Breast (3) (Malignant conditions) Flashcards
Carcinoma in situ
Malignancies that are contained within the basement membrane tissue.
invasive
any type of breast cancer that has spread (invaded) into the surrounding breast tissue.
carcinoma in situ is seen as
- pre-malignant condition, typically found on imaging and are rarely symptomatic at presentation
two types of carcinoma in situ
- Ductal carcinoma in situ (DCIS)
- Lobular carcinoma in situ (LCIS)
ductal carcinoma in situ (DCIS)
- Most common non-invasive breast malignancy (20%)
- Malignancy of ductal tissue of the breast- contained within basement membrane
- 20-30% of cases will develop invasive disease
-
Subtypes
- Comedo (microcalifcations), cribriform (multifocal), micropapillary (multifocal) and solid types, most are mixed
presentation of DCIS
- Usually asymptomatic
- Microcalcifications on mammography
investigations for DCIS
- Detected during screening
- Confirmed by biopsy
management of DCIS
- Completely wide excision, ensuring surrounding tissue of all margins have no residual disease
- Widespread or multifocal DCIS – complete mastectomy
lobular carcinoma in situ
Is a malignancy of the secretory lobules of the breast that is contained within the basement membrane.
They are much rarer than DCIS however individuals with LCIS are at greater risk of developing an invasive breast malignancy
RF for LCIS
before menopause
presentation of LCIS
asymptomatic
investigations of LCIS
- Incidental finding during biopsy of breast
management of LCIS
- Depends on extent of disease
- Low grade LCIS
- Monitoring rather than excision
- If invasive component and BRCA1 or BRCA2 positive à bilateral prophylactic mastectomy
invasive cancer can be classified into
Carcinoma most common in western world. Classification
- Invasive ductal carcinoma (80%)
- Invasive lobular carcinoma
- Other subtypes
- Medullary carcinoma
- Colloid carcinoma
RF for invasive cancer
- Female sex
- Older (doubles every 10 years until menopause)
- BRCA1 and BRCA2 mutation
- Family history
- Previous bening disease
- Obesity
- Alcohol
- Degree of exposure to oestrogen
- Early menarche
- Late menopause
- Nulliparous women
- First pregnancy after 30 years age
- Oral contraceptive or hrt
presentation of invasive cancer
- Can present symptomatically or asymptomatically via screening(particularly for ILC).
- Breast lump
- Asymmetry
- Swelling
- Abnormal nipple discharge
- Nipple retraction
- Skin changes (dimpling/peau d’orange or Pagets-like change)
- Mastalgia
- Palpable lump in axilla
investigations for invasive cancer
- Triple assessment:
- Clinical – history, family history, examination
- Radiographic imaging – mammogram (in older) and ultrasound scan (in younger)
- Pathology – core biopsy and fine needle aspiration cytology (FNAC)
- Receptor status
- Oestrogen, progesterone, human epidermal growth factor
prognosis of invasive cancer
Nodal status is the most important prognostic factor in breast cancer- size, grade and receptors status also influence prognosis
invasive ductal carcinoma
- Most common type of breast carcinoma, constituting 80% of all cases.
-
Further classified into
- tubular, cribriform, papillary, mucinous (/colloid), or medullary carcinomas, all showing distinct patterns of growth*.
- Most commonly incidental finding during screening
*Tubular, cribriform and papillary subtypes are well circumscribed and show the most favourable prognoses
what does an IDC look like
- Irregular
- Condensed part which tugs other tissue in e.g. inverted nipple or breast dimple
Invasive lobular carcinoma (ILC)
- Constituting 10% of all invasive breast cancers.
- RF more common in older women.
- It is characterised by a diffuse (stromal) pattern of spread that makes detection more difficult. By the time of diagnosis, tumours are often quite large.
