Breast Carcinoma Flashcards
(33 cards)
1
Q
Outline the epidemiology of breast cancer
A
- most common invasive cancer in women
- most common cancer-related cause of death in women
- lifetime risk 1 in 9 (women)
- 1% of breast cancers in UK are in males
- increase in incidence since 1970s
- 80% of cases occur in 50+ age group
- lower incidence in japan and africa
*
2
Q
What are risk factors for breast cancer?
A
- family history: 25% lifetime risk w/ first degree premenopausal relative
- age: avg age is 64yrs and increase in incidence >25yrs to menopause
- gender: females 100x more likely
- uninterrupted oestrogen exposure: nulliparity, no breast feeding, early menarche, late menopause, exogenous oestrogen (COCP, coil, HRT)
- obesity: inc synthesis of oestrogens in fat depots inc risk in postmenopausal obese women
- BRCA genes: BRCA1, BRCA2 - 80-90% penetrance, associated w/ ovarian Ca
- past breast cancer: irradiation from therapeautic exposure
- proliferative breast disease: inc risk in presence of sclerosing adenosis and epithelial hyperplasia, particularly artypical ductal or lobular hyperplasia
- carcinoma of contralateral breast/endometrium
- benign breast disease: duct hyperplasia
- xs alcohol consumption
3
Q
What is the link with family history/genetics and breast cancer?
A
- 5-10% of breast cancers familial
- BRCA1 + BRCA2 - tumour suppressor genes
- germline mutations in them -> account for 85% of familial cancers
- inherited in autosomal dominant fashion
- women w/ mutations in these genes have a lifetime risk of breast cancer of between 85-100%
- also at high risk of developing ovarian cancer + so prophylactic risk-reducing bilateral mastectomy/salpingo-oophorectomy considered
- germline mutations in P53 (Li-fraumeni syndrome) less common
4
Q
What are protective factors against breast cancer?
A
- physical activity -> reduces oestrogen + testosterone
- breastfeeding
- <20yo at first pregnancy
- diet
- NSAIDs
5
Q
Asymptomatic breast cancer is usually detected on screening. But what are the clinical features of breast cancer?
A
- nipple discharge -> bloody, unilateral, watery, serous, milky
- breast lump -> hard, tethered, irregular, painless, irregular
- skin tethering +/- ulceration
- inflammation -> inflammatory cancers
- skin changes -> peau d’orange, puckering, dimpling, colour
- ‘eczema’ of nipple -> DCIS (Paget’s)
- lymphadenopathy
- weight loss, anorexia, bone pain, jaundice, anaemia, malignant pleural + pericardial effusions
6
Q
What are differential diagnoses for a breast lump?
A
- fibroadenoma
- phylloides tumour
- fibrocystic breast (fibroadenosis)
- fat necrosis
- intra-ductal papilloma
- abscess
- adenoma
- atypical ductal/lobular dysplasia
- invasive breast cancer
- DCIS
- LCIS
7
Q
What type of tumours are breast tumours?
A
- almost all malignant tumours arising in breast = invasive adenocarcinomas
- adenocarcinoma = malignant tumour of glandular epithelium
- as breast = gland
8
Q
What are the two most common types of breast cancer?
A
- ductal carcinoma (approx 75%)
- lobular carcinoma (approx 10-15%)
NOTE: It used to be thought that ductal carcinoma arose in the ducts and lobular carcinoma arose in the lobules. We now know that this is not the case and it is accepted that virtually all breast cancers arise from epithelium lining the terminal duct lobular unit (TDLU). Therefore some people argue that the terms ‘ductal carcinoma’ and ‘lobular carcinoma’ are outdated and misleading.
other types: tubular, medullary, mucinous, myoepithelial, paget’s
9
Q
What is ductal carcinoma in situ (DCIS)?
A
- epithelial cells show cytological changes of malignancy
- pleomorphism, hyperchromasia, inc nuclear:cytoplasmic ratios, mitotic activity present in TDLU
- however, basement membrane in tact
- cells have not invaded into the surrounding tissue
- this is a form of carcinoma in situ
- does not form a mass usually
- associated w/ microcalcifications
- usually unifocal lesion conc in 1 area of breast
10
Q
Why is DCIS (ductal carcinoma in situ) not cancer?
