breast%20cancer
BREAST CANCER
Breast cancer is the presence of malignant breast nodule, mass or abscess.
Most common symptom of breast cancer is a new lump or mass in the breast. The lump or mass is usually painless, hard & irregular but it can also be tender, soft, rounded or painful.
Other signs & symptoms include breast pain or nipple pain, nipple discharge, nipple retraction and presence of breast skin changes (eg peau d' orange, nipple excoriation, scaling, inflammation, skin tethering, ulceration, abscess).

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 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
    • Colloid and tubular carcinoma are good prognosis cell types which are usually HER2 negative

History

Medical History

  • Ask for symptoms such as breast pain or presence of a new mass in the breast
  • Assess risk factors for breast cancer

Physical Examination

  • 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 

Imaging

Mammography

  • Done bilaterally, detects clinically occult breast lesions
  • Recommended screening method for women 50-74 years old every 1-2 years
  • Not done routinely as screening method in low- and moderate-risk women ages 40-49 years but should not be denied in women who would like to undergo the procedure
    • Some have recommended annual mammogram in women starting at age 40 years
  • 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 axillary LNs where primary cancer has not been identified
  • 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
  • Not recommended in women with invasive breast cancer, lobular neoplasia, DCIS, and atypical hyperplasia

Bone Scan

  • Recommended in patients complaining of bone pains, with elevated alkaline phosphatase (ALP) and with advanced breast cancer

Computed Tomography (CT) Scan

  • Should be performed in patients with clinically advanced breast cancer to evaluate the possibility of metastases to other organs

Laboratory 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

Fine Needle Aspiration (FNA) Cytology

  • Initial method of pathological evaluation for palpable breast lumps
  • Usually done in clinically positive axillary LN especially in large breast tumors
    • 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

Core Needle Biopsy

  • Also called percutaneous core breast biopsy which 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
  • Used as a complement for pathological diagnosis if FNA cytology is equivocal
  • Preferred method of tissue biopsy if there is suspicious or indeterminate solid lesion detected by ultrasound
  • 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 if there is an experienced sentinel node team and if the patient is an appropriate candidate for sentinel LN biopsy
    • May be done in clinically negative axillary node in large breast tumors

Other Tests

  • CBC, liver and renal function tests, alkaline phosphatase, calcium, liver ultrasound, and chest X-ray are recommended especially in patients with invasive breast carcinoma or advanced breast cancer

Tumor Tests

  • Include tests for hormone receptors [eg estrogen receptor (ER), progesterone receptor (PR)] and human epidermal growth factor receptor 2 or 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

Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)

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

Assessment

Triple Assessment

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

Criteria for Early Referral

  • Women >40 years old complaining of breast lump
  • Women at any age that has a lump >3 cm in diameter
  • Presence of clinical signs of malignancy

Clinical Evaluation

  • Includes complete medical history and physical examination

Staging

  • 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

Staging

Stage 0

  • Tis N0 M0
    •  Carcinoma in situ, may either be ductal or lobular carcinoma or Paget’s disease of the nipple without tumor; no regional LN metastasis and distant organ metastasis

Stage IA

  • T1 N0 M0
    •  Tumor size is ≤2 cm in widest dimension, no regional LN metastasis, no distant organ metastasis

Stage IB

  • T0 N1mi M0
    •  No evidence of primary tumor or distant organ metastasis, with metastasis to movable ipsilateral axillary LN that is >0.2 mm but ≤2 mm in widest dimension
  •  T1 N1mi M0
    •  Tumor size is ≤2 cm in widest dimension, with metastasis to movable ipsilateral axillary LN that is >0.2 mm but ≤2 mm in widest dimension, no distant organ metastasis

Stage IIA

  • T0 N1 M0
    •  No evidence of primary tumor, with metastasis to movable ipsilateral axillary LN that is >2 mm in widest dimension, no distant organ metastasis
  •  T1 N1 M0
    •  Tumor size is ≤2 cm in greatest dimension, with metastasis to movable ipsilateral axillary LN that is >2 mm in widest dimension, no distant metastasis
  •  T2 N0 M0
    • Tumor size is >2 cm but not >5 cm in widest dimension, no regional LN metastasis, no distant metastasis

