DREAM, a possible answer to the estrogen paradox of the Women's Health Initiative Trial.

Estrogen is thought to cause proliferation of all estrogen receptor positive (ER+) breast cancers. Paradoxically, in the Women's Health Initiative Trial, estrogen-only hormone replacement therapy reduced the incidence and mortality of low grade, ER+, HER2- breast cancer. We gave estradiol to 19 post-menopausal women with newly diagnosed low-grade, ER+, HER2- breast cancer in a prospective window of opportunity clinical trial and examined the changes in proliferation and gene expression before and after estradiol treatment. Ki67 decreased in 13/19 (68%) patients and 8/13 (62%) showed a decrease in Risk of Recurrence Score. We chose three prototypical estrogen responders (greatest decrease in ROR) and non-responders (no/minimal change in ROR) and applied a differential gene expression analysis to develop pre-treatment (PRESTO-30core) and post-treatment (PRESTO-45surg) gene expression profiles. The PRESTO-30core predicted adjuvant benefit in a published series of tamoxifen, the partial estrogen agonist. Of the 45 genes in the PRESTO-45surg, thirty contain the Cell cycle genes Homology Region (CHR) motif that binds the class B multi-vulva complex (MuvB) a member of the DREAM (Dimerization partner, retinoblastoma-like proteins, E2F, MuvB) complex responsible for reversible cell cycle arrest or quiescence. There was also near uniform suppression (89%) of the remaining DREAM genes consistent with estrogen induced activation of the DREAM complex to mediate cell cycle block after a short course of estrogens. To our knowledge, this is the first report to show estrogen modulation of DREAM genes and suggest involvement of DREAM pathway associated quiescence in endocrine responsive post-menopausal ER+ breast cancers.

Re-excision and survival following breast conserving surgery in early stage breast cancer patients: a population-based study.

BACKGROUND: Increasing population-based evidence suggests that patients who receive breast conserving surgery (BCS) plus radiotherapy have superior survival than those who receive mastectomy. It is unclear, however, how BCS followed by re-excision is associated with all-cause and breast cancer-specific mortality, and whether the BCS survival advantage is maintained if re-excision is needed. The aim of this study was to investigate the clinical, patient, provider and geographic variation associated with receipt of re-excision surgery, and to examine the relationship between re-excision and all-cause and breast cancer-specific mortality. METHODS: All women diagnosed with stage I-III breast cancer in Alberta, Canada from 2002 to 2009 were identified from the Alberta Cancer Registry, of which 11,626 were eligible for study inclusion. Type of first breast cancer surgery after diagnosis, subsequent re-excisions within 1 year, surgeon (anonymized), and hospital were obtained from provincial physician claims data. Multilevel logistic regression with surgeons and hospitals as crossed random effects was used to estimate the adjusted odds ratios of re-excision by the factors of interest. Poisson regression models were fitted to compare all-cause and breast cancer-specific mortality by surgical pattern. RESULTS: Re-excision surgery was received by 19% (N = 5659) of patients who initially received BCS. The adjusted odds of re-excision varied significantly by geography of surgery, and by individual surgeon among stage I and II patients beyond the variation explained by the factors investigated (Stage I OR standard deviation (SD) = 0.43; stage II OR SD = 0.39). Patients who were treated with BCS plus re-excision surgery with either mastectomy or further BCS had similar all-cause and breast cancer-specific mortality as those treated with BCS without re-excision. CONCLUSION: These results suggest that breast cancer patients who are treated with BCS plus re-excision surgery by either mastectomy or further BCS have similar survival as those treated with BCS without re-excision. The significant variation in the likelihood of re-excision by geography and by individual surgeon is concerning, especially given the costs to the patient associated with additional surgery and the financial costs to the health system.

Using Multilevel Models to Explain Variation in Clinical Practice: Surgeon Volume and the Surgical Treatment of Breast Cancer.

