The Influence Of Obesity On Results Of AT (Doxorubicin Plus Docetaxel) Neoadjuvant Chemotherapy In Locally Advanced Breast Cancer Patients
The achieve pathologic complete response is proven to be the most important parameter of prognosis. Thereports evaluating the impact of obesity on the obtained pathologic response to chemotherapy are unequal. The aim of the study was to evaluate in locally advanced breast cancer patients, treated with AT(doxorubicin plus docetaxel) neoadjuvant chemotherapy: 1. The relationship of obesity with obtaining pathological response. 2. The relationship of obesity and free of disease recurrence survival (DFS) and overall survival (OS) associated with the tumour. Material and methods. A retrospective study was carried out in a group of 105 patients with locally advanced breast cancer, treated with AT neoadjuvant chemotherapy and then treated with radical surgery. Two variants of pathological response have been adopted: a pCR (T0N0) and pCR1 (TisN0, TxN1, T1N0, T1N1, T0N1). The relationship of obesity with pathological response and survival was investigated. Results. In univariate analysis the pCR1 was obtained with its arising from the borderline of statistical significance with lower incidence of obesity. In pCR1 multivariate analysis, negative pCR1 relationship with obesity was on the borderline of the statistical significance. The multivariate analysis showed a significant negative association OS with obesity (p=0.047) and positive with the occurrence of menopause (p = 0.029). Conclusions. In patients with locally advanced breast cancer treated with AT neoadjuvant chemotherapy. 1. Obesity seems to be an independent and unfavourable predictor of the lack of obtaining pCR1 pathological response 2. In the multivariate analysis, the obesity was a significant independent factor related to shorter OS.
- West Pomeranian Oncological Center in SzczecinOrdynator:
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical UniversityKierownik: prof. dr hab.
- Department of General and Oncological Surgery, Pomeranian Medical UniversityKierownik: prof. dr hab.
- Department of Medical Oncology, Pomeranian Medical UniversityKierownik: dr hab. prof. PUM , email@example.com
- 1. Fiszer B, Brown A, Mamounas E et al.: Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical adjuvant Breast and Bowel Project B-18. J Clin Oncol 1997; 15: 2483-93.
- 2. Gianni L, Baselga J, Eiermann W et al.: Feasibility and tolerability of sequential Doxorubicin/paclitaxel followed by cyclophosphamide, metotrexat and fluorouracil and its effects on tumor response as preoperative therapy. Cancer Res 2005; 11: 8715-21.
- 3. Cataliotti L, Buzdar AU, Noguchi S et al.: Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor-positive breast cancer: the Pre-Operative "Arimidex" Compared to Tamoxifen (PROACT) trial. Cancer 2006; 15, 2095-2103.
- 4. Bear HD, Anderson S, Smith RE et al.: Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer. National surgical adjuvant and bowel project protocol B-27. J Clin Oncol 2006; 24: 2019-27.
- 5. Mrozikiewicz-Rakowska B, Krasnodębski P, Karnafel W: Otyłość i cukrzyca a występowanie chorób nowotworowych. Nowa Klinika 2008; 13: 3-4.
- 6. Sinicrope FA, Dannenberg AJ : Obesity and breast cancer prognosis: weight of the evidence. J Clin Oncol 2011; 29: 4-7.
- 7. MacDonald PC, Edman CD, Hamsell DL et al.: Effect of obesity on conversion of plasma androstenedione to estrone in postmenopausale women with and without endometrial cancer. Am J Obset Gynecol 1978; 130: 448.
- 8. Yumuk PF, Dane F, Yumuk VD et al.: Imapct of body mass index on cancer development. J Buon 2008; 13: 55-59.
- 9. Dal Maso L, Zucchetto A, Talamini R et al.: Prospective analysis of case-control study on environmental factors and health (PACE) study group. Effect of obesity and other lifestyle factors on mortality in women with breast cancer. Int Cancer 2008; 123: 2188-94.
- 10. Heys SD, Hutcheon AW, Sarkar TK et al.: Neoadjuvant docetaxel in breast cancer: 3-years survival results from Aberdeen trial. Clin Breast Cancer 2002; 3: 69-74.
