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Background Venous thromboembolism (VTE) prophylaxis has become routine for patients undergoing most operations, but it remains controversial for breast operations due to a perceived low risk of VTE. There is limited evidence to support routine or extended VTE prophylaxis in breast surgery. We investigated the benefits and risks of the Caprini risk stratification tool and corresponding prevention program, including extended prophylaxis for high-risk groups, in patients undergoing operations for benign and malignant breast lesions. Study Design Using Boston Medical Center data, we reviewed records of patients who underwent lumpectomy or total mastectomy (with or without axillary surgery and/or reconstruction), between 2011 and 2018, to collect information about operation, Caprini score, administration of prophylaxis, and postoperative VTE or bleeding events. Descriptive statistics were performed. Results Seven hundred fifty patients underwent 881 operations; 48.9% were at low or moderate risk of VTE, 43.8% were at high risk, and 7.3% were at highest risk. There were no VTE events in the low- and moderate-risk groups, 5 (1.3%) in the high-risk, and 1 (1.6%) in the highest-risk group. One patient was diagnosed with VTE during hospitalization. None of the 5 patients who developed VTE after discharge was prescribed the recommended extended chemoprophylaxis. There were 19 bleeding events that did not require reoperation; 3 patients returned to the operating room. There was no correlation of bleeding with receipt of extended chemoprophylaxis. Conclusions The Caprini protocol can identify high-risk breast surgery patients who may benefit from extended VTE chemoprophylaxis, as well as low-risk patients who require no chemoprophylaxis. Furthermore, administration of extended chemoprophylaxis was not associated with an increased risk of bleeding.

In the original article, there were errors in Table 1 that were not in accordance with requirements set by the Healthcare Cost and Utilization Project (HCUP) Data Use Agreement that apply to this article. Following is the corrected Table 1.

With the increases in complexity of care for breast health concerns, there is a growing need for efficient and effective clinical evaluation, especially for vulnerable populations at risk for poor outcomes. The Breast Health Center at Boston Medical Center is a multidisciplinary program, with internists providing care alongside breast surgeons, radiologists, and patient navigators. Using a triage system previously shown to have high provider and patient satisfaction, and the ability to provide timely care, patients are assigned to either a breast surgeon or internist. From 2007 to 2009, internists cared for 2,408 women, representing half of all referrals. Women served were diverse in terms of race (33% black, 30% Hispanic, 5% Asian), language (34% require language interpreter), and insurance status (51% had no insurance or public insurance). Most presented with an abnormal screen (breast examination 54% or imaging 4%) while the remainder were seen for symptoms such as pain (26%), non-bloody nipple discharge (4%), or risk assessment (7%). A majority of final diagnoses were made through clinical evaluation alone (n = 1,760, 73%), without the need for additional diagnostic imaging or tissue sampling; 9% (n = 214) received a benign diagnosis with the aid of breast imaging; 19% (n = 463) required tissue sampling. Only 4% went on to see a breast surgeon. Internists diagnosed 15 incident cancers with a median time to diagnosis of 19 days. Patient and provider satisfaction was high. These data suggest that a group of appropriately trained internists can provide quality breast care to a vulnerable population in a multidisciplinary setting. Replication of this model requires the availability of more clinical training programs for non-surgical providers.

Proliferative breast lesions, such as simple ductal hyperplasia (SH) and atypical ductal hyperplasia (ADH), are candidate precursors to ductal carcinoma in situ (DCIS) and invasive cancer. To better understand the relationship of breast lesions to more advanced disease, we used microdissection and DNA microarrays to profile the gene expression of patient-matched histologically normal (HN), ADH, and DCIS from 12 patients with estrogen receptor positive sporadic breast cancer. SH were profiled from a subset of cases. We found 837 differentially expressed genes between DCIS-HN and 447 between ADH-HN, with >90% of the ADH-HN genes also present among the DCIS-HN genes. Only 61 genes were identified between ADH-DCIS. Expression differences were reproduced in an independent cohort of patient-matched lesions by quantitative real-time PCR. Many breast cancer-related genes and pathways were dysregulated in ADH and maintained in DCIS. Particularly, cell adhesion and extracellular matrix interactions were overrepresented. Focal adhesion was the top pathway in each gene set. We conclude that ADH and DCIS share highly similar gene expression and are distinct from HN. In contrast, SH appear more similar to HN. These data provide genetic evidence that ADH (but not SH) are often precursors to cancer and suggest cancer-related genetic changes, particularly adhesion and extracellular matrix pathways, are dysregulated before invasion and even before malignancy is apparent. These findings could lead to novel risk stratification, prevention, and treatment approaches.

