Jacqueline Spayne

Prognostic and predictive molecular markers in DCIS: a review.

Eighteen percent of all new breast cancers detected on screening mammography are ductal carcinoma in situ (DCIS), a preinvasive lesion that is highly curable. However, some women with DCIS will develop life-threatening invasive breast cancer. Because the determinants of invasive recurrence are unknown, all women with DCIS require the same treatment (usually with surgery and radiation). Therefore, there is a need to identify biologic markers and create a profile that will provide prognostic information that is more accurate than the currently used van Nuys Index to predict invasive recurrence. In the present review, we examined the many biologic markers studied in breast cancer, describe their main biologic role and their expression in DCIS, and review the various studies regarding their ability to serve as prognostic factors in breast cancer with an emphasis on predicting invasive recurrence in patients with DCIS. This review covers established markers, namely, ER, PR and HER2/neu, that are used routinely to make treatment decisions as well as investigative biologic factors involved in cell proliferation, cell cycle regulation, extracellular molecules, factors involved in extracellular matrix degradation, and angiogenesis. However, controversies exist regarding the value of these prognostic factors, their interrelationship, and their advantages over morphologic evaluation.

Quantitative Ultrasound Evaluation of Tumor Cell Death Response in Locally Advanced Breast Cancer Patients Receiving Chemotherapy

Purpose: Quantitative ultrasound techniques have been recently shown to be capable of detecting cell death through studies conducted on in vitro and in vivo models. This study investigates for the first time the potential of early detection of tumor cell death in response to clinical cancer therapy administration in patients using quantitative ultrasound spectroscopic methods. Experimental Design: Patients (n = 24) with locally advanced breast cancer received neoadjuvant chemotherapy treatments. Ultrasound data were collected before treatment onset and at 4 times during treatment (weeks 1, 4, and 8, and preoperatively). Quantitative ultrasound parameters were evaluated for clinically responsive and nonresponding patients. Results: Results indicated that quantitative ultrasound parameters showed significant changes for patients who responded to treatment, and no similar alteration was observed in treatment-refractory patients. Such differences between clinically and pathologically determined responding and nonresponding patients were statistically significant (P < 0.05) after 4 weeks of chemotherapy. Responding patients showed changes in parameters related to cell death with, on average, an increase in mid-band fit and 0-MHz intercept of 9.1 ± 1.2 dBr and 8.9 ± 1.9 dBr, respectively, whereas spectral slope was invariant. Linear discriminant analysis revealed a sensitivity of 100% and a specificity of 83.3% for distinguishing nonresponding patients by the fourth week into a course of chemotherapy lasting several months. Conclusion: This study reports for the first time that quantitative ultrasound spectroscopic methods can be applied clinically to evaluate cancer treatment responses noninvasively. The results form a basis for monitoring chemotherapy effects and facilitating the personalization of cancer treatment. Clin Cancer Res; 19(8); 2163–74. ©2013 AACR.

Accelerated hypofractionated radiotherapy for early-stage non-small-cell lung cancer: long-term results.

PURPOSE To retrospectively review the results of a single-institution series of accelerated hypofractionated radiotherapy for early-stage non-small-cell lung cancer (NSCLC) in patients who are medically inoperable or who refuse surgery. METHODS AND MATERIALS Peripherally located T1 to T3 N0 M0 tumors were treated with 48 to 60 Gy in 12 to 15 fractions between 1996 and 2007. No elective nodal irradiation was delivered. Patient, tumor, and treatment information was abstracted from the medical records. RESULTS A total of 124 tumors were treated in 118 patients (56 male and 62 female). Median age at diagnosis was 76.3 years (range, 49-90 years). In all, 113 patients (95.8%) were not surgical candidates because of medical comorbidities. The 2- and 5-year overall survival (OS) rates were 51.0% and 23.3%, respectively, and the 2- and 5-year cause-specific survival (CSS) rates were 67.6% and 59.8%, respectively. The 2- and 5-year actuarial local control (LC) rates were 76.2% and 70.1%, respectively. Univariate analysis revealed that tumor size less than 3 cm compared with greater than 3 cm resulted in significantly improved OS (40.0% vs. 5.0% at 5 years; p = 0.0002), CSS (69.7% vs. 45.1% at 5 years; p = 0.0461), and a trend toward better LC (82.5% vs. 66.9% at 2 years, 76.6% vs. 60.8% at 5 years; p = 0.0685). Treatment was well tolerated and there were no treatment delays because of acute toxicity. CONCLUSIONS Accelerated hypofractionated radiotherapy with 48 to 60 Gy using fractions of 4 Gy per day provides very good results for small tumors in medically inoperable patients with early-stage NSCLC.

Conventional frequency evaluation of tumor cell death response in locally advanced breast cancer patients to chemotherapy treatment administration.

The aim of many cancer therapies is to induce cell death within a target tumor. A substantial body of research using in vitro and in vivo models has demonstrated that cell death can be detected via quantitative ultrasound techniques. This study investigates for the first time the potential to quantify tumor responses to therapy in patients, using spectral and signal envelope statistics analysis of ultrasound data. A clinical study was undertaken investigating the efficacy of ultrasound to quantify cell death in tumor responses with cancer treatment. Patients (n=20) with locally advanced breast cancer received anthracyline and taxane‐based chemotherapy treatments. Data collection consisted of acquiring tumor images and radiofrequency data prior to treatment onset and at 4 times during treatment (weeks 1, 4, and 8, and preoperatively). Data indicate increases of approximately 9 dBr (±1.67) in ultrasound backscatter in patients who responded to treatment. Patients assessed as responding poorly demonstrated s...