A
- not invasive
- no metastatic potential
- doesn’t fill two defining criteria for malignancy
- however, if left untreated, a significant proportion will progress to invasive ductal carcinoma
- DCIS is pre-cancer
- as it’s unifocal and can progress to IDC, DCIS is surgically excised
11
Q
What is invasive ductal carcinoma (IDC)?
A
- IDC invades through basement membrane into adjacent breast tissue + has potential to metastasise
- fulfils 2 defining criteria for a malignant tumour - it’s cancer
- usually presents as palpable breast mass
12
Q
How does breast cancer spread?
A
- direct extension: involves skin + subcut tissue causing skin dimpling, nipple retraction + ulceration. Extension involves pec major, serratus anterior and chest wall
- lymphatic: dermal lymphatics become blocked causing cutaneous oedema pitted by sweat gland orifices known as peau d’orange appearance. Later the whole chest wall becomes a firm mass of tumour tissue. Spread to axillary + thoracic lymph nodes and later to supraclavicular, abdo and groin and opposite axillary nodes
- blood stream: blood borne spread common to lung, liver + bone (in red marrow sites eg. skull, pelvis, ribs). Sometimes in brain, ovaries and suprarenals also
13
Q
What are the 4 core groups of the MDT in breast cancer?
A
- breast surgeons
- oncologists
- pathologists
- radiologists
then also:
- breast care nurse
- chemo nurse
- therapeutic radiographer
- research nurse
14
Q
Diseases of the breasts commonly present as palpable lumps. The most likely cause of a lump depends on age. In young women, fibroadenoma and fibrocystic changes are the most common cause; cancer is much less common. In older women, cancer becomes a more important cause, although fibroadenoma and fibrocystic changes also occur.
What does triple assessment consist of?
A
- clinical assessment - hx + exam
- radiological - <35 US, >35 US + mammogram
-
pathological:
- cystic lump -> aspirate
- residual mass -> core biopsy
- clear fluid -> discard fluid and reassure
- bloody -> cytology
- solid lump -> core biopsy
- cystic lump -> aspirate
15
Q
What investigation(s) is used for breast lesions that are not palpable?
A
- sterotactic fine needle aspiration
- mammographically detected
16
Q
What are other investigations for staging of spread?
A
- FBC: anaemia + leucopaenia -> bone marrow involvement?
- LFTs
- CXR
- isotope bone scan
- liver USS
Tumour markers are not usually tested but Ca 15.3 and Ca 27.29 are increased in malignant breast Ca
17
Q
What is the natural history of breast cancer and prognosis?
A
- invasive breast cancer is commonly staged as local, regional or distant disease
- larger tumours more likely to be detecte din advanced stages when compared to smaller tumours
- it is generally believed that majority of breast cancers begin in the local stage and transition from local to regional then to distant stages as tumour increases in size
- if left untreated, breast cancer commonly spreads to the bones, lungs, liver and brain
18
Q
What are the reporting categories for pathological assessment (FNA + core biopsy)?
A
- C1/B1 - inadequate or not diagnostic
- C2/B2 - benign* eg. fibroadenoma, fibrocystic change
- C3/B3 - equivocal, favour benign
- C4/B4 - equivocal, favour malignant
- C5/B5 - malignant (DCIS is included here)
*in this context, benign refers to any lesion that isn’t malignant or premalignant - thus includes benign tumours (eg. fibroadenoma) and also non-neoplastic lesions such as fibrocystic change, abscesses etc.
19
Q
TNM staging: Describe the ‘T’ stage in breast cancer
A
- TX - tumour can’t be assessed
- Tis - DCIS
- T1 - ≤ 2cm (further divided into mi,a,b,c)
- T2 - 2-5cm
- T3 - >5cm
-
T4:
- T4a - spread into chest wall
- T4b - spread into skin + breast might be swollen
- T4c - tumour spread to both skin + chest wall
- T4d - inflammatory carcinoma
20
Q
TNM staging: Describe the ‘N’ stage in breast cancer
A
- NX - lymph nodes can’t be assessed
- N0 - no cancer cells in any nearby nodes
- N1 - mobile ipsilateral nodes
- N2 - fixed ipsilateral nodes
- N3 - clavicular (above or below) lymph node involvement
21
Q
TNM staging: Describe the ‘M’ stage in breast cancer
A
- M0 - no sign of cancer spread
- M1 - cancer spread to another body part
22
Q
What histological factors are associated w/ prognosis?
