Weight changes during chemotherapy for breast cancer

spmj Sao Paulo Medical Journal Sao Paulo Med. J. 1516-3180 1806-9460 Associação Paulista de Medicina - APM São Paulo, SP, Brazil CONTEXTO: Pacientes recebendo quimioterapia adjuvante por câncer de mama têm tendência a ganhar peso. Esta tendência tem fatores determinantes não completamente definidos e seu significado prognóstico é incerto. OBJETIVO: Avaliar a variação de peso durante tratamento quimioterápico por câncer de mama em uma população definida, identificar fatores predisponentes e seu possível significado prognóstico. TIPO DE ESTUDO: Observacional, de coorte retrospectiva. LOCAL: Serviço privado de oncologia clínica. PARTICIPANTES: Cento e seis pacientes consecutivas com câncer de mama tratadas entre junho de 1994 e abril de 2000 e que receberam quimioterapia neoadjuvante (n = 8), adjuvante (n = 74) ou paliativa (n = 24). PROCEDIMENTOS: Revisão de prontuários médicos com coleta de dados clínicos incluindo peso corporal das pacientes antes do tratamento e nas avaliações subseqüentes. VRIÁVEIS ESTUDADAS: Variação de peso corporal expresso em percentual do peso corporal por mês em tratamento, influência de variáveis clínicas nesta variação de peso e influência da variação de peso na sobrevida global e sobrevida livre de doença. RESULTADOS: Houve um ganho de peso médio de 0,50 ± 1,42% (p = 0,21) do peso corpóreo por mês de tratamento. Constatamos uma correlação negativa entre presença de doença metastática e ganho de peso (r = -0,447, p < 0,0001). No grupo em quimioterapia adjuvante e neoadjuvante, houve um ganho de peso médio de 0,91 ± 1,19 % (p < 0,00001) do peso corpóreo por mês de tratamento, enquanto que, no grupo com doença metastática (paliativo), observamos uma perda de peso média de 0,52 ± 1,21% (p = 0,11) do peso corpóreo por mês de tratamento. Não observamos correlação estatisticamente significante entre variação de peso e sobrevida livre de doença ou sobrevida global. CONCLUSÕES: Mulheres com câncer de mama recebendo tratamento quimioterápico adjuvante e neo-adjuvante ganham peso, enquanto mulheres com câncer de mama metastático possivelmente perdem peso durante quimioterapia paliativa. Estudos subseqüentes são necessários para avaliar o valor prognóstico da variação de peso durante quimioterapia. Original Article Weight changes during chemotherapy for breast cancer Integrated Oncology and Hematology consultation office, São Paulo, Brazil. • Luciano José Megale Costa • Paulo César Spotti Varella • Auro del Giglio ABSTRACT CONTEXT: Patients receiving adjuvant chemotherapy for breast cancer have a tendency to gain weight. This tendency has determining factors not completely defined and an unknown prognostic impact. OBJECTIVE: To evaluate weight change during chemotherapy for breast cancer in a defined population and to identify its predisposing factors and possible prognostic significance. DESIGN: Observational, retrospective cohort study. SETTING: Private clinical oncology service. PARTICIPANTS: 106 consecutive patients with breast cancer treated between June 1994 and April 2000, who received neoadjuvant (n = 8), adjuvant (n = 74) or palliative (n = 24) chemotherapy. INTERVETION: Review of medical records and gathering of clinical information, including patients’ body weights before treatment and at follow-up reviews. MAIN MEASUREMENTS: Body weight change, expressed as percentage of body weight per month in treatment; role of clinical data in weight change; and influence of weight change in overall survival and disease-free survival. RESULTS: There was a mean increase of 0.50 ± 1.42% (p = 0.21) of body weight per month of treatment. We noted a negative correlation between metastatic disease and weight gain (r = -0.447, p < 0.0001). In the adjuvant and neoadjuvant therapy groups there was a mean weight gain of 0.91 ± 1.19 % (p < 0.00001) per month, whereas in the