Armando Hasudungan
Biology and Medicine videos

Breast Cancer

“A 35 Year old women presents with a 1cm hard lump in the upper quadrant of her right breast. She first noticed this when she was in the shower three months ago. She is worried that the lump might be malignant”

Overview of Breast Cancer

Summary

Overview

Overview Breast cancer is the most common cancer in women worldwide. It accounts for about 25% of all female malignancies, with a higher proportion in developed country. Despite the increasing incidence of breast cancer, death rates are falling owing to earlier diagnosis, better surgical and radiotherapy techniques, and improved systemic therapies.

  • Lifetime risk for women 9%
  • Commonest in Western Europe
  • Least common in Japan and Africa
Definition
Mastalgia: Breast pain
Gynaecomastia: Enlarged breast tissue in male
Galactorrhea: Discharge of milk from the breast tissue. In Postnatal women is normal, but otherwise galactorrhoea can be caused by pituitary adenoma

Breast Anatomy and Physiology

The breast is a subcutaneous structure composed of 15 to 20 lobes of mammary gland tissue and fat and typically extends into the axilla as the axillary tail. The ligaments of Cooper (fibrous septa running from the subcutaneous tissue to the fascia of the chest wall) separates the breast lobules. The nipple is surrounded by the pigmented areola. Each lobule drains by its lactiferous duct on to the nipple.

Boundaries and Borders

  • The female breast lies over the 2nd – 6th rib
  • Two-thirds of it rests on pectoralis major
  • One-third of it lies on the serratus anterior
  • The lower medial edge of the breast overlaps the upper part of the rectus sheath

Blood supply

  • Internal thoracic artery → Internal mammary artery
  • Subclavian artery → Axillary artery → Lateral thoracic artery → Lateral mammary artery
  • Subclavian artery → Axillary artery → Lateral thoracic artery → Acromiothoracic artery
  • Intercostal arteries → lateral perforating branches

Lymphatic drainage

  • Majority of lymph drained from the breast (75%) → axillary lymph nodes
  • Medial quadrants of the breast → parasternal lymph nodes along the internal thoracic vessels
  • Inferior quadrants (some lymph) → inferior phrenic nodes

Physiology – normal breast changes in women

  • Puberty – ↑Oestrogen → promotes the development of the mammary ducts and fatty tissue in breast.
  • Menstrual cycle – Second half of menstrual cycle (after ovulation). ↑Oestrogen and ↑Progesterone → tender and swollen.
  • Pregnancy – ↑Oestrogen and ↑Progesterone (placental oestrogen and progesterone) + ↑Prolactin → preparation for milk production
    • Women taking HRT get breast tenderness
  • Postnatal – ↓Oestrogen and ↓Progesterone and ↑Prolactin → Stimulate the alveoli and milk production
    • Suckling on breast by baby stimulates oxytocin release which stimulates myoepitheliual cell of the breast to contract ejecting milk to baby’s mouth.
  • Menopause – ↓Oestrogen → breast become softer, homogenous and atrophy.

Risk Factors

Risk Factors
Gender (99% female)
Age
Personal history
Family history
High breast density
Nulliparity, First pregnancy >30yo
Menarche <12yo, Menopause >55yo
Not breastfeeding long-term
Radiation exposure
Use of Hormone Replacement Therapy or oral contraceptives
Genetics (BRCA1 and BRCA2 gene mutation)
Alcohol use, obesity, sedentary lifestyle

Signs and Symptoms

General presentation

  • Breast lump (usually painless)
  • Screen-detected
  • Bone pain
  • Anaemia
Remember nipple discharge is the commonest symptom of cancer after ‘lump’. Beware of neoplasia if discharge is blood-stained, persistent, and from a single duct
Malignancy Triad: Sudden weight loss (anorexia), fever and night sweats

Examination

Breast lump

  • Hard and gritty
  • Immobile (within breast tissue), tethered (attached to surrounding breast tissue) or fixed (attached to chest wall)
  • Ill defined – irregular boarders

Skin changes

  • Dimpling or puckering
  • Peau d’orange – lymphoedema of skin
  • Inflammation
  • Late presentation: ulcerating or fungating

Nipple changes

  • Destroyed
  • Inverted
  • Deviated
  • Associated with bloody discharge
Bowen’s disease is a common superficial cancer of the skin. It appears most commonly as a slow-growing, persistent red scaly patch on areas of skin exposed to the sun.