PURPOSE: To investigate the relationship between surgeon caseload and surgery type, and variation in the surgical treatment of early stage breast cancer patients in Alberta, Canada. METHODS: All women diagnosed with stage I to III breast cancer in Alberta from 2002 to 2010 were identified from the Alberta Cancer Registry. Type of surgery, surgeon (anonymized), and hospital were obtained from provincial physician claims data. Multilevel logistic regression with surgeons and hospitals as crossed random effects was used to estimate adjusted odds ratios (OR) of receiving mastectomy by surgeon volume. Empirical Bayes estimation was used to estimate adjusted OR for individual surgeons and hospitals. RESULTS: Mastectomy was found to be inversely related to surgeon volume among stage I and II patients. Patients whose surgery was conducted by a low-volume surgeon had twice the odds of receiving mastectomy as those that had surgery performed by a very high-volume surgeon (stage I OR 2.36, 95 % confidence interval 1.40, 3.97; stage II OR 1.96, 95 % confidence interval 1.13, 3.42). OR of mastectomy varied widely by individual surgeon beyond the variation explained by the factors investigated. CONCLUSIONS: Surgeon characteristics, including surgeon volume, are associated with surgery type received by breast cancer patients in Alberta. Significant variation in the likelihood of breast-conserving surgery (BCS) by surgeon is concerning given the potential benefits of BCS for those who are eligible.

Factors related to breast cancer detection mode and time to diagnosis in Alberta, Canada: a population-based retrospective cohort study.

BACKGROUND: Understanding the factors affecting the mode and timeliness of breast cancer diagnosis is important to optimizing patient experiences and outcomes. The purposes of the study were to identify factors related to the length of the diagnostic interval and assess how they vary by mode of diagnosis: screen or symptom detection. METHODS: All female residents of Alberta diagnosed with first primary breast cancer in years 2004-2010 were identified from the Alberta Cancer Registry. Data were linked to Physician Claims and screening program databases. Screen-detected patients were identified as having a screening mammogram within 6-months prior to diagnosis; remaining patients were considered symptom-detected. Separate quantile regression was conducted for each detection mode to assess the relationship between demographic/clinical and healthcare factors. RESULTS: Overall, 38 % of the 12,373 breast cancer cases were screen-detected compared to 47 % of the screen-eligible population. Health region of residence was strongly associated with cancer detection mode. The median diagnostic interval for screen and symptom-detected cancers was 19 and 21 days, respectively. The variation by health region, however, was large ranging from an estimated median of 4 to 37 days for screen-detected patients and from 17 to 33 days for symptom-detected patients. Cancer stage was inversely associated with the diagnostic interval for symptom-detected cancers, but not for screen-detected cancers. CONCLUSION: Significant variation by health region in both the percentage of women with screen-detected cancer and the length of the diagnostic interval for screen and symptom-detected breast cancers suggests there could be important differences in local breast cancer diagnostic care coordination.

Treatment variation in patients diagnosed with early stage breast cancer in Alberta from 2002 to 2010: a population-based study.

BACKGROUND: Breast-conserving surgery (BCS) followed by radiotherapy is generally the preferred treatment for women diagnosed with early stage breast cancer. This study aimed to investigate the proportion of patients who receive BCS versus mastectomy and post-BCS radiotherapy, and explore factors associated with receipt of these treatments in Alberta, Canada. METHODS: A retrospective population-based study was conducted that including all patients surgically treated with stage I-III breast cancer diagnosed in Alberta from 2002-2010. Clinical characteristics, treatment information and patient age at diagnosis were collected from the Alberta Cancer Registry. Log binomial multiple regression was used to calculate stage-specific relative risk estimates of receiving BCS and post-BCS radiotherapy. RESULTS: Of the 14 646 patients included in the study, 44% received BCS, and of those, 88% received post-BCS radiotherapy. The adjusted relative risk of BCS was highest in Calgary and lowest in Central Alberta for all disease stages. Relative to surgeries performed in Calgary, those performed in Central Alberta were significantly less likely to be BCS for stage I (RR = 0.65; 95% 0.57, 0.72), II (RR = 0.58; 95% 0.49, 0.68), and III (RR = 0.62; 95% CI: 0.37, 0.95) disease, respectively, adjusting for patient age at diagnosis, clinical and treatment characteristics. No significant variation of post-BCS radiotherapy was found. CONCLUSIONS: Factors such as region of surgical treatment should not be related to the receipt of standard care within a publicly-funded health care system. Further investigation is needed to understand the significant geographic variation present within the province in order to identify appropriate interventions.

Rates of breast cancer surgery in Canada from 2007/08 to 2009/10: retrospective cohort study.