metastatic (palliative) group, we observed a mean loss of 0.52 ± 1.21% (p = 0.11) of body weight per month during the treatment. We did not observe any statistically significant correlation between weight changes and disease-free survival or overall survival. CONCLUSIONS: Women with breast cancer undergoing adjuvant or neoadjuvant chemotherapy gain weight, whereas metastatic cancer patients will probably lose weight during palliative chemotherapy. Further studies are needed in order to evaluate the prognostic significance of weight changes during chemotherapy. KEY WORDS: Breast Neoplasm. Chemotherapy adjuvant. Body weight. Obesity. INTRODUCTION Patients receiving adjuvant chemotherapy for breast cancer treatment have a tendency to progressively gain weight, as has been previously described in the literature.1-8 In these series, between 50% and 96% of patients had an increase in their weight, with 20% of them gaining more than 10 kg.1 Several factors may play a role in this setting, such as increased food intake due to anxiety or to alleviate chemotherapy-related nausea and emesis,4,8,9,10 decreased physical activity,11,12,13 and modification of basal metabolic rate.1,14 In addition, being premenopausal1,4,7,8 and the use of corticosteroids containing chemotherapy protocols1,3 have also been identified as risk factors for weight gain. Regardless of the mechanism involved, weight gains may predispose these patients to chronic diseases such as arterial hypertension, diabetes mellitus and osteoarthritis, thereby negatively influencing their quality of life6 and possibly their survival. In addition, in some series, weight gain during adjuvant chemotherapy may correlate with tumor relapse.1,15 Breast cancer has a high incidence and is the leading cause of cancer death among women in Brazil (Datasus, 1999). Despite one previous paper that investigated the correlation between body weight and breast cancer incidence in Brazil,16 there is little data on weight changes observed during chemotherapy in breast cancer patients in our country. We therefore decided to make a retrospective study to characterize weight changes during chemotherapy among a group of consecutive women with breast cancer followed up by a single Brazilian institution. We also attempted to identify factors that would predict weight changes in these patients as well as investigating possible associations between weight changes and risk of tumor relapse and overall survival. METHODS We performed a retrospective observational review-based study of the medical records of consecutive women with breast cancer seen at a private clinical oncology service between June 1994 and April 2000. Only records containing complete information regarding tumor staging, menopausal status, initial anthropometrical data, therapy protocol, number of cycles (if chemotherapy was used), and at least two weight records (during one or more cycles of chemotherapy with at least one month between them), were considered. The patients were weighted during medical visits that were held during the afternoon hours, while using light clothes and always before the next chemotherapy session. Following the aforementioned criteria, we selected for analysis 106 out of a total of 198 medical records. The major causes of exclusion were: no eligibility for chemotherapy (n = 24; 12.1%), drop-out (n = 39; 19.6%), and unsatisfactory weight data (n = 29; 14.6%). The mean follow-up was 4.9 months (minimum of one and maximum of 27 months) with a total of 520 patient-months. Seventy-four patients received adjuvant, 8 neoadjuvant and 24 palliative chemotherapy for metastatic disease. The median age was 49 years (minimum of 26 and maximum of 78 years) and 50 women (47.2%) were premenopausal. The initial body mass index (BMI) ranged between 16.9 and 41.8 kg/m2 (median of 25 kg/m2). The chemotherapy regimens employed in this study