Laura Kruper

Disparities in reconstruction rates after mastectomy: patterns of care and factors associated with the use of breast reconstruction in Southern California.

BackgroundMany factors influence whether breast cancer patients undergo reconstruction after mastectomy. We sought to determine the patterns of care and variables associated with the use of breast reconstruction in Southern California.Materials and MethodsPostmastectomy reconstruction rates were determined from the California Office of Statewide Health Planning and Development (OSHPD) inpatient database from 2003 to 2007. International Classification of Disease-9 codes were used to identify patients undergoing reconstruction after mastectomy. Changes in reconstruction rates were examined by calendar year, age, race, type of insurance, and type of hospital using a chi-square test. Univariate and multivariate odds ratios (OR) with 95% confidence intervals (95% CI) were estimated for relative odds of immediate reconstruction versus mastectomy only.ResultsIn multivariate analysis, calendar year, age, race, type of insurance, and type of hospital were statistically significantly associated with use of reconstruction. The proportion of patients undergoing reconstruction rose from 24.8% in 2003 to 29.2% in 2007. Patients with private insurance were 10 times more likely to undergo reconstruction than patients with Medi-Cal insurance (OR 9.95, 95% CI 8.46–11.70). African American patients were less likely (OR 0.58, 95% CI 0.46–0.73) and Asian patients one-third as likely (OR 0.37, 95% CI 0.29–0.47) to undergo reconstruction as Caucasians patients Most reconstructive procedures were performed at teaching hospitals and designated cancer centers.ConclusionsAlthough the rate of postmastectomy reconstruction is increasing, only a minority of patients undergo reconstruction. Age, race, type of insurance, and type of hospital appear to be significant factors limiting the use of reconstruction.

Papillary Carcinoma of the Breast: An Overview

Papillary carcinoma of the breast represents ~0.5% of all newly diagnosed cases of breast cancer. The prevalence of both invasive and in situ papillary carcinoma seems to be greater in older postmenopausal women and, in relative terms, in males. Histologic features of the tumor include cellular proliferations surrounding fibrovascular cores, with or without invasion. In this review, characteristics of both in situ and invasive disease are outlined. Immunohistochemical analyses of papillary carcinoma suggest the utility of markers such as smooth muscle myosin heavy chain, calponin, p63, and high molecular weight keratins, which can characterize the myoepithelial cell layer. With respect to radiographic evaluation of papillary carcinoma, ultrasonography is the most extensively studied imaging modality, though magnetic resonance mammography has potential utility. Available data suggest improved outcome for papillary carcinoma as compared to invasive ductal carcinoma. Treatment-related information for patients with papillary carcinoma is limited, and patterns noted in available series suggest a variable approach to this disease. The scarcity of information underscores the need for further treatment- and outcome-related studies in papillary carcinoma of the breast.

Regulation of adipose tissue T cell subsets by Stat3 is crucial for diet-induced obesity and insulin resistance

Dysregulated inflammation in adipose tissue, marked by increased proinflammatory T-cell accumulation and reduced regulatory T cells (Tregs), contributes to obesity-associated insulin resistance. The molecular mechanisms underlying T-cell-mediated inflammation in adipose tissue remain largely unknown, however. Here we show a crucial role for signal transducer and activator of transcription 3 (Stat3) in T cells in skewing adaptive immunity in visceral adipose tissue (VAT), thereby contributing to diet-induced obesity (DIO) and insulin resistance. Stat3 activity is elevated in obese VAT and in VAT-resident T cells. Functional ablation of Stat3 in T cells reduces DIO, improves insulin sensitivity and glucose tolerance, and suppresses VAT inflammation. Importantly, Stat3 ablation reverses the high Th1/Treg ratio in VAT of DIO mice that is likely secondary to elevated IL-6 production, leading in turn to suppression of Tregs. In addition, Stat3 in T cells in DIO mice affects adipose tissue macrophage accumulation and M2 phenotype. Our study identifies Stat3 in VAT-resident T cells as an important mediator and direct target for regulating adipose tissue inflammation, DIO, and its associated metabolic dysfunctions.

Inflammatory Biomarkers, Comorbidity, and Neurocognition in Women With Newly Diagnosed Breast Cancer.

