Changes in Surgical Management of the Axilla Over 11 Years - Report on More Than 1500 Breast Cancer Patients Treated with Neoadjuvant Chemotherapy on the Prospective I-SPY2 Trial.

BACKGROUND: Axillary surgery after neoadjuvant chemotherapy (NAC) is becoming less extensive. We evaluated the evolution of axillary surgery after NAC on the multi-institutional I-SPY2 prospective trial. METHODS: We examined annual rates of sentinel lymph node (SLN) surgery with resection of clipped node, if present), axillary lymph node dissection (ALND), and SLN and ALND in patients enrolled in I-SPY2 from January 1, 2011 to December 31, 2021 by clinical N status at diagnosis and pathologic N status at surgery. Cochran-Armitage trend tests were calculated to evaluate patterns over time. RESULTS: Of 1578 patients, 973 patients (61.7%) had SLN-only, 136 (8.6%) had SLN and ALND, and 469 (29.7%) had ALND-only. In the cN0 group, ALND-only decreased from 20% in 2011 to 6.25% in 2021 (p = 0.0078) and SLN-only increased from 70.0% to 87.5% (p = 0.0020). This was even more striking in patients with clinically node-positive (cN+) disease at diagnosis, where ALND-only decreased from 70.7% to 29.4% (p < 0.0001) and SLN-only significantly increased from 14.6% to 56.5% (p < 0.0001). This change was significant across subtypes (HR-/HER2-, HR+/HER2-, and HER2+). Among pathologically node-positive (pN+) patients after NAC (n = 525) ALND-only decreased from 69.0% to 39.2% (p < 0.0001) and SLN-only increased from 6.9% to 39.2% (p < 0.0001). CONCLUSIONS: Use of ALND after NAC has significantly decreased over the past decade. This is most pronounced in cN+ disease at diagnosis with an increase in the use of SLN surgery after NAC. Additionally, in pN+ disease after NAC, there has been a decrease in use of completion ALND, a practice pattern change that precedes results from clinical trials.

Hispanic Breast Cancer Patients Travel Further for Equitable Surgical Care at a Comprehensive Cancer Center.

Purpose: Disparities in surgical breast cancer care have been documented for racial and ethnic minorities. On average, these minorities are less likely to utilize National Cancer Institute (NCI)-designated cancer centers and travel shorter distances to receive care. With the growing population of Hispanic patients in California, we analyzed the travel distance and surgical care of Hispanic and non-Hispanic patients at our large referral cancer center. Methods: Patients included were those who initiated treatment for a new diagnosis of ductal carcinoma in situ or invasive breast cancer at our NCI-designated cancer center during the period 2010-2014. Ethnicity was dichotomized as Hispanic and non-Hispanic. Google Maps were used to determine the distance from patient zip code to our institution, classified as 0-10, 10-30, 30-60, and >60 miles. Results: A total of 1765 non-Hispanic and 173 Hispanic patients were identified. Clinical stage by tumor size and nodal status were comparable between the two groups. Hispanic patients were younger (p<0.001) and more had Medicaid insurance (p<0.001). Hispanic patients traveled further when compared with non-Hispanics (p<0.001). In non-Hispanics and Hispanics, rates of breast conservation were 57.4% and 52.3% (p=0.30), unilateral mastectomy 34.2% and 36.2% (p=0.44), bilateral mastectomy 8.4% and 11.5% (p=0.24), and immediate postmastectomy reconstruction 42.6% and 50.6% (p=0.34), respectively. Hispanic ethnicity was not associated with different odds of receiving breast conservation (odds ratio [OR] 1.01, confidence interval [CI] 0.73-1.40), unilateral mastectomy (OR 1.05, CI 0.75-1.44), bilateral mastectomy (OR 1.37, CI 0.81-2.31), or immediate postmastectomy breast reconstruction (OR 1.27, CI 0.86-1.88), when compared with non-Hispanic ethnicity, after controlling for patient age, insurance status, and distance traveled. Conclusions: Surgical care was similar for Hispanic and non-Hispanic patients treated at our NCI-designated cancer center. However, this Hispanic population traveled further than non-Hispanic patients. Our findings suggest that accessibility to transportation and institutional practices are instrumental in delivering equitable breast cancer surgical care for Hispanic patients.