BACKGROUND: Surgery is a common and important component of breast cancer treatment. We assessed the rates of breast cancer surgery across Canada from 2007/08 to 2009/10. METHODS: We used hospital and day surgery data from the Canadian Institute for Health Information to assemble a cohort of women who had undergone breast cancer surgery. We identified the index surgical procedure and subsequent surgical procedures performed within 1 year for each woman included in the analysis. We calculated the crude mastectomy rate for each province, and we calculated the adjusted mastectomy rate for select jurisdictions using a logistic regression model fitted using age, neighbourhood income quintile and travel time. RESULTS: In total, 57 840 women underwent breast cancer surgery during the study period. Among women with unilateral invasive breast cancer, the crude mastectomy rate was 39%. Adjusted rates for mastectomy varied widely by province (26%-69%). The rate of re-excision within 1 year for women who had breast-conserving surgery as their index procedure was 23% and varied by province in terms of frequency and type (mastectomy or repeat breast-conserving surgery). Among women who underwent mastectomy for unilateral invasive breast cancer, 6% also underwent contralateral prophylactic mastectomy, and 7% had immediate breast reconstruction following surgery. Of mastectomy procedures, 20% were performed as day surgery; for breast-conserving surgery, 70% were performed as day surgery. INTERPRETATION: There is substantial interprovincial variation in surgical care for breast cancer in Canada. Further research is needed to better understand such variation, and continued monitoring should be the focus of quality initiatives.

Completeness of dictated operative reports in breast cancer--the case for synoptic reporting.

BACKGROUND: Currently, the dictated operative report forms the cornerstone of documenting breast cancer surgery. Synoptic electronic reporting using a standardized template has been proposed for breast cancer operative notes to improve documentation. The goal of this study was to determine the current completeness of dictated operative reports for breast cancer surgery. METHODS: An iterative, consensus-based approach to determining elements of a proposed synoptic surgical operative report identified critical elements. We then evaluated the dictated operative reports of 100 consecutive breast cancer patients for completeness of these elements. RESULTS: Details regarding presentation and diagnosis were frequently incomplete (84%). Among patients undergoing mastectomy, the potential for breast conservation was partially described in only 60%. Only 41% had data regarding intra-operative margin assessment during breast conservation surgery. In axillary lymph node dissections, 92% of patients had complete data about preservation of nerves, yet only 14% of reports contained complete information regarding sentinel lymph node biopsy. Closure was partially described in 91%. CONCLUSIONS: The dictated operative report for breast cancer surgery does not adequately capture important data. A synoptic reporting system, which requires documentation of important elements, is a potentially beneficial tool in breast cancer surgery.

Urine metabolite analysis offers potential early diagnosis of ovarian and breast cancers.

PURPOSE: Metabolomics is a new, rapidly expanding field dedicated to the global study of metabolites in biological systems. In this article metabolomics is applied to find urinary biomarkers for breast and ovarian cancer. EXPERIMENTAL DESIGN: Urine samples were collected from early- and late-stage breast and ovarian cancer patients during presurgical examinations and randomly from females with no known cancer. After quantitatively measuring a set of metabolites using nuclear magnetic resonance spectroscopy, both univariate and multivariate statistical analyses were employed to determine significant differences. RESULTS: Metabolic phenotypes of breast and ovarian cancers in comparison with normal urine and with each other revealed significance at Bonferroni-corrected significance levels resulting in unique metabolite patterns for breast and ovarian cancer. Intermediates of the tricarboxylic acid cycle and metabolites relating to energy metabolism, amino acids, and gut microbial metabolism were perturbed. CONCLUSIONS: The results presented here illustrate that urinary metabolomics may be useful for detecting early-stage breast and ovarian cancer.

Re-evaluation of a scoring system to predict nonsentinel-node metastasis and prognosis in melanoma patients.

BACKGROUND: We previously developed a scoring system based on patient age and total sentinel node (SN) tumor size to predict nonsentinel node (NSN) metastasis. The score relied on the cutoff values of 55 years for age and 5 mm total SN tumor size to stratify SN-positive patients into 3 categories. Its validity, however, remains in doubt given that it was developed by retrospective review of a single, relatively small cohort of SN-positive melanoma patients. The purpose of this study was to validate this scoring system and to determine its value in predicting patient survival. STUDY DESIGN: A review of melanoma patients who had undergone sentinel node biopsy and completion lymph node dissection (CLND) at the Melanoma Institute Australia from June 1992 until April 2009 was undertaken. The significance of the correlation of each of the score variables (age and total SN tumor size) with NSN metastasis, melanoma-specific survival, and overall survival was tested. Cox logistic regression analysis was used to determine the degree of correlation of the score system to each of the 3 outcomes. RESULTS: Six hundred six SN-positive patients were identified and included in this study. The score system did not significantly correlate with NSN metastasis (p = 0.1049). However, it did significantly correlate with both overall survival (p < 0.0001) and disease-specific survival (p = 0.0014). CONCLUSIONS: Our results revealed that the previously developed scoring system does not predict NSN metastasis; however, it was found to be a powerful predictive tool for overall and disease-free survival in SN-positive melanoma patients.

