Mitotic rate is associated with positive lymph nodes in patients with thin melanomas.

BACKGROUND: The American Joint Commission on Cancer will remove mitotic rate from its staging guidelines in 2018. OBJECTIVE: Using a large nationally representative cohort, we examined the association between mitotic rate and lymph node positivity among thin melanomas. METHODS: A total of 149,273 thin melanomas in the National Cancer Database were examined for their association of high-risk features of mitotic rate, ulceration, and Breslow depth with lymph node status. RESULTS: Among 17,204 patients with thin melanomas with data on Breslow depth, ulceration, and mitotic rate who underwent a lymph node biopsy, there was a strong linear relationship between odds of having a positive lymph node and mitotic rate (R2 = 0.96, P < .0001, ß = 3.31). The odds of having a positive node increased by 19% with each 1-point increase in mitotic rate (odds ratio, 1.19; 95% confidence interval, 1.17-1.21). Cases with negative nodes had a mean mitotic rate of 1.54 plus or minus 2.07 mitoses/mm2 compared with 3.30 plus or minus 3.54 mitoses/mm2 for those with positive nodes (P < .0001). LIMITATIONS: The data collected do not allow for survival analyses. CONCLUSIONS: Mitotic rate was strongly associated with the odds of having a positive lymph node and should continue to be reported on pathology reports.

Breast cancer: risk assessment and prevention.

Breast cancer is the most common cancer and the second most common cause of cancer death in women. In 2008 there were 182,460 women diagnosed with breast cancer, and 40,480 women died of this disease. Breast cancer can be prevented by medical (tamoxifen or raloxifene) or surgical approaches (bilateral mastectomy or oophorectomy). Prevention is only recommended for women at high risk for developing breast cancer; therefore, proper risk calculation is essential in identifying women that may benefit from prevention measures. There is an easy-to-use and easily accessible risk calculation tool for determining a woman's risk of developing breast cancer and need for referral for counseling, gene testing, and possibly preventive therapy. This article reviews the components of risk assessment, the most frequently used risk calculation tool, and approaches to breast cancer risk reduction including medical and surgical therapies. The use of these therapies results in a risk reduction of 50-90%.

Early Melanoma Nodal Positivity and Biopsy Rates Before and After Implementation of the 7th Edition of the AJCC Cancer Staging Manual.

Importance: There has been a continued increase in the incidence of newly diagnosed melanomas, most of which are T1 melanomas. The associations between changes in tumor staging, implemented with the 7th edition of the AJCC Cancer Staging Manual (AJCC 7), and sentinel lymph node biopsy rates and nodal positivity rates remain to be seen. Objective: To evaluate the change that the implementation of the AJCC 7 had on staging criteria and the distribution of thin melanomas requiring nodal surgery and nodal positivity rates. Design, Setting, and Participants: Retrospective cross-sectional study from 2004 through 2013 of all adults (≥18 years) diagnosed with a T1 (Breslow depth ≤1.0 mm) melanoma using The National Cancer Database that captures 70% of all newly diagnosed cancers from accredited Commission on Cancer organizations, including both academic and community settings. Data were analyzed in May 2017. Exposures: Patients were grouped together based on year of diagnosis, before and after 2009. Main Outcomes and Measures: To determine the sentinel lymph node biopsy rate before and after the implementation of the AJCC 7. Results: A total of 141 280 patients met inclusion criteria. Of 86 846 patients diagnosed from 2004 through 2009, 53.7% (49 644) were male and had a mean (SD) age of 57.7 (16.4) years. Of 54 434 patients diagnosed from 2010 through 2013, 54.3% (31 086) were male and had a mean (SD) age of 59.5 (15.9) years. After 2010, there was a 3.8% decrease in the number of nodal surgeries performed (32 485 of 86 846 patients [37.6%] vs 18 379 of 54 434 patients [33.8%]; P < .001). The nodal positivity rate decreased 1.0% from (9.8% [3166 of 86 846] to 8.8% [1618 of 54 434]) (P < .001). An increase in the proportion of T1b melanomas being evaluated, from 48.8% to 62.2%, was seen (P < .001). Of T1b melanomas that underwent nodal evaluation from 2004 through 2009, 74.0% had Clark level IV (invasion of the reticular dermis) or Clark level V (invasion of the deep, subcutaneous tissue) and 9.5% were ulcerated. From 2010 through 2013, of the T1b melanomas undergoing nodal evaluation, 82.6% had an elevated mitotic rate only, 3.7% were ulcerated, and 13.7% had both ulceration and an elevated mitotic rate. Conclusions and Relevance: It appears that after the institution of AJCC 7, there was an overall decrease in the number of T1 melanomas undergoing nodal biopsy without a clinically relevant change in sentinel lymph node positivity, with an increase in the number of T1b melanomas undergoing nodal evaluation.