Addressing inherited predisposition for breast cancer in transplant recipients.

Consideration of prophylactic mastectomy surgery following transplantation requires complex medical decision-making, and bias against elective surgery exists because of concern for post-operative complications. Prevention of cancer in transplant recipients is of utmost importance, given the risks of treating malignancy in an immunosuppressed patient. We present a patient case and review of the literature to support a thorough pre-transplantation evaluation of family history and consideration of prophylactic interventions to safeguard the quality of life of transplant recipients. J. Surg. Oncol. 2016;113:605-608. © 2016 Wiley Periodicals, Inc.

DCIS in BRCA1 and BRCA2 mutation carriers: prevalence, phenotype, and expression of oncodrivers C-MET and HER3.

BACKGROUND: Studies report conflicting evidence regarding the existence of a DCIS-associated premalignant pathway in BRCA mutation carriers. We aimed to examine the prevalence, phenotype, and expression of oncodrivers in pure DCIS (pDCIS) and invasive breast cancer with concurrent DCIS (IBC + DCIS) in mutation carriers. METHODS: A cohort of BRCA1 and BRCA2 mutation carriers >18 years old who underwent surgery for breast cancer at an academic hospital (1992-2011) and had pathology available for review were included for study. Invasive breast cancer (IBC) and DCIS were stained for ER, PR, HER1, HER2, and HER3, and C-MET. DCIS prevalence was evaluated. Correlation of IBC and DCIS phenotypes was evaluated in patients with IBC + DCIS. DCIS and IBC expression of tumor markers were examined by BRCA mutation. RESULTS: We identified 114 breast tumors. Of all BRCA1-associated tumors, 21.1 % were pDCIS and 63.4 % were IBC + DCIS. Of all BRCA2-associated tumors, 23.3 % were pDCIS and 60.5 % were IBC + DCIS. In BRCA1 and BRCA2 mutation carriers with IBC + DCIS, there was a significant correlation in ER, PR, and HER3 expression between the DCIS and IBC components. Most BRCA1-associated DCIS did not express ER, PR or HER2, while most BRCA2-associated DCIS did express ER and PR. BRCA1- as well as BRCA2-associated DCIS had expression of HER3 and C-MET. CONCLUSIONS: The majority of BRCA-associated tumors had DCIS present. Concordance of DCIS and IBC phenotypes was high, arguing for the existence of a DCIS-associated premalignant pathway. Oncodrivers HER3 and C-MET were expressed in the DCIS of mutation carriers, suggesting an opportunity for prevention strategies.

Progressive loss of anti-HER2 CD4+ T-helper type 1 response in breast tumorigenesis and the potential for immune restoration.

Genomic profiling has identified several molecular oncodrivers in breast tumorigenesis. A thorough understanding of endogenous immune responses to these oncodrivers may provide insights into immune interventions for breast cancer (BC). We investigated systemic anti-HER2/neu CD4+ T-helper type-1 (Th1) responses in HER2-driven breast tumorigenesis. A highly significant stepwise Th1 response loss extending from healthy donors (HD), through HER2pos-DCIS, and ultimately to early stage HER2pos-invasive BC patients was detected by IFNγ ELISPOT. The anti-HER2 Th1 deficit was not attributable to host-level T-cell anergy, loss of immune competence, or increase in immunosuppressive phenotypes (Treg/MDSCs), but rather associated with a functional shift in IFNγ:IL-10-producing phenotypes. HER2high, but not HER2low, BC cells expressing IFNγ/TNF-α receptors were susceptible to Th1 cytokine-mediated apoptosis in vitro, which could be significantly rescued by neutralizing IFNγ and TNF-α, suggesting that abrogation of HER2-specific Th1 may reflect a mechanism of immune evasion in HER2-driven tumorigenesis. While largely unaffected by cytotoxic or HER2-targeted (trastuzumab) therapies, depressed Th1 responses in HER2pos-BC patients were significantly restored following HER2-pulsed dendritic cell (DC) vaccinations, suggesting that this Th1 defect is not "fixed" and can be corrected by immunologic interventions. Importantly, preserved anti-HER2 Th1 responses were associated with pathologic complete response to neoadjuvant trastuzumab/chemotherapy, while depressed responses were observed in patients incurring locoregional/systemic recurrence following trastuzumab/chemotherapy. Monitoring anti-HER2 Th1 reactivity following HER2-directed therapies may identify vulnerable subgroups at risk of clinicopathologic failure. In such patients, combinations of existing HER2-targeted therapies with strategies to boost anti-HER2 CD4+ Th1 immunity may decrease the risk of recurrence and thus warrant further investigation.