Exercise interventions for upper-limb dysfunction due to breast cancer treatment.

BACKGROUND: Upper-limb dysfunction is a commonly reported side effect of treatment for breast cancer and may include decreased shoulder range of motion (the range through which a joint can be moved) (ROM) and strength, pain and lymphedema. OBJECTIVES: To review randomized controlled trials (RCTs) evaluating the effectiveness of exercise interventions in preventing, minimi sing, or improving upper-limb dysfunction due to breast cancer treatment. SEARCH STRATEGY: We searched the Specialised Register of the Cochrane Breast Cancer Group, MEDLINE, EMBASE, CINAHL, and LILACS (to August 2008); contacted experts, handsearched reference lists, conference proceedings, clinical practice guidelines and other unpublished literature sources. SELECTION CRITERIA: RCTs evaluating the effectiveness and safety of exercise for upper-limb dysfunction. DATA COLLECTION AND ANALYSIS: Two authors independently performed the data abstraction. Investigators were contacted for missing data. MAIN RESULTS: We included 24 studies involving 2132 participants. Ten of the 24 were considered of adequate methodological quality.Ten studies examined the effect of early versus delayed implementation of post-operative exercise. Implementing early exercise was more effective than delayed exercise in the short term recovery of shoulder flexion ROM (Weighted Mean Difference (WMD): 10.6 degrees; 95% Confidence Interval (CI): 4.51 to 16.6); however, early exercise also resulted in a statistically significant increase in wound drainage volume (Standardized Mean Difference (SMD) 0.31; 95% CI: 0.13 to 0.49) and duration (WMD: 1.15 days; 95% CI: 0.65 to 1.65).Fourteen studies examined the effect of structured exercise compared to usual care/comparison. Of these, six were post-operative, three during adjuvant treatment and five following cancer treatment. Structured exercise programs in the post-operative period significantly improved shoulder flexion ROM in the short-term (WMD: 12.92 degrees; 95% CI: 0.69 to 25.16). Physical therapy treatment yielded additional benefit for shoulder function post-intervention (SMD: 0.77; 95% CI: 0.33 to 1.21) and at six-month follow-up (SMD: 0.75; 95% CI: 0.32 to 1.19). There was no evidence of increased risk of lymphedema from exercise at any time point. AUTHORS' CONCLUSIONS: Exercise can result in a significant and clinically meaningful improvement in shoulder ROM in women with breast cancer. In the post-operative period, consideration should be given to early implementation of exercises, although this approach may need to be carefully weighed against the potential for increases in wound drainage volume and duration. High quality research studies that closely monitor exercise prescription factors (e.g. intensity), and address persistent upper-limb dysfunction are needed.

Total sentinel lymph node tumor size predicts nonsentinel node metastasis and survival in patients with melanoma.

INTRODUCTION: In patients with a primary melanoma ≥1.0mm in Breslow thickness, the rate of metastasis to regional lymph nodes, as determined by sentinel node biopsy (SLNB), is approximately 20%. Among the patients with a positive SLNB result, however, only approximately 20% have tumor identified in additional non-SLNs. Therefore, many melanoma patients are still subjected to the morbidity of a complete lymph node dissection (CLND) without obvious benefit. In the current study, we analyzed the clinical and pathologic features of melanoma patients with positive SLNBs treated at the Melanoma Institute Australia. The aim was to correlate clinical and pathologic features of both the primary melanoma and the SLN metastases, including total SLN metastasis, with non-SN metastasis and (disease specific and overall) survival. METHODS: Total SLN tumor size was obtained by adding the largest diameters of all individual metastatic deposits within the SLN. Clinicopathological variables analyzed included patient age at the time of diagnosis, primary tumor characteristics (histologic type, Breslow thickness, ulceration, mitotic rate, site of primary tumor), and SLNB characteristics (date of SLNB procedure, location of LN field, number of draining LN fields, number of SLNs harvested, number of positive SLNs, size of largest metastatic deposit, total metastatic deposit size, location of metastasis within the SLN, extra nodal extension (ENE), and number of metastatic deposits within the SLN). The correlation between each of the predictor variables and outcome was determined by univariate analysis. The predictor variables that correlated with NSLN metastasis with a p value < 0.10 on univariate analysis were then entered into a multivariate model. RESULTS: There were 606 patients with a positive SNSNB result who proceeded to a CLND. The median number of NSNs in CLND specimens was 18 and the median number of positive NSLNs was 2.68. Of the patients with SN metastasis, 23.5% also had NSLN metastasis on CLND. Total SLN tumor size was significantly correlated to NSLN metastasis, melanoma-specific survival and overall survival on both univariate and multivariate analyses. CONCLUSION: Total SN tumor size predicts the likelihood of non-SLN metastasis, and also predicts survival outcome.