Stage IIB

  • T2 N1 M0
    •  Tumor size is >2 cm but not >5 cm in greatest dimension, with metastasis to ipsilateral axillary LN that is movable, no distant metastasis
  •  T3 N0 M0
    •  Tumor size is >5 cm in widest dimension, no regional LN metastasis, no distant metastasis

Stage IIIA

  • T0 N2 M0
    •  No evidence of primary tumor or distant organ metastasis; metastasis to ipsilateral axillary node(s) fixed or matted, or metastasis to ipsilateral internal mammary LN as detected by imaging studies, clinical assessment or grossly visible pathologically in the absence of clinically evident axillary LN metastasis
  •  T1 N2 M0
    •  Tumor size is ≤2 cm in widest dimension; metastasis to ipsilateral axillary node(s) fixed or matted, or metastasis to ipsilateral internal mammary LN as detected by imaging studies, clinical assessment or grossly visible pathologically in the absence of clinically evident axillary LN metastasis; no distant metastasis
  •  T2 N2 M0
    •  Tumor size is >2 cm but not >5 cm in greatest dimension; metastasis to ipsilateral axillary node(s) fixed or matted, or metastasis to ipsilateral internal mammary LN as detected by imaging studies, clinical assessment or grossly visible pathologically in the absence of clinically evident axillary LN metastasis; no distant organ metastasis
  •  T3 N1 M0
    •  Tumor size is >5 cm in greatest dimension, with metastasis to movable ipsilateral axillary LN, no distant metastasis
  •  T3 N2 M0
    •  Tumor size is >5 cm in greatest dimension; metastasis to ipsilateral axillary node(s) fixed or matted, or spread to ipsilateral internal mammary LN as detected by imaging studies, clinical assessment or grossly visible pathologically in the absence of clinically evident axillary LN metastasis; no distant metastasis

Stage IIIB

  • T4 N0 M0
    •  Tumor of any size with direct extension to chest wall (eg ribs, intercostal muscles and serratus anterior muscle) or skin; no regional LN metastasis
  •  T4 N1 M0
    •  Tumor of any size with direct extension to chest wall (eg ribs, intercostal muscles and serratus anterior muscle) or skin; metastasis to movable ipsilateral axillary LN
  •  T4 N2 M0
    •  Tumor of any size with direct extension to chest wall (eg ribs, intercostal muscles and serratus anterior muscle) or skin; metastasis in ipsilateral level I, II axillary LN that are clinically fixed or matted; or in clinically identifiable ipsilateral internal mammary nodes in the absence of clinically evident axillary LN metastases

Stage IIIC

  • Any T N3 M0
    •  Carcinoma in situ or tumor of any size with or without direct extension to chest wall or skin; metastasis to ipsilateral infraclavicular LN with or without axillary node involvement, or spread to ipsilateral internal mammary LN as detected by imaging studies, clinical assessment or grossly visible pathologically in the presence of clinically evident axillary LN metastasis; or metastasis in ipsilateral supraclavicular LN with or without axillary or internal mammary node involvement; no distant metastasis

Stage IV

  • Any T Any N M1
    •  Carcinoma in situ or tumor of any size with or without direct extension to chest wall or skin; with or without regional LN metastasis; with distant organ metastasis

Classification

Low Risk

  • Negative LN plus all of the following:
    • ≥35 years of age
    • Pathological tumor size (pT) of ≤2 cm
    • Absence of HER2/neu gene overexpression and amplification
    • No extensive peritumoral vascular invasion
    • Expression of ER and/or PR
    • Histologic and/or nuclear grade 1

Intermediate Risk

  • Negative LN plus at least 1 of the following:
    • <35 years of age
    • pT >2 cm
    • Histologic and/or nuclear grade 2-3
    • Extensive peritumoral vascular invasion
    • Absence of ER and PR expression
    • Presence of HER2/neu gene overexpression or amplification
    • Positive LN (1-3 nodes) and HER2 negative

High Risk

  • Positive LN (1-3 nodes) and HERs overexpression, or
  • Positive LN (≥4 nodes)
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