Clinical implications of recent studies using mTOR inhibitors to treat advanced hormone receptor-positive breast cancer

Cancer Management and Research

Volumn 6, Issue , 2014, Pages 389-395

  Arena, Francis ^a  

^a Department of Medicine   (United States)

Author keywords

Advanced breast cancer; Endocrine resistance; Hormone receptor positive; mTOR inhibitors

Indexed keywords

3 (2 AMINO 5 BENZOXAZOLYL) 1 ISOPROPYL 1H PYRAZOLO[3,4 D]PYRIMIDIN 4 AMINE; 4 (4 AMINO 5 (7 METHOXY 1H INDOL 2 YL)IMIDAZO[5,1 F][1,2,4]TRIAZIN 7 YL)CYCLOHEXANECARBOXYLIC ACID; ANASTROZOLE; AZD 2014; AZD 8055; CAPECITABINE; CC 223; EVEROLIMUS; EXEMESTANE; HORMONE RECEPTOR; LETROZOLE; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; PALOMID 529; PLACEBO; RAPAMYCIN; TAMOXIFEN; TEMSIROLIMUS; UNCLASSIFIED DRUG;

ANEMIA; ANOREXIA; BONE METASTASIS; BONE TURNOVER; BREAST CANCER; BREAST METASTASIS; CANCER GROWTH; CANCER INCIDENCE; CANCER RECURRENCE; CANCER RISK; DIARRHEA; DRUG EFFICACY; DRUG SAFETY; DYSPNEA; FATIGUE; HORMONE RESISTANCE; HUMAN; HYPERCHOLESTEROLEMIA; HYPERGLYCEMIA; HYPERTRIGLYCERIDEMIA; INFECTION; MULTICENTER STUDY (TOPIC); NOTE; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PNEUMONIA; POSTMENOPAUSE; PROGRESSION FREE SURVIVAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; RISK ASSESSMENT; STOMATITIS; TREATMENT DURATION; TREATMENT OUTCOME;

EID: 84908286172     PISSN: None     EISSN: 11791322     Source Type: Journal    
DOI: 10.2147/CMAR.S56802     Document Type: Note

References (39)

