Cancer Recurrence In Women Research Articles

Beliefs about medicine and illness are associated with fear of cancer recurrence in women taking adjuvant endocrine therapy for breast cancer

Adjuvant endocrine therapy for early-stage breast cancer has greatly reduced the morbidity and mortality associated with breast cancer recurrence. Despite this, a significant proportion of women report fears of cancer recurrence. This study examined the associations between fear of cancer recurrence (FoR) and illness perceptions, medication beliefs, and treatment side effects in women taking adjuvant endocrine therapy following breast cancer. A total of 153 post-menopausal women with early-stage breast cancer completed a postal survey. Analyses were conducted to examine the association between FoR and illness perceptions, medication beliefs, treatment side effects, demographic factors, and emotional distress and to identify which of these factors would be most strongly associated with FoR in a regression model. All illness perceptions (apart from personal control) were associated with FoR, as were patient beliefs about endocrine therapy. Although treatment side effects, being unemployed, and higher levels of anxiety and depression were associated with FoR, only illness perceptions (identity, treatment control, timeline, and emotional representation) and medication necessity beliefs were significantly correlated with FoR in the final model. It appears that, in addition to directly targeting FoR, it may be worthwhile to address the illness and medication beliefs supporting the fear. Additionally, helping women to differentiate everyday symptoms from those indicative of breast cancer may help to reduce fear of recurrence. What is already known on this subject? A significant proportion of women report fear of cancer recurrence following breast cancer. The literature shows that illness perceptions, side effects of treatment, and beliefs about medicines are related to fear of recurrence among cancer patients. However, because these variables have often been looked at in isolation, it is not clear whether some perceptions or cues are more likely to relate to fear of recurrence than others. What does this study add? This study shows illness perceptions and medication beliefs are strongly related to fears of cancer recurrence. The results point to ways in which the self-regulatory model of illness may be used to reduce patients' fear of recurrence. The study results show that women with higher fear of recurrence may be balancing a tension between believing that they need to take the medication to protect their future health alongside concerns that the treatment may not be working.

P-0182 A Common Gene Variant in PLS3 Predicts Colon Cancer Recurrence in Women

ABSTRACT Introduction Recent evidence suggests that T-Plastin (PLS3), a representative of actin-cross-linking and -bundling proteins, significantly increases invasive properties of cancer cells. Germline genetic variability in PLS3 may lead to an altered gene function and/or activity, resulting in inter-individual differences in tumor recurrence capacity. In the present study, we investigated the association of germline polymorphisms in PLS3 to predict time-to-tumor-recurrence (TTR) in patients with stage II and III colon cancer. Methods Putatively functional polymorphisms within PLS3 were selected using public literature resources and databases including: NCBI-PubMed, dbSNP, Ensembl, GeneCards and the Pharmacogenomics-Knowledge-Base. Stringent and pre-defined selection criteria used were: (a) minor allele frequency ≥10% in Caucasians; (b) polymorphism that could alter the function of the gene in a biologically relevant manner (predicted function using Functional-Single-Nucleotide-Polymorphism (F-SNP) database, http://compbio.cs.queensu.ca/F-SNP; (c) published clinical associations. A total of 264 patients with histologically confirmed colon cancer were included in this study. Germline DNA was genotyped for rs871773 C>T, rs757124 C>G, rs1557770 G>T, rs6643869 G>A and rs2522188 C>T in the PLS3 gene by 5'-exonuclease (TaqMan™) technology. Results There were no significant associations between the polymorphisms and TTR including all patients. However, the minor allele of PLS3 rs871773 C>T, which shows a potential function through transcriptional regulation, was significantly associated with decreased TTR in women (HR, 5.02; 95%CI, 1.251-20.114; p=0.023) and remained significant in multivariate analysis (HR, 6.165; 95%CI, 1.538-24.716; p=0.010). Female patients carrying at least one T allele in PLS3 rs871773 showed a median TTR of 69 months. In contrast, female patients with homozygous C/C had a median TTR of 112 months. Conclusion In conclusion, we identified a common gene variant in PLS3 as an independent prognostic marker in female patients with stage II and III colon cancer. Larger prospective trials are warranted to confirm these findings.