were CMF (Cyclophosphamide, Methotrexate, 5-Fluorouracil), FAC (5-Fluorouracil, Adriamycin, Cyclophosphamide), FEC and AC (Adriamycin, Cyclophosphamide)17 and forty-three patients (40.5%) received an anthracycline-based protocol (Table 1). None of the patients received corticosteroids as a part of their chemotherapy regimens, except for anti-nausea prophylaxis. Univariate and multiple regression analysis were performed to investigate the role of age, clinical stage, menopausal status, use of an anthracycline-based protocol and initial BMI, as the independent variables, with weight changes as a dependent variable. We used Kaplan-Mayer curves and the log-rank test to evaluate whether there was a statistically significant effect from weight changes on the disease-free and overall survival. Values of p < 0.05 were considered significant. RESULTS Considering all the patients (n = 106), there was a mean weight gain of 0.50 ± 1.42% of body weight per month of therapy (p = 0.21), ranging from -4.51% to 4.43%/month. The presence of metastatic disease was a strong negative predictor of weight gain (r = -0.446, p < 0.0001). No other analyzed factor correlated significantly with weight gain when all the patients undergoing chemotherapy were considered together (Table 2). When the patients receiving adjuvant chemotherapy were considered as a group (n = 74), 60 patients (81.1%) presented weight gain while on chemotherapy and 10 women (13.5%) had a weight gain of over 2% per month. The mean monthly weight gain was 0.91 ± 1.19 % of initial body weight (p < 0.00001), ranging from -2.60% to 4.44%/month (Figure 1). There was a tendency towards lower ages experiencing greater weight gain (r = -0.279, p = 0.069) (Table 3). In the group of women undergoing palliative chemotherapy for metastatic disease (n = 24), 12 patients (50%) lost weight while on chemotherapy. The mean monthly weight change was -0.52 ± 1.21% (p = 0.11) of initial body weight, ranging from 3.7% to 1.24%/month (Figure 2). None of the factors considered were predictive of weight changes in this group (Table 4). We found no statistically significant correlation between weight gain and disease-free survival in the group of women receiving adjuvant chemotherapy (Figure 3) or with weight loss and overall survival in the metastatic breast cancer group (Figure 4). DISCUSSION Several authors have already reported the occurrence of weight gains during adjuvant chemotherapy for breast cancer.1-7 Our similar findings in a series of patients treated at a Brazilian institution strengthen this association, with the lessening of the role of potential regional dietary or environmental factors. The weight gains that we observed in this study are thought to be of sufficient magnitude to foster a negative impact on corporal self-image, self-esteem and, consequently, the quality of life of the patients studied.6 Therefore, the attending physicians who care for such women need to be aware of this fact and may need to institute preventive measures such as exercise programs and dietary interventions to decrease weight gains during adjuvant chemotherapy.13 In our study no statistically significant correlation was found between weight gain and shorter disease-free or overall survival. Likewise, in the literature it was difficult to find convincing evidence for an association between weight gain during adjuvant chemotherapy and risk of relapse. In spite of positive conclusions from some series,1,18,19 this possible "new" risk factor for relapse has not been confirmed in other papers3,4,20 and this issue is therefore not settled definitively. The supposed biological plausibility for this phenomenon among obese women rests on greater peripheral conversion of androstenedione to estradiol and inhibition of synthesis of sexual hormones binding globulin with a consequent increase in levels of free estradiol which