BACKGROUND Neurocognitive dysfunction is reported in women with breast cancer even prior to receipt of adjuvant therapy; however, there is little understanding of underlying mechanisms. We tested the hypothesis that pretreatment neurocognitive dysfunction in newly diagnosed patients is related to immunological activation, as indexed by pro-inflammatory cytokines. METHODS One hundred seventy-four postmenopausal patients with newly diagnosed breast cancer underwent a comprehensive neuropsychological evaluation (assessment of cognitive function, mood, and fatigue) and measurement of key cytokine levels prior to surgery. Age-matched control participants without cancer were evaluated concurrently. Multivariable regression analyses examined the contribution of circulating Interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), and soluble TNF receptor type two (sTNF-RII) in predicting neurocognitive performance in patients after controlling for key factors thought to impact functioning. All tests of statistical significance were two-sided. RESULTS Memory performance was statistically significantly reduced, in patients compared with controls (P = .02). Of the three cytokines measured, only IL-1ra was statistically significantly elevated in cancer patients when compared with control participants (mean ± SD, 375 ± 239 pg/mL vs 291 ± 169 pg/mL, P = .007). After controlling for age, education, race, mood, fatigue, body mass index, and comorbidity, cytokines independently explained 6.0% of the total variance in memory performance (P = .01) in cancer patients but not control participants, with higher sTNF-RII associated with worse functioning. Exploratory analyses found that comorbidity statistically significantly explained variance in processing speed and executive functioning (P = .03 and P = .03, respectively). CONCLUSION An association of TNF with memory, previously reported in patients after exposure to chemotherapy, was found prior to initiation of any treatment, including surgery. This association requires further investigation as sTNF-RII was not higher in cancer patients relative to control participants.

Sentinel lymph node biopsy indications and controversies in breast cancer

Sentinel lymph node biopsy (SLNB) has become the standard of care for early breast cancer. Its use in breast cancer has been evaluated in several randomized controlled trials and validated in multiple prospective studies. Additionally, it has been verified that SLNB has decreased morbidity when compared to axillary lymph node dissection (ALND). The technique used to perform sentinel lymph node mapping was also evaluated in multiple studies and the accuracy rate increases when radiocolloid and blue dye are used in combination. As SLNB became more accepted, contraindications were delineated and are still debated. Patients who have clinically positive lymph nodes or core biopsy-proven positive lymph nodes should not have SLNB, but should have an ALND as their staging procedure. The safety of SLNB in pregnant patients is not fully established. However, patients with multifocal or multicentric breast cancer and patients having neoadjuvant chemotherapy are considered candidates for SLNB. However, the details of which specific neoadjuvant patients should have SLNB are currently being evaluated in a randomized controlled trial. Patients with ductal carcinoma in situ (DCIS) benefit from SLNB when mastectomy is planned and when there is a high clinical suspicion of invasion. With the advent of SLNB, pathologic review of breast cancer lymph nodes has evolved. The significance of occult metastasis in SLNB patients is currently being debated. Additionally, the most controversial subject with regards to SLNB is determining which patients with positive SLNs benefit from further axillary dissection.

Impact of modern chemotherapy on the survival of women presenting with de novo metastatic breast cancer

BackgroundData that directly associate utilization of novel systemic therapies with survival trends in metastatic breast cancer (MBC) are limited. In the setting of de novo MBC, large registry analyses cite positive temporal trends in survival, but the extent to which advances in systemic therapy have contributed to these gains is not clear.MethodsThe City of Hope Cancer Registry was used to identify a consecutive series of patients with de novo MBC who received their first line of therapy between 1985 and 2004. Comprehensive clinicopathologic and treatment-related data were collected for each patient. Univariate analyses were conducted via Cox regression to identify factors associated with improved survival. Multivariate analysis was also conducted via Cox regression and the stepwise procedure was used to identify independent predictors of survival.ResultsA total of 324 patients with de novo MBC were identified. After application of exclusion criteria, including the sole presence of supraclavicular node metastasis, 274 patients were retained in the analysis. The treatment-related characteristics associated with improved survival included: use of endocrine therapy (hazard ratio [HR] 0.60, 95%CI 0.47-0.77; P<0.0001), and addition of bisphosphonates (HR 0.70, 95%CI 0.52-0.96; P=0.02). However, recipients of novel cytotoxic agents (defined as drugs approved for MBC since 1994) had no improvement in survival relative to patients treated with older cytotoxic agents. On multivariate analysis, age (< 50), receipt of aromatase inhibitors, and receipt of zoledronic acid were independent predictors of survival.ConclusionsThe overall survival of women with de novo metastatic breast cancer has improved over the past 20 years. However, the contribution of conventional cytotoxic agents to this improvement is minimal.

Pathologic complete response rates in triple-negative, HER2-positive, and hormone receptor-positive breast cancers after anthracycline-free neoadjuvant chemotherapy with carboplatin and paclitaxel with or without trastuzumab

BACKGROUND Pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) is considered a surrogate for improved survival. Platinum-containing NCT, particularly in patients with HER2+ and triple-negative breast cancers (TNBC) may increase pCR rates. METHODS Tumor characteristics, pCR rates (no invasive disease in breast and lymph nodes), toxicities, and survival in patients who received carboplatin, a taxane, and trastuzumab (HER2+ disease) between April 2009 and December 2011, were reviewed. RESULTS Thirty eight patients (39 tumors) completed a median of 4 cycles of NCT. Eighteen of 39 (46%) tumors were HER2+, 8/18 (44%) responded with pCR; 13/18 HER2+ tumors were HR+ (72%) and 4/13 (31%) had a pCR. Ten of 39 (26%) tumors were TNBC; 6/10 (60%) had a pCR. At a median of 25-months no recurrences were observed in patients with pCR. CONCLUSIONS Prospective studies of anthracycline-free platinum-containing NCT are warranted in LABC patients with HER2+ and TNBC.