- 11. Buzdar AU, Ibrahim NK, Francis D et al.: Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol 2005; 23: 3676-85.
- 12. Gianni L, Eiermann W, Semiglazov V et al.: Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet 2010; 375: 377-84.
- 13. Sheng Chen, Can-Ming Chen, Ying Zhou et al.: Obesity or overweight is associated with worse pathological response to neoadjuvant chemotherapy pathological response to neoadjuvant chemotherapy among Chinese women with breast cancer. PLoS ONE 2012; 7: 41380.
- 14. Rastogi P, Anderson SJ, Bear HD et al.: Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Cancer. Bowel Project Protocols B-18 and B-27. J Clin Oncol 2008; 26: 778-85.
- 15. Litton JK, Gonzales-Angulo AM, Warneke CL et al.: Relationship between obesity and pathologic response to neoadjuvant chemotherapy among women with operable breast cancer. J Clin Oncol 2008; 26: 40727.
- 16. Kuerer HM, Newman LA, Smith TL et al.: Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 1999; 17: 460-69.
- 17. Kayung-Hun Lee, Bhumsuk Keam, Seock-Ahim et al.: Body mass index is not associated with treatment outcomes of breast cancer patients receiving neoadjuvant chemotherapy. J Breast Cancer 2012; 15: 427-33.
- 18. Shaheenah Dawood, Kristine Broglio, Shu-Wan Kau et al.: Prognostic value of initial clinical disease stage after achieving pathological complete response. The Oncologist 2008; 13: 6-15.
- 19. Rosner GL, Hargis JB, Hollis DR et al.: Relationship between toxicity and obesity in women receiving adjuvant chemotherapy for breast cancer. Results from Cancer and Leukemia Group b study 8541. J Clin Oncol 1996; 14: 3000-08.
- 20. Jaźwińska-Tarnowska E, Kubiak E, Wiela-Hojeńska A: Differences in pharmacokinetics in obesity. Do obese persons require changes in therapeutic schemes? Adv Clin Exp Med 2006; I5: 669-76.
- 21. Dan T. Vogl, Tao Wang, Waleska S et al.: Effect of obesity on outcomes after autologous hematopoietic stem cell transplantation for multiple myeloma. Biology of Blood and Marrow Transplantation 2011; 17: 1765-74.
- 22. Griggs JJ, Sorbero ME, Lyman GH: Undertreatment of obese women receiving breast cancer chemotherapy. Arch Intern Breast Cancer Res Treat 2010; 123: 627-35.
- 23 Colleoni M, Li S, Gelber RD et al.: Relation between chemotherapy dose, oestrogen receptor expression, and body-mass index. Lancet 2005; 366: 1108-10.
- 24. Hall RG, Jean GW, Sigler M, Shah S: Dosing considerations for obese patients receiving cancer chemotherapeutic agents. Ann Pharmacother 2013; 47: 1666-74.
- 25. Hanley MJ, Abernethy DR, Greenblatt DJ : Effect of obesity on the pharmacokinetics of drugs in humans. Clin Phar Pharmacokinet 2010; 49: 71-87.
- 26. Thompson LA, Lawson AP, Sutphin SD et al.: Description of current practices of empiric chemotherapy dose adjustment in obese adult patients. J.Oncol Pract 2010; 6: 141-45.
- 27. Griggs JJ, Mangu PB, Anderson H et al.: Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline American Society of Clinical Oncology. J Clin Oncol 2012; 30: 1553-61.
- 28. Greenman CG, Jagielski CH, Griggs JJ : Breast cancer adjuvant chemotherapy dosing in obese patients: dissemination of information from clinical trials to clinical practice. Cancer 2008; 15: 112.
- 29. Protani M, Coory M, Martin JH : Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer 2010; 123: 627-35.
- 30 Chan DSM, Vieira AR, Aune D, Bandera EV: Body mass index and survival in women with breast cancer – systematic literature review and meta-analysis of 82 follow-up studies. Ann Oncol 2014; 25: 1901-14.