stimulates residual neoplastic cells.21-24 Among patients undergoing palliative chemotherapy we found a tendency towards weight loss. In these women weight loss is probably associated with cachexia, anorexia or symptoms determined by the presence of advanced disease,25 with a possible negative impact on survival. Further studies with a greater number of patients undergoing adjuvant treatment protocols and with a longer follow-up are necessary so as to better define the real prognostic impact of weight gain in this setting. This association, if confirmed, will be an important argument in favor of employing aggressive strategies to control weight during chemotherapy. CONCLUSION Weight gain associated with adjuvant chemotherapy for breast cancer also occurs in our setting. Such an association was not found with palliative chemotherapy. The prognostic impact of weight changes associated with breast cancer chemotherapy remains unknown. RESUMO CONTEXTO: Pacientes recebendo quimioterapia adjuvante por câncer de mama têm tendência a ganhar peso. Esta tendência tem fatores determinantes não completamente definidos e seu significado prognóstico é incerto. OBJETIVO: Avaliar a variação de peso durante tratamento quimioterápico por câncer de mama em uma população definida, identificar fatores predisponentes e seu possível significado prognóstico. TIPO DE ESTUDO: Observacional, de coorte retrospectiva. LOCAL: Serviço privado de oncologia clínica. PARTICIPANTES: Cento e seis pacientes consecutivas com câncer de mama tratadas entre junho de 1994 e abril de 2000 e que receberam quimioterapia neoadjuvante (n = 8), adjuvante (n = 74) ou paliativa (n = 24). PROCEDIMENTOS: Revisão de prontuários médicos com coleta de dados clínicos incluindo peso corporal das pacientes antes do tratamento e nas avaliações subseqüentes. VRIÁVEIS ESTUDADAS: Variação de peso corporal expresso em percentual do peso corporal por mês em tratamento, influência de variáveis clínicas nesta variação de peso e influência da variação de peso na sobrevida global e sobrevida livre de doença. RESULTADOS: Houve um ganho de peso médio de 0,50 ± 1,42% (p = 0,21) do peso corpóreo por mês de tratamento. Constatamos uma correlação negativa entre presença de doença metastática e ganho de peso (r = -0,447, p < 0,0001). No grupo em quimioterapia adjuvante e neoadjuvante, houve um ganho de peso médio de 0,91 ± 1,19 % (p < 0,00001) do peso corpóreo por mês de tratamento, enquanto que, no grupo com doença metastática (paliativo), observamos uma perda de peso média de 0,52 ± 1,21% (p = 0,11) do peso corpóreo por mês de tratamento. Não observamos correlação estatisticamente significante entre variação de peso e sobrevida livre de doença ou sobrevida global. CONCLUSÕES: Mulheres com câncer de mama recebendo tratamento quimioterápico adjuvante e neo-adjuvante ganham peso, enquanto mulheres com câncer de mama metastático possivelmente perdem peso durante quimioterapia paliativa. Estudos subseqüentes são necessários para avaliar o valor prognóstico da variação de peso durante quimioterapia. PALAVRAS-CHAVE: Neoplasias. Mama. Quimioterapia Adjuvante. Peso. Corpóreo. Obesidade. PUBLISHING INFORMATION Luciano José Megale Costa, MD. Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. Paulo César Spotti Varella, MD. Hematologist and clinical oncologist at the Integrated Oncology and Hematology consultation office, São Paulo, Brazil. Auro del Giglio, MD. Chairman of Hematology and Clinical Oncology, Faculdade de Medicina da Fundação ABC; and Integrated Oncology and Hematology consultation office, São Paulo, Brazil Sources of funding: Not required. Conflict of Interest: None. Date of first submission: September 18, 2001 Last received: April 25, 2002 Accepted: May 13, 2002 Address for correspondence Auro del Giglio Professor titular de Hematologia e Oncologia Faculdade de Medicina da Fundação ABC Avenida