Perception of cancer recurrence risk: More information is better

ObjectiveBreast cancer is the most common cancer among women worldwide. Given the advances in extending survival, the number of recently diagnosed breast cancer patients and longer-term breast cancer survivors is growing. The goals of this study were to better understand (1) perceptions of provider cancer recurrence risk communication, (2) perceived risk of breast cancer recurrence in cancer patients and survivors, and (3) accuracy of perceived risk. MethodsA survey was conducted on women with a prior breast cancer (n=141). ResultsApproximately 40% of women perceived that providers had not talked about their breast cancer recurrence risk; although only 1 person reported not wanting a physician to talk to her about her risk. Women were largely inaccurate in their assessments of risk. Greater worry, living in a rural area, and longer time since diagnosis were associated with greater inaccuracy. Women tended to think about distal recurrence of cancer as often of local recurrence. ConclusionsPerceived risk of breast cancer recurrence was inaccurate, and patients desired more communication about recurrence risk. Practice implicationsConsistent with findings from other studies, greater efforts are needed to improve the communication of cancer recurrence risk to patients. Attention should be paid to those from rural areas and to distal cancer recurrence in women with a previous history of breast cancer.

Correlates of fear of cancer recurrence in women with ductal carcinoma in situ and early invasive breast cancer.

Fear of cancer recurrence (FCR) is a common and persistent concern among breast cancer survivors. Little is known about factors associated with FCR in women with ductal carcinoma in situ (DCIS) or early invasive breast cancer (EIBC). Women with first primary DCIS, or stages I-IIA breast cancer were prospectively enrolled in a quality-of-life study and completed interviews at 4-6 weeks, 6 months, and 2 years after definitive surgical treatment. In three stepwise multivariable linear regression models, including both time-independent and time-varying variables measured at each respective interview, we identified independent correlates of mean FCR scores (range 1-6) using four items from the Concern About Recurrence Scale (CARS) at 2-year follow-up. Of 506 disease-free patients at 2-year follow-up (mean [SD] age, 58 [10] years; 81% White; 34% DCIS), the average FCR score of 2.0 was low. However, 145 (29%) reported moderate-to-high levels of FCR (scores 3.0-6.0). All three models showed that younger age, stage IIA breast cancer (vs. DCIS), lower social support, and elevated anxiety were consistently associated with higher FCR at 2-year follow-up (each P < 0.05; final models R (2) = 0.25-0.32). DCIS patients reported lower FCR than stage IIA patients (each P ≤ 0.01) but had similar FCR as stage I patients. Although mean FCR was low, 29% of DCIS and EIBC survivors reported moderate-to-high levels of FCR at 2-year follow-up. Management of anxiety, provision of social support, and patient education may help reduce FCR among DCIS and EIBC survivors, especially among younger survivors.

Paravertebral anesthesia: how substance P and the NK-1 receptor could be involved in regional block and breast cancer recurrence

In a retrospective study, Exadaktylos et al. [1] reported a beneficial relationship between paravertebral block and cancer recurrence in women undergoing mastectomy and axillary clearance for breast cancer. In fact, these authors concluded that ‘‘breast cancer patients undergoing surgery with paravertebral anesthesia and analgesia combined with general anesthesia have a lower incidence of cancer recurrence or metastasis during the initial years of followup than patients undergoing surgery with general anesthesia and patient-controlled morphine analgesia’’ [1]. These authors speculated that regional anesthesia might attenuate the perioperative factors that enhance tumor growth and spreading [1]. In this sense, regional anesthesia may help to maintain normal perioperative immune function by attenuating the surgical stress response by blocking noxious inputs mediated by substance P [2]. It is known that the stress response induces an inhibition of the immune function (i.e., there is a marked attenuation of natural killer cells, these cells being involved in preventing tumor dissemination) [3]. Paravertebral anesthesia also spares patients from postoperative opioids (e.g., morphine), which inhibit both cellular and humoral immune function [4, 5]; in addition, it is known that morphine exerts a proangiogenic effect [6]. In sum, the authors surmised that regional anesthesia and analgesia may help to preserve immune function by attenuating the surgical stress response and diminishing the need for opioids. However, until now the underlying mechanisms remain unknown. The reason for this letter is to provide additional data that could support and explain the relationship between regional anesthesia, analgesia, and the recurrence of cancer. Many reports have clearly established an overexpression of neurokinin-1 (NK-1) receptors in tumor cells and others have reported the roles in which substance P (SP) is involved [7]. Summing up these investigations, it could be stated that:

Risk of breast cancer recurrence in women initiating tamoxifen with CYP2D6 inhibitors

CRA508 Background: Tamoxifen (TAM) is metabolized to its active form, endoxifen, by hepatic cytochrome P450 (CYP) 2D6. Diminished CYP2D6 function, both by genetic variation or concurrent use of pharmacologic inhibitors, can significantly reduce endoxifen plasma concentrations and may lead to reduced TAM effectiveness. Methods: We interrogated an integrated research database comprised of de-identified medical and pharmacy claims (Rx) data for 10.7 million U.S. health plan members to identify women with breast cancer (BrCa) new to TAM therapy in a 30-month period from 2003 to 2005, and investigated the risk of recurrent BrCa as a function of concurrent use of potent and moderate inhibitors of CYP2D6. Inclusion criteria were: greater than or equal to 24 months of follow-up data and adherence to TAM (medication possession ratio &gt; 70%) over 2 years (N = 1,298). Disease recurrence was defined by BrCa ICD-9 codes or CPT codes for mastectomy, lumpectomy, lymph node dissection, or radiation therapy occurring at least 6 months after the index TAM Rx. Two study groups were identified: TAM alone (N = 945) or TAM + a CYP2D6 inhibitor concomitantly (N = 353). BrCa recurrence rates were compared using Kaplan-Meier analysis with log-rank test, and univariate hazard ratios (HR) with 95% confidence intervals (CI) were estimated by Cox proportional hazards model. Results: The study groups were similar at baseline. Median age was 52 years (TAM) and 53 years (TAM + CYP2D6 inhibitor). Interventions performed in the TAM alone group included mastectomy in 54%, lumpectomy in 36%, and radiation therapy in 47%, and were 52%, 38%, 46%, respectively, in the TAM + CYP2D6 inhibitor group. Among women on a CYP2D6 inhibitor, the median duration of overlap with TAM was 255 days. Patients receiving TAM + a CYP2D6 inhibitor had a 2-year BrCa recurrence rate of 13.9% versus 7.5% in patients receiving TAM alone (HR 1.92, 95% CI 1.33–2.76, p &lt; 0.001). Conclusions: Our findings support the presence of a clinically significant drug interaction between TAM and known CYP2D6 inhibitors. This resulted in a significant 1.9 fold higher BrCa recurrence within 2 years of initiating TAM therapy. [Table: see text]

Risk of breast cancer recurrence in women initiating tamoxifen with CYP2D6 inhibitors

CRA508 Background: Tamoxifen (TAM) is metabolized to its active form, endoxifen, by hepatic cytochrome P450 (CYP) 2D6. Diminished CYP2D6 function, both by genetic variation or concurrent use of pharmacologic inhibitors, can significantly reduce endoxifen plasma concentrations and may lead to reduced TAM effectiveness. Methods: We interrogated an integrated research database comprised of de-identified medical and pharmacy claims (Rx) data for 10.7 million U.S. health plan members to identify women with breast cancer (BrCa) new to TAM therapy in a 30-month period from 2003 to 2005, and investigated the risk of recurrent BrCa as a function of concurrent use of potent and moderate inhibitors of CYP2D6. Inclusion criteria were: greater than or equal to 24 months of follow-up data and adherence to TAM (medication possession ratio > 70%) over 2 years (N = 1,298). Disease recurrence was defined by BrCa ICD-9 codes or CPT codes for mastectomy, lumpectomy, lymph node dissection, or radiation therapy occurring at least 6 months after the index TAM Rx. Two study groups were identified: TAM alone (N = 945) or TAM + a CYP2D6 inhibitor concomitantly (N = 353). BrCa recurrence rates were compared using Kaplan-Meier analysis with log-rank test, and univariate hazard ratios (HR) with 95% confidence intervals (CI) were estimated by Cox proportional hazards model. Results: The study groups were similar at baseline. Median age was 52 years (TAM) and 53 years (TAM + CYP2D6 inhibitor). Interventions performed in the TAM alone group included mastectomy in 54%, lumpectomy in 36%, and radiation therapy in 47%, and were 52%, 38%, 46%, respectively, in the TAM + CYP2D6 inhibitor group. Among women on a CYP2D6 inhibitor, the median duration of overlap with TAM was 255 days. Patients receiving TAM + a CYP2D6 inhibitor had a 2-year BrCa recurrence rate of 13.9% versus 7.5% in patients receiving TAM alone (HR 1.92, 95% CI 1.33–2.76, p < 0.001). Conclusions: Our findings support the presence of a clinically significant drug interaction between TAM and known CYP2D6 inhibitors. This resulted in a significant 1.9 fold higher BrCa recurrence within 2 years of initiating TAM therapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Medco Health Solutions, Inc. LabCorp, Medco Health Solutions, Inc., Roche Molecular Diagnostics Medco Health Solutions, Inc. Roche Molecular Systems, Inc.