Patterns and Trends in Immediate Postmastectomy Reconstruction in California: Complications and Unscheduled Readmissions.

Background: Immediate reconstruction rates after mastectomy are increasing but remain low. Little is known about hospital readmissions after these procedures. The authors studied unscheduled readmissions after immediate reconstruction. Methods: Using the Healthcare Cost and Utilization Project California State database, the authors identified patients undergoing mastectomy only or with immediate reconstruction for ductal carcinoma in situ and invasive breast cancer from 2005 to 2009. Immediate reconstruction included tissue expander/implant and autologous tissue reconstructions. The authors evaluated temporal trends in immediate reconstruction and factors associated with 30-day unscheduled readmissions after reconstruction. Results: The cohort contained 48,414 patients (mastectomy only, 35,648; immediate reconstruction, 12,766; tissue expander/implant, 10,437; autologous tissue, 2329). Readmission rates were not significantly different between mastectomy only and immediate reconstruction (3.55 percent versus 3.39 percent; p = 0.39); however, autologous tissue reconstruction was associated with a significantly higher readmission rate compared with tissue expander/implant reconstruction (4.08 percent versus 3.24 percent; p = 0.04). Conclusions: Immediate reconstruction does not result in higher readmission rates compared with mastectomy only. All women undergoing mastectomy should be offered consultation for reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Rural and urban disparities in the evolution of sentinel lymph node utilization in breast cancer

BACKGROUND Sentinel lymph node biopsy (SLNB) has become the preferred method for axillary nodal staging. The authors examined SLNB utilization in urban versus rural settings as this procedure was adopted and hypothesized that SLNB rates among urban populations increased faster, while the technology shift and acceptance of SLNB were slower at rural centers. METHODS The Surveillance, Epidemiology and End Results database was used to identify patients with invasive node-negative ductal or lobular breast cancer diagnosed from 1998 to 2008. Exclusion criteria were distant metastatic disease, T4 tumors, or incomplete data. Residential setting was divided into groups on the basis of population density. RESULTS The overall rate of SLNB increased with time (from 10% in 1998 to 73% in 2008). The adoption of SLNB was slower in rural settings than among urban populations (P < .001). By 2003, only urban areas were using SLNB in >50% of cases. Overall, there was a 2-year lag between the increases in SLNB utilization rates in these groups. There was a significant difference in SLNB rates according to tumor size. CONCLUSION The overall rate of SLNB remained near 50% and was lower in rural locations in 2004. By 2008, the SLNB rate for T1 and T2 tumors had increased to >50% in all population categories. SLNB utilization was lower in all population categories as tumor size increased. There was an overall 2-year lag in the adoption of SLNB in less populated areas. Although this may represent a more conservative approach, the difference may be attributable to a shortage of experienced surgeons, lack of training, or lack of technological support at smaller institutions.

Characterization of patient-derived tumor xenografts (PDXs) as models for estrogen receptor positive (ER+HER2- and ER+HER2+) breast cancers.

The research was to appraise the utility of the patient-derived tumor xenografts (PDXs) as models of estrogen receptor positive (ER+HER2- and ER+HER2+) breast cancers. We compared protein expression profiles by Reverse Phase Protein Array (RPPA) in tumors that resulted in PDXs compared to those that did not. Our overall PDX intake rate for ER+ breast cancer was 9% (9/97). The intake rate for ER+HER2+ tumors (3/16, 19%) was higher than for ER+HER2- tumors (6/81, 7%). Heat map analyses of RPPA data showed that ER+HER2- tumors were divided into 2 groups by luminal A/B signature [protein expression of ER, AR, Bcl-2, Bim (BCL2L11), GATA3 and INPP4b], and this expression signature was also associated with the rate of PDX intake. Cell survival pathways such as the PI3K/AKT signaling and RAS/ERK pathways were more activated in the specimens that could be established as PDX in both classes. Expression of the ER protein itself may have a bearing on the potential success of an ER+ PDX model. In addition, HER2 and its downstream protein expressions were up-regulated in the ER+HER2+ patient tumors that were successfully established as PDX models. Moreover, the comparison of RPPA data between original and PDX tumors suggested that the selection/adaptation process required to grow the tumors in mice is unavoidable for generation of ER+ PDX models, and we identified differences between patient tumor samples and paired PDX tumors. A better understanding of the biological characteristics of ER+PDX would be the key to using PDX models in assessing treatment strategies in a preclinical setting.