Improved long-term survival with contralateral prophylactic mastectomy among young women.

BACKGROUND: Despite mixed survival data, the utilization of contralateral prophylactic mastectomy (CPM) for the prevention of a contralateral breast cancer (CBC) has increased significantly over the last 15 years, especially among women less than 40. We set out to look at our own experience with CPM, focusing on outcomes in women less than 40, the sub-population with the highest cumulative lifetime risk of developing CBC. With an extended follow-up, we hoped to demonstrate differences in the long-term disease free survival (DFS) and overall survival (OS) among groups who underwent the procedure (CPM) versus those that did not (NCPM). MATERIALS AND METHODS: We performed a retrospective review of all breast cancer patients less than age 40 diagnosed at Mount Sinai Medical Center between January 1, 1980 and December 31, 2010 (n=481). Among these patients, 42 were identified as having undergone CPM, while 195 were confirmed as being CPM-free during the observation period. A univariate and multivariate analyses were performed. RESULTS: The CPM group had a significantly higher percentage of patients who were diagnosed between 2000 and 2010 (95.2% vs 40%, p=0.0001). The CPM group had significantly smaller tumors (0-2cm.: 41.7% vs 24.8%, p=0.04). Among the entire group of patients, the overall five- and 10-year DFS were 81.3% and 73.3%, respectively. CPM was significantly associated [HR 2.35 (1.02, 5.41); p=0.046] with 10-year OS, although a similar effect was not observed for five-year OS. CONCLUSIONS: We found that CPM has increased dramatically over the last 15 years, especially among white women with locally advanced disease. In patients less than 40, who are thought to be at greatest cumulative risk of secondary breast cancer, CPM provided an OS advantage, regardless of genetics, tumor or patient characteristics, and which was only seen after 10 years of follow-up.

Prognostic significance of TP53 mutations and single nucleotide polymorphisms in acute myeloid leukemia: a case series and literature review.

BACKGROUND: The response to treatment and overall survival (OS) of patients with acute myeloid leukemia (AML) is variable, with a median ranging from 6 months to 11.5 years. TP53 is associated with old age, chemotherapy resistance, and worse OS. Using genetic sequencing, we set out to look at our own experience with AML, and hypothesized that both TP53 mutations and SNPs at codon 72 would mimic the literature by occurring in a minority of patients, and conferring a worse OS. MATERIALS AND METHODS: We performed a pilot study of randomly selected, newly diagnosed AML patients at Mount Sinai Medical Center, diagnosed from 2005-2008 (n=10). TP53 PCR sequencing was performed using DNA from bone marrow smears. Analysis was accomplished using Mutation Surveyor software with confirmation of the variants using the COSMIC and dbSNP databases. RESULTS: Fewer than half of the patients harbored TP53 mutations (40%). There was no significant difference in OS based on gender, AML history, risk-stratified karyotype, or TP53 mutation. There were possible trends toward improved survival among patients less than 60 (11 vs 4 months, p=0.09), Hispanics (8 vs 1 months, p=0.11), and those not harboring SNP P72R (8 vs 2 months, p=0.10). There was a significant improvement in survival among patients with better performance status (28 vs 4 months, p=0.01) and those who did not have a complex karyotype (8 vs 1 months, p=0.03). The most commonly observed TP53 mutation was a missense N310K (40%) and the most commonly observed SNP was P72R (100.0%). CONCLUSIONS: Our study confirms previous reports that poor PS and the presence of a complex karyotype are associated with a decreased OS. In our cohort, TP53 mutations were relatively common, occurring more frequently in male patients with an adverse karyotype. Although there was no significant difference in survival between TP53 mutated and un-mutated patients, there was a possible trend toward worse OS among patients with SNP P72R. Larger studies are needed to validate these findings.

Long-term survival of women with locally advanced breast cancer with ≥ 10 involved lymph nodes at diagnosis.

BACKGROUND: Axillary lymph node status at diagnosis remains the strongest predictor of long-term survival in breast cancer. Patients with more than ten axillary lymph nodes at diagnosis have a poor long-term survival. In this single institutional study, we set out to evaluate the prognosis of this high-risk group in the era of multimodality therapy. MATERIALS AND METHODS: In this retrospective study, we looked at all breast cancer patients with greater than ten axillary lymph nodes diagnosed at Mount Sinai Medical Center (MSMC) from January 1st 1990 to December 31st 2007 (n=161). In the univariate analysis, descriptive frequencies, median survival, and 5- and 10-year survival rates were estimated for common prognostic factors. A multivariate prognostic analysis for time-to-event data, using the extended Cox regression model was carried out. RESULTS: With a median and mean follow-up of 70 and 89.9 months, respectively, the overall median survival was estimated to be 99 months. The five-year disease-free survival (DFS) was 59.3% and the ten-year DFS was 37.9%, whereas the five- and ten-year overall survival (OS) was 66.6% and 43.9%, respectively. Multivariate analysis revealed a significant improvement in DFS among black patients compared to whites (p=0.05), improved DFS and OS among young patients (ages 21-45) compared to elderly patients (age greater than 70) (p=0.00176, p=0.0034, respectively), and improved DFS and OS among patients whose tumors were ER positive (p=0.049, p=0.0034). CONCLUSIONS: In this single institution study of patients with greater than 10 positive axillary nodes, black patients had a significantly improved DFS compared with white patients. Young age and ER tumor positivity was associated with improved outcomes. Using multivariate analysis, there were no other variables associated with statistically significant improvements in DFS or OS including date of diagnosis. Further work is needed to improve breast cancer survival in this subgroup of patients.