Risk of breast cancer recurrence in women initiating tamoxifen with CYP2D6 inhibitors

CRA508 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. [Table: see text]

Implementing a Low-Fat Eating Plan in the Women's Intervention Nutrition Study

The Women's Intervention Nutrition Study is a randomized clinical trial designed to evaluate if a lifestyle intervention targeting fat intake reduction influences breast cancer recurrence in women with early stage, resected disease receiving conventional cancer management. This report details the concept, content, and implementation of the low-fat eating plan used in the dietary intervention group of this trial. Intervention group participants were given a daily fat gram goal. The intervention was delivered by centrally trained, registered dietitians who applied behavioral, cognitive, and motivational counseling techniques. The low-fat eating plan was implemented in an intensive phase with eight biweekly (up to Month 4), individual counseling sessions followed by a maintenance phase (Month 5 up to and including Year 5) with registered dietitian visits every 3 months and optional monthly group sessions. Self-monitoring (daily fat gram counting and recording), goal setting, and motivational interviewing strategies were key components. Dietary fat intake was equivalent at baseline and consistently lower in the intervention compared with the control group at all time points (percent eneregy from fat at 60 months 23.2%±8.4% vs 31.2%±8.9%, respectively, P<0.0001) and was associated with mean 6.1 lb mean weight difference between groups ( P=0.005) at 5 years (baseline and 5 years, respectively: control 160.0±35.0 and 161.7±32.8 lb; intervention 160.2±35.1 and 155.6±32.1 lb). Together with previously reported efficacy results, this information suggests that a lifestyle intervention that reduces dietary fat intake and is associated with modest weight loss may favorably influence breast cancer recurrence. The Women's Intervention Nutrition Study low-fat eating plan can serve as a model for implementing such a long-term dietary intervention in clinical practice.

Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors: the Life After Cancer Epidemiology study

Soy isoflavones, structurally similar to endogenous estrogens, may affect breast cancer through both hormonally mediated and non-hormonally related mechanisms. Although the effects of soy are not well understood, some breast cancer survivors increase their soy intake post-diagnosis in attempt to improve their prognosis. Therefore, we examined the role of soy isoflavone intake and the risk of breast cancer recurrence by hormone receptor status, menopausal status, and tamoxifen therapy. A cohort of 1,954 female breast cancer survivors, diagnosed during 1997-2000, was prospectively followed for 6.31 years and 282 breast cancer recurrences were ascertained. Isoflavone intake was assessed by mailing modified Block and supplemental soy food frequency questionnaires to participants, on average 23 months post-diagnosis. Risk of breast cancer recurrence, measured by hazard ratios (HR) and 95% confidence intervals (CI), was estimated using multivariable delayed entry Cox proportional hazards models. Suggestive trends for a reduced risk of cancer recurrence were observed with increasing quintiles of daidzein and glycetin intake compared to no intake among postmenopausal women (P for trend: P = 0.08 for daidzein, P = 0.06 for glycetin) and among tamoxifen users (P = 0.10 for daidzein, P = 0.05 for glycetin). Among postmenopausal women treated with tamoxifen, there was an approximately 60% reduction in breast cancer recurrence comparing the highest to the lowest daidzein intakes (>1,453 vs. <7.7 microg/day; HR, 0.48; 95% CI, 0.21-0.79, P = 0.008). Soy isoflavones consumed at levels comparable to those in Asian populations may reduce the risk of cancer recurrence in women receiving tamoxifen therapy and moreover, appears not to interfere with tamoxifen efficacy. Further confirmation is required in other large prospective studies before recommendations regarding soy intake can be issued to breast cancer survivors.

