Breast Cancer Research and Treatment

, Volume 153, Issue 2, pp 353–360 | Cite as

Octreotide LAR and tamoxifen versus tamoxifen in phase III randomize early breast cancer trials: NCIC CTG MA.14 and NSABP B-29

  • Judith-Anne W. ChapmanEmail author
  • Joseph P. Costantino
  • Bin Dong
  • Richard G. Margolese
  • Kathleen I. Pritchard
  • Lois E. Shepherd
  • Karen A. Gelmon
  • Norman Wolmark
  • Michael N. Pollak
Clinical Trial


NCIC CTG MA.14 and NSABP B-29 trials examined the addition of Octreotide LAR (OCT) to 5 years of tamoxifen (TAM). Gallbladder toxicity led to B-29 discontinuation of OCT, and MA.14 OCT administration shortened to 2 years. Median follow-up was 9.8 years for 667 MA.14 patients and 6.8 years for 893 B-29 patients. The primary endpoint was disease-free survival (DFS), defined as time from randomization to time of breast cancer recurrence; second primary cancer other than squamous or basal cell skin carcinoma, cervical carcinoma in situ, or lobular breast carcinoma in situ; or death. The primary statistical test was a univariable pooled stratified log-rank test; multivariable assessment was with Cox regression. For MA.14, 97 % of patients were ≥50 years; for B-29, 62 %. MA.14 patients were 53 % lymph node negative (LN−) while B-29 were 100 % LN−; 33 % of MA.14 patients received adjuvant chemotherapy, 2 % concurrently, while B-29 had 53 % concurrent chemotherapy. MA.14 patients were 90% hormone receptor positive; B-29, 100 %. MA.14 patients experienced 5-year DFS of 80 % with TAM, 76 % with TAM + OCT; B-29 patients had 5-year DFS of 88 % for both arms. Pooled univariable TAM + OCT to TAM hazard ratio (HR) was 0.99 (95% CI 0.81–1.20; p = 0.69): for MA.14, HR = 0.94 (0.73–1.20; p = 0.50); for B-29, HR = 1.09 (0.80–1.50; p = 0.59). Multivariable pooled HR = 0.98 (0.81–1.20; p = 0.84). Older patients (p < 0.001), with higher T stage (p < 0.001), and LN + (p < 0.001) had shorter DFS. Addition of OCT to TAM did not significantly improve DFS; gallbladder toxicity shortened the additional administration of OCT. This does not negate targeting the insulin–IGF-I receptor family with less toxic therapeutics.


Early breast cancer Tamoxifen Octeotide LAR Insulin pathway 



This work was supported for NCIC Clinical Trials Group MA.14 (NCT00002864) by the Canadian Cancer Society through the Canadian Cancer Society Research Institute (Grant Number 16512 to MNP), a grant from Novartis Pharmaceuticals Canada (MNP), and a NCIC Clinical Trials Group postdoctoral fellowship (BD). The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-29 (NCT00002967) was supported by the United States National Cancer Institute, Department of Health and Human Services Grants (Grant Numbers U10-CA-12027, U10-CA-69651, U10-CA-37377, U10-CA-69974, U10-CA180868, UG1-CA189867, U10-CA180822, U24-CA196067, and U24-CA114732).

Compliance with ethical standards

Conflict of interest

Dr. Kathleen I Pritchard has declared conflict of interest with AstraZeneca, Pfizer, Roche, Amgen, Novartis, GlaxoSmithKline, and Eisai. Dr. Karen A. Gelmon has declared conflict of interest with Novartis, AstraZeneca, Pfizer, and Roche. No other authors have declared any conflict of interest.

