Does Tamoxifen Work in ER Negative Tumors?

Several preclinical studies have demonstrated that tamoxifen acts:
- Not only by blocking the ER pathway:
  - But also by modulating the production of:
    - Transforming growth factor-alpha
    - Transforming growth factor-beta
    - By increasing the levels of sex hormone-binding globulin in serum
    - Increasing natural killer cell counts
    - By decreasing insulin-like growth factor
The NSABP protocol B-23:
- Was developed to determine whether:
  - Tamoxifen has a role in patients with ER negative cancer
- Patients with ER negative tumors were randomized to:
  - Four cycles of adjuvant doxorubicin and cyclophosphamide (AC) or 6 cycles of adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) with or without tamoxifen
- The results of B-23 demonstrated:
  - No significant improvement in DFS or overall survival (OS) with tamoxifen added to chemotherapy:
    - DFS:
      - CMF, 83%; CMF plus tamoxifen, 83%
      - AC, 83%; AC plus tamoxifen, 82%
    - OS:
      - CMF, 89%; CMF plus tamoxifen, 89%
      - AC, 90%; AC plus tamoxifen, 91%
  - Additionally, protocol B-23 confirmed the results of protocol B-15:
    - That found that four cycles of AC are equivalent to 6 cycles of CMF in terms of DFS and OS
NSABP B-24:
- Also demonstrated the effectiveness of tamoxifen only on ER+ ductal carcinoma in situ (DCIS):
  - As did a study by Allred et al. on the risk reduction of a subsequent breast cancer in ER+ DCIS treated with tamoxifen

References

1. Fisher B, Anderson S, Tan-Chiu E, Wolmark N, Wickerham DL, Fisher ER,et al. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001;19(4):931-942.

2. Wapnir IL, Dignam JJ, Fisher B, Mamounas EP, Anderson SJ, Julian TB, et al. Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst. 2011;103(6):478-488.

3. Allred DC, Anderson SJ, Paik S, Wickerham DL, Nagtegaal ID, Swain SM, et al. Adjuvant tamoxifen reduces subsequent breast cancer in women with estrogen receptor-positive ductal carcinoma in situ: a study based on NSABP protocol B-24. J Clin Oncol. 2012;30(12):1268-1273.