Breast Cancer

Question 1

How does Tamoxifen cause hot flushes and what can be used to treat it?

Answer 1

Tamoxifen is metabolised by CYP2D6 into Endoxifen (Active metabolite). lack of CYP2D6 can cause tamoxifen accumulation –> hot flushes
Venlafaxine –> not a CYP2D6 inhibitor (can possibly use)

Question 2

What are the risk factors for breast ca?

Answer 2

1. Genetic Mutation
2. Chest RT
3. Dense breast tissue
4. prev DCIS/LCIS
5. Fam Hx
6. Hormonal Factors: HRT, Nulliparity, early menarche
7. lifestyle : obese, smoking

Question 3

What is the management for BRCA Mutation?

Answer 3

BRCA1: Triple Neg Breast Ca (44% Ovarian Ca)
BRCA2: HER+VE breast Ca (17% Ovarian Ca)
- both also have pancreas and prostate risk
Prevention
1. Bilat Mastectomy
2. Bilat Salpingo-oopherectomy
3. SERM/Aromatase inhibitors
Surveillance - annual MRI

Question 4

What non-BRCA genetic mutations associated with breast Ca?

Answer 4

p53 (Li Fraumeni Syndrome) (45% Breast, also brain, adrenocortical)
PTEN (Cowden syndrome) (77% breast, thyroid, renal, endometrial, colon)
STK11 (Peutz Jegher) (45% breast, Small Bowel, pancreas, colon, ovary)
Other CDH1, CHEK2, ATM,

Question 5

When do you do genetic testing in Breast ca?

Answer 5

women < 30 yo

men < 59 yo

Question 6

What is the general Management of breast ca?

Answer 6

Large >2cm/LN - NEOADJ CHEMO > RESECT/RT > ADH CHEMO (ER+ also Endo)
Small - RESECT/RT > ADJ CHEMO (ER+ also Endo)
no ADJ if good prognosis
- >50yo, <10mm
- ER+VE, PR+VE, HER2-VE
- Ki67 <15%, no nodal disease

Question 7

What chemotherapy is given in Breast ca?

Answer 7

ADJ
A) ER+ PR+: Endocrine Tx (SERM/AI) +/- Chemo
B) HER2+: Traztuzumab + Chemo
C) BRCA + HER2- : PARPi (Olaparib)
D) Triple Neg: Chemo

METASTATIC
A) ER+ PR:
- Fulvestrant (selective esotrogen receptor down regulator) + AI
- ET + CK4/6 inhibitors (Palbociclib, ribociclib, abemaciclib)
- Alpha specific PI3 kinase inhibitors: Alpelisib + Fulvestrant can be used for ER+ PR + HER2 -metastatic breast cancer after failure of CDK4/6 in those with activating PIK3CA mutations

B) HER2 +

• 1st Line: Trastuzumab + Pertuzumab
• 2nd Line: Trastuzumab Emtansine (T-DMI/Kadcyla)

(C) TRIPLE NEGATIVE

• Immunotherapy: PDL1 inhibitor Atezolizumab + nab-paclitaxel
• Sacituzumab govitecan - targets Trop 2 (antibody-drug conjugate)

Question 8

Side Effects of Tamoxifen and Aromatase Inhibitors

Answer 8

Tamoxifen: VTE 2-3x placebo, uterine bleeding, hyperplasia, cancer, increased risk fo cataracts, Fatty liver disease;

Aromatase Inhibitor: osteoporosis, MSK pains and stiffness

Question 9

How to Treat Hot Flushes from Tamoxifen

Answer 9

SNRI/SSRI - Interact with CYP2D6 - decrease hot flush but ? interact with efficacy