Adjuvant endocrine therapy

 Ref: ASCO education book 2022

1. What is the correct duration of endocrine therapy?

• 10 yr if node positive, although 7 yr may be sufficient for AI
• 10 yr for tamoxifen based on ATTOm and ATLAS trials : absolute reduction in disease recurrence of approximately 3% to 4%, and in breast cancer mortality of 2.8%

2.  Benefit of endocrine therapy

-50% recurrences happen in the first 5 yr. 2% recurrence per year LN neg, 4% per yr if LN +

-MA-17 trial showed a 4.6% absolute reduction in recurrences for patients receiving 5 additional years of letrozole after 5 years of tamoxifen, with an improvement in disease-free survival (DFS) observed in lymph node–negative and –positive disease as early as 2 years

-But OS benefit only in LN + patients

3. Role of adjuvant CDK4/6 in the adjuvant setting: who and how long?

Abema 2 yr if high risk- high risk means 4 or more LN. If 1-3 LN, for tumors > 5cm or grade 3--> IDFS benefit of 7% at 4 yr in abema group ( 85 v 76%)

Ribociclib 3 yr- intermediate or high risk: stage IIA (either N0 with additional risk factors or 1-3 axillary lymph nodes [N1]), stage IIB, or stage III per AJCC 

-3 yr IDFS 90% versus 87%. Overall, the addition of ribociclib reduced the risk for recurrence by 25%

4. Premenopausal women: choice of therapy

Tamoxifen versus Tamoxifen with OFS: OS benefit with the addition of OFS to tamoxifen: reduction of recurrence by 1.4% and risk of death by 2.3% at 12 yr, SOFT trial.

-12-year OS was more than 95% in pre-menopausal women with grade 1 or 2, less than 2 cm, node neg

-12 yr OS in women who got chemo: adding OFS to tamoxifen produced an absolute reduction in distant recurrence/death of 2.6%/4.7% at 12 years (OS improved from 78.9% to 83.6%).

- ER+ HER2-negative disease who received neoadjuvant chemotherapy or were younger than age 35, absolute survival improvement was in the range of 10% for either oral endocrine agent combined with OFS compared with tamoxifen alone

- AI versus Tamoxifen in addition to OFS: distant recurrence less with AI, no survival difference so far in premenopausal women

5. Males with breast cancer

Tamoxifen or AI with GnRH agonists

Need Germline testing.

Were included in the NATALEE trial

6. Role of bisphosphonates: ASCO and Cancer Care Ontario guidelines

- Strongly consider in post menopausal women - zoledronic acid q 6 months for 3-5  yr. Clodronate may be used. Not enough data to support denosumab. No conclusive evidence that 5 yr is better than 3 yr.

-Educate about risk of ONJ, renal failure, hypocalcemia and risk of ocular complications. Monitor calcium, renal function and ask for dental issues, ocular symptoms before each treatment.

- In women age ≤ 60 years with a previous hysterectomy and ovaries left in place, luteinizing hormone, follicle-stimulating hormone, and serum estradiol should be in the postmenopausal range and measured prior to initiation of any systemic therapy to receive adjuvant bisphosphonates

-In postmenopausal women, the addition of bisphosphonates led to an absolute 2.2% reduction in the risk of bone recurrence (rate ratio, 0.72) and a 3.3% reduction in the risk of breast cancer mortality (rate ratio, 0.82) with a greater effect in older women, whereas no substantial effect was observed in premenopausal patients

- addition of bisphosphonates should be considered in women who were premenopausal at breast cancer diagnosis and who receive OFS as part of their endocrine therapy

7. De-escalation of endocrine therapy: When to use BCI

-in year 4 of planned 5 yr of AI, if patient is intolerant, do BCI to see if it would help to continue

- if HER 2+ and ER+, BCI can identify low risk patients who can stop AI at 5 yr