Women’s Health - Breast Medicine Flashcards
(35 cards)
How common is breast cancer
Breast cancer is the most common form of cancer in the UK. It mostly affects women and is rare in men (about 1% of UK cases). Around 1 in 8 women will develop breast cancer in their lifetime.
56,000 new cases annually
Risk factors for breast cancer
Age- second biggest risk factor (time to aquire mutations)
Female - (99% of breast cancers) biggest risk factor
Increased oestrogen exposure (earlier onset of periods and later menopause)
More dense breast tissue (more glandular tissue)
Obesity (in post-menoupausal)
Exercise
Smoking
Alcohol
Family history (first-degree relatives) - only 5-10%
COCP - oestrogen again.
HRT - oestrogen stimualtes proliferation of the breast epithelium. Women should be on the lowest dose of HRT for the shortest period of time to get them over the worst symptoms of menopause
What is ductal carcinoma in situ and how does it differ from invasive carcinoma histologically and behavoirally?
Rx?
DCIS is pre-invasive disease and a pre-cursor to invasive breast cancer. It involves neoplastic proliferation of epithelial cells - confined to duct without invasion through the basement membrane - therefore cannot metastasise anywhere else
Most DCIS cases are completely asymptomatic and are detected by breast screening - microcalcifications on mammography, but occasionally it can present as a lump. The lining epithelium of the breast ducts becomes thickened as the cells proliferate and eventually appear full of cells, often with central necrosis. Cytologically the cells appear malignant but they have not yet acquired the ability to invade the basement membrane and therefore cannot metastasise.
Treatment primarily involves wide excision or rarely mastectomy if the disease is more extensive. LECTURE- WE JUST TREAT IT THE SAME AS BREAST CANCER ATM.
LCIS - The other type of pre-invasive breast cancer is lobular carcinoma in situ. This is where there is neoplastic ploriferation of epithelial cells that is confined to the terminal ductal lobular units.
Basic breast anatomy
The breast is made up of the following main components:
Most of the breast is adipose (fatty) tissue.
Lobules are part of the glandular system; they are glands that produce breast milk. Lobules are found in groups which together form a lobe.
Ducts are small tubes that carry breast milk from the lobules to the nipple.
Breast cancers most commonly arise in the ducts that transport milk from the lobules to the nipple. These are known as ductal cancers. Some breast cancers can develop in the lobules, which are known as lobular cancers.
What is invasive breast cancer and what are the 2 different histological types
Invasive carcinoma means that the cells have penetration through basement membrane. There are two common histological types of invasive breast cancer; ductal (70%) and lobular (10%).
- Invasive ductal carcinoma (commonest - 75%). Neoplastic proliferation of epithelial cells that invades through the ductal basement membrane.
- Invasive lobular carcinoma - harder to feel, less likely to be visible on mammography, more diffuse and therefore more difficult to excise and more prone to be bilateral or multi-focal.
Rarer subtypes include tubular, mucinous and medullary but the treatment is largely the same regardless. Tubular and mucinous tumours tend to be grade 1 (better differentiated) and therefore have a better prognosis than the more usual types. Medullary may be of high grade. Other rare subtypes include phyllodes tumour, spindle cell tumours, primary breast sarcomas and lymphomas of the breast.
INVASIVE/MALIGNANT BREAST CANCER (80%) IS DIFFERENT FROM METASTATIC BREAST CANCER (25% of cases - spread to other organs)
What is padget’s disease of the nipple
- This is an eczematous change of the nipple (Erythematous, scaly rash) due to an underlying malignancy (invasive or in-situ).
- should be suspected in apparent nipple eczema that does not resolve with two weeks of steroid/anti fungal cream.
- Indicates breast cancer involving the nipple, may represent DCIS or invasive breast cancer
- Requires biopsy, staging and treatment, as with any other invasive breast cancer
What are the BRCA genes and on what chromosomes are they found.
