The Prevalence of Sentinel Lymph Node Positivity and Implications for the Utility of Frozen Section Diagnosis Following Neoadjuvant Systemic Therapy in Patients with Clinically Node-Negative HER2-Positive or Triple-Negative Breast Cancer.

BACKGROUND: Axillary dissection is the standard of care for patients with positive sentinel lymph nodes (SLNs) following neoadjuvant systemic therapy. Frozen section can provide intraoperative information regarding the need for axillary dissection during the index operation. However, there are limited data on the utility of frozen section in patients with clinically node-negative (cN0) HER2-positive or triple-negative breast cancer. METHODS: We conducted a single-institution observational cohort study including patients with non-inflammatory, cN0, HER2-positive or triple-negative breast cancer treated with neoadjuvant systemic therapy between 2015 and 2019. We estimated the prevalence of SLN positivity and the diagnostic test characteristics of SLN frozen section. RESULTS: Overall, 662 patients were eligible for inclusion, and 44 patients had one or more positive SLNs (prevalence: 6.6%, 95% confidence interval [CI] 4.9-8.8). There were 490 (74.0%) patients who had intraoperative frozen section, and 19 (3.9%) tested positive among 33 (6.7%) with positive final pathology. Frozen section sensitivity was 57.6% (95% CI 39.2-74.5), specificity was 100% (95% CI 99.2-100), positive predictive value was 100% (95% CI 82.4-100), and negative predictive value was 97.0% (95% CI 95.1-98.4). The sensitivity of frozen section for detection of micrometastases or isolated tumor cells was 35.3% (95% CI 14.2-61.7). CONCLUSION: In patients with cN0 HER2-positive or triple-negative breast cancer who have been treated with neoadjuvant therapy, positive SLNs are uncommon and frozen section sensitivity is modest. Decisions to defer SLN evaluation to final pathology, which may be reasonable in many settings, can be informed, in part, by these findings.

Impact of long-term lipid-lowering therapy on clinical outcomes in breast cancer.

INTRODUCTION: The use of statins has been associated with improved survival in patients with breast cancer in several studies but results have been mixed. This study evaluates the impact of duration of statin use on breast cancer patient outcomes. METHODS: This is a single-institution, retrospective cohort, examining the impact of statin use on the outcomes of 1523 women diagnosed with operable breast cancer between1995 and 2015. Clinical variables were compared using Student's t test, Fisher's exact and Chi square tests. Overall (OS) and disease-free (DFS) survival were performed using Kaplan-Meier and Cox-Proportional Hazard (Cox-PH) analysis in the statistical software R. RESULTS: Patients were grouped by duration of statin use: never-statin user [N] (n = 1092), short (< 3 years) [S] (n = 115), moderate [M] (3-5 years) (n = 109) and long [L] (> 5 years) (n = 207) term. Over a median follow-up of 70.2 months, 138 women died (84 died of breast cancer) and 125 had disease recurrence. On multivariable Cox-PH analysis adjusting for clinical variables including metabolic comorbidities using the Charlson comorbidity index, OS in the [S] and [M] subgroups did not differ [N], while OS was improved in [L] (adjusted hazard ratio (AHR) 0.38, confidence interval (CI) 0.17-0.85, p < 0.018). DFS was also significantly improved in the [L] subgroup (adjusted HR 0.15, CI 0.05-0.48, p < 0.001). Subanalysis stratified by receptor status showed a trend towards improved DFS in all tumor subtypes including triple-negative breast cancer. CONCLUSIONS: Our retrospective analyses suggest that long-term statin use (> 5 years) was associated with improved OS and DFS in women with breast cancer regardless of receptor subtype, even after adjusting for metabolic comorbidities.

The impact of aspirin use on breast cancer subtype and clinical course.

BACKGROUND: The use of aspirin has been associated with improved survival in patients with breast cancer, but the results have been mixed. We aim to analyze the impact of aspirin use before or after breast cancer diagnosis on breast cancer clinical characteristics and outcomes. MATERIALS AND METHODS: We performed a single-institution, retrospective analysis of 1113 women diagnosed with operable breast cancer between 1995 and 2015. Patients were grouped according to their aspirin use: never (944), before diagnosis (79), and after diagnosis (90). Clinical variables, overall survival (OS), and disease-free survival (DFS) were compared between groups. RESULTS: Women using aspirin before diagnosis were older, more likely to be black, and to have associated medical comorbidities than patients in other groups (all P <0.001). These patients were also more likely to present with hormone receptor-negative cancers, including triple-negative breast cancer (P = 0.002). Aspirin use before diagnosis was associated with a worse OS in univariate and multivariate analyses (both P <0.001), but there were no other differences in OS or DFS related to aspirin use. CONCLUSIONS: Despite a potential impact on tumor subtype in patients using aspirin before their breast cancer diagnosis, aspirin use does not appear to alter breast cancer-related survival.

The impact of preoperative magnetic resonance imaging and lumpectomy cavity shavings on re-excision rate in pure ductal carcinoma in situ-A single institution's experience.

