Breast cancer, papilloma, pagets disease of the nipple Flashcards
What is the background for breast cancer?
● Breast cancer is the commonest cancer in the UK (15% of new cancer cases annually).
● There are approximately 56,000 new cases of breast cancer every year.
What are the pre-invasive types of
breast cancer?
- Ductal carcinoma in situ (DCIS).
● Neoplastic proliferation of epithelial cells - confined to duct without
invasion through basement membrane.
● Precursor to invasive breast cancer.
● Comedo and non-comedo subtypes. - Lobular carcinoma in situ (LCIS).
● Neoplastic proliferation of epithelial cells, confined to TDLU.
What are the invasive (penetration through basement membrane) types of breast cancer?
- Invasive ductal carcinoma (commonest - 75%).
● Neoplastic proliferation of epithelial cells that invades through the ductal
basement membrane. - Invasive lobular carcinoma
- Medullary carcinoma
● More prevalent in the younger population.
● Higher grade than IDC. - Many others - including mucinous, tubular, papillary, inflammatory etc.
What is the Nottingham criteria which we use to grade how bad a breast cancer is?
What is it scored on?
○ Gland formation
○ Nuclear atypia / pleomorphism
○ Mitosis counts (indicates rate of cellular reproduction)
● A higher grade carcinoma is one that is markedly different from normal breast tissue
and is considered poorly differentiated.
What is the aetiology and pathophysiology of breast cancer?
● Complex series of genetic mutations and deranged cellular signalling leads to generation
of malignant cells.
● Breast cancer can be linked to inherited genetic mutations such as BRCA1.
What is the 5 step process for malignant cells to metastasise?
- Invasion through basement membrane
- Intravasation (entry into circulation)
- Circulation
- Extravasation
- Colonisation
What are the commonest sites of breast cancer metastasis?
bones, liver, lungs and brain.
What are the RFs for breast cancer?
- Increasing age
- Female sex (100:1 F:M incidence)
- Family history
- Inherited genetic mutations e.g. BRCA1
- Endogenous oestrogen exposure:
a. Early menarche
b. Nulliparity / absence of breastfeeding
c. Late menopause - Exogenous oestrogen and progestin exposure:
a. Systemic hormonal HRT
b. Systemic hormonal contraception
Female (99% of breast cancers)
Increased oestrogen exposure (earlier onset of periods and later menopause)
More dense breast tissue (more glandular tissue)
Obesity
Smoking
Family history (first-degree relatives)
What are the signs and symptoms of breast cancer?
● Symptoms include: breast lump
● Signs include: nipple discharge, nipple retraction, skin changes e.g. peau d’orange,
axillary lymphadenopathy.
What are the metastatic features of breast cancer?
weight loss, bony pain, shortness of breath.
What are the different types of staging we use for breast cancer?
● TNM staging (tumour, node, metastasis) - see Cancer Research UK for full details.
● Alternative staging:
○ Stage 1A: <2cm, isolated to breast
○ Stage 1B: <2cm, minor axillary LN spread
○ Stage 2A: <2cm, spread to 1-3 ipsilateral LNs.
○ Stage 2B: 2 - 5cm, minor axillary nodal spread or 2 - 5cm with 1-3 ipsilateral
nodes or >5cm, no nodal spread
○ Stage 3A: 4-9 ipsilateral nodes or >5cm with 1-3 ipsilateral nodes
○ Stage 3B: spread to skin / chest wall
○ Stage 3C: >10 axillary nodes or supraclavicular spread or parasternal + axillary
spread
○ Stage 4: distant metastatic spread to organs.
What is the screening programme for breast cancer?
● NHS screening programme: 3-yearly mammogram for women aged 50-71.
What is the 2 week wait criteria for breast cancer?
○ Unexplained breast lump in a woman aged >30.
○ Unexplained axillary lump in a woman aged >30.
○ Unilateral nipple changes in a woman aged >50.