BRCA refers to the BReast CAncer gene. The BRCA genes are tumour suppressor genes. Mutations in these genes lead to an increased risk of breast cancer (as well as ovarian and other cancers).
mnemonic - 1+2 = 3, 17+13 = 30
The BRCA1 gene is on chromosome 17. In patients with a faulty gene:
Around 70% will develop breast cancer by aged 80
Around 50% will develop ovarian cancer
Also increased risk of bowel and prostate cancer
The BRCA2 gene is on chromosome 13. In patients with a faulty gene:
Around 60% will develop breast cancer by aged 80
Around 20% will develop ovarian cancer
There are other rarer genetic abnormalities associated with breast cancer (e.g., TP53 and PTEN genes).
KEY
What is the UK breast cancer screening programme? - 3 things to know
Aim of the screening programme?
Minor point but some key downsides to screening
The NHS breast cancer screening program offers 2 mammogram every 3 years to women aged 50 – 70 years.
3 things you need to know:
- every 3 years
- 50-71
- 2 mamograms (low dose X-rays)
Screening aims to detect breast cancer early, which improves outcomes. Roughly 1 in 100 women are diagnosed with breast cancer after going for a mammogram.
There are some potential downsides to screening:
Overdiagnosis - Unnecessary further tests or treatment of cancers would never caused symptoms in the womans lifetume.
Anxiety and stress
Exposure to radiation, with a very small risk of causing breast cancer
Missing cancer, leading to false reassurance
Generally, the benefits far outweigh the downsides and breast cancer screening is recommended.
Note from lecture - if screening is positive called for repeat mamorgram, US/biopsy
Who is considered high risk for developing breast cancer and what is their management ?
The following patients are considered high risk and should be referred to secondary care:
A first-degree relative with breast cancer under 40 years
A first-degree male relative with breast cancer
A first-degree relative with bilateral breast cancer, first diagnosed under 50 years
Two first-degree relatives with breast cancer
Management:
- Genetic counselling is mandatory before genetic testing to explain the risks, benefits, and implications for the patient and their family.
ME - i think genetic testing and comprehensive risk assessment is the key here. Only women at high risk following this (not just having the above risk factors) are offered management below - chemopreventual, annual screening and possible surgicval prevention.
- Enhanced screening (starting from age 30) is recommended for women at high risk, with annual mammograms and possibly MRI scans.
- Chemoprevention (tamoxifen or anastrozole) is recommended for high-risk women based on their menopausal status.
- Risk-reducing bilateral mastectomy or bilateral oophorectomy (removing the ovaries) is an option for women at high risk. This is suitable for only a small number of women and requires significant counselling and weighing up risks and benefits.
KEY - Once a patient has been referred for specialist services under a two week wait referral for suspected breast cancer usually for a breast lump. How are they assessed for breast cancer?
Two key terms - how are these results assessed
They should initially receive a triple diagnostic assessment comprising of:
Clinical assessment (history and examination)
Imaging (ultrasound or mammography)
Biopsy (fine needle aspiration or core biopsy)
Note - A biopsy is only required for any suspicious mass or lesions on imaging or clinical assessement, not for all referals
Lecture: Concordence - each is given a ranking from 1-5 (1 being normal, 2- benign (fibro-adenoma), 5- cancer)
All of these results get discussed in MDT
- if the three things dont match (no concodance) p4, tissue 2 - have to repeat the biopsy!
BOLD ARE THE EXAM QUESTION ANSWERS
Presentation of breast cancer
Clinical features that may suggest breast cancer are:
Lumps that are hard, irregular, painless or fixed in place (fixed means tethered to the skin or the chest wall)
Nipple retraction
Skin dimpling or oedema (peau d’orange - INFLAMMATORY BC- T4 - Involves the skin)
Reduced lymph drainage - poor prognosis
Lymphadenopathy, particularly in the axilla
Bloody nipple discharge
What is inflammatory breast cancer
Inflammatory breast cancer where cancerous cells block the lymph drainage resulting in an inflamed appearance of the breast. This accounts for around 1 in 10,000 cases of breast cancer.
Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer that develops rapidly and causes noticeable inflammation in the breast. Unlike most breast cancers, IBC doesn’t usually form a lump, which can make it harder to detect early.