A
- young age
- premenopausal
- tumour size
- grade of tumour
- lymph (axillary) node involvement
- oestrogen + progesterone receptor negative
- vascular invasion
Eg. the estimated 10yr survival probability is approx 95% for small (1
23
Q
What link do oestrogen receptors have with breast cancer?
A
- breast carcinomas can express ER (oestrogen receptors)
- this correlates with aggressiveness + predicts response to therapy
- ER positive tumours tend to be lower grade and less aggressive and likely to respond to hormonal therapy
- ER negative tumours tend to be higher grade and more aggressive and unlikely to respond to hormonal therapy
24
Q
What link does the HER-2 gene have with breast cancer?
A
- an oncogene
- encodes a transmembrane tyrosine kinase receptor
- it is overexpressed in about 15% of invasive breast cancers
- HER2 over-expression by an invasive breast carcinoma is associated with:
- poorer prognosis
- good response to Herceptin (monoclonal antibody against HER2 receptor)
25
What is the NHS **breast screening** programme?
* Women aged **47-73**
* Offered mammogram **every 3 years**
* Saves ~ 1400 lives per year
* Trans men (without chest recon) and trans women (hormones) also invited
* **Mammogram results:**
* satisfactory → no radiological evidence (96% have normal result)
* abnormal → further ix needed (25% of these will have breast cancer)
* unclear → inadequate image, further investigations needed
26
Who should **genetic** **testing** be offered to?
* Consider age, med hx, FHx + indications
* In pts \< 50 with triple-negative breast cancer (ER -ve, PR -ve and no excess HER2) → offer test for BRCA 1 / BRCA 2
27
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_, what factor relating to the breast cancer determines management?
_Presence or absence of axillary lymphadenopathy_
* **No palpable axillary lympadenopathy at presentation** → pre-operative axillary USS before primary surgery, if positive → sentinel node biopsy to assess nodal burden
* **Clinical palpable lymphadenopathy** → axillary node clearance indicated at primary surgery → may lead to arm lypmhedema and functional arm impairment
28
What are the **two** **options** for breast cancer surgery?
* **Breast conservation** → wide local excision; consider size and location for aesthetics; whole breast radiotherapy indicated to reduce risk of local recurrence; margins must be checked
* **Matectomy** → if unfavourable tumour to breast ratio; if radiotherapy contraindicated; if multifocal or recurrent tumours
Breast reconstruction should be offered to both
29
What are **principles** of **breast** **reconstruction** for breast cancer patients?
* May be completed or started **immediately** at time of mastectomy
* Or **delayed** as separate procedure
* Surgery may be staged over 2+ procedures
* Immediate recon may impact timing of further treatment with chemo and radiotherapy
30
What are principles of **radiotherapy** for breast cancer?
* Whole breast radiotherapy after **wide-local excision**
* This may reduce risk of recurrence by 66%
* For women who've had **mastectomy**, radiotherapy offered for T3-4 tumours and for those with 4+ positive axillary nodes
31
What are principles of **chemotherapy** for breast cancer?
* Based upon stage, co-morbidities + pt wishes
* **Neoadjuvant** → prior to surg, guided by MDT, also in inflammatory breast ca
* **Adjuvant** → Fluorouracil, Epirubicin + Cyclophophamide
32
What **biological** **therapy** is used for breast cancer?
* **Trastuzumab** (Herceptin)
* For **HER2** positive
* Avoid in cardiac disorders
33
What are principles of **endocrine**/**hormonal** therapy for breast cancer?
* Commenced after adjuvant chemo + lasts for 5 yrs
* **ER/PR positive** disease - 2 options
* **Tamoxifen** → selective oestrogen receptor modulator, first-line for men and pre-menopausal women; risks = blood clots, endometrial Ca, osteoporosis; women should not get pregnant whilst on tamoxifen or for 2m later
* **Aromatase inhibitors (eg anastrozole)** → first-line for post-menopausal women at medium/high risk recurrence; inhibits peripheral conversion of androgens to oestrogens; SEs = menopausal symptoms, osteoporosis, MSK pain