Background The overall effect of prophylactic tamoxifen in women depends on the balance between the effects of the drug, which include preventing breast cancer and altering cardiovascular risk. In a recent clinical trial, postmenopausal estrogen-progestin therapy was shown to increase the risk of early cardiovascular events among women with a history of coronary heart disease (CHD). The cardiovascular effects of tamoxifen in women with and without CHD are not known. The National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial (BCPT) is the only clinical trial that provides data to assess the cardiovascular effects of tamoxifen in women with and without CHD. Methods A total of 13 388 women at increased risk for breast cancer were randomly assigned in the BCPT to receive either tamoxifen (20 mg/day) or placebo. Cardiovascular follow-up was available for 13 194 women, 1048 of whom had prior clinical CHD. Fatal and nonfatal myocardial infarction, unstable angina, and severe angina were tabulated (mean follow-up: 49 months). All statistical tests were two-sided. Results Cardiovascular event rates were not statistically significantly different between women assigned to receive tamoxifen and those assigned to receive placebo, independent of pre-existing CHD. Among women without CHD (6074 on tamoxifen versus 6072 on placebo), risk ratios (95% confidence intervals [CIs]) for tamoxifen users were 1.75 (0.44 to 8.13) for fatal myocardial infarction, 1.11 (0.55 to 2.28) for nonfatal myocardial infarction, 0.69 (0.29 to 1.57) for unstable angina, and 0.83 (0.32 to 2.10) for severe angina. In women with CHD (516 on tamoxifen versus 532 on placebo), risk ratios (95% CIs) for tamoxifen users were 0.00 (0 to 1.58) for fatal myocardial infarction, 1.25 (0.32 to 5.18) for nonfatal myocardial infarction, 2.26 (0.87 to 6.55) for unstable angina, and 1.39 (0.23 to 9.47) for severe angina. There was no evidence that the lack of association between tamoxifen and cardiovascular events was related to an early increase in risk that may have been offset by a late decrease in risk. Conclusion When used for breast cancer prevention in women with or without heart disease, tamoxifen is not associated with beneficial or adverse cardiovascular effects.

Background We hypothesized that the method of breast cancer margin assessment may be associated with different rates of positive margins and residual carcinoma. Methods A total of 178 breast cancer specimens were divided into 2 groups (A and B) based on the margin assessment method used. Rates of positive margins, re-excision, and residual carcinoma at re-excision were compared and analyzed statistically. Results At least 1 margin was positive in 64.7% in group A and in 65.2% in group B. At directed re-excision 54% in group A and 51% in group B had residual carcinoma. The lateral margin was positive in 44% in group A compared with 26% in group B ( P = .06). The posterior margin was positive in 19% in group A and in 51% in group B ( P = .001). Conclusions Two different breast cancer specimen margin assessment methods had comparable rates of positive margins and residual carcinoma at re-excision. Different patterns of specific margin positivity suggest that the method of margin assessment may alter results.