Symptoms
- Redness or rash on the breast (often mistaken for infection)
- Swelling and warmth in the breast
- Skin that looks pitted or dimpled (like an orange peel, known as peau d’orange)
- Rapid increase in breast size
- Tenderness or pain
- Inverted nipple or changes in the nipple
- Sometimes a swollen lymph node under the arm or near the collarbone
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Treatment
Because it’s aggressive, treatment typically starts quickly and includes:
- Chemotherapy (first, to shrink the tumor)
- Followed by surgery (usually mastectomy)
- Then radiation therapy
- Targeted therapy or hormone therapy, depending on the cancer’s characteristics
What imaging can be used to investigate breast lumps. What is involved and when is each suitable - 3 types?
Ultrasound scans cannot be used as a screening tool but can be used to assess lumps in younger women (e.g., under 40 years). They are helpful in distinguishing solid lumps (e.g., fibroadenoma or cancer) from cystic (fluid-filled) lumps. Lecture - hard to survery entire breast with US, much more focussed Ix
Mammograms are used as both a screening tool and an investigation for lumps. They are generally more effective in older women - above the age of 40, but remember screening starts at 50 (or for women on HRT) the breast tissue is usually too dense to pick up any cancer and therefore they are less useful. They can pick up calcifications missed by ultrasound. Calcification - DCIS - Exam Key
The breast is compressed in 2 planes, the first is cranio-caudal (CC) with the plates horizontal. This view gives a good image of the medial part of the breast and the deeper part near the chest wall. The second view is with the breast squeezed obliquely, the medio-lateral oblique, (MLO) view. This gives a better view of the axillary tail and
lateral breast.
MRI scans may be used:
- For screening in women at higher risk of developing breast cancer (e.g., strong family history)
- To further assess the size and features of a tumour, to help with management planning
- Used for Lobular cancers - they are diffuse sheetes (E-cadherin negative)
How are breast lumps biopsied?
Core Biopsy - under local anaesthetic and ultrasound guidance, a needle mounted to a spring loaded biopsy gun removes an apple core of tissue from the lump.
Formerly fine needle aspiration cytology was used - lower sensitivity and specificity - cytology but not histology (looks at aspirated cells not sections of tissues).
Lecture - therefore Core biopsy allows you to distinguish DCIS from invase but needle aspiraiton doesn’t (both are malignant cells but can now see them in relation to teh BM)
Investigations for axillary lymph node involvement and management in breast cancer
Women diagnosed with breast cancer require an assessment to see if cancer has spread to the lymph nodes (up to 40% of women with breast cancer will have cancer in their axillary nodes at diagnosis) . All women are offered an ultrasound of the axilla (armpit) and ultrasound-guided biopsy of any abnormal nodes.
If no cancer is seen in the initial USS -> a sentinel lymph node biopsy may be used during breast cancer surgery where the initial ultrasound does not show any abnormal nodes to confirm that the nodes are clear. 25% of cases the nodes seem normal on ultrasound but cancer is detected on histology after sentinel node biopsy.
If the USS scan/SNB DOES show signs of cancer in the nodes -> full ANC is the management.
SO THE KEY BIT TO MEMORISE IS EVERYONE GETS AN USS. Positive -> ANC, negative -> SNB
The purpose of surgery to the axillary lymph nodes is twofold. It aims to remove any breast cancer deposits within the glands and so provide local disease control and also to provide valuable prognostic information which will determine whether any additional or adjuvant treatments are needed post-operatively.
Sentinel Lymph Node Biopsy:
Sentinel node biopsy is performed during breast surgery for cancer. An isotope contrast (technitium) and a blue dye are injected into the tumour area. The contrast and dye travel through the lymphatics to the first lymph node (the sentinel node). The first node in the drainage of the tumour area shows up blue and on the isotope scanner. These first nodes are removed and sent for histology to determine if the axilla is involved.
ANC:
If a women if known to have axillary invovlement from USS or from sentinal node biopsy then Axillary node clearance surgery is usually performed. Axillary clearance involves removal of all of the lymph nodes in the axilla. This has a low rate of axillary recurrence (good local control and prognostic information) but can lead to seroma, nerve damage and lymphoma.
