Bootcamp during neoadjuvant chemotherapy for breast cancer: a randomized pilot trial

Roshni Rao, Veronica Cruz, Yan Peng, Amy Harker-Murray, Barbara B Haley, Hong Zhao, Xian-Jin Xie, David Euhus, Roshni Rao, Veronica Cruz, Yan Peng, Amy Harker-Murray, Barbara B Haley, Hong Zhao, Xian-Jin Xie, David Euhus

Abstract

Introduction: Exercise may improve cancer outcomes. Neoadjuvant chemotherapy (NC) for breast cancer provides a unique setting to evaluate intervention effects. Treatments leading to decreased post-neoadjuvant Ki-67 levels, smaller tumor size, and higher pathologic response are associated with improved survival and lower recurrence. This randomized, prospective pilot trial evaluates the feasibility of supervised exercise during NC for breast cancer.

Methods: Stage II-III, ER positive, cancer patients with BMI > 25 receiving NC were randomized to standard NC with supervised bootcamp (NC + BC) or NC alone. Ki-67, C-peptide, BMI, and tumor size were measured before chemotherapy and at time of surgery.

Results: There were no initial differences between groups in regards to tumor size, C-peptide, BMI, and Ki-67. The NC + BC (n = 5) group had a lower mean BMI at the conclusion of NC compared with those (n = 5) in the NC group (28.0 versus 35.8, P = 0.03). Final tumor size was 2.59 cm in the NC + BC group versus 3.16 cm for NC (P = 0.76) Mean Ki-67 for NC + BC was 7% versus 29% with NC (P = 0.14). C-peptide (ng/mL) was equivalent between the two groups (4.55 NC + BC versus 4.74 NC, P = 0.85).

Conclusions: Adding a supervised exercise program to NC is feasible, decreases BMI, and may lead to lower Ki-67 levels and improved survival.

Keywords: Ki-67; breast cancer; exercise; neoadjuvant chemotherapy.

Figures

Figure 1
Figure 1
Study design. Note: Schema of randomized pilot trial. Abbreviations: ER, estrogen receptor; BMI, body mass index; IGF-1, IGF-insulin like growth factor 1.
Figure 2
Figure 2
Ki-67 change. Notes: Ki-67 initial reflects Ki-67 in core biopsy sample, final reflects Ki-67 after neoadjuvant chemotherapy in final surgical specimen for each patient. Bootcamp arm had marked changes in Ki-67, a potential indicator of improved breast cancer prognosis.
Figure 3
Figure 3
BMI change. Notes: Patient BMI at the time of diagnosis and at the conclusion of neaodjuvant chemotherapy. Statistically significant changes (P=0.03) in BMI were noted in the bootcamp arm.