Single cell analysis of human tissues and solid tumors with mass cytometry.

BACKGROUND: Mass cytometry measures 36 or more markers per cell and is an appealing platform for comprehensive phenotyping of cells in human tissue and tumor biopsies. While tissue disaggregation and fluorescence cytometry protocols were pioneered decades ago, it is not known whether established protocols will be effective for mass cytometry and maintain cancer and stromal cell diversity. METHODS: Tissue preparation techniques were systematically compared for gliomas and melanomas, patient derived xenografts of small cell lung cancer, and tonsil tissue as a control. Enzymes assessed included DNase, HyQTase, TrypLE, collagenase (Col) II, Col IV, Col V, and Col XI. Fluorescence and mass cytometry were used to track cell subset abundance following different enzyme combinations and treatment times. RESULTS: Mechanical disaggregation paired with enzymatic dissociation by Col II, Col IV, Col V, or Col XI plus DNase for 1 h produced the highest yield of viable cells per gram of tissue. Longer dissociation times led to increasing cell death and disproportionate loss of cell subsets. Key markers for establishing cell identity included CD45, CD3, CD4, CD8, CD19, CD64, HLA-DR, CD11c, CD56, CD44, GFAP, S100B, SOX2, nestin, vimentin, cytokeratin, and CD31. Mass and fluorescence cytometry identified comparable frequencies of cancer cell subsets, leukocytes, and endothelial cells in glioma (R = 0.97), and tonsil (R = 0.98). CONCLUSIONS: This investigation establishes standard procedures for preparing viable single cell suspensions that preserve the cellular diversity of human tissue microenvironments. © 2016 International Clinical Cytometry Society.

Nationwide trends in mastectomy for early-stage breast cancer.

IMPORTANCE: Accredited breast centers in the United States are measured on performance of breast conservation surgery (BCS) in the majority of women with early-stage breast cancer. Prior research in regional and limited national cohorts suggests a recent shift toward increasing performance of mastectomy in patients eligible for BCS. OBJECTIVE: To examine whether mastectomy rates in patients eligible for BCS are increasing over time nationwide, and are associated with coincident increases in breast reconstruction and bilateral mastectomy for unilateral disease. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective cohort study of temporal trends in performance of mastectomy for early-stage breast cancer using multivariable logistic regression modeling to adjust for pertinent covariates and interactions. We studied more than 1.2 million adult women treated at centers accredited by the American Cancer Society and the American College of Surgeons Commission on Cancer from January 1, 1998, to December 31, 2011, using the National Cancer Data Base. EXPOSURES: Year of breast cancer diagnosis. MAIN OUTCOMES AND MEASURES: Proportion of women with early-stage breast cancer who underwent mastectomy. Secondary outcome measures include temporal trends in breast reconstruction and bilateral mastectomy for unilateral disease. RESULTS: A total of 35.5% of the study cohort underwent mastectomy. The adjusted odds of mastectomy in BCS-eligible women increased 34% during the most recent 8 years of the cohort, with an odds ratio of 1.34 (95% CI, 1.31-1.38) in 2011 relative to 2003. Rates of increase were greatest in women with clinically node-negative disease (odds ratio, 1.38; 95% CI, 1.34-1.41) and in situ disease (odds ratio, 2.05; 95% CI, 1.95-2.15). In women undergoing mastectomy, rates of breast reconstruction increased from 11.6% in 1998 to 36.4% in 2011 (P < .001 for trend). Rates of bilateral mastectomy for unilateral disease increased from 1.9% in 1998 to 11.2% in 2011 (P < .001). CONCLUSIONS AND RELEVANCE: In the past decade, there have been marked trends toward higher proportions of BCS-eligible patients undergoing mastectomy, breast reconstruction, and bilateral mastectomy. The greatest increases are seen in women with node-negative and in situ disease. Mastectomy rates do not yet exceed current American Cancer Society/American College of Surgeons Commission on Cancer accreditation benchmarks. Further research is needed to understand factors associated with these trends and their implications for performance measurement in American Cancer Society/American College of Surgeons Commission on Cancer centers.