staging- nottingham prognostic index
Nottingham prognostic index
It is calculated by:
- (Size x 0.2) + Nodal Status + Grade
Size is the diameter of the lesion in cm, nodal status is number of axillary lymph nodes involved (0 nodes=1, 1-4 nodes=2, >4 nodes=3), and grade is based on Bloom-Richardson classification
how does breast cancer spread
- Lymph nodes via lymphatics– usually in the ipsilateral axilla
- Distant metastases via blood vessels – bones (most frequent site), lungs, liver, brain
- Invasive lobular carcinoma can spread to odd sites – peritoneum, retroperitoneum, leptomeninges, gastrointestinal tract, ovaries, uterus
molecular classification of breast cancer
basically if you are receptor positive, then your prognosis is better
- Oestrogen receptor positive= better prognosis
- Her2 positive and oestrogen positive= better prognosis (can have Herceptin)
- Oestrogen receptor negative and HER2 negative = poor prognosis and usually BRCA1
treatment of breast cancer involves
- Surgical
- Hormone treatment
- Oncoplastic management
surgical management
- breast conserving
- mastectomy
- axillary surgery
breast conserving surgery
- Indication
- Localised operable disease with no evidence of metastatic disease
- Focal smaller cancers
- Dependent on location and size of breast
- Wide local excision (WLE) most common treatment
- Excision of tumour with 1cm margin of macroscopically normal tissue
- Localised operable disease with no evidence of metastatic disease
mastectomy
- Removes all of the tissue of the affected breast along with signif portion of overlying skin (muscles of the chest wall left intact)
- Indication
- Multifocal disease
- High tumour: breast tissue ration
- Disease recurrence
- Patient choice (or in risk-reducing cases)
axillary surgery
- Why? Most commonly performed alongside WLE and mastectomies in order to asses nodal status and removal of nodal disease
sentinel node biopsy (nodal status)
- Removing first lymph node into which the tumour drains
- Method: blue dye (with associated radioisotope) is injected into the peri-areolar skin
- The sentinel node is identified by its radioactivity and visual assessment (as node becomes blue)
- Node removed and sent for histological analysis
axillary node clearance
- (removal of nodal disease)
- Removing all nodes in the axilla
complications of axillary node clearance
- Complications
- Paraesthesia
- Seroma formation
- Lymphedema in upper limb
A risk-reducing mastectomy is
an operation to remove healthy breast tissue in order to reduce the risk of developing breast cancer.
Risk-reducing mastectomy is only suitable for patients with a high risk of developing breast cancer and requires appropriate counseling to reach this difficult decision. In cases of suspected genetic risks, then patients are often referred to a genetic counsellor.
when to consider risk reducing mastectomy
- A strong family history of breast or ovarian cancer
- Testing positive for genetic mutations, such as BRCA1 or BRCA2, PTEN, or TP53 mutations
- Previous history of breast cancer
systemic control of invasive disease includes
chemotherapy
hormonal treatment
herceptin
chemotherapy
if benefits thought to outweigh the risks; if given before surgery = neoadjuvant
hormonal treatment
e.g. tamoxifen – depending on oestrogen receptor status (approximately 80% of cancers are ER positive)
herceptin treatment
- depending on Her2 receptor status (approximately 20% of cancers are Her2 positive)
- Her2 is a member of the human epidermal growth factor receptor family
- Encodes a transmembrane tyrosine kinase receptor
- Herceptin = trastuzumab = humanised monoclonal antibodies against the Her2 protein
indication of hormonal treatments
Although several treatments options e.g. chemo, radiotherapy and immunotherapy, hormone manipulation is the biggest contributor to improved survival
Indication
- In malignant non-metastatic disease, therapy for breast cancer is adjuvant so as to reduce the risk of relapse.
- Medical treatment is commenced usually after primary surgery
- It can often be the treatment of choice in elderly patients or in those unfit for surgery.
tamoxifen
Indication
- Pre-menopausal women
MOA
- SERM- selective oestrogen receptor modulator
- converse effects in breast and endometrial tissue
- in endometrium = ER agonist
- in breast = ER antagonist
- cell cycle arrest
- converse effects in breast and endometrial tissue
- Blockage of oestrogen receptor in breast tissue
ADR
- Risk of thromboembolism during and after surgery or during periods of immobility
- Uterine carcinoma (due to pro-oestrogenic effect on the uterus)
aromatase inhibitors
Aromatase Inhibitors (post-menopausal)
e.g such as Anastrozole, Letrozole, or Exemestane
Indication
- Post-menopausal patients as adjuvant therapy, shown to be superior in this patient subgroup to Tamoxifen, however are more expensive.
MOA
- Act through binding to oestrogen receptors to inhibit further malignant growth and preventing further oestrogen production, as well as blocking the conversion of androgens to oestrogen in peripheral tissues.
pre-menopausal women
tamoxifen
post menopausal women
aromatase inhibitors
immunotherapy for breast cancer eg
herceptin
Herceptin
Indication
- Immunotherapy may be used in patients whose cancers express specific growth factor receptors.
- It can be used either as adjuvant therapy or as a monotherapy in patients who have received at least two chemotherapy regimens for metastatic breast cancer*.
MOA
- One of the most common targets is the human epidermal growth factor receptor(HER-2 positive malignancies) for which Herceptin (Trastuzumab) is a monoclonal antibody that targets its activity.
side effect of herceptin
*A common side-effect of treatment is cardiotoxicity, hence cardiac function must be monitored before and during treatment
oncoplastic management- surgical reconstructive techniques
Several surgical reconstructive techniques in oncoplastic treatment of breast malignancy. Broadly divided into
- Mammoplasty
- Flap formation
mammoplasty
- A therapeutic mammoplasty involves a WLE combined with a breast reduction technique.
- The end-result is a smaller and uplifted breast, with the nipple and areola preserved along with their blood supply and the nipple relocated to suit the new breast.
flap formation can use
Latissimus dorsi
Transverse rectus abdominal muscle (TRAM) flap
Deep inferior epigastric perforator (DIEP) flap