Differential Diagnosis

Breast lump

Differential Diagnosis of Breast Lump

More info on Breast Lumps

Investigations

General

  • Ultrasound – to differentiate between cystic and solid
  • MRI
  • Mammography
  • Genetic screening
  • Needle aspiration and cytology – For impalpable lesions, stereotactic techniques can be used to localise the lesion for needle aspiration.
  • Wide bore core needle biopsy – provides a sample of tissue for histological rather than cytological examination
Remember Mammographic abnormalities that warrant further investigation include:

  • Radiological masses undetected on clinical examination
  • Microcalcifications
  • Stellate densities
  • Architectural distortion
  • Change from a previous mammogram.

Diagnosis – Triple assessment

  1. Clinical Examination
  2. Imaging (mammogram, ultrasound, MRI)
  3. Pathology – fine needle aspiration/biopsy
Think The predictive value for benign disease when all three components of the triple assessment are benign is 99%

tripleass


Staging – TNM classification

Remember Diagnosis of breast cancer is based upon multidisciplinary team work using triple assessment of clinical examination, imaging (mammography and ultrasound), and needle biopsy

Pathology

Most carcinomas originate as in situ carcinoma before becoming invasive

  • Ductal adenocarcinoma in situ -> Invasive Ductal Adenocarcinoma (80%)
  • Lobular adenocarcinoma in situ -> Invasive Lobular Adenocarcinoma (20%)
  • Other Invasive breast tumours:
    • Paget’s Disease
    • Tubular Adenocarcinoma
    • Medullary Adenocarcinoma
    • Inflammatory
    • Sarcoma (rare)
    • Lymphoma (rare)

Classifcation

Carcinoma in situ Carcinoma in situ (CIS) refers to the period during which normal epithelial cells undergo apparent malignant transformation but do not invade through the basement membrane. There are two forms:

  • Lobular Carcinoma in Situ
  • Ductal Carcinoma in Situ Classification (more common)
    • Comedo
    • Non-comedo
      • Cribriform
      • Micropapillary
      • Papillary
      • Solid
      • Clinging
WHO histological classification of Breast Cancer
Epithelial tumours

  • Invasive Ductal carcinoma (most common)
  • Lobular carcinoma
  • Invasive Tubular carcinoma
  • Medullary carcinoma
  • Colloid carcinoma
  • Papillary carcinoma
Myoepithelial lesions (includes myoepitheliosis, adenomyoepithelioma, and malignant myoepithelioma)
Mesenchymal tumours (includes haemangiopericytoma, angiosarcoma, and leiomyosarcoma)
Fibroepithelial tumours (includes fibroadenoma, phyllodes tumour, and low-grade periductal stromal sarcoma)
Tumours of the nipple (includes Paget’s disease of the nipple)
Malignant lymphoma (includes diffuse large B-cell lymphoma, Burkitt’s lymphoma, and follicular lymphoma)
Metastatic tumours
Tumours of the male breast (includes invasive and in situ carcinoma)

