Breast Cancer Overview and Risk Factors

Breast Cancer Overview

• Breast cancer is the most common non-skin cancer in women
• Lifetime risk is 1 in 8
• Incidence is increasing
• Treatments have significantly evolved

Learning Objectives

• Recognize epidemiology and risk factors of breast cancer
• Understand the pathological classification of breast cancer
• Identify and interpret clinical presentations of breast cancer
• Describe treatment options for breast cancer
• Discuss the principles of breast cancer screening

Risk Factors - Age

• Risk increases with age, with 70% of cases occurring in women over 50
• Rare before the age of 25

Risk Factors - Family History

• Approximately 10% of cases are due to genetic predisposition
• BRCA1 gene mutations occur on chromosome 17
• BRCA2 gene mutations occur on chromosome 13
• Risk increases twofold with affected first-degree relatives under 50

Risk Factors - Hormonal

• Age at menarche and menopause
• Age at first pregnancy
• Exogenous oestrogens (e.g., hormone replacement therapy)
  • Relative risk increases by 1.02 per year of therapy
  • Increased incidence observed, but less evidence of increased mortality
• Risk persists for 5 years after cessation of hormone treatment
• Type of preparation (presence/type of progestogen) is important
• Oral contraceptive pills

Risk Factors - Lifestyle

• Radiation exposure increases risk
• Alcohol consumption is a risk factor
• Smoking is a risk factor
• Obesity (particularly post-menopausal) is a risk factor

Summary of Risk Factors

• Age
• Family history
• Early menarche
• Nulliparity/older age at first child
• Late menopause
• Oral contraceptive pill (OCP)
• Hormone replacement therapy (HRT)
• Obesity
• Smoking
• Alcohol
• Radiation exposure

Pathology of Breast Cancer

• Anatomical location (ductal/lobular)
• Pathological characteristics (invasive/non-invasive)

Pathology - Carcinoma in Situ

• Ductal carcinoma in situ (DCIS) has the potential to become invasive
• Different grades exist (low, intermediate, high)
  • High-grade DCIS has a greater risk of progression
• Numerous subtypes including comedo, solid, cribriform, papillary, and micropapillary
• Comedo necrosis carries a poor prognosis
• Lobular carcinoma in situ involves abnormal cells filling lobules

Pathology - Invasive Cancer

• Ductal carcinoma accounts for 80% of invasive cancers
• Lobular carcinoma accounts for 10% of invasive cancers
• Other, less frequent, invasive types include mucinous, medullary, tubular, and papillary carcinomas
• Relatively better prognosis is associated with invasive cancers displaying a tubular pattern or mucin-producing tumors.

Pathology - Paget's Disease of the Nipple

• A form of ductal carcinoma originating in excretory ducts
• Often associated with underlying DCIS or (less commonly) invasive cancer
• Characterized by nipple ulceration, surrounding hyperaemia, and an underlying lump in 50% of cases

Clinical Presentation

• Most frequently with a palpable lump
• Other symptoms include:
  • Breast size/shape changes
  • Skin dimpling
  • Recent nipple inversion/skin changes
  • Nipple discharge (often bloody)
  • Skin ulceration (in advanced cases)
  • Arm swelling
• Pain is not usually a symptom

Metastatic Symptoms

• Less common presentation, featuring symptoms of distant spread
• Examples include breathing difficulties, bone pain/fractures, hypercalcemia symptoms, abdominal distension, jaundice, neurological signs, and cognitive impairment

Signs of Breast Cancer

• Skin dimpling
• Visible mass
• Mass in right breast with nipple asymmetry
• Inflammatory tumor in left breast
• Peau d'orange
• Nipple retraction

Clinical Symptoms Checklist

• Breast lump
• Skin dimpling
• Nipple discharge
• Inverted nipple
• Axillary lump
• Skin changes

Triple Assessment

• Aim: Establish a firm breast cancer diagnosis prior to definitive treatment
• 1. History and physical exam:
• Essential for diagnosis
• Collect accurate symptom history
• Assess risk factors
• Examine tumor characteristics and spread (axillary nodes, distant metastases)

