Faculty Bibliography

Obesity is one of the risk factors for developing lymphedema following breast cancer treatment. We prospectively enrolled 140 women and followed the participants for 12 months after surgery to investigate patterns of obesity and lymph fluid level in the first year of cancer treatment. Electrical bioimpedance devices were used to measure weight, BMI, and percent of body fat as well as lymph fluid level. General instructions were given to the participants on maintaining pre-surgery weight. Among the 140 participants, 136 completed the study with 2.9% attrition. More than 60% of the participants were obese (30.8%) or overweight (32.4%), while only two participants were underweight and about 35% had normal weight. This pattern of obesity and overweight was consistent at 4-8 weeks and 12 months post-surgery. At 12 months post-surgery, the majority of the women (72.1%) maintained pre-surgery weight and 15.4% had >5% weight loss; 12.5% of the women increase >5% of their weight. Significantly more patients in the obesity group had lymphedema defined by L-Dex ratio >7.1 than those in the normal/underweight and overweight group at pre-surgery and 4-8 weeks post-surgery. There was a trend of more patients in the obesity group had L-Dex ratio >7.1 at 12 months post-surgery. Obesity and overweight remain among women at the time of cancer diagnosis and the patterns of obesity and overweight continue during the first year of treatment. General instructions on having nutrition-balanced and portion-appropriate diet and physical activities daily or weekly can be effective to maintain pre-surgery weight.

Many breast cancer survivors have coexistent chronic diseases or comorbidities at the time of their cancer diagnosis. The purpose of the study was to evaluate the association of comorbidities on breast cancer survivors' quality of life. A prospective design was used to recruit 140 women before cancer surgery, 134 women completed the study. Comorbidities were assessed using self-report and verified by medical record review and the Charlson Comorbidity Index (CCI) before and 12-month after cancer surgery. Quality of life was evaluated using Short-Form Health Survey (SF-36 v2). Descriptive statistics, chi-square tests, t-tests, Fisher's exact test, and correlations were performed for data analysis. A total of 28 comorbidities were identified. Among the 134 patients, 73.8% had at least one of the comorbidities, 54.7% had 2-4, and only 7.4% had 5-8. Comorbidities did not change at 12 months after surgery. Numbers of comorbidities by patients' self-report and weighted categorization of comorbidities by CCI had a similar negative correlation with overall quality of life scores as well as domains of general health, physical functioning, bodily pain, and vitality. Comorbidities, specifically hypertension, arthritis, and diabetes, were associated with poorer quality of life in multiple domains among breast cancer survivors. Future research should consider the combined influence of comorbidity and cancer on patients' quality of life.

Objective Sentinel lymph node biopsy (SLNB) is a widely accepted and safe technique that increases the accuracy of axillary staging in breast cancer for patients with clinically node-negative disease. Results from the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial found no benefit for completion axillary lymph node dissection (ALND) in patients with breast cancer involving 1 to 2 positive sentinel nodes. The purpose of our study was to characterize the population of patients who had ALND since the publication of the Z0011 results. Methods This was an IRB-approved retrospective review of women with newly diagnosed breast cancer between 1/2010 and 6/2013 who were clinically node-negative and had >1 positive sentinel lymph node (SLN). Variables of interest included age, method of presentation, body mass index (BMI), tumor characteristics, surgery type, and preop imaging. Patients who received neoadjuvant therapy were excluded. Descriptive statistics and Pearson's chisquare analyses were utilized. Results Out of a total of 1,513 patients, 191 (12%) patients had >1 positive SLN in their initial surgery. The mean age was 56 years. Of the patients with a positive SLN, 139 (73%) went on to have a completion ALND. The distribution of age and tumor type was similar in patients who had SLNB alone and who underwent completion ALND. However, a higher proportion of patients who underwent completion ALND had later stage disease (p < 0.0001), larger tumors (p = 0.012), and greater number of positive SLN (p = 0.004), and had a higher BMI (p = 0.05). Among the 139 patients who went on to have a complete ALND, 127 (91%) patients had frozen section analysis with > 1 positive lymph node. Of these patients, 72 (57%) had 1 lymph node positive for metastasis and 41 (32%) had 2 lymph nodes positive for metastasis on final pathology. Conclusion Our study showed that women who had a completion ALND presented with later stage disease, larger tumors, and greater number of positive SLN. Frozen section analysis at the time of SLNB led to ALND in 113 patients with 1 or 2 positive SLN on final pathology. These patients would not meet the criteria for axillary dissection based on the results of Z0011. This suggests that patients should either undergo completion axillary dissection if 3 or more lymph nodes are found to have metastatic disease on frozen section or that completion dissection should be deferred until final pathology confirms the presence of 3 or more positive lymph nodes