Impact of histological subtype on long-term outcomes of neuroendocrine carcinoma of the breast.

Although rare, neuroendocrine carcinoma of the breast (NECB) is becoming an increasingly recognized entity. The current literature is limited to case reports and small series and therefore a comprehensive population-based analysis was conducted to investigate the clinicopathologic features and long-term outcomes associated with NECB. We included all patients in the SEER Database from 2003 to 2010 with a diagnosis of NECB. The 2012 WHO classification system was used to categorize patients based on histopathologic diagnosis: well-differentiated neuroendocrine tumors, small/oat cell or poorly differentiated neuroendocrine tumors, adenocarcinoma with neuroendocrine features (ANF), large cell neuroendocrine and carcinoid tumors. Survival analysis was performed for disease specific (DSS) and overall (OS) survival. Of the 284 cases identified, 52.1% were classified as well-differentiated, 25.7% small cell, 14.8% ANF, 4.9% large cell, and 2.5% carcinoid. In general, patients presented with advanced disease: 36.2% had positive lymph node metastases and 20.4% presented with systemic metastases. Five-year DSS rates for stage I-IV NECB were 88.1, 67.8, 60.5, and 12.4%, respectively, while five-year OS rates were 77.9, 57.3, 52.9, and 8.9%, respectively. DSS and OS were significantly different for well-differentiated neuroendocrine tumors and ANFs compared to small cell and carcinoid tumors. On univariate Cox proportional hazards regression, small cell carcinoma was significantly associated with worse DSS (OR 1.97, 95% CI 1.05-3.67) and OS (OR 2.66, 95% CI 1.49-4.72) compared to other neuroendocrine tumors. NECB is associated with advanced stage disease at presentation and an unfavorable prognosis for stage II-IV disease and small cell, large cell, and carcinoid histologic subtypes.

Racial disparities in the use of outpatient mastectomy.

BACKGROUND: Racial disparities exist within many domains of cancer care. This study was designed to identify differences in the use of outpatient mastectomy (OM) based on patient race. METHODS: We identified patients in the American College of Surgeons National Surgical Quality Improvement Program Participant Use File (during the years 2007-2010) who underwent a mastectomy. The association between mastectomy setting, patient race, patient age, American Society of Anesthesiology physical status classification, functional status, mastectomy type, and hospital teaching status was determined using the chi-square test. A multivariable logistic regression analysis was developed to assess the relative odds of undergoing OM by race, with adjustment for potential confounders. RESULTS: We identified 47,318 patients enrolled in the American College of Surgeons National Surgical Quality Improvement Program Participant Use File who underwent a mastectomy during the study time frame. More than half (62.6%) of mastectomies were performed in the outpatient setting. All racial minorities had lower rates of OM, with 63.8% of white patients; 59.1% of black patients; 57.4% of Asian, Native Hawaiian, or Pacific Islander patients; and 43.9% of American Indian or Alaska Native patients undergoing OM (P < 0.001). After adjustment for multiple confounders, black patients, American Indian or Alaska Native patients, and those of unknown race were all less likely to undergo OM (odds ratio [OR], 0.86; 95% confidence interval [CI], 0.80-0.93; OR, 0.55; 95% CI, 0.41-0.72; and OR, 0.70; 95% CI, 0.64-0.76, respectively) compared with white patients. CONCLUSIONS: Disparities exist in the use of OM among racial minorities. Further studies are needed to identify the role of cultural preferences, physician attitudes, and insurer encouragements that may influence these patterns of use.

