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Flashcards in Adjuvant Breast - Hormones Deck (20):
1

What are the ways that you can suppress/ablate ovarian function?

1) Drugs
2) Radiotherapy
3) Oophrectomy

2

What are the Aromatase Inhibitors that you know of?

1) 1st Generation (adrenal suppression)
- Aminogluthetimide
2) 2nd Generation
- Fadrozole
- Formestane
3) 3rd Generation (>98% inhibition)
- Steroidal (Irreversible) - Exemestane
- Non-steroidal (Reversible) - Anastrozole, Letrozole

3

Define menopause

1) 60 years old and above
2) If

4

Why is AI not appropriate as monotherapy for women with intact ovarian function?

AI only blocks peripheral conversion

May have return of ovarian function during f/u or may experience deactivation of ovarian function on an AI

5

How does Tamoxifen work?

It is a SERM
Inhibits growth of breast cancer cells by competitive antagonism of Estrogen receptor

6

What are the S/e of Tamoxifen?

Thromboembolic disease
Higher risk of CVA
Uterine cancer (4% vs 1%)
Hot flushes, vaginal discharge, sexual dysfunction, menstrual irregularities

7

What contributes to Tamoxifen resistance?

1) Variable expression of ER alpha and beta isoforms
2) Intererence with binding of co-activators and co-repressors
3) Alternative splicing of ER mRNA variants
4) Modulators of ER expression
5) Inherited drug metabolizing CYP2D6 genotype

8

What is the NCIC CTG MA.17 trial about

N>5000 post menopausal women s/p 5 years of Tamoxifen

2 groups:
1) Additional 5 years of Letrozole
2) Placebo

RESULTS:
- Improvement in DFS compared with placebo HR 0.5
- Improvement in OS HR0.6
- Women who had been randomized to placebo, but subsequently chose to take Letrozole also experienced an improvement in DFS despite a substantial lack in time.

9

What are the side-effects of AI?

1) Osteoporosis and fractures
2) Cardiovascular risk
3) Hypercholestolemia
4) Lower risk of venous thrombosis and lower risk of endometrial cancer
5) MSK Symptoms
6) Fatigue, forgetfulness, insomnia
7) May reactivate ovarian function, esp in those with chemo-induced amenorrhea

10

What are the AI-associated MSK Syndrome?

Arthralgia
Joint stiffness
Bone pain

11

How do you manage AI-associated MSK Syndrome?

1) Exercise
2) NSAIDs
3) Alternate AI, after stopping for 2-8 weeks
4) Switch AI to Tamoxifen
5) Limited Tx with Duloxetine
6) HOPE trial (Hormones and Physical Exercise)
- n=120 post-menopausal women
- 2 arms: Exercise regimen vs usual care
>> 2x per week supervised resistance and strength training + modest aerobic exercise for 150min/week
- 2013 San Antonio Breast Cancer symposium
>> Significantly greater reduction in their worst pain score and severity
>> More weight loss and improvement in exercise capacity

12

When is the 21-gene RT-PCR Assay (Oncotype Dx) appropriate?

Node negative, Her2 negative
Tumor > 0.5cm

13

Briefly describe the Oncotype Dx and how it correlates with treatment

Low recurrence score

14

What is Oncotype Dx based upon?

Retrospective and not prospective.

It is prognostic and predictive, based on NSABP 14/20 and SWOG studies.

It is a RT PCR-based gene profiling assay
Based on 16 cancer genes and 5 reference genes

Gives a continuous variable, estimating a 10-year recurrence rate.
Risk: Low, Intermediate and high.
Based on the score, a recommendation of endocrine, endocrine+/-chemo, chemo will be suggested.

Patient profile:
- Stage I/II
- Node negative
- ER+

1/3 of the overall population switched from C+H to H, based on low recurrence score.
4% of overall population switched from H to C+H based on high recurrence score

15

How did we come about to use CMF?

Milan Trial, Bonadona et al NEJM 1976, 19y update in NEJM 1995

N=400
S/p radical mastectomy. 2 arms:
1) Observation
2) Oral CMF Q4w X 12 (1 year)

Results (Updated):
Persistent RFS and OS benefit

16

Btwn Oral and IV CMF. Which one?

Oral CMF > IV CMF
In both met and adjuvant setting

1) EORTC 10808 Eur J Cancer 1991
2) IBCSG JCO 1998

17

What is the duration of CMF advised. Why?

6 months of oral CMF.

1)

18

Btwn CMF and anthracyclines-based regimens?

1) INT 0102
- Oral CAF x6 > CMFx6 in terms of RFS and OS marginally
- n=4400, Node negative

2) NSABP B-15 JCO 1990
- 6 Oral CMF = 4AC = 4AC-->CMF

3) NSABP B-23 JCO 2001
- 6 Oral CMF = 4AC
- Node negative patients
- Tam = No Tam

4) GEICAM Ann Oncol 2003
- FAC > CMF for node-negative breast cancer
- OS same in Node+ patients

19

Tell me about the INT-0102 trial

Hutchins JCO 2005

Aim:
to evaluate efficacy of CMF vs CAF in N- breast cancer;
With and without Tamoxifen

N=2700
Node negative, Tumor >2cm, HR - or high S-phase fraction

2x2 factorial design
1) CMF
2) CAF
3) CMF+Tam
4) CAF+Tam

RESULTS:
10y OS 85% (CAF) vs 82% (CMF)
10y DFS 77% (CAF) vs 75% (CMF) but not sig
Toxicity was greater with CAF, but did not increase with Tam.
Tam had no benefits In HR- patients

20

Tell me about the NSABP B-23 trial

Bernard Fisher JCO 2001

N=2000
ER-, Axillary LN-

2x2 factorial design
1) CMF + Placebo
2) CMF + Tam
3) AC + Placebo
4) AC + Tam
Tam given daily for 5 years
6# CMF and 4# AC

RESULTS:
- No difference in RFS, EFS, or OS
- AC = CMF