Adjuvant Hormonal Therapy for Breast Cancer

• After 10 years of follow-up from NSABP B-14:
  • A randomized, double-blind, placebo-controlled trial:
    • Comparing tamoxifen to placebo in women with node-negative estrogen receptor-positive invasive breast cancer
  • A statistically significant:
    • Disease-free survival (DFS) benefit was derived with the use of tamoxifen for 5 years:
      • 69% vs 57%, P<0.0001
  • Tamoxifen was also associated with:
    • A 37% reduction in contralateral breast cancers
• The NSABP B-24 trial:
  • Was designed to determine whether lumpectomy and postoperative breast irradiation plus prolonged tamoxifen therapy:
    • Is more effective than lumpectomy and breast irradiation without tamoxifen in preventing the subsequent occurrence of ipsilateral and contralateral breast cancers in patients with non-invasive ductal carcinoma in situ
• The results of NSABP B-14 paved the way:
  • For the administration of additional adjuvant hormonal therapy
  • More specifically:
  • The administration of aromatase inhibitors after completion of tamoxifen therapy became of interest
• NSABP B-33 was developed to compare:
  • Exemestane with placebo:
    • In recurrence-free postmenopausal women who completed 5 years of tamoxifen therapy
  • Accrual to this study was terminated prematurely:
    • When results of NCIC-CTG MA.17 showed:
      • A significant improvement with letrozole after 5 years of tamoxifen
      • With a median follow-up of 64 months, the hazard ratios of letrozole after 5 years of tamoxifen compared to placebo after similar tamoxifen therapy were:
        • 0.52 (95% confidence interval [CI], 0.45 to 0.61; P<.001) for DFS
        • 0.51 (95% CI, 0.42 to 0.61; P<.001) for distant DFS
        • 0.61 (95% CI, 0.52 to 0.71; P<.001) for overall survival
• The patients in NSABP B-33:
  • Were then unblinded and offered 5 years of exemestane
    • The improvement in relapse-free survival observed in NSABP B-33 with exemestane:
      • Was similar to that observed in the NCIC-CTG MA.17 trial with letrozole
• To further examine the benefits of aromatase inhibitors as primary therapy or after 2 to 5 years of tamoxifen in women with early-stage, hormone receptor-positive breast cancer:
  • The MA.17R trial:
    • Analyzed prolonging duration of therapy to 10 years:
      • With DFS as the primary endpoint
    • The results of this study were recently presented:
      • The study randomized 1918 women to placebo versus letrozole
      • Median follow-up of 6.3 years
      • DFS was 95% for the letrozole group and 91% for the placebo group
      • There was also an improvement in the annual incidence of contralateral breast cancer:
        • With the letrozole group at 0.21% versus 0.49% for the placebo group
      • These data support:
        • A new standard of care for this patient population, ie, to improve DFS through 10-year treatment with aromatase inhibitors

REFERENCES

1. Fisher B, Dignam J, Bryant J, Wolmark N. Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial. J Natl Cancer Inst. 2001;93:684-690.
2. Fisher B, Jeong JH, Dignam J, et al. Findings from recent National Surgical Adjuvant Breast and Bowel Project studies in stage I breast cancer. J Natl Cancer Inst Monogr. 2001;93:62-66.
3. Ingle JN, Tu D, Pater JL, et al. Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCIC CTG MA.17. Ann Oncol. 2008;19:877-882.
4. Jin H, Tu D, Zhao N, Shepherd LE, Goss PE. Long-term outcomes of letrozole versus placebo after 5 years of tamoxifen in the NCIC CTG MA.17 trial: analyses adjusting for treatment crossover. J Clin Oncol. 2012;30:718-721.
5. Lemieux J, Goss PE, Parulekar WR, et al. Patient-reported outcomes from MA.17R: a randomized trial of extending adjuvant letrozole for 5 years after completing an initial 5 years of aromatase inhibitor therapy alone or preceded by tamoxifen in postmenopausal women with early-stage breast cancer. J Clin Oncol. 2016;34 (suppl; abstr LBA506).
6. Mamounas EP, Jeong JH, Wickerham DL, et al. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast and Bowel Project B-33 trial. J Clin Oncol. 2008;26:1965-1971.

#Arrangoiz #Surgeon #BreastSurgeon #CancerSurgeon BreastCancer #SurgicalOncologist