Breast Cancer in the Elderly: Is MRI Helpful?

Appropriate use of magnetic resonance imaging (MRI) in elderly breast cancer (BC) patients remains unclear; we sought to identify the indications and implications of MRI use in our elderly BC population. Women 70 years of age or older at first BC diagnosis with an MRI performed at our institution either perioperatively or in follow-up were included from a prospectively maintained database from 2000 to 2010. Univariate logistic regression was used to test associations with disease identified by MRI only (additional ipsilateral, contralateral, or new cancer) following perioperative MRI. 305 BCs were imaged in 286 patients. 133 were imaged with MRI in the perioperative setting alone, 88 had only follow-up MRIs after BC treatment, and 65 had both. Indications for perioperative MRI include: extent of disease evaluation (181; 91%); occult primary (10; 5%); high-risk screening (5; 3%); and abnormal physical exam with negative conventional imaging (2; 1%). Disease identified by MRI only for occult primary cases was 4/10 (40%; 95% confidence interval: 12.2-73.8%) and 14/181 (7.7%; 95% confidence interval: 4.3-12.6%) for perioperative MRIs performed for extent of disease evaluation. Analysis of imaging and tumor characteristics failed to find significant predictors of disease identified by MRI only. A total of 369 post-treatment follow-up MRIs were performed in 148 patients with a median of 2 MRIs per patient (range 1-8), with seven cases of disease identified by MRI only (1.9%; 95% confidence interval: 0.8-3.9%). MRI had the greatest benefit in women presenting with an occult primary cancer and minimal additional benefit in elderly patients with BC undergoing MRI imaging for extent of disease evaluation or in post-treatment surveillance.

Extent of microinvasion in ductal carcinoma in situ is not associated with sentinel lymph node metastases.

BACKGROUND: Ductal carcinoma in situ with microinvasion (DCISM) is a rare diagnosis with a good prognosis. Although nodal metastases are uncommon, sentinel lymph node biopsy (SLNB) remains standard care. Volume of disease in invasive breast cancer is associated with SLNB positivity, and, thus we hypothesized that in a large cohort of patients with DCISM, multiple foci of microinvasion might be associated with a higher risk of positive SLNB. METHODS: Records from a prospective institutional database were reviewed to identify patients with DCISM who underwent SLNB between June 1997 and December 2010. Pathology reports were reviewed for number of microinvasive foci and categorized as 1 focus or ≥2 foci. Demographic, pathologic, treatment, and outcome data were obtained and analyzed. RESULTS: Of 414 patients, 235 (57 %) had 1 focus of microinvasion and 179 (43 %) had ≥2 foci. SLNB macrometastases were found in 1.4 %, and micrometastases were found in 6.3 %; neither were significantly different between patients with 1 focus versus ≥2 foci (p = 1.0). Patients with positive SLNB or ≥2 foci of microinvasion were more likely to receive chemotherapy. At median 4.9 years (range 0-16.2 years) follow-up, 18 patients, all in the SLNB negative group, had recurred for an overall 5-year recurrence-free proportion of 95.9 %. CONCLUSIONS: Even with large numbers, there was no higher risk of nodal involvement with ≥2 foci of microinvasion compared with 1 focus. Number of microinvasive foci and results of SLNB appear to be used in decision making for systemic therapy. Prognosis is excellent.

Relative contributions of codon usage, promoter efficiency and leader sequence to the antigen expression and immunogenicity of HIV-1 Env DNA vaccine.

Optimized antigen expression is critical to the immunogenicity of DNA vaccines. A number of approaches have been proposed to enhance the antigen expression and/or immunogenicity of DNA vaccines, but their relative contributions have not been compared in a same antigen system. In the current study, optimization of codon usage, enhancement of viral promoter function and selection of secretary leader sequences were evaluated for their roles in improving the immunogenicity of a same model antigen, the HIV-1 envelope glycoprotein. Our data demonstrated that all these factors can work synergistically to improve the final antigen expression and immunogenicity of HIV-1 Env DNA vaccines, indicating they work through different mechanisms. The best result came from the approach that optimized all three components in a DNA vaccine design. Our study further revealed that the levels of HIV-1 env-specific RNA transcripts in transiently transfected 293T cells were higher from the codon-optimized gene than the wild type counterpart. This finding suggested other mechanism may also contribute to the increased antigen expression and immunogenicity of codon-optimized DNA vaccines in addition to the improved tRNA usage in mammalian cells for codon-optimized viral genes as previously reported.