Breast cancer Flashcards
Risk factors for Breast Ca? (4)
- FH - BRCA1/BRCA2 is the strongest RF
- Obesity (most relevant from population perspective)
- Longer exposures to oestrogen: early monarchy, late menopause, nulliparity, late first-pregnancy
- Previous RTx (x10 RR if <30y age)
What are the specific questions you need to ask in Breast Ca long-case in (“Current status”)? (3)
What impact does the Cancer have on patient, particularly
- Sexual problems: vaginal atrophy, dyspareunia
- Low-self esteem due to lack of breast/ scars or it’s appearance
- Depression
Breast cancer staging?
Stage 1: localised, small lesion (<2cm)
Stage 2: localised, larger lesion (>5cm) without nodes or smaller lesion with LN (1-3)
Stage 3: Large lesion (>5cm) with LN involvement or locally advanced disease (extending to chest wall or skin)
Stage 4: Mets.
Prognosis of Breast Ca based on staging?
5y survival as below
I - 100%
II - 80%
III - 50%
IV - poor, 2 years overall survival (median)
If patient had masectomy, lumpectomy (instead of breast conserving surgery) what useful information does it tell you?
Breast-conserving surgery is not recommended in below situations
- Tumour was larger than 5cm
- involvement of nipple or areola
- Multi-focal
Hence the patient must have had high-risk features and mastectomy was performed to reduce the risk of recurrence.
if the patient had RTx following surgery, what useful information does it tell you in the LC?
RTx is not usually indicated following surgery, except when high-risk features are present.
- Margin not clear
- Larger than 5cm
- ≥4 LN involvement
- Inflammatory Breast cancer
What adjuvant endocrine therapies are given to pre vs. postmenopausal women with Hormone receptor +ve breast Ca following breast surgery?
Pre-menopausal: Tamoxifen (SERM)
Post-menopausal: Aromatase inhibitors
Side effects of Tamoxifen? (4) how is Raloxifen beneficial compared with Tamoxifen?
VTE (1-2%)
Endometrial Ca (1%)
Hot flushes
Cataracts
Raloxifen: no endometrical Ca risk, lower risk of VTE and Cataracts.
Side effects of aromatase inhibitors? (4)
Early (days to weeks): Vasomotor (Hot flushes), fluid retention, dyslipidaemia
Late: arthralgia, vaginal atrophy and Osteoporosis
Specific side effects to ask about in Breast Ca long case for patients? 4
Cognitive dysfunction
Osteoporosis**
Sexual problems: dyspareunia, vaginal atrophy
Vasomotor symptoms: flushing
Depression is common in patients with Breast Ca. Which anti-depressants must be avoided in patients who are on Tamoxifen?
Paroxetine, Fluoxetine - these are CYP2D6 inhibitors (hence impairs metabolism of Tamoxifen)
Would you biopsy the recurrent breast tumour and why?
Yes - as secondary cancers usually have different hormone receptors hence would change management.
Criteria for testing BRCA? (5)
Any of the:
- ≥3 Breast or Ovarian Ca in family
- 2 breast Ca <50y in family
- Triple -ve & <50y
- Bilateral breast Ca
- Male Breast Ca
What is the age-appropriate Breast Ca surveillance in non-BRCA population?
2 yearly Mamogram from 50-70.
Surveillance protocol for BRCA patients?
Yearly Mamogram and MRI from age 30
Consider prophylactic bilateral salpingo-oophorectomy or mastectomy (if family completed) - improved survival and reduction in Breast Ca risk by 90%.
Can a mamogram be used for younger patients (<40) for Breast Ca surveillance?
No, use USS or MRI as breasts are denser, MRI has higher sensitivity.
What is the general principle of management of Breast Ca - early or locoregional disease (pharm)?
Surgery + Sentinal node biopsy +/- RTx then consider Adjuvant therapy depending on molecular/receptor profile.
Surgery
- WLE + RTx if no node involvement
- Mastectomy if big tumour without node (big or if many LN)
- RTx if >5cm or ≥4 LN
Sentinal node biopsy - if +ve (met >2mm) → axillary node clearance
Adjuvant therapy
- Chemotherapy (taxanes): if node +ve or high-risk (triple -ve, high Ki67, HER2+)
-
Hormone therapy (if ER or PR+)
- Treat for 10y: Tamoxifen if pre, AI if post-menopausal
- Trastuzumab if HER2+, consider combination therapy with Lapatinib
What are the risk factors for Cardiotoxicity with Trastuzumab use? (3)
- Age
- Baseline poor LVEF
- Previous use of Anthracyclin (Daunorubicin - all -Rubicins)
- Do not use it with Anthracyclins
Pharmacological Tx of Metastatic Breast Ca?
ER/PR+: Hormonal therapy. At progression switch to another (e.g. AI to Tamoxifen, steroidal to nonsteroidal AI), can add mTOR inhibitor.
HER2+: trastuzumab + chemo +/- pertuzmab.
Bone metastasis: Denosumab > Zolendronic acid.
Give some names of Aromatase inhibitors?
AIs work by inhibiting aromatase - which converts androgens to estrogens
Letrozole
Anastrozole
exemestane
Definition of menopause? (2)
Prior Bilateral oophorectomy
No menstruation for 12 months - while undergoing ovarian suppression, tamoxifen, chemotherapy.
Treatment options for hormone+ve, HER2-ve metastatic breast ca (postmenopausal women)?
- Low-burden
- Normo-burden
- High-burden
Postmenopausal - CDK 4/6 (Ribo/Pablocyclib) + AI (e.g. Letrozole)
Alternative = single agent AI: if patient prefers or cannot tolerate or have low burden disease
High-burden (rapidly progressive or extensive visceral mets with end-organ dysfunction): Chemotherapy
Treatment options for hormone+ve, HER2-ve metastatic breast ca (premenopausal women)?
- Low-burden
- Normo-burden
- High-burden
Postmenopausal - Ovarian suppression + CDK 4/6 (Ribo/Pablocyclib) + Tamoxifen
Alternative = single-agent tamoxifen or OS/OA (ovarian suppression or ablation - check estradiol level) with tamoxifen if patient prefers or cannot tolerate or have low burden disease
High-burden (rapidly progressive or extensive visceral mets with end-organ dysfunction): Chemotherapy
Treatment for HER2+ metastatic breast Cancer?
Combination Trastuzumab + Pertuzumab + Taxane
If not tolerated, dual Trastuzumab and Taxane
If Hormone +ve, ET + Trastuzumab is a reasonable alternative. However if high-burden or rapidly progressive disease, will need Chemo.
General treatment strategy for triple -ve breast ca (early/locally advanced)?
Neoadjuvant or adjuvant chemotherapy + Surgery (if lesion >0.5cm)
Treatment for metastatic triple -ve breast Ca? What are essential work up? (2)
PDL-1 expression
Germline BRCA mutations
If PDL-1 expression >1%, Atezolizumab + Nab-Paclitaxel (1b)
Germline BRCA mutations - above regime or PARPi
If all -ve, standard chemotherapy.
CDK4/6 inhibitor (Ribociclib/Palbociclib) side effects? (5)
Cytopaenia
Hepatotoxicity
Cardiac - QT prolongation
Pulmonary Toxicity
Diarrhoea
Electrolytes: low Ca, K, Phos
Overall: a bit like immunotoxicity