○ Skin changes suggestive of breast cancer, any age.
What is first line for breast cancer investigations for breast cancer?
breast imaging
○ >30 or highly suspicious for cancer: mammogram
○ <30: breast ultrasound
○ Plus: ultrasound of the axilla +/- needle biopsy
What is second line investigations for breast cancer?
biopsy
○ Fine needle aspiration and cytology
○ Plus: oestrogen / progesterone receptor testing, HER2 receptor testing.
If the patient has symptoms/ signs suggestive of metastasis what should we do?
○ CT scan (CT thorax-abdomen-pelvis, CT head).
What are the features of a mammogram?
● Pre-invasive: unifocal / widespread microcalcifications
● Invasive carcinoma:
1. Irregular spiculated mass
2. Clustered microcalcifications
3. Linear branching calcifications.
What is first line management for breast cancer?
● Dependent on histology, staging, receptor positivity, physiological reserve; but broadly:
● First Line: surgery
○ Tumour excision or mastectomy +/- breast reconstruction
○ Plus sentinel lymph node biopsy (no evidence of nodal spread) or axillary node
clearance.
● Plus: radiotherapy
○ Whole breast / partial-breast
○ If tumour is invasive (i.e. not DCIS, LCIS), systemic third line therapy is indicated:
What is adjuvant therapy for breast cancer?
systemic therapy (guided by the PREDICT tool)
○ Oestrogen-receptor positive:
■ Pre-menopausal / male - tamoxifen (anti-oestrogen)
■ Post-menopausal - anastrozole / letrozole (aromatase inhibitor, prevents
peripheral oestrogen synthesis).
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■ Note - tamoxifen therapy can be continued long-term (5 years) before
switching to an aromatase inhibitor.
○ HER2 (human epidermal growth factor receptor 2) positive:
■ Trastuzumab (Herceptin)
○ Chemotherapy:
■ Including a taxane and an anthracycline
■ E.g. ACT: doxorubicin, cyclophosphamide and paclitaxel
What is systemic therapy for breast cancer
systemic therapies can be neoadjuvant i.e. used to reduce tumour size before
attempting surgery.
What is Paget’s disease of the nipple/ breast
Rare cutaneous breast cancer manifestation
What does pagets disease of the bone cause?
Eczema like skin changes in nipple, areola
What is the pathogenesis for Paget’s?
- Epidermotropic theory: underlying mammary carcinoma present > malignant cells migrate through ductal system > nipple epidermis
- In situ transformation theory: nipple keratinocyte transformation > malignant cells
What are the S + S of pagets?
- Unilateral
- Nipple + adjacent areolar skin
- scaly
- itching
- burning
- erythematous
- Bloody nipple discharge
- nipple inversion
- pain
- palpable masses - worst prognosis
What investigations are done for paget’s?
Mammogram- identify assosciated mass, microcalcifications, tissue distortion
US guided mass core bopsy, histopathological analysis
Nipple scrape cytology/full-thickness wedge/ punch biopsy
Malignant, intraepithelial adenocarcinoma cells (paget cells) present
What is the treatment for Paget’s?
Mastectomy, breast-conserving surgery
Whole breast radiotherapy
What is an intraductal papilloma?
warty lesion that grows within one of the ducts in the breast. It is the result of the proliferation of epithelial cells
What is the typical presentation of an intraductal papilloma?
The typical presentation is with clear or blood-stained nipple discharge.
What type of tumours are intraductal papilloma’s?
Intraductal papillomas are benign tumours; however, they can be associated with atypical hyperplasia or breast cancer.
What are the S + S of intraductal papilloma?
Intraductal papillomas can occur at any age, but most often occur between 35-55 years.
Intraductal papillomas are often asymptomatic. They may be picked up incidentally on mammograms or ultrasound.
They may present with:
Nipple discharge (clear or blood-stained)
Tenderness or pain
A palpable lump
How is one diagnosed with papilloma?