BACKGROUND AND OBJECTIVES: The impact of preoperative magnetic resonance imaging (pMRI) and cavity shave margins (CSM) on re-excision rate (RR) in DCIS is unclear. We investigated whether either modality was associated with RR in DCIS. METHODS: This is a single-institution retrospective study of 295 women undergoing breast conservation surgery for pure DCIS (2010-2013). CSM were the systematic resection of 4-6 margins during lumpectomy whereas selective shave margins (SSM) were the selective resection of 1-3 margins. Patient demographics and clinical characteristics were abstracted. RR was analyzed according to the use of pMRI, SSM, or CSM with respect to three high-volume breast surgeons at our institution. RESULTS: RR was not associated with the use of pMRI (P = 0.87). Any shave margins (P = 0.05), DCIS size (P < 0.001), and DCIS grade (P = 0.14) associated with a lower RR. Of our high-volume surgeons, RR was lower for Surgeon A (P = 0.02). Multivariate analyses showed larger DCIS (OR 1.35, P = 0.005) and practices specific to surgeons B (OR 3.23, P = 0.04) and C (OR 3.57, P = 0.04) increased re-excision odds. CONCLUSIONS: SSM/CSM and pMRI use varied among surgeons. Our results suggested the routine use of CSM, not pMRI, could lower re-excision rate, which highlighted a quality improvement opportunity at our institution.

Breast cancer subtype distribution is different in normal weight, overweight, and obese women.

PURPOSE: Obesity is associated with tumor promoting pathways related to insulin resistance and chronic low-grade inflammation which have been linked to various disease states, including cancer. Many studies have focused on the relationship between obesity and increased estrogen production, which contributes to the pathogenesis of estrogen receptor-positive breast cancers. The link between obesity and other breast cancer subtypes, such as triple-negative breast cancer (TNBC) and Her2/neu+ (Her2+) breast cancer, is less clear. We hypothesize that obesity may be associated with the pathogenesis of specific breast cancer subtypes resulting in a different subtype distribution than normal weight women. METHODS: A single-institution, retrospective analysis of tumor characteristics of 848 patients diagnosed with primary operable breast cancer between 2000 and 2013 was performed to evaluate the association between BMI and clinical outcome. Patients were grouped based on their BMI at time of diagnosis stratified into three subgroups: normal weight (BMI = 18-24.9), overweight (BMI = 25-29.9), and obese (BMI > 30). The distribution of breast cancer subtypes across the three BMI subgroups was compared. RESULTS: Obese and overweight women were more likely to present with TNBC and normal weight women with Her2+ breast cancer (p = 0.008). CONCLUSIONS: We demonstrated, for the first time, that breast cancer subtype distribution varied significantly according to BMI status. Our results suggested that obesity might activate molecular pathways other than the well-known obesity/estrogen circuit in the pathogenesis of breast cancer. Future studies are needed to understand the molecular mechanisms that drive the variation in subtype distribution across BMI subgroups.

Mammographic breast density decreases after bariatric surgery.

PURPOSE: Breast density (BD), an important risk factor for breast cancer, can change over time in some women, but the underlying mechanism is unclear. Very little is known about the impact of surgical weight loss on BD. Our hypothesis is that weight loss after bariatric surgery is associated with a significant and favorable change in mammographic BD. METHODS: We identified 1097 women 40 years of age or older who underwent gastric bypass or sleeve gastrectomy at our institution from 2010 to 2014. Women who did not have either pre- and post-bariatric surgery mammograms performed at our institution were excluded; 110 had both mammograms and comprised the cohort. Breast density was determined both qualitatively, using reported BI-RADS density, and quantitatively, using the Laboratory for Individualized Breast Radiodensity Assessment. RESULTS: Qualitative BI-RADS density, quantitative breast area, and percent BD significantly decreased in post-bariatric surgery mammograms (p = 0.009, <0.001, and <0.001, respectively). CONCLUSIONS: Our retrospective study demonstrated that surgical weight loss was associated with a significant decrease in breast density. Additional studies are warranted to validate our findings and elucidate the molecular mechanisms underlying breast density change after weight loss surgery.

Accessibility of academic plastic surgeons as mentors to medical students.

BACKGROUND: Determining a field of specialty can be a difficult decision for medical students. Career plans are often fostered through exposure to the field and mentorship, but it is often hard to identify accessible mentors. The purposes of this study were to determine the prevalence of accessible mentors among academic plastic surgery faculty and to characterize predictors of accessibility. METHODS: An audit was conducted of academic plastic surgeon faculty affiliated with integrated and combined residency programs. A request for mentorship was sent from a medical student enrolled at the faculty member's affiliated medical school. Sources for e-mail addresses included residency program Web sites, the American Society of Plastic Surgeons Web site, and a manual PubMed search. Independent predictors of accessible mentors were determined. RESULTS: There were 498 e-mails delivered and 363 responses received (response rate of 73%). In total, there were 283 positive responses, resulting in 56.8% of plastic surgeons contacted identifying themselves as accessible for mentorship. Younger age [odds ratio (OR), 1.72; P = 0.005], Fellow of the American College of Surgeons (OR, 1.49; P = 0.035), and faculty members of medical schools ranked in the top 20 (OR, 1.75; P = 0.003) were associated with an increased odds of accessibility. CONCLUSIONS: Most academic plastic surgeons are accessible as mentors (78%). Medical students enrolled at a highly ranked medical school seeking younger faculty mentors may have the greatest access to research opportunities and career advice. Encouraging faculty to participate in mentorship is important in developing the next generation of plastic surgeons.