Is PCR testing of sentinel lymph nodes ready for clinical application in breast cancer?

While the majority of breast cancer patients with histologically lymph node-negative cancers are cured by local therapy alone, approximately 25% will develop recurrent breast cancer and die of their disease in the absence of systemic adjuvant chemotherapy [1]. Cytotoxic chemotherapy markedly improves outcome for some of these patients. Assays that could better distinguish those nodenegative patients who are more likely to suffer distant recurrence could prove very useful in optimizing patient selection for chemotherapy. Technologies based on DNA microarray analysis using polymerase chain reaction (PCR) amplification seem like ideal candidates for the development of novel prognostic and predictive assays. The Oncotype DX TM test is a clinically validated, multigene assay performed on samples processed from primary invasive breast carcinomas. The assay provides a quantitative assessment of the likelihood of distant breast cancer recurrence in women with estrogen receptor-positive, node-negative disease, and also assesses the potential benefit from chemotherapy in these women [2]. A major strength of its 21-gene recurrence score is that it has been tested against outcomes data derived from the NSABP-B20 randomized trial in which cancer recurrence and survival is already known with several years of clinical follow-up. It seems likely that future assays will be developed using similar technology to address important clinical questions related to staging and cancer therapy.

Regional Block and Cancer Recurrence: Too Early to Tell

We read with much interest the recently published study by Exadaktylos et al. 1Their retrospective cohort study identified a beneficial relation between paravertebral block and cancer recurrence in women undergoing breast cancer surgery. The authors opined that regional anesthesia might help to maintain normal perioperative immune function and reduce the risk of tumor recurrence and metastases. If these findings are real, it would be the first demonstration that anesthesia per se protects from cancer recurrence—a true revolution.However, before such conclusions can be drawn, a number of limitations of this study should be addressed. Although some were discussed in the excellent accompanying editorial by Ochroch et al. ,2some major ones seem to have gone unnoticed.First, the authors state that prognostic factors and particularly the Nottingham Prognostic Score were similar in both groups. As a consequence, the smaller number of cancer recurrence and metastases observed in the paravertebral group seems to be due to the inherent benefits of the regional technique. However, the Nottingham Prognostic Score is not a measure of the propensity for tumor recurrence or metastasis.3It has never been validated as such. Only axillary node extension and histologic grade of the tumor have been demonstrated to do this. There is evidence from the literature suggesting that patients with high-grade (grade III) histologic breast tumors undergoing surgery are more at risk of recurrence and metastasis than patients with lower grades.4,5Reanalyzing the study data of Exadaktylos et al. ,1it seems that 54% of patients in the nonblock group compared with 42% of patients in the paravertebral block group had high-grade breast tumors and increased risk of cancer recurrence. Had categorical variables from the histologic grades been compared as is recommended,6with the chi-square test (and not the Mann–Whitney U test for nonnormally distributed numerical variables), it would have been found that patients in the nonblock group had poorer prognosis at a P value less than 0.001.Second, the authors assume a cause–effect phenomenon between the predictor (the anesthetic technique) and the outcome (cancer recurrence or metastasis). However, the opposite may be true here: The outcome may have caused the predictor to occur. Treatment allocation seemed to be mainly influenced by the anesthesiologist’s decision to use a paravertebral block. A block may not have been offered to patients in whom it was not indicated (e.g. , patients with extensive metastases, recurrent or bilateral breast tumors).7As a consequence, patients with extensive, recurring, or bilateral tumors were less likely to have a paravertebral block. Cancer recurrence might have guided the choice of the anesthetic technique and not the opposite. This effect–cause phenomenon is recognized bias of cross-sectional, case–control, and retrospective cohort studies.8There are some well-known examples in the literature, such as the protective effect of tobacco smoking against Parkinson disease or the deleterious effect of low levels of blood cholesterol in cancer patients.9,10In both cases, presumed consequences (Parkinson disease–cancer) are actually causes of lower tobacco smoking and blood cholesterol.Finally, in the study of Exadaktylos et al. ,1paravertebral blocks were performed by the same anesthesiologist, and all such cases were performed by the same surgeon and managed by the same oncologist. What about the “nonblock” cases? Were the latter patients managed by a range of surgeons and oncologists, perhaps with different approaches to treatment? There may be other explanations as to why the latter patients had poorer outcomes.11In conclusion, the only study design able to reliably answer whether paravertebral block really protects from breast cancer recurrence is a randomized controlled trial. This should be done as soon as possible before an unproven hypothesis becomes a standard of practice in breast cancer surgery.*Geneva University Hospital, Geneva, Switzerland, and Monash University, Melbourne, Australia. guy.haller@hcuge.ch

