Second primary ipsilateral breast cancer with contralateral axillary involvement: a case report and literature review.

After breast-conserving surgery for an initial breast cancer, the incidence of lymphatic drainage to sites other than the ipsilateral axilla, such as the contralateral axilla, increases significantly at the time of a second primary ipsilateral breast cancer. Given the likelihood of altered lymphatic drainage, and in the absence of distant metastatic sites, consideration should be given to treating patients with a second primary ipsilateral breast cancer and contralateral axillary lymph node involvement with curative intent. This clinical issue may become more common as the incidence of second primary ipsilateral breast cancer would be expected to increase due to widespread adoption of breast-conserving surgery, improved prognosis for patients with an initial early-stage breast cancer, and highly sensitive screening modalities such as magnetic resonance imaging.

Tumor-specific urinary matrix metalloproteinase fingerprinting: identification of high molecular weight urinary matrix metalloproteinase species.

PURPOSE: We have previously reported that matrix metalloproteinases MMP-2, MMP-9, and the complex MMP-9/NGAL can be detected in urine of patients with a variety of cancers including prostate and bladder carcinoma. In addition, we also detected several unidentified urinary gelatinase activities with molecular weights >125 kDa. The objective of the current study was to identify these high molecular weight (HMW) species, determine their potential as predictors of disease status, and ask whether a tumor-specific pattern existed based on urinary MMP analysis. EXPERIMENTAL DESIGN: Chromatography, zymography, and mass spectrometry was used to identify HMW gelatinase species of approximately 140, 190, and >220 kDa in urine of cancer patients. To determine whether a tumor-specific pattern of appearance existed among the MMPs detected, we analyzed the urine of 189 patients with prostate or bladder cancer and controls. RESULTS: The approximately 140, >220 kDa, and approximately 190 HMW gelatinase species were identified as MMP-9/tissue inhibitor of metalloproteinase 1 complex, MMP-9 dimer, and ADAMTS-7, respectively. The frequency of detection of any MMP species was significantly higher in urine from prostate and bladder cancer groups than controls. MMP-9 dimer and MMP-9 were independent predictors for distinguishing between patients with prostate and bladder cancer (P < 0.001 for each) by multivariable analysis. CONCLUSIONS: This study is the first to identify a tumor-specific urinary MMP fingerprint that may noninvasively facilitate identification of cancer presence and type. This information may be of diagnostic and prognostic value in the detection and/or clinical monitoring of disease progression and therapeutic efficacy in patients with bladder or prostate cancer.

Urinary metalloproteinases: noninvasive biomarkers for breast cancer risk assessment.

Matrix metalloproteinases (MMP) and a disintegrin and metalloprotease 12 (ADAM 12) can be detected in the urine of breast cancer patients and provide independent prediction of disease status. To evaluate the potential of urinary metalloproteinases as biomarkers to predict breast cancer risk status, urine samples from women with known risk marker lesions, atypical hyperplasia and lobular carcinoma in situ (LCIS), were analyzed. Urine samples were obtained from 148 women: 44 women with atypical hyperplasia, 24 women with LCIS, and 80 healthy controls. MMP analysis was done using gelatin zymography and ADAM 12 analysis was done via immunoblotting with monospecific antibodies and subsequent densitometric measurement. Positive urinary MMP-9 levels indicated a 5-fold risk of atypical hyperplasia and >13-fold risk of LCIS compared with normal controls. Urinary ADAM 12 levels were significantly elevated in women with atypical hyperplasia and LCIS from normal controls, with receiver operating characteristic curve analysis showing an area under the curve of 0.914 and 0.950, respectively. To assess clinical applicability, a predictive index was developed using ADAM 12 in conjunction with Gail risk scores for women with atypia. Scores above 2.8 on this ADAM 12-Gail risk prediction index score are predictive of atypical hyperplasia (sensitivity, 0.976; specificity, 0.977). Our data suggest that the noninvasive detection and analysis of urinary ADAM 12 and MMP-9 provide important clinical information for use as biomarkers in the identification of women at increased risk of developing breast cancer.

A three-field breast treatment technique with precise geometric matching using multileaf collimator-equipped linear accelerators.

PURPOSE: Many authors have studied the problems associated with the three-field breast treatment, yet the proposed solutions present their own difficulties. This study presents a technique that overcomes these difficulties, reduces scatter to the contralateral breast, and improves setup reproducibility. METHODS AND MATERIALS: Patients are set up with both arms raised superiorly on a breast board. A precise field-match is achieved by rotating the couch and collimator of the tangents, while the supraclavicular field is half-beam blocked using an independent jaw. The posterior borders of the tangents are conformally defined by multileaf collimation. Measurements were performed to verify the field matching and evaluate scatter doses. RESULT: A smooth dose transition was found at the match line at all depths. Corner blocks and lower wedges were not used, which reduced the scatter to the contralateral breast compared with our prior technique. CONCLUSION: The technique achieves a precise match while removing constraints on the tangents' length and decreasing scatter dose. Procedures for simulation, planning, and treatment have been devised, along with a new patient setup routine incorporating orthogonal setup films and tattoos. This technique has been successfully implemented in routine treatment since September 2001. A program calculating the setup parameters is available at our website.

A Phase I/II trial of concurrent docetaxel and radiation after induction chemotherapy in patients with poor prognosis squamous cell carcinoma of the head and neck.

BACKGROUND: The authors conducted a Phase I/II study in patients with a poor prognosis who had locally advanced squamous cell carcinoma of the head and neck (SCCHN) and who were treated initially with induction chemotherapy. Patients were treated with weekly docetaxel and concurrent daily fractionated radiation therapy to determine the maximum tolerated dose (MTD) of docetaxel and the efficacy of the regimen. METHODS: Twenty-two patients were enrolled, and 21 patients were treated. Eight patients had Stage III SCCHN, and 13 patients had Stage IV SCCHN without distant metastases and were treated first with 2-3 cycles of induction chemotherapy, which consisted of cisplatin plus 5-fluorouracil with or without leucovorin. Patients with a poor prognosis were identified as those who achieved a partial response to induction treatment, achieved a complete response with a positive biopsy, or were at high risk for developing recurrent disease. Patients were treated subsequently with concurrent, escalating doses of docetaxel (given weekly x 6) and once daily 200-centigray radiation fractions. RESULTS: Three patients were treated with a weekly docetaxel dose of 20 mg/m(2) without dose-limiting toxicity (DLT). Both patients who were treated at the next dose level of 30 mg/m(2) experienced DLT. A dose of 25 mg/m(2) was studied without DLT in the 16 patients who were treated, establishing this as the MTD. Sixty-seven percent of the patients are alive without disease at a median follow-up of 35 months (range, 12-59 months) after the initiation of chemoradiotherapy. CONCLUSIONS: The MTD of weekly docetaxel with concurrent daily radiation therapy in the postinduction setting was 25 mg/m(2). Disease free survival data from this study were good and indicated that this regimen was effective in the treatment of patients with SCCHN who had a poor prognosis.