PURPOSE: Somatostatin analogs act directly on breast cancer cells and indirectly on insulin and insulin-like growth factor 1 (IGF-1) levels. This trial was undertaken to assess whether octreotide would lower insulin and IGF-1 levels and reduce risk of breast cancer recurrence. PATIENTS AND METHODS: The NCIC CTG MA.14 (NCIC Clinical Trials Group MA.14) trial randomly assigned postmenopausal women to 5 years of tamoxifen 20 mg daily (TAM) or TAM plus 2 years of octreotide 90 mg depot intramuscular injections monthly (TAM-OCT) as adjuvant therapy. The primary end point was event-free survival (EFS). Secondary end points were relapse-free survival (RFS), overall survival (OS), toxicity, and effects of treatment on IGF physiology. RESULTS: Among 667 women with a median follow-up of 7.9 years, 220 events occurred-108 with TAM-OCT and 112 with TAM. Adjusted hazard ratios (HRs; TAM-OCT to TAM) were 0.93 for EFS (95% CI, 0.71 to 1.22; P = .62), 0.84 for RFS (95% CI, 0.59 to 1.18; P = .31), and 0.97 for OS (95% CI, 0.69 to 1.37; P = .86). Among patients with normal baseline gallbladder imaging, cholecystectomy was required in 23.0% of those receiving TAM-OCT but in only 1.4% of those receiving TAM (P < .001). At 4 months, TAM-OCT had significantly (P < .001) lowered IGF-1, IGF binding protein 3, and C-peptide levels. Older age (P = .02), tumor size (P = .001), nodal status (P = .01), high C-peptide levels (P < .001), and higher body mass index (BMI) in models excluding C-peptide (P < .001) were associated with poorer EFS in multivariate analysis. CONCLUSION:Octreotide-related changes in circulating IGF-1 and C-peptide levels were statistically significant. Octreotide did not add significant clinical benefit. High C-peptide levels (surrogate for insulin secretion rate) and high BMI were associated with poor outcome.
RCT Entities:
PURPOSE: Somatostatin analogs act directly on breast cancer cells and indirectly on insulin and insulin-like growth factor 1 (IGF-1) levels. This trial was undertaken to assess whether octreotide would lower insulin and IGF-1 levels and reduce risk of breast cancer recurrence. PATIENTS AND METHODS: The NCIC CTG MA.14 (NCIC Clinical Trials Group MA.14) trial randomly assigned postmenopausal women to 5 years of tamoxifen 20 mg daily (TAM) or TAM plus 2 years of octreotide 90 mg depot intramuscular injections monthly (TAM-OCT) as adjuvant therapy. The primary end point was event-free survival (EFS). Secondary end points were relapse-free survival (RFS), overall survival (OS), toxicity, and effects of treatment on IGF physiology. RESULTS: Among 667 women with a median follow-up of 7.9 years, 220 events occurred-108 with TAM-OCT and 112 with TAM. Adjusted hazard ratios (HRs; TAM-OCT to TAM) were 0.93 for EFS (95% CI, 0.71 to 1.22; P = .62), 0.84 for RFS (95% CI, 0.59 to 1.18; P = .31), and 0.97 for OS (95% CI, 0.69 to 1.37; P = .86). Among patients with normal baseline gallbladder imaging, cholecystectomy was required in 23.0% of those receiving TAM-OCT but in only 1.4% of those receiving TAM (P < .001). At 4 months, TAM-OCT had significantly (P < .001) lowered IGF-1, IGF binding protein 3, and C-peptide levels. Older age (P = .02), tumor size (P = .001), nodal status (P = .01), high C-peptide levels (P < .001), and higher body mass index (BMI) in models excluding C-peptide (P < .001) were associated with poorer EFS in multivariate analysis. CONCLUSION:Octreotide-related changes in circulating IGF-1 and C-peptide levels were statistically significant. Octreotide did not add significant clinical benefit. High C-peptide levels (surrogate for insulin secretion rate) and high BMI were associated with poor outcome.
Authors: Judith-Anne W Chapman; Joseph P Costantino; Bin Dong; Richard G Margolese; Kathleen I Pritchard; Lois E Shepherd; Karen A Gelmon; Norman Wolmark; Michael N Pollak Journal: Breast Cancer Res Treat Date: 2015-08-15 Impact factor: 4.872
Authors: Young Kwang Chae; Mimi I Hu; Ruth L Katz; Mariana Chavez-MacGregor; Paul Haluska; Funda Meric-Bernstam; Ana M Gonzalez-Angulo; Amal Melhem-Bertrandt Journal: J Clin Oncol Date: 2013-06-24 Impact factor: 44.544
Authors: Manuel Valdivieso; Benjamin W Corn; Janet E Dancey; D Lawrence Wickerham; L Elise Horvath; Edith A Perez; Alison Urton; Walter M Cronin; Erica Field; Evonne Lackey; Charles D Blanke Journal: Semin Oncol Date: 2015-07-10 Impact factor: 4.929
Authors: Pamela J Goodwin; Wendy R Parulekar; Karen A Gelmon; Lois E Shepherd; Jennifer A Ligibel; Dawn L Hershman; Priya Rastogi; Ingrid A Mayer; Timothy J Hobday; Julie Lemieux; Alastair M Thompson; Kathleen I Pritchard; Timothy J Whelan; Som D Mukherjee; Haji I Chalchal; Conrad D Oja; Katia S Tonkin; Vanessa Bernstein; Bingshu E Chen; Vuk Stambolic Journal: J Natl Cancer Inst Date: 2015-03-04 Impact factor: 13.506
Authors: Judy-Anne W Chapman; Kathleen I Pritchard; Paul E Goss; James N Ingle; Hyman B Muss; Susan F Dent; Ted A Vandenberg; Brian Findlay; Karen A Gelmon; Carolyn F Wilson; Lois E Shepherd; Michael N Pollak Journal: World J Clin Oncol Date: 2014-12-10
Authors: Marianne Ewertz; Kathryn P Gray; Meredith M Regan; Bent Ejlertsen; Karen N Price; Beat Thürlimann; Hervé Bonnefoi; John F Forbes; Robert J Paridaens; Manuela Rabaglio; Richard D Gelber; Marco Colleoni; István Láng; Ian E Smith; Alan S Coates; Aron Goldhirsch; Henning T Mouridsen Journal: J Clin Oncol Date: 2012-10-08 Impact factor: 44.544
Authors: Sara B Jones; Gwendolyn A Thomas; Sara D Hesselsweet; Marty Alvarez-Reeves; Herbert Yu; Melinda L Irwin Journal: Cancer Prev Res (Phila) Date: 2012-12-04