Pathophysiology

Pathophysiology

Pathophysiology of ductal cell carcinoma and progression to metastasis

Management

Medical Treatment

  • Endocrine (aim to reduce estrogen levels) – Tamoxifen, aromatase inhibitors, GnRH analogues
  • Chemotherapy
  • Radiotherapy – Is indicated following breast conservation surgery, and reduced the risk of local recurrence.
Pharmacology Aromatase antagonist inhibit the enzyme aromatase which normally converts testosterone to oestrogen. The majority of breast cancer is oestrogen receptor positive, meaning they grow in response to oestrogen, by inhibiting this cancer stops growing. Side effects (menopause): such as hot flashes, night sweats, and vaginal dryness, low libido. Serious side effect: osteoporosis (caution to use in frail women)
Pharmacology Tamoxifen is a nonsteroidal agent that binds to estrogen receptors (ER), inducing a conformational change in the receptor → blocking the effects of oestrogen on the cell. Side effects (menopause): hot flashes, vaginal dryness, low libido, mood swings, and nausea.

Surgical Treatment (usually in conjunction with chemotherapy +/- radiation)

  • Partial Masectomy
    • Wide local excision
  • Total Mastectomy
    • Simple
    • Skin sparing
    • Radical
  • Surgical excision of lymph node
  • Sentinel Lymph node biopsy – results in fewer arm complications compared with axillary lymph node dissection in the treatment of breast cancer
Think If lymph node involvement is demonstrated following axillary lymph node sampling or sentinel node biopsy, axillary radiotherapy is given to help control axillary nodal metastasis, or an axillary clearance is performed. However, if an axillary clearance is performed as the primary intervention, radiotherapy for positive nodes is unnecessary‐all the diseased nodes have been removed. In addition, after clearance, radiotherapy is associated with a high incidence of lymphoedema of the arm because of the combined surgical and X‐ray damage to lymphatics.
Side note Breast-conserving surgery should be followed by radiation therapy in women with early-stage invasive or locally advanced breast cancer.
Side note Preoperative chemotherapy for locally advanced breast cancer increases the success of breast-conserving surgery

Complications and Prognosis

Medication Complication

  • Tamoxifen induced endometrial cancer
  • Tamoxifen related DVT
  • Tamoxifen related PE
  • Aromatase induced osteopenia/osteoporosis
  • Menopausal symptoms

Radiotherapy Complication

  • Redness and soreness of the field of radiation
  • Lymphoedema after treatment of the axilla
  • Breast‐feeding from the affected breast is unlikely
  • Cardiac damage following left breast irradiation
  • Brachial plexus palsy
  • Osteitis of the ribs
  • Shoulder stiffness
  • Pulmonary fibrosis

Chemotherapy Complication

  • Nausea/vomiting
  • Neutropenia/neutropenic fever
  • Leukaemia
  • Ovarian failure

Surgery Complication

  • Lymphedema
  • Breast haematoma
  • Wound infection
  • Seroma of the skin flap
  • Pscyhological effects on body image

Prognosis

PROGNOSITC FACTORS (other than TNM)
Biological factors Favourable Unfavourable
Histological type Tubular, colloid, papillary Scrirrhous
Grade Low High
Necrosis Absent Present
Lymphocytic infiltration Present Absent
Oestrogen status Positive Negative
Reactive lymph nodes Present Absent
Proliferative rate Low S phase Aneuploid
Chromosomal defects Deletion/alteration 1, 3, 6, 7, 9. Shortening of allele on chromosome 11
Proto-oncogenes c‐erbB/c‐H‐ras
Growth Factors (GF) Epidermal GF, Transforming GF, Platelet‐derived GF, Fibroblast GF, Insulin‐like GF

Prevention

The early detection methods are:

  • Breast awareness – awareness by a woman of the normal look and feel of her breasts
  • Clinical breast examination – physical examination of an asymptomatic woman’s breasts by a medical or allied health professional
  • Screening mammography – use of mammography in asymptomatic women to detect breast cancer at an early stage (BreastScreen Australia is the national mammographic screening program).

It is recommended that women aged 50–69 years attend the BreastScreen Australia Program every 2 years for screening mammograms.

Remember Mammograms are performed earlier for women with family history of breast cancer
Side note <40yo screening is not recommended. However breast awareness is recommended for all ages.

References

Best Practice