Estrogen receptors (ER) are detected in 50-85% of all breast tumors, and are clinically important because they tend to identify patients with a higher probability of responding to hormonal or endocrine manipulations. However, approximately 30-40% of all ER+ patients do not respond to hormonal manipulations. The lack of response to hormonal manipulations in ER+ patients could be the result of nonfunctional ER, as determined by its inability to recognize and bind to specific DNA-responsive elements and/or its inability to recruit other transcriptional activation factors. The functional status of ER in 34 human breast tumors was assessed determining the structural integrity of the ER DNA-binding domain using site-directed monoclonal anti-estrogen receptor antibody and sucrose density gradient analysis. Based on the fraction of ER containing an intact DNA-binding domain, the tumors were classified into three groups: group I with > 65% of intact ER, group II with > 30% of intact ER, group III with < 30% of intact ER. Clinical and pathologic data were obtained only for patients who were treated with the anti-estrogen tamoxifen and correlated with ER functional status. In group I, 11 of 13 (84.6%) patients were responsive to hormonal therapy with favorable clinical outcome; two patients had unfavorable clinical outcome. In group II, 13 of 15 patients (86.7%) had favourable clinical outcome, and two patients 13.3% had unfavorable outcome. In group III, three of six patients appeared to be hormone responsive with favorable clinical outcome, and three of the patients in this group had unfavorable response to therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Introduction: We hypothesised that gene expression in histologically normal (HN) epithelium (NlEpi) would differ between breast cancer patients and usual-risk controls undergoing reduction mammoplasty (RM), and that gene expression in NlEpi from cancer-free prophylactic mastectomy (PM) samples from high-risk women would resemble HN gene expression. Methods: We analysed gene expression in 73 NlEpi samples microdissected from frozen tissue. In 42 samples, we used microarrays to compare gene expression between 18 RM patients and 18 age-matched HN (9 oestrogen receptor (ER)+, 9 ER−) and 6 PM patients. Data were analysed using a Bayesian approach (BADGE), and validated with quantitative real-time PCR (qPCR) in 31 independent NlEpi samples from 8 RM, 17 HN, and 6 PM patients. Results: A total of 98 probe sets (86 genes) were differentially expressed between RM and HN samples. Performing hierarchical analysis with these 98 probe sets, PM and HN samples clustered together, away from RM samples. qPCR validation of independent samples was high (84%) and uniform in RM compared with HN patients, and lower (58%), but more heterogeneous, in RM compared with PM patients. The 86 genes were implicated in many processes including transcription and the MAPK pathway. Conclusion: Gene expression differs between the NlEpi of breast cancer cases and controls. The profile of cancer cases can be discerned in high-risk NlEpi from cancer-free breasts. This suggests that the profile is not an effect of the tumour, but may mark increased risk and reveal the earliest genomic changes of breast cancer.

Normal-appearing epithelium of cancer patients can harbor occult genetic abnormalities. Data comprehensively comparing gene expression between histologically normal breast epithelium of breast cancer patients and cancer-free controls are limited. The present study compares global gene expression between these groups. We performed microarrays using RNA from microdissected histologically normal terminal ductal-lobular units (TDLU) from 2 groups: (i) cancer normal (CN) (TDLUs adjacent to untreated ER+ breast cancers (n = 14)) and (ii) reduction mammoplasty (RM) (TDLUs of age-matched women without breast disease (n = 15)). Cyber-T identified differentially expressed genes. Quantitative RT-PCR (qRT-PCR), immunohistochemistry (IHC), and comparison to independent microarray data including 6 carcinomas in situ (CIS), validated the results. Gene ontology (GO), UniProt and published literature evaluated gene function. About 127 probesets, corresponding to 105 genes, were differentially expressed between CN and RM (p < 0.0009, corresponding to FDR