How Much Is Enough? The Continuing Debate on the Axillary Lymph Node Dissection in Breast Cancer

How Much Is Enough? The Continuing Debate on the Axillary Lymph Node Dissection in Breast Cancer

Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.

The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive, lymph node-negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (> or = 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, -1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit. The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer, but also predicts the magnitude of chemotherapy benefit.

Post-diagnosis weight gain and breast cancer recurrence in women with early stage breast cancer

To examine whether weight gain after diagnosis of breast cancer affects the risk of breast cancer recurrence. Patients included 3215 women diagnosed with early stage breast cancer (Stage I >1 cm., II, and IIIA) who were enrolled either in an observational cohort of breast cancer survivors or were part of the comparison group of a dietary intervention trial to prevent breast cancer recurrence. We computed weight change from 1 year prior to diagnosis to study enrollment. Delayed entry Cox proportional hazards models were used to evaluate associations of categories of weight change with time to recurrence, controlling for known prognostic factors. Neither moderate (5-10%) nor large (> 10%) weight gain (HR 0.8, 95% CI, 0.6-1.1; HR 0.9, 95% CI, 0.7-1.2, respectively) after breast cancer diagnosis was associated with an increased risk of breast cancer recurrence in the early years post-diagnosis (median time of 73.7 months from diagnosis). Our research provides evidence that weight gain commonly seen in the first several years following a breast cancer diagnosis does not increase a woman's risk for breast cancer recurrence in the first 5-7 years post-diagnosis. However, this research does not address the effects of weight gain on overall survival or on the risk of other new cancers, other prognostic outcomes of concern to the breast cancer survivor.

Impact of body mass index on outcomes and treatment-related toxicity in patients with stage II and III rectal cancer: findings from Intergroup Trial 0114.

To study the relationship between body mass index (BMI) and rates of sphincter-preserving operations, overall survival, cancer recurrence, and treatment-related toxicities in patients with rectal cancer. We evaluated a nested cohort of 1,688 patients with stage II and III rectal cancer participating in a randomized trial of postoperative fluorouracil-based chemotherapy and radiation therapy. Obese patients were more likely to undergo an abdominoperineal resection (APR) than normal-weight patients (odds ratio, 1.77; 95% CI, 1.27 to 2.46). When analyzed by sex, increasing adiposity in men was a strong predictor of having an APR (P <.0001). Obese men with rectal cancer were also more likely than normal-weight men to have a local recurrence (hazard ratio [HR], 1.61; 95% CI, 1.00 to 2.59). In contrast, obesity was not predictive of cancer recurrence in women, nor was BMI predictive of overall mortality in either men or women. Underweight patients had an increased risk of death (HR, 1.43; 95% CI, 1.08 to 1.89) compared with normal-weight patients but no increase in cancer recurrences. Among all study participants, obese patients had a significantly lower rate of grade 3 to 4 leukopenia, neutropenia, and stomatitis and a lower rate of any grade 3 or worse toxicity when compared with normal-weight individuals. Increasing BMI in male patients with rectal cancer is associated with a decreased likelihood of sphincter preservation and a higher chance of local recurrence. For both men and women, overweight and obese patients experience less toxicity associated with adjuvant chemoradiotherapy, suggesting that actual body weight dosing of fluorouracil for obese patients is justified.