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Hormone positive disease-adjuvant endocrine treatment

  • ER &/or PR positive (IHC > 10%): Always needs endocrine tx. Use of chemo depends on node status & molecular assays
  • ER &/or PR low (IHC < 10%): Consider endocrine tx
  • Premenopausal: If high risk (age < 35 y +/− any high-risk factor, eg, node +) → OFS+TAM or OFS+AI (based on distant relapse & OS ↑). Note: OFS+AI > OFS + TAM (based on recurrence risk), no OS benefit. (SOFT/TEXT, NEJM 2018;379:122-137; NEJM 2014;371:107-118; JCO 2016;34:1689)
  • OFS: Achieve w/ LHRH analogues vs. b/l oophorectomy
  • Tox: ↑ menopausal sxs (Grade 3,4 ∼ 30%) & ↓ bone density
  • Low risk: TAM alone, ↓ breast CA mortality (Lancet 1998;351:1451-1467)
  • Extended TAM: ↓ breast CA mortality Δ 2.8% vs. 5-y tx, slight ↑ DVT/PE & endometrial CA (ATLAS, Lancet 2012;381:805; aTTom JCO 2013;13:(suppl; abstr 5))
  • TAM tox: DVT, endometrial CA, hot flashes
  • Postmenopausal: AI either upfront or sequentially after 5 y of TAM.
  • Extended AI (10 y): ↓ Contralateral breast CA, w/ absolute benefit of 4%. No OS benefit. (MA.17R, NEJM 2016;375:209; NSABP-B42, SABC, 2019).
  • AI types: (1) Nonsteroidal: Anastrozole, letrozole (2) Steroidal: Exemestane
  • AI tox: Arthralgias, ↓ bone density, vaginal dryness
  • Additional strategies: Zometa OR denosumab (60 mg q6mos) ↓ skeletal related events & ↑ DFS for pts on AI, independent of BMD (Lancet 2015;386:433; ABCSG, SABC, 2015)
  • CDK4/6 inhibitors + AI currently under investigation (monarchE, PALLAS, NATALEE, PENELOPE B)
  • Hormone-positive disease-adjuvant chemotherapy
  • Oncotype DX: 21-gene signature RT-PCR assay to calculate Risk Score (RS)-predicts 9-y distant recurrence rate: Low (RS ≤11); Intermediate (RS 12-25); High (RS ≥26)
  • Any pT ≥5 mm, pN0, & RS 0-11: ET alone. RS 12-25: ET alone, but consider chemo if <50 & high clinical risk. RS ê26: Chemo then ET (TAILORx trial: NEJM 2015;373:2005; NEJM 2018;379:111-121, NEJM 2019;380:2395-2405)
  • pN1 (1-3 N+), postmenopausal pt, & RS ≤25: ET only (IDFS ET alone ∼ chemo + ET); RS >25: Chemo then ET. If premenopausal, chemo always indicated regardless of RS (RxPONDER, NEJM 2021;385:2336-2347)
  • Hormone-positive disease-prognostic models
  • MammaPrint: 70-gene signature to categorize into 2 groups-good vs. poor prog irrespective of ER status; if high clinical risk, including 1-3 LN, but good prog on genetic risk, may be able to avoid chemo in postmenopausal pts (MINDACT, Lancet 2005;365:671; updated NEJM 2016;375:717, SABCS 2020)

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