Background: Initial fi ndings from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial (P-1) demonstrated that tamoxifen reduced the risk of estrogen receptor – positive tumors and osteoporotic fractures in women at increased risk for breast cancer. Side effects of varying clinical signifi cance were observed. The trial was unblinded because of the positive results, and follow-up continued. This report updates our initial fi ndings. Methods: Women (n = 13 388) were randomly assigned to receive placebo or tamoxifen for 5 years. Rates of breast cancer and other events were compared by the use of risk ratios (RRs) and 95% confi dence intervals (CIs). Estimates of the net benefi t from 5 years of tamoxifen therapy were compared by age, race, and categories of predicted breast cancer risk. Statistical tests were two-sided. Results: After 7 years of follow-up, the cumulative rate of invasive breast cancer was reduced from 42.5 per 1000 women in the placebo group to 24.8 per 1000 women in the tamoxifen group (RR = 0.57, 95% CI = 0.46 to 0.70) and the cumulative rate of noninvasive breast cancer was reduced from 15.8 per 1000 women in the placebo group to 10.2 per 1000 women in the tamoxifen group (RR = 0.63, 95% CI = 0.45 to 0.89). These reductions were similar to those seen in the initial report. Tamoxifen led to a 32% reduction in osteoporotic fractures (RR = 0.68, 95% CI = 0.51 to 0.92). Relative risks of stroke, deep-vein thrombosis, and cataracts (which increased with tamoxifen) and of ischemic heart disease and death (which were not changed with tamoxifen) were also similar to those initially reported. Risks of pulmonary embolism were approximately 11% lower than in the original report, and risks of endometrial cancer were about 29% higher, but these differences were not statistically signifi cant. The net benefi t achieved with tamoxifen varied according to age, race, and level of breast cancer risk. Conclusions: Despite the potential bias caused by the unblinding of the P-1 trial, the magnitudes of all benefi cial and undesirable treatment effects of tamoxifen were similar to those initially reported, with notable reductions in breast cancer and increased risks of thromboem bolic events and endometrial cancer. Readily identifi able sub sets of individuals comprising 2.5 million women could derive a net benefi t from the drug. [J Natl Cancer Inst 2005;97:1652 – 62]

Summary Background We have shown previously that lumpectomy with radiation therapy was more effective than lumpectomy alone for the treatment of ductal carcinoma in situ (DCIS). We did a double-blind randomised controlled trial to find out whether lumpectomy, radiation therapy, and tamoxifen was of more benefit than lumpectomy and radiation therapy alone for DCIS. Methods 1804 women with DCIS, including those whose resected sample margins were involved with tumour, were randomly assigned lumpectomy, radiation therapy (50 Gy), and placebo (n=902), or lumpectomy, radiation therapy, and tamoxifen (20 mg daily for 5 years, n=902). Median follow-up was 74 months (range 57–93). We compared annual event rates and cumulative probability of invasive or non-invasive ipsilateral and contralateral tumours over 5 years. Flndings Women in the tamoxifen group had fewer breast-cancer events at 5 years than did those on placebo (8·2 vs 13·4%, p=0·0009). The cumulative incidence of all invasive breast-cancer events in the tamoxifen group was 4·1% at 5 years: 2·1% in the ipsilateral breast, 1·8% in the contralateral breast, and 0·2% at regional or distant sites. The risk of ipsilateral-breast cancer was lower in the tamoxifen group even when sample margins contained tumour and when DCIS was associated with comedonecrosis. Interpretation The combination of lumpectomy, radiation therapy, and tamoxifen was effective in the prevention of invasive cancer.

PURPOSE In 1993, findings from a National Surgical Adjuvant Breast and Bowel Project (NSABP) trial to evaluate the worth of radiation therapy after lumpectomy concluded that the combination was more beneficial than lumpectomy alone for localized intraductal carcinoma-in-situ (DCIS). This report extends those findings. PATIENTS AND METHODS Women (N = 818) with localized DCIS were randomly assigned to lumpectomy or lumpectomy plus radiation (50 Gy). Tissue was removed so that resected specimen margins were histologically tumor-free. Mean follow-up time was 90 months (range, 67 to 130). Size and method of tumor detection were determined by central clinical, mammographic, and pathologic assessment. Life-table estimates of event-free survival and survival, average annual rates of occurrence for specific events, relative risks for event-specific end points, and cumulative probability of specific events comprising event-free survival are presented. RESULTS The benefit of lumpectomy plus radiation was virtually unchanged between 5 and 8 years of follow-up and was due to a reduction in invasive and noninvasive ipsilateral breast tumors (IBTs). Incidence of locoregional and distant events remained similar in both treatment groups; deaths were only infrequently related to breast cancer. Incidence of noninvasive IBT was reduced from 13.4% to 8.2% (P = .007), and of invasive IBT, from 13.4% to 3.9% (P < .0001). All cohorts benefited from radiation regardless of clinical or mammographic tumor characteristics. CONCLUSION Through 8 years of follow-up, our findings continue to indicate that lumpectomy plus radiation is more beneficial than lumpectomy alone for women with localized, mammographically detected DCIS. When evaluated according to the mammographic characteristics of their DCIS, all groups benefited from radiation.

