Faculty Bibliography

Use of nipple-sparing mastectomy (NSM) for risk-reduction and therapeutic breast cancer resection is growing. The role for intraoperative frozen section of the nipple-areolar complex remains controversial. Records of patients undergoing NSM at our institution from 2006 to 2013 were reviewed. Records from 501 nipple-sparing mastectomies were reviewed (216 therapeutic, 285 prophylactic). Of the 480 breasts with sub-areolar biopsies, 307 had intraoperative frozen sections and 173 were evaluated with permanent paraffin section only. Among the 307 intraoperative frozen sections, 12 biopsies were positive on permanent paraffin section (3.9% or 12/307). Of the 12 positive permanent biopsies, five were false negative and the remaining seven concordant intraoperatively. Sensitivity and specificity of sub-areolar frozen section were 0.58 and 1, respectively. Positive sub-areolar biopsies consisted primarily of ductal carcinoma in situ (62% or 13/21). The nipples or nipple-areolar complex were resected in a separate procedure following mastectomy (10/21), intraoperatively following frozen section results (7/21) or during second-stage breast reconstruction (3/21; 1 additional scheduled). Only 30% (6/20) of resected specimens had abnormal residual pathology. Intraoperative frozen section is highly specific and moderately sensitive for the detection of positive sub-areolar biopsies in NSM. Its use can help guide intraoperative reconstructive planning. The presence of positive sub-areolar biopsies in both contralateral and high-risk prophylactic mastectomy specimens emphasizes the need to perform sub-areolar biopsies in all nipple-sparing mastectomies.

BACKGROUND: Permanent paraffin subareolar biopsy during nipple-sparing mastectomy (NSM) tests for occult cancer at the nipple-areolar complex. Intraoperative subareolar frozen section can provide earlier detection intraoperatively. Cost analysis for intraoperative subareolar frozen section has never been performed. METHODS: NSM cases from 2006-2013 were reviewed. Patient records including financial charges were analyzed. RESULTS: Of 480 subareolar biopsies for NSM from 2006-2013, 21 were abnormal (4.4 %). A total of 307 of the subareolar biopsies included intraoperative frozen section. Of the 307, 12 (3.9 %) were abnormal with 7 of 12 detected on intraoperative frozen section. The median baseline charge for an intraoperative subareolar frozen section was $309 for an estimated total cost of $94,863 in 307 breasts. The median baseline charge for interval operative resection of a nipple-areolar complex following an abnormal subareolar pathology result was $11,021. Intraoperative subareolar biopsy avoided an estimated six return trips to the operating room for savings of $66,126. At our institution, routine use of intraoperative frozen section resulted in an additional $28,737 in healthcare charges or $95 per breast. CONCLUSIONS: We present the first cost analysis to evaluate intraoperative subareolar frozen section in NSM. This practice obviated an estimated six return trips to the operating room. With our institutional frequency of abnormal subareolar pathology, intraoperative frozen sections resulted in a marginal increased charge per mastectomy.

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.

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.

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.

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