Immediate reconstruction following nipple-sparing mastectomy: one option for young breast cancer patients with early stage disease.

The article entitled "Application of immediate breast reconstruction with silicon prosthetic implantation following bilateral mammary gland excision in treatment of young patients with early breast cancer" published in Journal of Thoracic Disease, examined the oncologic and cosmetic outcomes of the aforementioned procedures. We aimed to describe the unique circumstances of young breast cancer patients with early stage disease and highlight the multitude of surgical treatment and reconstructive options available to these patients.

The virtual-patient pilot: testing a new tool for undergraduate surgical education and assessment.

BACKGROUND: The virtual patient (VP) is a web-based tool that allows students to test their clinical decision-making skills using simulated patients. METHODS: Three VP cases were developed using commercially available software to simulate common surgical scenarios. Surgical clerks volunteered to complete VP cases. Upon case completion, an individual performance score (IPS, 0-100) was generated and a 16-item survey was administered. Surgery shelf exam scores of clerks who completed VP cases were compared with a cohort of students who did not have exposure to VP cases. Descriptive statistics were performed to characterize survey results and mean IPS. RESULTS: Surgical clerks felt that the VP platform was simple to use, and both the content and images were well presented. They also felt that VPs enhanced learning and were helpful in understanding surgical concepts. Mean IPS at conclusion of the surgery clerkship was 69.2 (SD 26.5). Mean performance on the surgery shelf exam for the student cohort who had exposure to VPs was 86.5 (SD 7.4), whereas mean performance for the unexposed student cohort was 83.5 (SD 9). DISCUSSION: The VP platform represents a new educational tool that allows surgical clerks to direct case progression and receive feedback regarding clinical-management decisions. Its use as an assessment tool will require further validation.

Trends in immediate breast reconstruction across insurance groups after enactment of breast cancer legislation.

BACKGROUND: To improve access to breast reconstruction for mastectomy patients, the United States enacted the Women's Health and Cancer Rights Act in January of 1999. The objective of the current study was to evaluate the impact of this legislation on patients with different insurance plans. METHODS: Women aged ≥18 years who underwent mastectomy for cancer were identified in the Nationwide Inpatient Sample database (2000-2009) and were classified according to their immediate breast reconstruction (IBR) status. Trends in rates of IBR were described for each insurance category. Multivariable logistic regression analysis with adjustment for age, race, estimated household income, and Elixhauser comorbidity index was performed to evaluate the relation between insurance status and IBR. RESULTS: In total, 168,236 patients were identified who underwent a mastectomy during the study interval. Across the 10-year study period, rates of IBR increased 4.2-fold in Medicaid patients, 2.9-fold in Medicare patients, 2.6-fold in privately insured patients, and 2.1-fold in self-pay patients (P < .01). However, after adjustment for confounders, women without private insurance were less likely to undergo IBR compared with women who had private insurance (Medicaid: odds ratio [OR], 0.34; 95% confidence interval [CI], 0.32-0.37; Medicare: OR, 0.53; 95% CI, 0.49-0.58; self-pay: OR, 0.43; 95% CI, 0.37-0.50; other types of nonprivate insurance: OR, 0.64, 95% CI, 0.56-0.73). CONCLUSIONS: After the enactment of policy designed to improve access to IBR, Medicaid and Medicare patients experienced the greatest relative increase in rates of IBR. Although policy changes had the most impact on traditionally underserved populations, disparities still exist. Future studies should endeavor to understand why such disparities have persisted.

Racial disparities in immediate breast reconstruction after mastectomy: impact of state and federal health policy changes.