1. Jemal A, Bray F, Center M M, Ferlay J, Ward E, Forman D, Global cancer statistics, 2011. CA Cancer J Clin. 2011;61(2):69–90.
2. American Cancer Society. Cancer facts and figures, 2013. Atlanta, GA, USA: American Cancer Society; 2013. Available from: http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-036845.pdf. Accessed March 5, 2014.
3. Setiawan VW, Monroe KR, Wilkens LR, Kolonel LN, Pike MC, Henderson BE. Breast cancer risk factors defined by estrogen and progesterone receptor status: the Multiethnic Cohort Study. Am J Epidemiol. 2009;169(10):1251–1259.
4. Anderson WF, Chatterjee N, Ershler WB, Brawley OW. Estrogen receptor breast cancer phenotypes in the Surveillance, Epidemiology, and End Results database. Breast Cancer Res Treat. 2002;76(1):27–36.
5. Bachman KE, Argani P, Samuels Y, et al. The PIK3CA gene is mutated with high frequency in human breast cancers. Cancer Biol Ther. 2004;3(8):772–775.
6. Saal LH, Holm K, Maurer M, et al. PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res. 2005;65(7):2554–2559.
7. Perez-Tenorio G, Alkhori L, Olsson B, et al. PIK3CA mutations and PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer. Clin Cancer Res. 2007;13(12):3577–3584.
8. Huang J, Manning BD. The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem J. 2008;412(2):179–190.
9. Margariti N, Fox SB, Bottini A, Generali D. Overcoming breast cancer drug resistance with mTOR inhibitors. Could it be a myth or a real possibility in the short-term future? Breast Cancer Res Treat. 2011;128(3): 599–606.
10. Villarreal-Garza C, Cortes J, Andre F, et al. MTOR inhibitors in the management of hormone receptor-positive breast cancer: the latest evidence and future directions. Ann Oncol. 2012;23(10):2526–2535.
11. Miller TW, Hennessy BT, Gonzalez-Angulo AM, et al. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer. J Clin Invest. 2010;120(7):2406–2413.
12. Beeram M, Tan QT, Tekmal RR, Russell D, Middleton A, deGraffenried LA. Akt-induced endocrine therapy resistance is reversed by inhibition of mTOR signaling. Ann Oncol. 2007;18(8):1323–1328.
13. deGraffenried LA, Friedrichs WE, Russell DH, et al. Inhibition of mTOR activity restores tamoxifen response in breast cancer cells with aberrant Akt activity. Clin Cancer Res. 2004;10(23):8059–8067.
14. Wyeth/Pfizer. Study Evaluating Temsirolimus (CCI-779) In Breast Neoplasms. In: ClinicalTrials.gov [website on the Internet]. Bethesda, MD: US National Library of Medicine; 2003 [updated April 13, 2011]. Available from http://clinicaltrials.gov/ct2/show/NCT00062751. NLM identifier: NCT00062751. Accessed March 11, 2014.
15. Carpenter J, Roche H, Campone M, et al. Randomized 3-arm, phase 2 study of temsirolimus (CCI-779) in combination with letrozole in postmenopausal women with locally advanced or metastatic breast cancer. Abstract 564 presented at the American Society of Clinical Oncology Annual Meeting, May 13–17, 2005, Orlando, FL, USA.
16. Wyeth/Pfizer. Study Evaluating CCI-779 and Letrozole in Post-menopausal Women With Breast Cancer. In: ClinicalTrials.gov [website on the Internet]. Bethesda, MD: US National Library of Medicine; 2004 [updated November 7, 2011]. Available from http://clinicaltrials.gov/ct2/show/NCT00083993?term=NCT00083993&rank=1. NLM identifier:NCT00083993. Accessed March 11, 2014.
17. Wolff AC, Lazar AA, Bondarenko I, et al. Randomized phase III placebo-controlled trial of letrozole plus oral tmsirolimus as first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancer. J Clin Oncol. 2013;31(2):195–202.
18. Bhattacharyya GN, Biswas J, Singh JH, et al. Reversal of tamoxifen resistance (hormone resistance) by addition of sirolimus (mTOR inhibitor) in metastatic breast. Abstract 16LBA presented at the 2011 European Multidisciplinary Cancer Congress, September 23–27, 2011, Stockholm, Sweden.
19. Awada A, Cardoso F, Fontaine C, et al. The oral mTOR inhibitor RAD001 (everolimus) in combination with letrozole in patients with advanced breast cancer: results of a phase I study with pharmacokinetics. Eur J Cancer. 2008;44(1):84–91.
20. ARCAGY/GINECO Group. Tamoxifen-RAD001 Versus Tamoxifen Alone in Patients With Anti-aromatase Resistant Breast Metastatic Cancer. In: ClinicalTrials.gov [website on the Internet]. Bethesda, MD: US National Library of Medicine; 2011. Available from http://clinicaltrials.gov/ct2/show/NCT01298713?term=NCT01298713&rank=1. NLM identifier:NCT01298713. Accessed March 11, 2014.
21. Bachelot T, Bourgier C, Cropet C, et al. Randomized Phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J Clin Oncol. 2012;30(22):2718–2724.
22. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone receptor-positive advanced breast cancer. N Engl J Med. 2012;366(6):520–529.
23. Hortobagyi GN, Piccart M, Rugo H, et al. Everolimus for postmenopausal women with advanced breast cancer: updated results of the BOLERO 2 Phase III trial. Abstract S3-7 presented at the CTRC-AACR San Antonio Breast Cancer Symposium, December 6–10, 2011, San Antonio, TX, USA.