Triple Assessment - Radiological

• Mammogram: Detects 80-90% of cancers; typically offered to women >35; useful for tumors not clinically palpable
• Ultrasound: Useful in younger patients, provides additional info; often performed first for women under 35

Triple Assessment - Cytology/Pathology

• Fine-needle aspiration cytology (FNAC): Performed in outpatient setting; assesses aspirate for malignant cells; does not distinguish invasive/non-invasive
• Core biopsy: Performed under local anesthetic; provides tissue sample; can distinguish invasive/non-invasive; preferred over FNAC
• Results are categorized as:
  • C1 or B1: No diagnosis possible
  • C2 or B2: Benign
  • C3 or B3: Atypical, probably benign
  • C4 or B4: Suspicious for malignancy
  • C5 or B5: Malignant

Triple Assessment - Wire Guided Biopsy

• Occasionally required to sample impalpable abnormalities for diagnostic tissue
• Wire is placed under radiologic guidance to the area of abnormality
• Acts as a guide for surgeon
• Performed under general anesthetic

Staging of Breast Cancer

• Based on:
• Clinical findings
• Pathological analysis
• Imaging studies for metastatic disease (e.g., chest X-rays, liver ultrasounds, bone scans)
• TNM staging classification (includes tumor size, lymph node involvement, and distant metastasis)

Treatment - Invasive Cancer

• Surgery: The primary treatment for invasive breast cancer; includes surgery to the breast and the axilla
• Adjuvant therapies
• Hormonal therapy: Used for estrogen receptor positive tumours; Tamoxifen reduces relapse; Aromatase inhibitors are more effective in post-menopausal patients
• Radiotherapy: Routinely after breast-conserving surgery; also used in selected cases of mastectomies
• Chemotherapy: Decision made by a multidisciplinary setting; commonly considered for node-positive tumors, or for high-risk node-negative patients, in combination with other therapies
• Breast-conserving surgery versus mastectomy: Decision depends on patient preference, tumor size, location, multifocality, and prior breast cancer history
• Reconstruction options: Implant reconstruction, autologous reconstruction, pedicled flaps, free flaps (e.g., DIEP flap)

Treatment - Axilla

• Staging the axilla (removes axillary nodes) reduces risk of axillary recurrence
• Axillary clearance vs. sentinel node biopsy
• Axillary clearance removes all axillary lymph nodes; side effects can include lymphoedema (20-40%) and arm/axillary numbness (80%)
• Sentinel node biopsy identifies and removes the first lymph node draining from the breast cancer. Examined for cancer cells; if negative, no further surgical intervention; if positive, patient has axillary clearance

Treatment - Adjuvant Therapies (Further Options)

• Radiotherapy: After breast-conserving surgeries or as indicated.
• Chemotherapy: In selected high-risk individuals or combination with certain therapies.
• Hormonal therapies (e.g. Tamoxifen, Aromatase inhibitors): If receptor positive, to prevent recurrence.
• Herceptin: Antibody therapy targeted at Her2neu in a portion of breast cancers (20%).

Breast Cancer Screening

• The application of a test to detect cancer in the absence of symptoms
• Aims to detect cancers early, altering disease progression and lifespan
• The screened population exhibits reduced mortality compared to unscreened groups.

Screening - Principles of Detection

• High morbidity, mortality costs
• High incidence and prevalence
• Known natural history and biology
• Pre-clinical phase often presents at high levels
• Effective treatment for early disease.
• Able to detect disease before clinical symptoms become apparent.
• Safe, effective, inexpensive, and acceptable methods are required

Screening - Biases

• Lead time bias: Survival time appears longer, but mortality rates are not immediately reduced
• Length bias: Detection preferentially skews towards slow-growing cancers
• Important to conduct rigorous studies to account for these biases

Screening - Mammography

• Screening is recommended for women over 50; it reduces mortality approximately 30%
• Screening interval is typically every two years between 50 and 69.