Synoptic surgical reporting for breast cancer surgery: an innovation in knowledge translation.

BACKGROUND: Extensive literature identifies that the quality of surgery not only influences morbidity and mortality but also long-term survival and function. This mandates that we develop a system to capture this information on a real-time basis. METHODS: A synoptic surgical template for breast cancer was created; this was digitized and made available to all surgeons in Alberta. RESULTS: The data reference 1,392 breast cancer procedures. Ninety-one percent of reports were submitted within 1 hour and 97% of reports were submitted within 24 hours. Fifty-two percent of reports were completed within 5 minutes. Information quality with respect to completeness of staging information was present in 89%. Eighty-four percent complied with practice guidelines and 89% of breast surgeons adopted the template. Seventy-five percent of users were moderately or highly satisfied with the system. CONCLUSIONS: The experience with the development and implementation of synoptic surgical reporting has proven to be a successful tool for generating quality surgical data.

Predictors of sentinel lymph node metastasis in melanoma.

BACKGROUND: Several studies have examined the correlation between patient and tumour characteristics and sentinel lymph node (SLN) metastasis in patients with melanoma. Although most studies have identified Breslow thickness as an important factor, results for other variables have been conflicting. Much of this variability is probably because of differences in measurement techniques and reporting practices at different institutions. We sought to identify the predictors of SLN melanoma metastasis in our institution and patient population. METHODS: We performed a retrospective chart review of 348 patients with malignant melanoma who underwent SLN biopsy at a single institution from January 1999 to April 2007. We compared multiple variables related to patient demographics, primary tumour characteristics and SLN characteristics between patients in the positive and negative SLN groups. RESULTS: Breslow thickness and nodular tumour type were independent factors significantly correlated with a positive SLN biopsy result in our study. Head and neck tumour location correlated with a lower likelihood of positive SLN status in univariate but not multivariate analyses. CONCLUSION: This study confirms the status of Breslow thickness as a reproducible predictor of positive SLN status. We also found that nodular type was predictive of positive SLN status, an outcome that has not been reported by others.

Validation of a scoring system to predict non-sentinel lymph node metastasis in melanoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has been widely accepted as the lymph node sampling procedure of choice for melanoma patients. Current standards of practice suggest completion lymph node dissection (CLND) for patients with a positive SLNB result. The rationale for SLNB+/-CLND is for staging and prognosis as well as local control and possibly survival improvement. CLND, however, entails significant morbidity. In addition, most patients (approximately 80%) will have no further melanoma metastases in non-sentinel nodes and these patients may not benefit from the additional dissection. We had previously developed a score (based on patient age and the total size of metastasis within the SLN) that predicted which SLN-positive patients would have a positive CLND. Utilization of this scoring system would spare a significant number of melanoma patients the risks associated with CLND. The purpose of this study was to validate this score using different melanoma populations. METHODS: A retrospective chart review of all patients that had undergone SLNB for melanoma at four different Canadian centers was undertaken. Data from the Calgary Foothills Medical Center, the Winnipeg Health Sciences Center, and the Toronto Sunnybrook Health Sciences Center from January 1999 to present was collected. In addition, we identified all patients from April 2007 to present at the Misericordia Hospital in Edmonton for this study. This patient information had not been utilized when we were developing this score. The collected variables included patient age, Breslow thickness, result of SLNB, total size of SLN metastasis, largest size of SLN metastasis, and results of CLND. Logistic regression was used to test the significance of a score system's correlation (based on cutoff age of 55 years and cutoff total SLN metastasis of 5 mm) with the CLND results. We also used logistic regression to test the correlation of cutoff values of total SLN metastasis with non-sentinel lymph node (NSLN) metastasis. RESULTS: Data were collected on 599 patients across the four centers. Breslow thickness significantly correlated with SLN metastasis. The risk score system (based on patient age and total SLN metastasis) was significantly predictive of the CLND result in SLNB-positive patients. However, the age became non-significant on multivariate analysis. Total SLN metastasis emerged as the variable that is most predictive of NSLN metastasis. Patients with total SLN metastasis less than 2 mm had a 3.6% risk of NSLN metastasis, those with SLN metastasis from 2-5 mm had a 12.5% risk of NSLN metastasis, whereas those with total SLN metastasis of 5 mm or greater had a 30% risk of NSLN metastasis. CONCLUSION: Using cutoff values of 2 and 5 mm for total SLN metastasis, prediction of NSLN metastasis can be made in melanoma patients. Patients with less than 2 mm of total SLN metastasis are unlikely (<3.67% likelihood) to harbor NSLN metastasis; these patients may not benefit from additional nodal dissection beyond SLNB.