Radiotherapy:
Some women with low risk axillary disease are offered radiotherapy to the axilla instead of surgical management.
What 3 receptors are targetted in breast cancer therapy
Breast cancer cells may have receptors that can be targeted with breast cancer treatments. These receptors are tested for on samples of the tumour and help guide treatment. There are three types of receptors:
Oestrogen receptors (ER)
Progesterone receptors (PR)
Human epidermal growth factor (HER2) - Rx with trastuzumab
Triple-negative breast cancer is where the breast cancer cells do not express any of these three receptors. This carries a worse prognosis, as it limits the treatment options for targeting the cancer.
Where does breast cancer most commonly metastasise to
25% of breast cancers are metastastic
You can remember the notable locations that breast cancer metastasis occur using 2 Ls and 2 Bs:
L – Lungs
L – Liver - bad prognosis
B – Bones
B – Brain - bad prognosis
Notably, breast cancer can metastasise to anywhere in the body, like melanoma.
How is breast cancer staged
The TNM system is used to stage breast cancer. This scores the size and spread of the tumour (T), nodes (N) and metastasis (M).
T= tumour size/diametre
N = spread to lymph nodes
M = spread to another part of the body
Staging is different to grading - Tumour grade varies from grade 1, where the cells are well differentiated with
a low mitotic rate (and look very similar to normal breast glands down the microscope) to grade 3 where the reverse is true, and the cells look very abnormal and have many more mutations in the genes.
JUST NEED TO KNOW WHAT THE 3 THINGS ARE
General management options for breast cancer:
- main treatment for vast majority of patients
- axillary management
- radiotherapy indications - 2
- Hormone therapy - indications
- bioloigical therapy option
- 2 indications for chemotherapy
The management of breast cancer depends on the staging, tumour type and patient background. It may involve any of the following:
Surgery
Radiotherapy
hormone therapy
biological therapy
chemotherapy
Surgery:
The vast majority of patients who have breast cancer diagnosed will be offered surgery. An exception may be a very frail, elderly lady with metastatic disease who may be better managed with hormonal therapy.
Prior to surgery, the presence/absence of axillary lymphadenopathy determines management:
women with no palpable axillary lymphadenopathy at presentation should have a pre-operative axillary ultrasound before their primary surgery
if negative then they should have a sentinel node biopsy to assess the nodal burden in patients with breast cancer who present with clinically palpable lymphadenopathy, axillary node clearance is indicated at primary surgery
this may lead to arm lymphedema and functional arm impairment
Radiotherapy
Whole breast radiotherapy is recommended after a woman has had a wide-local excision as this may reduce the risk of recurrence by around two-thirds. For women who’ve had a mastectomy radiotherapy is offered for T3-T4 tumours and for those with four or more positive axillary nodes
Hormonal therapy
Adjuvant hormonal therapy is offered if tumours are positive for hormone receptors. For many years this was done using tamoxifen for 5 years after diagnosis. Tamoxifen is still used in pre- and peri-menopausal women. In post-menopausal women, aromatase inhibitors such as anastrozole are used for this purpose*. This is important as aromatisation accounts for the majority of oestrogen production in post-menopausal women and therefore anastrozole is used for ER +ve breast cancer in this group.
Important side effects of tamoxifen include an increased risk of endometrial cancer, venous thromboembolism and menopausal symptoms.
Biological therapy
The most common type of biological therapy used for breast cancer is trastuzumab (Herceptin). It is only useful in the 20-25% of tumours that are HER2 positive.
Trastuzumab cannot be used in patients with a history of heart disorders.
Chemotherapy
Cytotoxic therapy may be used either prior to surgery (‘neoadjuvanant’ chemotherapy) to downstage a primary lesion or after surgery depending on the stage of the tumour, for example, if there is axillary node disease - FEC-D is used in this situation.
