Tamoxifen

• Selective Estrogen Receptor Modulators

• Method of action ⇒ Selective Oestrogen Receptor Modulator (SERM)

  • Competitive antagonist of ER receptor in breast
  • Agonist on Endometrium, Bone and Lipids

Risk reduction

• Tamoxifen 20mg daily for 5 years reduces breast cancer risk for at least 20 years
• Reduces the risk by at least 1/3
• Cannot recommend in BRCA 1 pts – most cancers are triple negative
• Can consider for women with family hx and proliferative breast disease (ADH, LCIS)
• On-going benefit even after ceasing treatment

Adjuvent treatment Indications:

• Mainly used in pre-menopausal women
  • Can be used in post-menopausal pts but Aromatase inhibitors usually better
• ER/PR +ve pts (± may benefit pts of unknown ER status) if Ca > 1cm
• OR > 0.5cm with unfavourable features – e.g. Poorly diff, LVI, Grade 3)
  • NB: If pt is HER2 +ve & ER +ve → Tamoxifen may be ineffective, Aromatase inhibitor probably better

Dose

• 20mg Daily for 5-10 years

Duration

• Minimum of 5 years
• Can be extended to 10 years - balance of risk of recurrence and side effects

Timing

• Start after chemo/radiotherapy
• Anti-proliferative effects of Tamoxifen seem to make chemo slightly less effective
• No data re: radiotherapy sequencing

Efficacy

• EBCTG 1998 – Treatment 5 years
  • Decrease risk of contralateral breast cancer by 40-50%
• EBCTG 2000 / Cochrane 2001:
  • Decreased likelihood of recurrence by 15% (45 → 33%) at 15yrs (i.e. 41% RR↓)
    • ↓ RR risk of mets by 15% in ER/PR +ve patients
  • Absolute mortality reduction = 10% (<35yrs→26%) @ 15yrs (i.e. 34% RR↓), irrespective of age, menopausal status or chemotherapy
  • In addition to chemo RR of recurrence = 10%
    • N+ 11% absolute decreased mortality, N -ve 5% absolute decreased mortality
• Adding chemo to Tamoxifen is esp. beneficial in younger women

Other Benefits

• Prevents bone demineralization
• Beneficial effect on cardiovascular morbidity (lowers cholesterol)

Tamoxifen Side Effects

• Common: Hot flushes, irregular periods, vaginal dryness, fluid retention, weight gain
• Rare: Headache, dizziness, fatigue, nausea, rash, depression
• Other: Interacts with warfarin (enhances warfarin); hypercalcemia

Risks:

• Due to its partial oestrogenic effect
  • DVT (same as COC or HRT: 1→2:1000; RR 3)
  • Endometrial Ca (<1/100 over ten years): RR 2.5; usually stage 1, good prognosis
    • Combined these two risks have a 10 yr mortality risk of 0.2%
    • CF 30% reduction in breast cancer mortality
• Contraindicated if pregnant or breast feeding (or for 2 months after stopping Tamoxifen)
• Interacts with SSRIs (Paroxetine)