References

    1. Ogunleye AA, Holmes MD. Physical activity and breast cancer survival. Breast Cancer Res. 2009;11:106.
    1. Meyerhardt JA, Giovannucci EL, Holmes MD, et al. Physical activity and survival after colorectal cancer diagnosis. J Clin Oncol. 2006;24:3527–34.
    1. Holmes MD, Chen WY, Feskanich D, Kroenke CH, Colditz GA. Physical activity and survival after breast cancer diagnosis. JAMA. 2005;293:2479–86.
    1. Jones LW, Douglas PS, Eves ND, et al. Rationale and design of the Exercise Intensity Trial (EXCITE): a randomized trial comparing the effects of moderate versus moderate to high-intensity aerobic training in women with operable breast cancer. BMC Cancer. 2010;10:531.
    1. Pierce JP, Stefanick ML, Flatt SW, et al. Greater survival after breast cancer in physically active women with high vegetable-fruit intake regardless of obesity. J Clin Oncol. 2007;25:2345–51.
    1. Abrahamson PE, Gammon MD, Lund MJ, et al. Recreational physical activity and survival among young women with breast cancer. Cancer. 2006;107:1777–85.
    1. Reigle BS, Wonders K. Breast cancer and the role of exercise in women. Methods Mol Biol. 2009;472:169–89.
    1. McNeely ML, Campbell KL, Rowe BH, Klassen TP, Mackey JR, Courneya KS. Effects of exercise on breast cancer patients and survivors: a systematic review and meta-analysis. CMAJ. 2006;175:34–41.
    1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics. CA Cancer J Clin. 2010;60:277–300.
    1. Holick CN, Newcomb PA, Trentham-Dietz A, et al. Physical activity and survival after diagnosis of invasive breast cancer. Cancer Epidemiol Biomarkers Prev. 2008;17:379–86.
    1. Irwin ML, Smith AW, McTiernan A, et al. Influence of pre- and postdiagnosis physical activity on mortality in breast cancer survivors: the health, eating, activity, and lifestyle study. J Clin Oncol. 2008;26:3958–64.
    1. West-Wright CN, Henderson KD, Sullivan-Halley J, et al. Long-term and recent recreational physical activity and survival after breast cancer: the California Teachers Study. Cancer Epidemiol Biomarkers Prev. 2009;18:2851–9.
    1. Ligibel JA, Giobbie-Hurder A, Olenczuk D, et al. Impact of a mixed strength and endurance exercise intervention on levels of adiponectin, high molecular weight adiponectin and leptin in breast cancer survivors. Cancer Causes Control. 2009;20:1523–8.
    1. Ligibel JA, Campbell N, Partridge A, et al. Impact of a mixed strength and endurance exercise intervention on insulin levels in breast cancer survivors. J Clin Oncol. 2008;26:907–12.
    1. Stull VB, Snyder DC, Demark-Wahnefried W. Lifestyle interventions in cancer survivors: designing programs that meet the needs of this vulnerable and growing population. J Nutr. 2007;137:243S–8S.
    1. Carlson RW, Allred DC, Anderson BO, et al. Breast cancer: Clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2009;7:122–92.
    1. Kaufmann M, von Minckwitz G, Bear HD, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol. 2007;18:1927–34.
    1. Lee J, Im YH, Lee SH, et al. Evaluation of ER and Ki-67 proliferation index as prognostic factors for survival following neoadjuvant chemotherapy with doxorubicin/docetaxel for locally advanced breast cancer. Cancer Chemother Pharmacol. 2008;61:569–77.
    1. Courneya KS, Segal RJ, Mackey JR, et al. Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. J Clin Oncol. 2007;25:4396–404.
    1. Polcher M, Friedrichs N, Rudlowski C, et al. Changes in Ki-67 labeling indices during neoadjuvant chemotherapy for advanced ovarian cancer are associated with survival. Int J Gynecol Cancer. 2010;20:555–60.
    1. Guarneri V, Piacentini F, Ficarra G, et al. A prognostic model based on nodal status and Ki-67 predicts the risk of recurrence and death in breast cancer patients with residual disease after preoperative chemotherapy. Ann Oncol. 2009;20:1193–8.
    1. Nishimura R, Osako T, Okumura Y, Hayashi M, Arima N. Clinical significance of Ki-67 in neoadjuvant chemotherapy for primary breast cancer as a predictor for chemosensitivity and for prognosis. Breast Cancer. 2010;17:269–75.
    1. Billgren AM, Rutqvist LE, Tani E, Wilking N, Fornander T, Skoog L. Proliferating fraction during neoadjuvant chemotherapy of primary breast cancer in relation to objective local response and relapse-free survival. Acta Oncol. 1999;38:597–601.
    1. Vatten LJ, Holly JM, Gunnell D, Tretli S. Nested case-control study of the association of circulating levels of serum insulin-like growth factor I and i nsulin-like growth factor binding protein 3 with breast cancer in young women in Norway. Cancer Epidemiol Biomarkers Prev. 2008;17:2097–100.
    1. Espelund U, Cold S, Frystyk J, Orskov H, Flyvbjerg A. Elevated free IGF2 levels in localized, early-stage breast cancer in women. Eur J Endocrinol. 2008;159:595–601.
    1. Goodwin PJ, Ennis M, Pritchard KI, et al. Insulin-like growth factor binding proteins 1 and 3 and breast cancer outcomes. Breast Cancer Res Treat. 2002;74:65–76.
    1. Ibrahim YH, Yee D. Insulin-like growth factor-I and breast cancer therapy. Clin Cancer Res. 2005;11:944s–50s.
    1. Goodwin PJ, Ennis M, Pritchard KI, et al. Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol. 2002;20:42–51.
    1. Barnard RJ, Gonzalez JH, Liva ME, Ngo TH. Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro. Nutr Cancer. 2006;55:28–34.
    1. Irwin ML, Varma K, Alvarez-Reeves M, et al. Randomized controlled trial of aerobic exercise on insulin and insulin-like growth factors in breast cancer survivors: the Yale Exercise and Survivorship study. Cancer Epidemiol Biomarkers Prev. 2009;18:306–13.
    1. Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007;25:4414–22.
    1. Irwin ML, Duggan C, Wang CY, et al. Fasting C-peptide levels and death resulting from all causes and breast cancer: the health, eating, activity, and lifestyle study. J Clin Oncol. 2011;29:47–53.
    1. Keinan-Boker L, Bueno De Mesquita HB, et al. Circulating levels of insulin-like growth factor I, its binding proteins −1,−2,−3, C-peptide and risk of postmenopausal breast cancer. Int J Cancer. 2003;106:90–5.
    1. Janssen JA, Stolk RP, Pols HA, Grobbee DE, Lamberts SW. Serum total IGF-I, free IGF-I, and IGFB-1 levels in an elderly population: relation to cardiovascular risk factors and disease. Arterioscler Thromb Vasc Biol. 1998;18:277–82.
    1. Williams NH, Hendry M, France B, Lewis R, Wilkinson C. Effectiveness of exercise-referral schemes to promote physical activity in adults: systematic review. Br J Gen Pract. 2007;57:979–86.
    1. Courneya KS, Friedenreich CM, Reid RD, et al. Predictors of follow-up exercise behavior 6 months after a randomized trial of exercise training during breast cancer chemotherapy. Breast Cancer Res Treat. 2009;114:179–87.
    1. Del Rio G, Zironi S, Valeriani L, et al. Weight gain in women with breast cancer treated with adjuvant cyclophosphomide, methotrexate and 5- fluorouracil. Analysis of resting energy expenditure and body composition. Breast Cancer Res Treat. 2002;73:267–73.
    1. Demark-Wahnefried W, Kenyon AJ, Eberle P, Skye A, Kraus WE. Preventing sarcopenic obesity among breast cancer patients who receive adjuvant chemotherapy: results of a feasibility study. Clin Exerc Physiol. 2002;4:44–9.

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