Rebouças, 3387 São Paulo/SP - Brasil - CEP 05410-040 Tel./Fax [phone] E-mail:[e-mail] 1. Camoriano JK, Loprinzi CL, Ingle JN, Therneau TM, Krook JE, Veeder MH. Weight change in women treated with adjuvant therapy or observed following mastectomy for node-positive breast cancer. J Clin Oncol 1990;8:1327-34. Weight change in women treated with adjuvant therapy or observed following mastectomy for node-positive breast cancer J Clin Oncol 1990 1327 34 8 Camoriano JK Loprinzi CL Ingle JN Therneau TM Krook JE Veeder MH 2. Bonadonna G, Valagussa P. Systemic therapy in resectable breast cancer. Hematol Oncol Clin North Am 1989;3:727-42. Systemic therapy in resectable breast cancer Hematol Oncol Clin North Am 1989 727 42 3 Bonadonna G Valagussa P 3. Goodwin PA, Panzarella T, Boyd NF. Weight gain in women with localized breast cancer - a descriptive study. Breast Cancer Res Treat 1988;11:59-66. Weight gain in women with localized breast cancer: a descriptive study Breast Cancer Res Treat 1988 59 66 11 Goodwin PA Panzarella T Boyd NF 4. Heasman KZ, Sutherland HJ, Campbell JA, Elhakim T, Boyd NF. Weight gain during adjuvant chemotherapy for breast cancer. Breast Cancer Res Treat 1985;5:195-200. Weight gain during adjuvant chemotherapy for breast cancer Breast Cancer Res Treat 1985 195 200 5 Heasman KZ Sutherland HJ Campbell JA Elhakim T Boyd NF 5. Subramian VP, Raich PC, Walker BK. Weight gain in breast cancer patients undergoing chemotherapy. Breast Cancer Res Treat 1981;1:170 (abstr). Weight gain in breast cancer patients undergoing chemotherapy Breast Cancer Res Treat 1981 170 1 Subramian VP Raich PC Walker BK abstr 6. Knobf MK, Mullen JC, Xistris D, Moritz DA. Weight gain in women with breast cancer receiving adjuvant chemotherapy. Oncol Nurs Forum 1983;10:28-33. Weight gain in women with breast cancer receiving adjuvant chemotherapy Oncol Nurs Forum 1983 28 33 10 Knobf MK Mullen JC Xistris D Moritz DA 7. Goodwin PJ, Ennis M, Pritchard KI, et al. Adjuvant treatment and onset of menopause predict weight gain after breast cancer diagnosis. J Clin Oncol 1999;17:120-9. Adjuvant treatment and onset of menopause predict weight gain after breast cancer diagnosis J Clin Oncol 1999 120 9 17 Goodwin PJ Ennis M Pritchard KI 8. Huntington MO. Weight gain in patients receiving adjuvant chemotherapy for carcinoma of the breast. Cancer 1985;56:472-4. Weight gain in patients receiving adjuvant chemotherapy for carcinoma of the breast Cancer 1985 472 4 56 Huntington MO 9. Mukhopadhyay MG, Larkin S. Weight gain in cancer patients on chemo therapy. Proc Am Soc Clin Oncol 1986;5:254 (abstr 992). Weight gain in cancer patients on chemo therapy Proc Am Soc Clin Oncol 1986 254 5 Mukhopadhyay MG Larkin S abstr 992 10. Brewin TB. Can a tumor cause the same appetite perversion or taste change as a pregnancy? Lancet 1980;2:907-8. Can a tumor cause the same appetite perversion or taste change as a pregnancy? Lancet 1980 907 8 2 Brewin TB 11. Meyerowitz BE, Sparks FC, Spears IK. Adjuvant chemotherapy for breast carcinoma: psychosocial implications. Cancer 1979;43:1613-8. Adjuvant chemotherapy for breast carcinoma: psychosocial implications Cancer 1979 1613 8 43 Meyerowitz BE Sparks FC Spears IK 12. Silberfarb PM, Maurer LH, Crouthamel CS. Psychological aspects of neoplastic disease: I. Functional status of breast cancer patients during different treatment regimens. Am J Psychiatry 1980;137:450-5. Psychological aspects of neoplastic disease: I. Functional status of breast cancer patients during different treatment regimens Am J Psychiatry 1980 450 5 137 Silberfarb PM Maurer LH Crouthamel CS 13. Demark-Wahnefried W, Peterson BL, Winer EP, et al. Changes in weight, body composition, and factors influencing energy balance among premenopausal breast cancer patients receiving adjuvant chemotherapy. J Clin Oncol 2001;19:2381-9. Changes in weight, body composition, and factors