Current challenges and future perspectives of radiotherapy for locally advanced breast cancer.

Purpose of reviewTo discuss current issues in the field of radiation oncology for locally advanced breast cancer (LABC). Recent findingsLarge randomized studies involving nodal irradiation have recently been completed. The incremental benefit of treating the internal mammary nodes (IMNs) remains controversial. A randomized study specifically evaluating internal mammary node radiation (IMNR) failed to demonstrate significant benefit. A high impact, population-based study detected a proportional increase in major coronary events with increasing radiation dose. Advanced treatment techniques should be employed to reduce cardiac exposure.In patients with stage IV breast cancer (BCa), there is increasing evidence to suggest that locoregional treatments may improve overall survival (OS). Radiotherapy alone, without surgery, may provide equivalent local control and OS in patients with distant metastasis. High-dose stereotactic radiation regimens can be used to treat breast tumors with good local control rates in as few as three visits.BCa biomarkers are predictive of locoregional recurrence risk and should be used to guide radiotherapy in conjunction with standard staging. Clinically validated genetic profiling can measure tumor radiosensitivity and also help to predict normal tissue toxicity. SummaryWe are entering an era of personalized radiotherapy for LABC. Radiation treatments must be tailored to each individual patients risk and intrinsic tumor biology.

Quantitative ultrasound evaluation of tumor cell death response in locally advanced breast cancer patients to chemotherapy treatment administration

A clinical study was undertaken investigating the efficacy of ultrasound to quantify cell death in tumor responses with cancer treatment. Patients (n = 25) with locally advanced breast cancer received anthracyline and taxane-based chemotherapy treatments over four to six months. The majority of patients went on to have a modified radical mastectomy and correlative whole mount histopathology. Data collection was carried out using an Ultrasonix-RP and an L15-5 6 cm transducer pulsed at 10 MHz with RF data collected five times during neoadjuvant chemotherapy. Data indicated increases of approximately 9 dBr (+/−1.67) maximally in ultrasound backscatter in patients who clinically responded to treatment. Patients assessed as responding poorly demonstrated significantly lower increases (2.3 +/− 1.7 dBr). Increases in 0-MHz intercept followed similar trends while increases in spectral slope were observed locally from tumor regions demonstrating increases in tissue echogenicity. This study demonstrates the potenti...

Histiocytoid variant of lobular carcinoma: a triple negative case.

erythematous and petechial vasculitic rash with areas of confluence together with well-demarcated areas of ulceration affecting her legs (Fig. 3). She referred throat pain and ear ache and oropharynx study showed palate ulceration. Head computarized axial tomography confirmed pharynx and cavum areas of inflammation. Urinalisys revealed microscopic hematuria (more than 100 red cells per field). Immunology revealed antinuclear antigen (ANA, DNA, ENA) and ENA (SSA, SSB, RNP, Sm, Jo-1, SCL-70) negative. But C-ANCA and PR3 were positive (305.0 U ⁄ mL). Breast biopsy reported acute mastitis upon chronic mastitis with lymphocytic lobulillitis and include noncaseating granulomas, necrosis, giant cell formation, intravascular thrombus, lymphoplasmacytic infiltration in small and medium size vessels. These findings were compatible with Wegener’s granulomatosis (WG) (Figs. 4 and 5). Skin lessions in legs were biopsied and the result was leucocytoclastic vasculitis affecting vessels in dermis. Thoracic computarized axial tomography showed a 7.5 cm cavitated nodule in superior left pulmonar lobule, probably WG. She also presented arthritis (ankle pain and swelling). Our patient presented enough diagnostic criteria of Wegener used by American College of Rheumatology criteria and Chapel Hill Consensus Conference definitions. Diagnosis was confirmed by C-ANCA and PR3. Final diagnosis was Wegener’s granulomatosis. Clinicians should be aware about this possibility in differential diagnosis of mastitis and breast abscess showing atypical evolution.

From high-frequency to low-frequency cell death detection: quantitative ultrasound evaluation of tumor response in breast cancer

Pre-clinical and clinical studies were undertaken investigating the efficacy of ultrasound to quantify cell death in tumor responses with cancer treatment. Animals bearing tumours (n=48), and patients (n=24) with locally advanced breast cancer received various therapies including for patients anthracyline and taxane-based chemotherapy treatments over four to six months. Tumour cell-death was assessed in specimens after treatment using histopathology. Pre-clinical ultrasound data collection was carried out at low-frequency and high-frequency. For human imaging, low-frequency ultrasound data were collected 5 times during neoadjuvant chemotherapy. Data indicated considerable increases in ultrasound backscatter in animal tumours after treatment. Similar findings were observed in patients who clinically responded to treatment. Patients assessed as responding poorly demonstrated significantly lower increases. Increases in 0-MHz intercept followed similar trends while increases in spectral slope were observed lo...