What are the 2 options for breast cancer surgery
The objective is to remove the cancer tissue along with a clear margin of normal breast tissue. The 2 options are:
- Breast-conserving surgery (e.g., wide local excision), usually coupled with radiotherapy to reduce the risk fo recurrance
- Mastectomy (removal of the whole breast), potentially with immediate or delayed breast reconstruction (lecture- reconstructions delays chemo and radio)
Lecture - size of the lumps vs the rest of the breast is what determines which one. other indications for mastetcomy - multiple lumps. Patient choice. Breast-conserving surgery + radiotherapy has the same outcomes as mastectomy. BRCA gene carriers because more likely to develop a second cancer.
Extra information:
- Removal of the axillary lyph nodes is offered when cancer cells are found in the nodes, there is a risk of chronic lyphaodema in that arm
BACKGROUND
The purpose of surgery in breast cancer is primarily to gain local control of the disease and to determine the prognostic features of the primary cancer.
The biological features and stage of the cancer will often have determined whether a patient has micro-metastases at the time of surgery and surgery will have no influence on this distant disease. These micro-metastases are the reason for giving systemic therapy (adjuvant chemotherapy, trastuzumab and endocrine therapy) after surgery depending on the prognostic features of the primary cancer. Micro-metastases, if present, may not develop into symptomatic metastases for many years. Once metastatic disease has developed, breast cancer becomes incurable (i think this means if you allow the micro-metastasis to establish).
When is chemotherapy used in breast cancer treatment - 3 reasons
Chemotherapy is used in one of three scenarios:
Neoadjuvant therapy – intended to shrink the tumour before surgery. Lecture - Inflammatory cancer.
Adjuvant chemotherapy – given after surgery to prevent recurrence (aim is to target micro-metastases or microscopic disease at the primary site).
Treatment of metastatic or recurrent breast cancer. Also given for more aggressive cances in younger patients.
Breast cancer - what are the two options for hormone treatment
Patients with oestrogen-receptor positive breast cancer are given treatment that disrupts the oestrogen stimulating the breast cancer.
There are two main first-line options for this:
Tamoxifen for premenopausal women
Aromatase inhibitors for postmenopausal women (e.g., letrozole, anastrozole or exemestane)
Tamoxifen is a selective oestrogen receptor modulator (SERM). It either blocks or stimulates oestrogen receptors, depending on the site of action. It blocks oestrogen receptors in breast tissue, and stimulates oestrogen receptors in the uterus and bones. This means it helps prevent osteoporosis, but it does increase the risk of endometrial cancer.
Aromatase is an enzyme found in fat (adipose) tissue that converts androgens to oestrogen. After menopause, the action of aromatase in fat tissue is the primary source of oestrogen. Aromatase inhibitors work by blocking the creation of oestrogen in fat tissue.
Tamoxifen or an aromatase inhibitor are given for 5 – 10 years to women with oestrogen-receptor positive breast cancer.
TOM TIP: It is worth committing tamoxifen and aromatase inhibitors (e.g., letrozole) to memory, their relationship to menopausal status and their basic mechanism of action. These are good facts for examiners to test you on.
Lecture - Bisphosphonate are given with aromatse inhibitors to prevent osteoperosis and also reduces chances of bony mets
Key - what are the two possible management options for the axillar
If USS shows axillary nodes are clear of disease then it’s a sentinel node biopsy to confirm it’s all clear
If USS shows disease then full axillary node clearance is used
Sidenote: 2 options for breast are lumpectomy and mastectomy.
What is mammary duct ectasia?
How does it present
Ix?
how is it managed?
Mammary duct ectasia is a benign condition of unknown aetiology where there is dilation of the large ducts in the breasts and they fill with debris.
There is inflammation in the ducts, leading to intermittent discharge from the nipple. The discharge may be white, grey or green. It ususally occours in perimenaupause.
Mammary duct ectasia may present with:
Nipple discharge
Tenderness or pain
Nipple retraction or inversion
A breast lump (pressure on the lump may produce nipple discharge)
Ix is to exclude breast cancer with tripple assessment.
Management is usually expectant, it can cause infections (periductal mastitis) and surgery may be required in problematic cases.