24. Yardley DA, Noguchi S, Pritchard KI, et al. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013;30(10): 870–884.
25. Novartis Pharmaceuticals. Everolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole (BOLERO2). In: ClinicalTrials.gov [website on the Internet]. Bethesda, MD: US National Library of Medicine; 2009 [updated October 18, 2013]. Available from http://clinicaltrials.gov/ct2/show/NCT00863655?term=NCT00863655&rank=1. NLM identifier:NCT00863655. Accessed March 11, 2014.
26. Burris H, Gnant M, Hortobagyi G, et al. Characterization of response to everolimus (EVE) in BOLERO-2: a phase 3 trial of EVE plus exemestane (EXE) in postmenopausal women with HR+, HER2- advanced breast cancer. Abstract P2-16-17 presented at the San Antonio Breast Cancer Symposium, December 10–14, 2013, San Antonio, TX, USA.
27. Pritchard KI, Burris HA III, Ito Y, et al. Safety and efficacy of everolimus with exemestane vs exemestane alone in elderly patients with HER2-negative, hormone receptor-positive breast cancer in BOLERO-2. Clin Breast Cancer. 2013;13(6):421–432.
28. Campone M, Bachelot T, Gnant M, et al. Effect of visceral metastases on the efficacy and safety of everolimus in postmenopausal women with advanced breast cancer: subgroup analysis from the BOLERO-2 study. Eur J Cancer. 2013;49(12):2621–2632.
29. Beck JT, Hortobagyi GN, Campone M, et al. Everolimus plus exemestane as first-line therapy in HR+ HER2- advanced breast cancer in BOLERO-2. Breast Cancer Res Treat. 2014;144(3):459–467.
30. Burris HA III, Lebrun F, Rugo HS, et al. Health-related quality of life of patients with advanced breast cancer treated with everolimus plus exemestane versus placebo plus exemestane in the phase 3, randomized, controlled, BOLERO-2 trial. Cancer. 2013;119(10):1908–1915.
31. Maass N, Harbeck N, Mundhenke C, et al. Everolimus as treatment for breast cancer patients with bone metastases only: results of the phase II RADAR study. J Cancer Res Clin Oncol. 2013;139(12): 2047–2056.
32. Gnant M, Baselga J, Rugo HS, et al. Effect of everolimus on bone marker levels and progressive disease in bone in BOLERO-2. J Natl Cancer Inst. 2013;105(9):654–663.
33. Hadji P, Lüftner D, Fasching PA, et al. 4EVER: Does mTOR inhibition have a major clinical impact on bone health in postmenopausal women with hormone receptor positive (HR+) locally advanced breast cancer treated with everolimus (EVE) in combination with exemestane (EXE)? Abstract P6-06-32 presented at the San Antonio Breast Cancer Symposium, December 10–14, 2013, San Antonio, TX, USA.
34. Novartis Pharmaceuticals. Open-label, Phase II, Study of Everolimus Plus Letrozole in Postmenopausal Women With ER+, HER2Metastatic or Locally Advanced Breast Cancer (Bolero-4). In: ClinicalTrials.gov [website on the Internet]. Bethesda, MD: US National Library of Medicine; 2012 [updated February 6, 2014]. Available from http://clinicaltrials.gov/ct2/show/NCT01698918?term=NCT01698918&rank=1. NLM identifier:NCT01698918. Accessed February 6, 2014.
35. Gradishar WJ, Bachelot TD, Saletan S, et al. BOLERO-4: multicenter, open-label, phase II study of everolimus plus letrozole as first-line therapy in ER+, HER2- metastatic breast cancer. Abstract TPS661 presented at the American Society of Clinical Oncology Annual Meeting, May 31 to June 4, 2013, Chicago, IL, USA.
36. Novartis Pharmaceuticals. A Phase II Study of Everolimus in Combination With Exemestane Versus Everolimus Alone Versus Capecitabine in Advance Breast Cancer. (BOLERO-6). In: ClinicalTrials.gov [website on the Internet]. Bethesda, MD: US National Library of Medicine; 2013 [updated February 28, 2014]. Available from http://clinicaltrials.gov/ct2/show/NCT01783444?term=NCT01783444&rank=1. NLM identifier:NCT01783444. Accessed February 28, 2014.
37. Ejlertsen B, Jerusalem GHM, Hurvitz SA, et al. BOLERO-6: Phase II study of everolimus plus exemestane versus everolimus or capecitabine monotherapy in HR+, HER2- advanced breast cancer. Abstract TPS660 presented at the American Society of Clinical Oncology Annual Meeting, May 31 to June 4, 2013, Chicago, IL, USA.
38. Treilleuz I, Arnedos M, Cropet C, et al. Predictive markers of everolimus efficacy in hormone receptor positive (HR+) metastatic breast cancer (MBC): final results of the TAMRAD trial translational study. Abstract 510 presented at the American Society of Clinical Oncology Annual Meeting, May 31 to June 4, 2013, Chicago, IL, USA.
39. Hortobagyi GN, Piccart-Gebhart MJ, Rugo HS, et al. Correlation of molecular alterations with efficacy of everolimus in hormone receptor–positive, HER2-negative advanced breast cancer: results from BOLERO-2. Abstract LBA509 presented at the American Society of Clinical Oncology Annual Meeting; May 31 to June 4, 2013, Chicago, IL, USA.