Prediction of nonsentinel lymph node metastasis in malignant melanoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is the standard at many institutions caring for melanoma patients. Patients with positive SLNB results are currently offered completion lymph node dissection (CLND) of the affected lymph node basin. This procedure entails considerable morbidity and is often applied to patients with shortened life expectancies. Because 80% of CLNDs yield no additional positive nodes and there is no proof that CLND leads to survival improvement, criteria are needed to limit this procedure to those most likely to harbor nonsentinel lymph node (SLN) metastases. METHODS: A retrospective review of 349 cases of melanoma from January 1999 to April 2007 that underwent sentinel lymph node biopsy at a single institution was done. Statistical analysis was used to compare two subgroups of patients: a positive CLND group and a negative CLND group. These two groups were compared with regards to multiple variables related to patient demographics, primary tumor characteristics, and SLN tumor burden. RESULTS: Age and total size of SLN tumor deposit were the factors with the strongest correlation with CLND positivity. By applying a risk score model that uses the cutoff values of age 55 y and SLN tumor deposit of 5 mm, it is possible to predict CLND positivity in SLN-positive melanoma patients. CONCLUSION: The likelihood of CLND positivity in SLN-positive melanoma patients can be predicted from two criteria readily available: size of SLN tumor deposit and patient age.

Merkel cell carcinoma with squamous and sarcomatous differentiation.

Merkel cell carcinoma is an aggressive neuroendocrine tumor historically thought to arise from neural crest-derived cutaneous neuroendocrine cells. Recent evidence supports an epidermal origin. We present a case of Merkel cell carcinoma arising on the upper arm of a 94-year-old woman that had multiple morphologic patterns: small cells typical of Merkel cell carcinoma, malignant cells with squamous differentiation and malignant poorly differentiated spindle cells. Subsequent metastatic disease in regional lymph nodes showed only the small cells and the malignant spindle cells. To our knowledge, this is the first case of Merkel cell carcinoma showing these three patterns of differentiation at first presentation. This morphology raises the possibility that Merkel cell carcinomas may arise from epidermal stem cells that can differentiate along different lines.

Early removal of postmastectomy drains is not beneficial: results from a halted randomized controlled trial.

BACKGROUND: Closed-suction drainage to reduce seromas is standard after mastectomy. This study evaluates the safety of early drain removal. METHODS: Women undergoing mastectomy were randomized to early removal on postoperative day 2 or standard removal (< 30 mL drainage in 24 hours or postoperative day 14). Primary endpoints were time to drain removal and physician visits. Secondary endpoints were number of seroma aspirations, drain reinsertions, and infections. RESULTS: Twenty-seven patients were recruited before an interim analysis was performed to address safety concerns. Three patients withdrew before trial completion, leaving 14 patients in the standard group and 10 in the early group. Patients in the standard group had significantly fewer seroma aspirations, fewer drain reinsertions, and fewer physician visits. The trial was halted because of the higher rate of events in the early group. CONCLUSION: Surgical drains cannot be safely removed on postoperative day 2 after mastectomy. Early removal significantly increases the occurrence of seromas requiring treatment.