Enhanced recovery after surgery (ERAS) protocol reduces perioperative narcotic requirement and length of stay in patients undergoing mastectomy with implant-based reconstruction.

INTRODUCTION: Enhanced Recovery after Surgery (ERAS) protocols have contributed to shortened hospital stays and reduced narcotic use after common surgical procedures. Though ERAS protocols exist for breast surgery, they have not been studied for implant-based reconstruction after mastectomy. METHODS: Twenty-three consecutive patients undergoing mastectomy with implant-based reconstruction were treated with perioperative gabapentin, acetaminophen, and NSAIDs. Data regarding clinical course and medication requirement were compared to a historical control cohort (n = 23) receiving usual care after mastectomy. Opioid analgesics were converted to oral morphine equivalents (OMEs) for comparison between groups. RESULTS: Patients treated with the ERAS protocol required significantly fewer narcotics as measured in OMEs over postoperative days 0-2. Patient reported pain scores were equivalent between groups, as were postoperative complication rates of nausea, hematoma, and infection. Additionally, ERAS patients had significantly shorter mean length of hospital stay (1.3 vs. 2.5 days, p = 0.037). CONCLUSIONS: Patients receiving perioperative gabapentin, acetaminophen, and NSAIDs under an ERAS protocol required significantly fewer narcotics and shorter length of stay. This protocol may merit consideration for use at other centers.

Overall survival is similar between women who seek care at one or more institutions after diagnosis of operable breast cancer in the community.

BACKGROUND: As breast cancer diagnoses increase, so does the number of patients who are critically evaluating hospital attributes to determine where to receive their treatment. Evidence suggests that complex surgeries have better outcomes in high volume academic centers. Whether clinical outcomes of women diagnosed with operable breast cancer, who are treated by multiple disciplines including non-complex surgical approaches, differ for those received all or part of their treatment at their community cancer center is unclear. We hypothesize that the clinical outcomes do not differ for those who received all or part of their care at their community cancer center. Our aim is to analyze data from the National Cancer Database (NCDB) to assess the clinical characteristics and outcomes of patients who received all their treatment at community cancer center when compared with those who had part or all of their care elsewhere. METHODS: A cohort of 162,803 women diagnosed at a community cancer center with an operable breast cancer (clinical stage I - III) between 2005 and 2014 from the NCDB was evaluated. Demographics, cancer-specific characteristics and overall survival differences between patients who stay at or leave their home institution for breast cancer treatment were compared. RESULTS: Within this cohort, patients treated at multiple institutions were younger, traveled further from home for their care, and were more likely to have no comorbidities (p < 0.001). Overall survival adjusted for demographics and cancer stage and subtype did not differ based on treatment at one or multiple institutions. CONCLUSIONS: The decision for patients to undergo breast cancer treatment in a different institution after being diagnosed in a community center does not appear to impact overall survival.

Safety and Efficacy of Intratumoral Injections of Chimeric Antigen Receptor (CAR) T Cells in Metastatic Breast Cancer.

Chimeric antigen receptors (CAR) are synthetic molecules that provide new specificities to T cells. Although successful in treatment of hematologic malignancies, CAR T cells are ineffective for solid tumors to date. We found that the cell-surface molecule c-Met was expressed in ∼50% of breast tumors, prompting the construction of a CAR T cell specific for c-Met, which halted tumor growth in immune-incompetent mice with tumor xenografts. We then evaluated the safety and feasibility of treating metastatic breast cancer with intratumoral administration of mRNA-transfected c-Met-CAR T cells in a phase 0 clinical trial (NCT01837602). Introducing the CAR construct via mRNA ensured safety by limiting the nontumor cell effects (on-target/off-tumor) of targeting c-Met. Patients with metastatic breast cancer with accessible cutaneous or lymph node metastases received a single intratumoral injection of 3 × 107 or 3 × 108 cells. CAR T mRNA was detectable in peripheral blood and in the injected tumor tissues after intratumoral injection in 2 and 4 patients, respectively. mRNA c-Met-CAR T cell injections were well tolerated, as none of the patients had study drug-related adverse effects greater than grade 1. Tumors treated with intratumoral injected mRNA c-Met-CAR T cells were excised and analyzed by immunohistochemistry, revealing extensive tumor necrosis at the injection site, cellular debris, loss of c-Met immunoreactivity, all surrounded by macrophages at the leading edges and within necrotic zones. We conclude that intratumoral injections of mRNA c-Met-CAR T cells are well tolerated and evoke an inflammatory response within tumors. Cancer Immunol Res; 5(12); 1152-61. ©2017 AACR.