Supplementary material

10549_2015_3547_MOESM1_ESM.pdf (585 kb)
Supplementary material 1 (PDF 585 kb)
10549_2015_3547_MOESM2_ESM.pdf (814 kb)
Supplementary material 2 (PDF 814 kb)


  1. 1.
    Pollak M, Polychronakos C, Guyda H (1989) Somatostatin analogue SMS 201-995 reduces serum IGF-I levels in patients with neoplasms potentially dependent on IGF-I. Anticancer Res 9:889–892PubMedGoogle Scholar
  2. 2.
    van Eijck CH, Krenning EP, Bootsma A et al (1994) Somatostatin-receptor scintigraphy in primary breast cancer. Lancet 343(8898):640–643CrossRefPubMedGoogle Scholar
  3. 3.
    Weckbecker G, Tolcsvai L, Stolz B et al (1994) Somatostatin analogue octreotide enhances the antineoplastic effects of tamoxifen and ovariectomy on 7, 12-dimethylbenz(a)anthracene-induced rat mammary carcinomas. Cancer Res 54(24):6334–6337PubMedGoogle Scholar
  4. 4.
    Pritchard KI, Shepherd LE, Chapman JW et al (2011) A randomized trial of tamoxifen versus combined tamoxifen and octreotide lar therapy in the adjuvant treatment of early stage breast cancer in post-menopausal women: NCIC CTG MA.14. J Clin Oncol 29(27):3869–3876CrossRefPubMedGoogle Scholar
  5. 5.
    Pollak MN, Chapman JAW, Pritchard KI, et al. (2010) Tamoxifen versus tamoxifen plus octreotide LAR as adjuvant therapy for early stage breast cancer in postmenopausal women: Update of NCIC CTG MA14 trial. J Clin Oncol 28 (15S, pt I): 77s (Abstract)Google Scholar
  6. 6.
    Goss PE, Ingle JN, Pritchard KI, et al.; for the NCIC CTG MA.27 Study Investigators (2013). Exemestane versus Anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27 A Randomized Controlled Phase III Trial. J Clin Oncol 31(11):1398–1404Google Scholar
  7. 7.
    Chapman JW, Meng D, Shepherd L et al (2008) Competing causes of death from a randomized trial of extended adjuvant endocrine therapy for breast cancer. J Natl Cancer Inst 100(4):252–260PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Chapman JW, Pritchard KI, Goss PE et al (2014) Competing risks of death in younger and older postmenopausal breast cancer patients. World J Clin Oncol 5(5):1088–1096PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Cuzick J (2008) Primary endpoints for randomized trials of cancer therapy. Lancet Oncol 371(9631):2156–2158CrossRefGoogle Scholar
  10. 10.
    Pollak M (2012) Investigating metformin for cancer prevention and treatment: the end of the beginning. Cancer Discov 2(9):778–790CrossRefPubMedGoogle Scholar
  11. 11.
    Yee D (2015) A tale of two receptors: insulin and insulin-like growth factor signaling in cancer. Clin Cancer Res 21(4):667–669CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Judith-Anne W. Chapman
    • 1
    Email author
  • Joseph P. Costantino
    • 2
  • Bin Dong
    • 1
  • Richard G. Margolese
    • 3
  • Kathleen I. Pritchard
    • 4
  • Lois E. Shepherd
    • 1
  • Karen A. Gelmon
    • 5
  • Norman Wolmark
    • 6
  • Michael N. Pollak
    • 7
  1. 1.NCIC Clinical Trials GroupQueen’s UniversityKingstonCanada
  2. 2.NRG Oncology and the Department of BiostatisticsUniversity of PittsburghPittsburghUSA
  3. 3.NRG Oncology and the Jewish General HospitalMcGill UniversityMontrealCanada
  4. 4.Sunnybrook Odette Cancer CentreUniversity of TorontoTorontoCanada
  5. 5.British Columbia Cancer AgencyVancouverCanada
  6. 6.NRG Oncology and the Allegheny Cancer Center at Allegheny General HospitalPittsburghUSA
  7. 7.Jewish General HospitalMcGill UniversityMontrealCanada

Personalised recommendations