Breast%20cancer Diagnosis

Histologic Diagnosis

Carcinoma in Situ

• Cancer cells confined to the lobules or ducts without spread into surrounding tissues in the breast or to other organs in the body
• Includes lobular neoplasia/LCIS and DCIS

Invasive Breast Cancer

• Most common breast cancer
• Cancer cells infiltrating the interlobular stroma
• Includes invasive ductal carcinoma, invasive lobular neoplasia, mixed tumors, medullary cancer, metaplastic tumors, inflammatory breast cancer, colloid carcinoma, tubular carcinoma, papillary carcinoma
  
  • Colloid and tubular carcinoma are good prognosis cell types which are usually HER2 negative

Medical History

• Ask for symptoms such as breast pain or presence of a new mass in the breast
• Assess risk factors for breast cancer ie history of breast cancer, chest irradiation, strong family history (see Risk Factors section)

• Complete breast examination
  
  • Inspection and palpation of the breasts should be done in upright and supine positions to determine subtle shape or contour changes in the breasts
  • Determine the presence of palpable lump or mass and its characteristics (eg location, size, texture, mobility, presence of asymmetric thickening or nodularity, retraction, nipple discharge, and skin changes)
  • Assess for axillary, supraclavicular and internal mammary lymph nodes, and other organs for metastatic disease

• In patients with nipple discharge without a palpable mass, evaluate the character of discharge for other causes
• In asymptomatic patients with negative physical exam, perform risk assessment followed by appropriate screening and follow-up as recommended 

Mammography

• Done bilaterally, detects clinically occult breast lesions
• Recommended screening method for women ≥40 years old annually
• Not done routinely as screening method in low- and moderate-risk women ages <40 years but should not be denied in women who would like to undergo the procedure
• Preferred initial evaluation for high-risk women starting at age ≥30 years
• Screening with both mammography and MRI provides more sensitivity than mammography alone
• Further evaluation is necessary after bilateral mammography

Ultrasound

• Preferred initial test for women age <30 years
• Used as an adjunct to mammography
• Determines the nature of the mass, whether fluid-filled or solid tissue, and assesses regional lymph nodes (LNs)
• May be useful in patients under 35 years old with focal breast disease

Magnetic Resonance Imaging (MRI)

• May be used in patients with metastatic deposits in the axilla or axillary LNs where primary cancer has not been identified
• 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
• 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
• May be performed for staging evaluation to determine extent of cancer or presence of multifocal or multicentric cancer in the ipsilateral breast, or as screening of the contralateral breast cancer at time of initial diagnosis
• Not recommended in women with invasive breast cancer, lobular neoplasia, DCIS, and atypical hyperplasia
• May be performed in patients with suspicious nipple discharge and mammography and ultrasound are not diagnostic

Bone Scan

• Recommended in patients complaining of bone pains, with elevated alkaline phosphatase (ALP) and with advanced breast cancer
• May be an option as a staging method in patients with stage III invasive cancer and may not be performed if 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 with 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
• Should be performed in patients with clinically advanced breast cancer to evaluate the possibility of metastases to other organs

• 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
  • May help identify unsuspected regional nodal disease and/or distant metastases when performed together with other tests

Histologic/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

• Diagnostic option for pathological evaluation for palpable breast lumps
• Usually done in clinically positive axillary LN especially in large breast tumors, ≥3 suspicious nodes on imaging or when preoperative systemic therapy is being considered but suspicious LNs are present
• Ultrasound-guided FNA can be performed in nonpalpable lesions

• Minimally invasive method with low cost but needs a pathologist with specific expertise in test result interpretation and performing a follow-up tissue biopsy when atypia or malignancy is seen
• May be replaced by core needle biopsy for highly suspicious lesions

Core Needle Biopsy

• Also called percutaneous core breast biopsy, with image-detectable clips or markers, it can be performed under imaging guidance
  
  • May also be done under vacuum assistance which collects adequate tissue from a breast lesion without the need for multiple needle insertions

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

Surgical or Excisional Biopsy

• Gold standard of diagnosis with almost 100% sensitivity
• Recommended following diagnosis by core biopsy of an indeterminate lesion, atypical hyperplasia, lobular neoplasia/LCIS, or a benign and image-discordant lesion
• Provides larger tissue samples but is a more invasive method than a core needle biopsy and also requires needle localization in a nonpalpable mass

Sentinel Lymph Node Biopsy

• Preferred method of axillary LN 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 LN biopsy

Other Tests

• 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 prognosis (eg EndoPredict^®,Mammostrat test, MammaPrint, Prosigna^®, Oncotype Dx^®)
  • Not all tests mentioned are available in all countries.
• Comprehensive germline and somatic profiling in patients with recurrent or metastatic disease may be considered to identify candidates for additional targeted therapies
• Include tests for hormone receptors [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 decision regarding HER2-targeted therapy
    
    • Helps in accurately identifying patients who would benefit from HER2-targeted treatment and thereby preventing unnecessary side effects and cost of therapy
    • Helps differentiate recurrent disease from new primary disease
• For recurrent or stage IV disease, assess for the following:
  • PIK3CA mutation for possible Alpelisib therapy
  • Germline BRCA1/2 testing for patients with HER2-negative tumors being considered for chemotherapy
  • PD-L1 biomarker status on tumor-infiltrating immune cells to test if patient with triple-negative breast cancer will be responsive to immune checkpoint inhibitors
• Ki-67 testing should be considered in patients being considered for Abemaciclib treatment

Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)

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

Triple Assessment

• Established method to diagnose breast cancer
• Consists of clinical evaluation, imaging (ie mammography and/or ultrasound) and pathology (histology and/or cytology)

Clinical Evaluation

• Includes complete medical history and physical examination

• Determines the extent of cancer upon diagnosis
• Important factor in the choice of treatment and provides information about the prognosis of the disease
• Since asymptomatic metastases are rare, routine staging assessment is for local regional disease

Tumor, Nodes and Metastases (TNM) System

• Developed by the American Joint Committee on Cancer and Union Internationale Contre le Cancer