Exercise to Prevent Aromatase Inhibitor Side Effects in Breast Cancer Patients

Hormone receptor-positive tumors are the most common breast cancers in postmenopausal women, and drug therapies, which block the production or effects of estrogen, are the mainstay of treatment in these patients. Due to their effectiveness in postmenopausal women, aromatase inhibitors (AIs) are the standard of care for long-term estrogen suppression in these patients. Estrogen deficiency, however, results in multiple side effects. Some of the most common side effects in women taking AIs are joint and muscle aches, which promote physical deconditioning. Because of the long term use of AIs in postmenopausal breast cancer patients and the improvements in cancer-related outcomes that are observed with their use, identifying methods to reduce these side effects to maintain adherence to treatment is important. Exercise interventions in breast cancer patients also improve quality of life and reduce fatigue. Understanding the role of exercise in AI side effect prevention will allow us to translate these findings into therapy guidelines.

Sex

Female

Minimum age

40 Years

Maximum age

80 Years

Inclusion Criteria:

* At least mild fatigue in 2 of the 4 areas of the Piper Fatigue Scale (score ≥ 1-3)
* Completion of standard surgery +/- chemotherapy for breast cancer (may undergo radiation therapy during study)
* 25-OH vitamin D \> 20 ng/ml
* Histological evidence of stage I-III hormone receptor-positive breast cancer
* Body Mass Index \>/=18 and \<50 kg/m2
* 40-80 years of age
* Non-smoking (non smoking for at least 12 months: cigarettes, cigars, pipes
* Menopause over one year (absence of menses for 12 months or greater)
* Sedentary (exercise no \>60 min 2 times/week)

Exclusion Criteria:

* Taking oral steroids, warfarin, or other medications interfering with fat metabolism that may not be safely discontinued temporarily for specific produces (i.e. for 72 hours prior)
* Symptomatic heart disease, coronary artery disease, congestive heart failure, or uncontrolled hypertension (systolic blood pressure over 180 mm HG)unless medically stabilized
* Participant is, in the opinion of the investigator, unable to adhere to the study protocol due to medical or orthopedic conditions that limit ability to exercise or travel to the Baltimore VA for protocol procedures
* Chronic pulmonary disease (on supplemental O2)
* Abnormal renal function (BUN above 40 mg/dl, Cr above 1.3 mg/dl, CrCl\<60mg/dl)
* Unstable lymphedema
* Evidence of cancer metastases or recurrence
* Anemia HCT below 30 mg/dl, platelets below 80,000/cm3
* Type 1 diabetes; insulin treatment for diabetes, poorly controlled diabetes, HgA1c\>10%
* Abnormal response to exercise test (ST segment depression greater than 2mm, chest pain, significant arrhythmias, extreme shortness of breath, cyanosis, exercising BP above 240/120 mm HG, or other contraindications to exercise) confirmed with further diagnostic evaluations.
* Abnormal liver function
* Untreated dyslipidemia with National Cholesterol ATPIII 10 year cardiac risk score greater than 10% (www.nhlbi.nih.gov/guidelines/cholesterol/atp3upd04.htm)
* Metal implants or devices (i.e. pacemaker) if undergoing CT scan
* History of seizures or taking anti-seizure or anti convulsion medication
* Allergic to lidocaine
* Mini-mental state examination below 24, dementia, or unstable clinical depression by exam

• BACKGROUNDSociety AC. Cancer Facts & Figures 2013. Atlanta: American Cancer Society 2013.
• BACKGROUNDThomson CA, Thompson PA, Wright-Bea J, Nardi E, Frey GR, Stopeck A. Metabolic syndrome and elevated C-reactive protein in breast cancer survivors on adjuvant hormone therapy. J Womens Health (Larchmt). 2009 Dec;18(12):2041-7. doi: 10.1089/jwh.2009.1365. PMID 20044868
• BACKGROUNDCurt GA. Impact of fatigue on quality of life in oncology patients. Semin Hematol. 2000 Oct;37(4 Suppl 6):14-7. doi: 10.1016/s0037-1963(00)90063-5. PMID 11068951
• BACKGROUNDCramp F, Daniel J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD006145. doi: 10.1002/14651858.CD006145.pub2. PMID 18425939
• BACKGROUNDBraithwaite D, Satariano WA, Sternfeld B, Hiatt RA, Ganz PA, Kerlikowske K, Moore DH, Slattery ML, Tammemagi M, Castillo A, Melisko M, Esserman L, Weltzien EK, Caan BJ. Long-term prognostic role of functional limitations among women with breast cancer. J Natl Cancer Inst. 2010 Oct 6;102(19):1468-77. doi: 10.1093/jnci/djq344. Epub 2010 Sep 22. PMID 20861456
• BACKGROUNDBerger AM, Gerber LH, Mayer DK. Cancer-related fatigue: implications for breast cancer survivors. Cancer. 2012 Apr 15;118(8 Suppl):2261-9. doi: 10.1002/cncr.27475. PMID 22488700
• BACKGROUNDCollado-Hidalgo A, Bower JE, Ganz PA, Cole SW, Irwin MR. Inflammatory biomarkers for persistent fatigue in breast cancer survivors. Clin Cancer Res. 2006 May 1;12(9):2759-66. doi: 10.1158/1078-0432.CCR-05-2398. PMID 16675568
• BACKGROUNDLin NU, Winer EP. Advances in adjuvant endocrine therapy for postmenopausal women. J Clin Oncol. 2008 Feb 10;26(5):798-805. doi: 10.1200/JCO.2007.15.0946.