BACKGROUND: Federal and Pennsylvania state policies instituted in the late 1990s were designed to improve access to postmastectomy breast reconstruction. We sought to evaluate the impact of these policy changes on access to care among racial minorities. METHODS: Mastectomy patients ≥18 years old were identified in the Pennsylvania Health Care Cost Containment Council inpatient database (1994-2004) and classified by immediate breast reconstruction (IBR) status. Rates of IBR were calculated by patient characteristics and year. Patients were stratified by race before (1994-1997) and after (2001-2004) policy changes, and relative odds of IBR were estimated by univariate and multivariate logistic regression analyses with adjustment for known confounders. RESULTS: Overall rates of IBR were significantly higher in the time period after policy change compared to before policy change (18.5 vs. 32.7 %, p < 0.01). White, black, and Asian patients all saw a significant rise in rates of IBR. However, after adjustment for potential confounders, black patients, Asian patients, and those of mixed or other races all remained less likely to undergo IBR when compared to white patients after policy changes (odds ratio [OR] 0.66, 95 % confidence interval [CI] 0.55-0.80; OR 0.30, 95 % CI 0.18-0.49; OR 0.29, 95 % CI 0.16-0.51, respectively). CONCLUSIONS: Rates of IBR increased across all racial groups after policy changes. However, not all races were affected equally, and thus disparities remained. Future studies are needed to investigate the role of other factors, including cultural preferences in utilization of IBR that might explain residual disparities.

Tertiary hyperparathyroidism in kidney transplant recipients: characteristics of patients selected for different treatment strategies.

BACKGROUND: Several treatment options exist for kidney transplant patients with tertiary hyperparathyroidism. However, the decision to endorse observation (OBS), medical therapy, or parathyroidectomy (PTX) remains controversial. METHODS: We performed a retrospective cohort study of kidney transplant patients with tertiary hyperparathyroidism at a single institution over a 7-year period. Patients were classified by treatment mode: OBS, medical therapy with cinacalcet (CIN), or PTX. Descriptive statistics were performed. Serum calcium levels and change in serum creatinine level were compared using analysis of variance with comparisons between individual groups using the Student's t test with a Bonferroni correction. Time to treatment was compared between CIN and PTX groups using the Student's t test. Complication rates were compared using the Fisher exact test. RESULTS: We identified 83 patients: 52 were treated by OBS; 13 were treated with CIN, and 18 underwent PTX. Six weeks after treatment, PTX resulted in lower serum calcium level (9.28 mg/dL) compared with CIN (10.20 mg/dL) (P<0.01). There was no difference in the change in serum creatinine level 1 year after treatment initiation (P=0.98). Time to treatment was shorter (1.7 vs. 3.3 years, P<0.01), and the highest pretreatment calcium level was higher (12.2 vs. 11.7 mg/dL, P<0.01) in patients treated with PTX compared with CIN. Complication rates differed by treatment group (P<0.01). A quarter of OBS patients showed persistent hypercalcemic symptoms, compared with only 7.7% in the CIN group and 0% in the PTX group (P<0.01). CONCLUSIONS: PTX led to a greater reduction in serum calcium level and lower chance of persistent hypercalcemic symptoms, without any appreciable harm to the kidney allograft.

The surgery clerkship: an opportunity for preclinical credentialing in urinary catheterization.

BACKGROUND: At our hospital, medical students lost privileges to perform urinary catheterization because of concern regarding catheter-associated urinary tract infections. We hypothesized that trained medical students could perform urinary catheterization with the same proficiency as licensed practitioners. METHODS: Medical students completed a credentialing program in urinary catheterization. Prospectively, the rate of catheter-associated urinary tract infections after urinary catheterization performed by medical students was compared with the health system-wide rate of catheter-associated urinary tract infections after urinary catheterization performed by non-medical students using an incidence rate ratio (IRR). RESULTS: Over 9 months, a total of 432 and 55,401 catheter days accrued in patients who underwent urinary catheterization by medial students and non-medical students, resulting in 1 and 129 catheter-associated urinary tract infections, respectively. The incidence rate of catheter-associated urinary tract infections per 1,000 catheter days was 2.31 in the medical student-placed catheters and 2.33 in the non-MS-placed catheters (IRR = .99, P = .55). CONCLUSIONS: Preclinical credentialing in urinary catheterization resulted in the reinstatement of urinary catheterization privileges to qualified medical students. Student proficiency in urinary catheterization can match that of licensed practitioners.