PURPOSE: The accumulation of wound fluid known as seroma in the chest cavity following breast surgery is a common occurrence that can persist for many weeks. While the pro-inflammatory composition of seroma is well established, there has been remarkably little research to determine whether seroma contains pro-oncogenic factors, and whether this is influenced by previous malignant disease. METHODS: We developed a clinical trial in which we obtained post-surgical seroma fluids from women with benign or malignant disease 1 or 2 weeks following lumpectomy or mastectomy. We conducted an analysis of more than 80 different cytokines, chemokines and growth factors. RESULTS: We found that surgical cavity seroma from breast cancer patients has a higher expression of key tumor-promoting cytokines and lower expression of important tumor-inhibiting factors when compared to benign lesions from non-cancer patients. Patients with high body mass index also had higher levels of leptin regardless of malignancy. CONCLUSIONS: We conclude that the breast post-surgical tumor cavity contains factors that are pro-inflammatory regardless of malignant or benign disease, but in malignant disease there is significant enrichment of additional pro-oncogenic chemokines, cytokines and growth factors, and reduction in tumor-inhibiting factors. These results are consistent with tumor conditioning of surrounding normal stromal tissue and creation of a pro-oncogenic environment that persists long after surgical removal of the tumor.

Breast cancer-related lymphedema is a syndrome of abnormal swelling coupled with multiple symptoms resulting from obstruction or disruption of the lymphatic system associated with cancer treatment. Research has demonstrated that with increased number of symptoms reported, breast cancer survivors' limb volume increased. Lymphedema symptoms in the affected limb may indicate a latent stage of lymphedema in which changes cannot be detected by objective measures. The latent stage of lymphedema may exist months or years before overt swelling occurs. Symptom report may play an important role in detecting lymphedema in clinical practice. The purposes of this study were to: 1) examine the validity, sensitivity, and specificity of symptoms for detecting breast cancer-related lymphedema and 2) determine the best clinical cutoff point for the count of symptoms that maximized the sum of sensitivity and specificity. Data were collected from 250 women, including healthy female adults, breast cancer survivors with lymphedema, and those at risk for lymphedema. Lymphedema symptoms were assessed using a reliable and valid instrument. Validity, sensitivity, and specificity were evaluated using logistic regression, analysis of variance, and areas under receiver operating characteristic curves. Count of lymphedema symptoms was able to differentiate healthy adults from breast cancer survivors with lymphedema and those at risk for lymphedema. A diagnostic cutoff of three symptoms discriminated breast cancer survivors with lymphedema from healthy women with a sensitivity of 94% and a specificity of 97% (area under the curve =0.98). A diagnostic cutoff of nine symptoms discriminated at-risk survivors from survivors with lymphedema with a sensitivity of 64% and a specificity of 80% (area under the curve =0.72). In the absence of objective measurements capable of detecting latent stages of lymphedema, count of symptoms may be a cost-effective initial screening tool for detecting lymphedema.

IntroductionEstrogen inhibition is effective in preventing breast cancer in only up to 50% of women with precancerous lesions and many experience side effects that are poorly tolerated. As insulin-like growth factor I (IGF-I) underlies both estrogen and progesterone actions and has other direct effects on mammary development and carcinogenesis, we hypothesized that IGF-I inhibition might provide a novel approach for breast cancer chemoprevention.MethodsIn total, 13 women with core breast biopsies diagnostic of atypical hyperplasia (AH) were treated for 10 days with pasireotide, a somatostatin analog which uniquely inhibits IGF-I action in the mammary gland. They then had excision biopsies. 12 patients also had proliferative lesions and one a ductal carcinoma in situ (DCIS). Primary outcomes were changes in cell proliferation and apoptosis after treatment. Expression of estrogen receptor (ER), progesterone receptor (PR), and phosphorylated Insulin-like growth factor I receptor (IGF-1R), protein kinase B (AKT) and extracellular signal-regulated kinases 1/2 (ERK1/2) were also assessed. Core and excision biopsies from 14 untreated patients served as non-blinded controls. Hyperglycemia and other side effects were carefully monitored.ResultsPasireotide decreased proliferation and increased apoptosis in all AH (from 3.6 inverted question mark+/- inverted question mark2.6% to 1.3 inverted question mark+/- inverted question mark1.2% and from 0.3 inverted question mark+/- inverted question mark0.2% to 1.5 inverted question mark+/- inverted question mark1.6%, respectively) and proliferative lesions (from 3.8 inverted question mark+/- inverted question mark2.5% to 1.8 inverted question mark+/- inverted question mark1.8% and from 0.3 inverted question mark+/- inverted question mark0.2% to 1.3 inverted question mark+/- inverted question mark0.6%, respectively). The DCIS responded similarly. ER and PR were not affected by pasireotide, while IGF-1R, ERK1/2 and AKT phosphorylation decreased significantly. In contrast, tissue from untreated controls showed no change in cell proliferation or phosphorylation of IGF-1R, AKT or ERK 1/2. Mild to moderate hyperglycemia associated with reduced insulin levels was found. Glucose fell into the normal range after discontinuing treatment. Pasireotide was well tolerated and did not cause symptoms of estrogen deprivation.ConclusionsIGF-I inhibition by pasireotide, acting through the IGF-1R, was associated with decreased proliferation and increased apoptosis in pre-malignant breast lesions and one DCIS. Assuming hyperglycemia can be controlled, these data suggest that inhibiting the IGF-I pathway may prove an effective alternative for breast cancer chemoprevention.Trial registration NCT01372644 Trial date: July 1, 2007.