HRT and Breast Cancer therapies

Question 1

Which hormones increase during menopause

Answer 1

FHS, LH

Question 2

Oral Estrogens

Answer 2

CEE (conjugated equine estrogen + estrone sulfate)

Esterified estrogens (estrogen mixture)

Estradiol

• Micronized for better absorption
• Liver metabolism to estrone, less potent

Question 3

Topical Estrogens

Answer 3

Estradial patch, emulsion, gel, spray

No first pass effect, so estrogen levels similar to pre menopausal

Question 4

Vaginal Estrogens

Answer 4

For vaginal atrophy

CEE cream (Premarin)
Estradiol cream (Estrace)

Estradiol ring (Estring) 
Estradiol tablet (Vagifem)
*sustained release, less systemic effect*

Question 5

Estrogen ADRs and indications

Answer 5

Indication: Relief of vasomotor symptoms

ADRs
Nausea, HA, breast tenderness, bleeding

Serious ADRs
CHD, CVA, VTE
Breast cancer
Gallbladder disease

ADRs are less likely w transdermal estrogens

Question 6

Estrogen WARNINGS

Answer 6

Increased risk of stroke and VTE (venous thromboembolism)

Endometrial Cancer in unopposed estrogen for patients with a uterus

Breast cancer, increased risk in combined HRT over long term

Slight increased risk of Dementia in estrogen only therapy

Question 7

Estrogen only vs Estro + Progest HRT, Risks

Answer 7

Estrogen Only

• Higher risk of Stroke
• About same risk of DVT

Estro + Progest

• Higher risk of Breast Cancer
• Higher risk of Dementia
• Lower risk of Stroke

Question 8

3 categories of phytoestrogens

Answer 8

Lignans
- flax

Isoflavones
- soy, garbanzo, red clover, lentils, beans

Coumestens
- Red clover, sunflower seeds, sprouts

Question 9

Indications for Soy

Answer 9

mild reduction in vasomotor symptoms - hot flashes

Question 10

Drug for premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD)

Answer 10

Flibanserin

Question 11

Contraindications for Flibanserin

Answer 11

EtOH, P450 3A4 inhibitors, hepatic impairment

Question 12

Flibanserin ADRs

Answer 12

Sedation, hypotension, syncope, CNS depression

REMS program: hypotension, syncope with EtOH use

Question 13

At what age do the benefits of HRT outweigh the risks

Answer 13

women < 60 yrs

Question 14

Estrogen therapy effectively treats

Answer 14

vasomotor symptoms (Sleep, Irritability, Concentration, Reduced QOL)

Vulvar and vaginal atrophy (Vaginal dryness, Dyspareunia, Atrophic vaginitis

Question 15

General HRT guideline

Answer 15

“lowest dose, shortest period necessary”

unopposed estrogen should not be used in women with intact uterus

Question 16

HRT and Osteoporosis

Answer 16

HRT may be used for the prevention and treatment of osteoporosis within the context of the overall benefit-versus-risk analysis of each patient.

Question 17

3 classes of breast cancer treatment

Answer 17

1. Selective Estrogen Receptor Modulators (SERMs)
2. Steroidal Estrogen Receptor Antagonist
3. Aromatase Inhibitors

Question 18

SERMs

Answer 18

Tamoxifen

Toremifene

Raloxifene

Question 19

Steroidal Estrogen Receptor Antagonists

Answer 19

Fulvestrant

Question 20

Aromatase Inhibitors

Answer 20

Anastrozole

Exemestane

Letrozole

Question 21

SERMs effects on breast vs other tissues

Answer 21

Breast: ESTROGEN ANTAGONIST

Endometrium, bone, liver, coag system: ESTROGEN AGONIST

Question 22

Indications for use of Tamoxifen

Answer 22

ER+ Breast Cancers:

1. Adjuvant therapy for breast cancer
2. Metastatic breast cancer
3. Reduce risk of invasive cancer from Ductal carcinoma in situ
4. Breast cancer prevention in high risk women

Question 23

Tamoxifen ADRs

Answer 23

Menopausal symptoms

- vasomotor, vaginal atrophy, N/V, menstrual irregularities

Question 24

Tamoxifen WARNINGS

Answer 24

Increased risk DVT, PE

Increased incidence Endometrial cancer

Liver abnormalities

Ocular cataracts (high dose only)

Hypercalcemia

PREGNANCY CATEGORY D

Question 25

Tamoxifen (SERM) drug interactions

Answer 25

P450 / 3A4, 2D6 Metabolism Warfarin Rifampin Anastrazole (chemo therapy) Paroxetine, Fluoxetine, Bupropion (SSRI)

Question 26

WHAT ARE SERMS GOOD FOR

Answer 26

Reduces breast cancer risk Lowers LDL cholesterol Strengthens bones

Question 27

WHAT ARE SERMS BAD FOR

Answer 27

Increases uterine cancer risk Increases clot risk

Question 28

Raloxifene (SERM) indication

Answer 28

Breast cancer prevention in high risk patients - slightly less effective prevention than Tamoxifen but FEWER cases uterine cancer and clots **same ADR / warning profile**

Question 29

SERMs for vasomotor symptoms

Answer 29

Bazedoxifene Ospemifene Same SERM class ADR/Warnings

Question 30

Aromatase Inhibitor Indications | Anastrozole, Exemestane, Letrozole

Answer 30

Better efficacy than SERMs for advanced breast cancer *first-line for adjuvant breast cancer treatment in post menopausal women* an aromatase inhibitor is the best hormonal therapy to start. When treating early-stage, hormone-receptor-positive breast cancer, aromatase inhibitors have more benefits and fewer serious side effects than tamoxifen.

Question 31

Fulvestrant (SERD) Indications

Answer 31

Pure anti-estrogen - inhibits and degrades estrogen receptors Indicated for postmenopausal women with hormone receptor–positive metastatic breast cancer that has progressed on tamoxifen No P450 interactions Well tolerated (Nausea, hot flashes, headaches)