influencing energy balance among premenopausal breast cancer patients receiving adjuvant chemotherapy J Clin Oncol 2001 2381 9 19 Demark-Wahnefried W Peterson BL Winer EP 14. den Besten C, Vansant G, Weststrate JA, Deurenberg P. Resting metabolic rate and diet-induced thermogenesis in abdominal and gluteal-femoral obese women before and after weight reduction. Am J Clin Nutr 1988;47:840-7. Resting metabolic rate and diet-induced thermogenesis in abdominal and gluteal-femoral obese women before and after weight reduction Am J Clin Nutr 1988 840 7 47 den Besten C Vansant G Weststrate JA Deurenberg P 15. Tretli S, Haldorsen T, Ottestad L. The effect of pre-morbid height and weight on the survival of breast cancer patients. Br J Cancer 1990;62:299-303. The effect of pre-morbid height and weight on the survival of breast cancer patients Br J Cancer 1990 299 303 62 Tretli S Haldorsen T Ottestad L 16. Vasconcelos AB, Mendonça GAS, Sichieri R. Height, weight, weight change and risk of breast cancer in Rio de Janeiro, Brazil. São Paulo Med J 2001;119:62-6. Height, weight, weight change and risk of breast cancer in Rio de Janeiro, Brazil São Paulo Med J 2001 62 6 119 Vasconcelos AB Mendonça GAS Sichieri R 17. Hortobagui GN. Treatment of Breast Cancer. N Engl J Med 1998;339:974-84. Treatment of Breast Cancer N Engl J Med 1998 974 84 339 Hortobagui GN 18. Chlebowski RT, Weiner JM, Reynolds R, Luce L, Bucalvage L, Bateman JR. Long-term survival following relapse after 5-FU but not CMF adjuvant breast cancer therapy. Breast Cancer Res Treat 1986;7:23-30. Long-term survival following relapse after 5-FU but not CMF adjuvant breast cancer therapy Breast Cancer Res Treat 1986 23 30 7 Chlebowski RT Weiner JM Reynolds R Luce L Bucalvage L Bateman JR 19. Holmes MD, Stampfer MJ, Colditz GA, Rosner B, Hunter DJ, Willett WC. Dietary factors and the survival of women with breast carcinoma. Cancer 1999;86:826-35. Dietary factors and the survival of women with breast carcinoma Cancer 1999 826 35 86 Holmes MD Stampfer MJ Colditz GA Rosner B Hunter DJ Willett WC 20. DeConti RC. Weight gain in the adjuvant chemotherapy of breast cancer. Proc Am Soc Clin Oncol 1982;1:73 (abstr C-279). Weight gain in the adjuvant chemotherapy of breast cancer Proc Am Soc Clin Oncol 1982 73 1 DeConti RC abstr C-279 21. Bruning PF, Bonfrer JM, Hart AA. Non-protein-bound oestradiol, sex hormone binding globulin, breast cancer and breast cancer risk. Br J Cancer 1985;51:479-84. Non-protein-bound oestradiol, sex hormone binding globulin, breast cancer and breast cancer risk Br J Cancer 1985 479 84 51 Bruning PF Bonfrer JM Hart AA 22. Ingram DM, Nottage E, Ng S, Sparrow L, Roberts A, Dillcox D. Obesity and breast disease. The role of the female sex hormones. Cancer 1989;64:1049-53. Obesity and breast disease The role of the female sex hormones. Cancer 1989 1049 53 64 Ingram DM Nottage E Ng S Sparrow L Roberts A Dillcox D 23. Ota DM, Jones LA, Jackson GL, Jackson PM, Kemp K, Bauman D. Obesity, non-protein-bound estradiol levels and distribution of estradiol in the sera of breast cancer patients. Cancer 1986;57:558-62. Obesity, non-protein-bound estradiol levels and distribution of estradiol in the sera of breast cancer patients Cancer 1986 558 62 57 Ota DM Jones LA Jackson GL Jackson PM Kemp K Bauman D 24. Schapira DV, Kumar NB, Lyman GH. Obesity, body fat distribution, and sex hormones in breast cancer patients. Cancer 1991;67:2215-8. Obesity, body fat distribution, and sex hormones in breast cancer patients Cancer 1991 2215 8 67 Schapira DV Kumar NB Lyman GH 25. Viganó A, Bruera E, Jhangri GS, Newman SC, Fields AL, Suarez-Almazor ME. Clinical survival predictors in patients with advanced cancer. Arch Intern Med 2000;160:861-8. Clinical survival predictors in patients with advanced cancer Arch Intern Med 2000 861 8 160 Viganó A Bruera E Jhangri GS Newman SC Fields AL Suarez-Almazor ME