CSIM 1.7 Breast Cancer Case 39 Continued Flashcards
Until what age is breast development similar in both sexes?
Puberty
What do female breasts develop in response to at puberty?
Pituitary and ovarian hormones
What happens to the breast after menopause?
Atrophy and involution
What does glandular tissue of the breast develop from?
Modified apocrine sweat glands along ‘milk lines’
How many glandular breast lobes are in each breast? What connects to these?
15-20
Terminal duct (–> lactiferous duct)
What lies between breast lobules?
Interlobular adipose connective tissue
Describe the histology of a normal breast lobule
One single cell layer of secretory epithelium
Describe the histology of a normal terminal duct
Two layers of cells:
• Inner cell layer
• Basal cell layer
What are the different types of breast disease?
- Benign breast disease
- Pre-malignant atypical ductal hyperplasia
MALIGNANT:
• Non-invasive carcinomas:
- Ductal carcinoma in situ
- Lobular carcinoma in situ
• Invasive carcinomas
What are the forms of benign breast disease?
- Solitary cyst
- Fibrocystic disease
- Papilloma
- Sclerosing lesions
- Radial scars
In what proportion of women is benign breast disease seen in?
80%
What is the significance of benign breast disease?
- Can be associated with pain
* Associated with an increased risk of getting cancer
How are localisation excision biopsies guided?
With a guidewire & CT imaging
What are the types of biopsy used for retrieval of breast tissue?
- Mammotome - Vacuum assisted biopsy
- Core biopsy
- Localisation excision biopsy
What is atypical ductal hyperplasia?
What does this often cause?
Pre-malignant: somewhere between benign and non-invasive malignant
Neoplastic proliferation of the ductal epithelial cells, so that some of the cells cross the lumen and divide it into 2 spaces - does not fulfil the criteria of a non-invasive cancer
Complex sclerosing lesions
What is the recommendation after identification and why?
A wider excision, because this tissue is associated with a moderate risk of developing (generalised bilateral risk) breast cancer
What is the commonest cause of death in women aged 35-55?
Breast cancer
What proportion of women will develop breast cancer?
1 in 9
What proportion of all cancers in women are made up of breast cancer cases?
30%
What are the risk factors for breast cancer?
- Female
- Age
- Long time between menarche and menopause
- Obesity
- Atypical ductal hyperplasia
- Family history
Outline the multistep process/progression leading to carcinoma in breast tissue
1) Normal cells
2) Proliferative cells
3) Atypical hyperplasia
4) Carcinoma in situ
5) Invasive carcinoma
1 & 2 = Benign
3 = Pre-malignant
4 & 5 = Malignant
Describe how non-invasive carcinomas spread within their compartment
Spreads within the lobule and ductile system, underneath the basement membrane.
What happens if you do not treat a non-invasive carcinoma?
It may rupture the basement membrane and become invasive
Why is there an increased risk of malignancy when atypical hyperplasia is present?
Each step in the multistep process requires random/chance genetic changes. There are fewer steps remaining to reach a malignancy once the atypical hyperplasia is reached.
Which genes are associated with breast cancer when certain alleles are present or when damaged?
- BRCA 1
- BRCA 2
- p53
Which cancer genetic predisposition is associated with the p53 gene?
Li-Fraumeni syndrome
What age range of women are invited to the NHS breast screening programme?
50-70
What does the NHS breast screening programme involve?
Mammogram every 3 years
What is searched for in mammograms?
- Densities
* Calcifications
If there is an anomaly, where is the woman sent?
One stop clinic
What is performed at a one stop clinic?
A triple assessment of:
• Clinical examination
• Radiology (mammography, US, MRI)
• Pathology (the three biopsies)
This information is used to form a diagnosis
What are the clinical features of breast cancer?
- Pain
- Palpable mass
- Nipple discharge
- Nipple retraction
- Peau d’orange & erythema
- Axillary lymphadenopathy
What are the two types of non-invasive carcinoma?
- Ductal carcinoma in situ
* Lobular carcinoma in situ
What does ductal carcinoma in situ look like?
Massively proliferated cells so that the lumen(s) are minimal. These are classed based on their diameter (e.g. 15mm)
Nuclear neomorphism is present
What proportion of INVASIVE carcinomas are made up of infiltrating ductal and infiltrating lobular carcinomas?
• 75% infiltrating ductal
• 10% infiltrating lobular
( • 15% other)
How are tumours graded?
Grades 1-3 which grade the amount the tumour cell has differentiated, depending on:
- Tubule formation:
- Nuclear pleomorphism
- Mitoses
1 = most similar to normal cells, best prognosis
3 = more aggressive, poor prognosis
How is cancer staging deduced?
The extent of cancer spread based on TNM (tumour, nodes, metastasis):
Primary tumour extent:
• T1 = 100mm
Presence and extent of lymph node metastasis:
• N0 = Nodes negative
• N1 = Axillary nodes mobile metastases
• N2 = Axillary nodes fixed metastases
• N3 = Supraclavicular nodes or oedema
Presence of distant metastasis
• M0 = Not present
• M1 = Present
What local areas can breast metastases spread?
Skin & muscle
What distant areas can breast metastases spread to?
- Lymph nodes
- Lungs
- Liver
- Bone
- Brain
- Adrenal glands
Which lymph nodes can breast metastases spread to?
- Axillary
- Supraclavicular
- Internal mammary
What are the treatment options for breast malignancy?
- Surgery
- Radiotherapy
- Chemotherapy
- Hormone therapy
- Herceptin
What oncogenes does the treatment received by a patient depend on?
Presence of:
• ERBB2 / HER-2
• Oestrogen receptors
• Progesterone receptors
How does ERBB2/HER-2 alteration lead to carcinogenesis?
Gene is over-amplifies and the membrane-related protein is overexpressed
What is the impact of ERBB2/HER-2 on prognosis?
Poorer prognosis
What is trastuzumab the trade name for and what does this treat?
What is this used in conjunction with as a standard treatment?
Herceptin - an antibody used to treat women whose cancers have HER-2 molecular alteration present
Chemotherapy used with it.
What is cancer called if it has none of the three oncogene alterations? What is the typical characteristic of this?
Triple-negative breast cancer
Associated with BRCA1 and is more aggressive and resistant to treatment due to lack of a target for therapies
Which type of malignancies most commonly are caused by BRCA2-associated breast cancers?
Predominantly high-grade invasive carcinomas
What is the overall
risk for male breast carcinoma?
0.11%
gynecomastia is not a risk factor
Why do men present at later stages than women?
There is no breast cancer screening programme for males
How is male breast cancer treated?
- Mastectomy
* Axillary node dissection