Background The standard of care for early-stage breast cancer includes surgical removal of the tumor and axillary lymph node dissection (ALND). Despite increased use of breast-conserving surgery, lymphedema rates are similar to those with more radical surgery. Hypothesis Women who experience breast cancer–related lymphedema have a measurable reduction in quality of life compared with women without lymphedema. Design In a retrospective cohort study, we explored the association between lymphedema and quality of life, controlling for patient demographics, surgical factors, and treatment types. Settings An urban academic medical center and a community hospital. Participants A total of 151 women surgically treated for early-stage breast cancer (stages 0-II) were assessed at least 1 year after their ALND. The women had been treated with either conservative surgery and radiation or mastectomy without radiation. Main Outcome Measures Arm volume was measured by water displacement. Grip strength and range-of-motion measurements assessed arm function. The Functional Assessment of Cancer Therapy–Breast (FACT-B) quality-of-life instrument assessed breast, emotional, functional, physical, and social well-being. Results Lymphedema (an arm volume difference ≥200 cm 3 ) was measured in 42 women (27.8%). Mastectomy or conservative surgery patients had similar lymphedema rates. Women with lymphedema in both surgical groups scored significantly lower on 4 of the 5 subsections than women without lymphedema, even after adjusting for other factors influencing quality of life. Conclusions Lymphedema occurs at appreciable rates, and its impact on long-term quality of life in survivors of early-stage breast cancer should not be underestimated.

The purpose of this study was to determine if a “sling” made of polyglycolic acid (PGA) would be a reliable method of preventing small bowel descent into the pelvis following abdominal surgery. Baboons were used, as they respond to infection and ambulate similarly to humans. Animals had the small bowel mobilized to the upper abdomen and had the PGA “sling” sewn into place. Documentation of small bowel position was evaluated by upper gastrointestinal series over the 12-month study. Small bowel descent into the pelvis was prevented by utilization of the PGA “sling.” Animals were sacrificed and autopsied, and sections of small bowel were taken. There was no evidence of mesh, obstruction, sepsis, fistulae, or herniation in animals at autopsy. Small bowel sections were considered normal histologically. Utilization of PGA sling appears to be a safe and reliable method of preventing small bowel descent into the pelvis after abdominal surgery.

Radiation enteritis is seen in patients receiving radiation therapy for various pelvic malignancies. Attempts to prevent this have included various surgical as well as nutritional approaches with little success. The use of a polyglycolic acid mesh sling sewn above the pelvic inlet has prevented small bowel descent into the true pelvis in rats and in humans. The technique has been successful in both with no attendant morbidity during an 11-month follow up. Several patients have received additional doses of radiation therapy that would not have been given if the small bowel were not removed from the area to be irradiated.

The purpose of this study was to determine if a “sling” made of polyglycolic acid (PGA) would be a reliable method of preventing small bowel descent into the pelvis following abdominal surgery. Baboons were used, as they respond to infection and ambulate similarly to humans. Animals had the small bowel mobilized to the upper abdomen and had the PGA “sling” sewn into place. Documentation of small bowel position was evaluated by upper gastrointestinal series over the 12-month study. Small bowel descent into the pelvis was prevented by utilization of the PGA “sling.” Animals were sacrificed and autopsied, and sections of small bowel were taken. There was no evidence of mesh, obstruction, sepsis, fistulae, or herniation in animals at autopsy. Small bowel sections were considered normal histologically. Utilization of PGA sling appears to be a safe and reliable method of preventing small bowel descent into the pelvis after abdominal surgery.