricity, genetic high risk, patients with breast implants or foreign bodies, diagnosis of recurrence, follow-up after neoadjuvant therapy, or in patients with dense breasts.  

MRI may be performed for staging evaluation to determine the extent of cancer or the presence of multifocal or multicentric cancer in the ipsilateral breast or as a screening of the contralateral breast cancer at the time of initial diagnosis. It may aid in breast cancer evaluation before and after preoperative systemic therapy to define disease extent, treatment response, and the potential for breast-conservation therapy. It may be performed in patients with suspicious nipple discharge and mammography and ultrasound are not diagnostic. It is not recommended in women with invasive breast cancer, lobular neoplasia, ductal carcinoma in situ, and atypical hyperplasia.  

Bone Scan  

A bone scan is recommended in patients complaining of bone pains, with elevated alkaline phosphatase (ALP), and with advanced breast cancer. It may be an option as a staging method in patients with stage III invasive cancer and may not be performed if fluorodeoxyglucose (FDG) PET/CT shows bone metastases.  

Computed Tomography (CT) Scan  

Abdominal with or without pelvic CT scan with contrast may be used in patients with invasive breast cancer with elevated ALP, abnormal liver enzyme levels, and abnormalities upon physical examination of the abdomen or pelvis. Chest CT scan with contrast may be used in patients with invasive breast cancer if exhibiting pulmonary symptoms, or with or without contrast in patients with recurrent or metastatic breast cancer. It should be performed in patients with clinically advanced breast cancer to evaluate the possibility of metastases to other organs.  

Positron Emission Tomography/CT (PET/CT)  

Sodium fluoride or fluorodeoxyglucose (FDG) PET/CT should be considered in patients with clinical stage IIIA ≥T2N1M0 invasive and metastatic breast cancer or when conventional methods are inconclusive. It may help identify unsuspected regional nodal disease and/or distant metastases when performed together with other tests.