Rita A. Blanchard

Triple-negative breast cancers are increased in black women regardless of age or body mass index

IntroductionWe investigated clinical and pathologic features of breast cancers (BC) in an unselected series of patients diagnosed in a tertiary care hospital serving a diverse population. We focused on triple-negative (Tneg) tumours (oestrogen receptor (ER), progesterone receptor (PR) and HER2 negative), which are associated with poor prognosis.MethodsWe identified female patients with invasive BC diagnosed between 1998 and 2006, with data available on tumor grade, stage, ER, PR and HER2 status, and patient age, body mass index (BMI) and self-identified racial/ethnic group. We determined associations between patient and tumour characteristics using contingency tables and multivariate logistic regression.Results415 cases were identified. Patients were racially and ethnically diverse (born in 44 countries, 36% white, 43% black, 10% Hispanic and 11% other). 47% were obese (BMI > 30 kg/m2). 72% of tumours were ER+ and/or PR+, 20% were Tneg and 13% were HER2+. The odds of having a Tneg tumour were 3-fold higher (95% CI 1.6, 5.5; p = 0.0001) in black compared with white women. Tneg tumours were equally common in black women diagnosed before and after age 50 (31% vs 29%; p = NS), and who were obese and non-obese (29% vs 31%; p = NS). Considering all patients, as BMI increased, the proportion of Tneg tumours decreased (p = 0.08).ConclusionsBlack women of diverse background have 3-fold more Tneg tumours than non-black women, regardless of age and BMI. Other factors must determine tumour subtype. The higher prevalence of Tneg tumours in black women in all age and weight categories likely contributes to black womens unfavorable breast cancer prognosis.

Turbo STIR magnetic resonance imaging as a whole‐body screening tool for metastases in patients with breast carcinoma: Preliminary clinical experience

This study was undertaken to assess the utility of whole‐body turbo short tau inversion recovery (STIR) magnetic resonance imaging (MRI) to detect metastases to liver, brain, and bone as a single examination in women with breast cancer. Seventeen patients with biopsy‐proven breast cancer and suspected metastatic disease attending over a 12‐month period referred for both conventional imaging and whole‐body MRI were included in the study. Three patients were found to be free of metastases at both conventional and MR imaging. Appendicular or axial skeletal metastases were identified in 11 of 17 patients, with correlation between findings at whole‐body MRI and scintigraphy in 15 of the 17 patients. Five patients had evidence of hepatic metastases on whole‐body MRI, of which metastases were identified in only three patients at CT despite contrast enhancement. Four patients had brain abnormalities (metastases in three patients, meningioma in one patient) detected on both whole‐body and dedicated brain MRI. Preliminary clinical experience suggests that turbo STIR whole‐body MRI may represent a convenient and cost‐effective method of total body screening for metastases in patients with breast carcinoma. J. Magn. Reson. Imaging 2000;11:343–350.

Fetal and neonatal von Willebrand factor (vWF) is unusually large and similar to the vWF in patients with thrombotic thrombocytopenic purpura

Summary. We have investigated the distribution of vWF multimers in blood from the umbilical cord of infants delivered vaginally and by caesarean section, from heel‐stick blood collected 1 d post‐partum, and from fetuses undergoing evaluation for Rh compatibility. To examine vWF multimers. plasma was separated by electrophoresis on SDS‐agarose gels, overlaid with 125I‐anti‐vWF, and analysed by densitometry of autoradiographs. Neonatal and fetal plasma contained unusually large von Willebrand factor multimers (ULvWFM), not present in normal adult plasma, in shed blood from adults, in maternal plasma at the time of birth, or in plasma from adults deficient in vitamin K‐dependent coagulation proteins. We conclude that ULvWFM, similar in size to vWF present in the Weibel Paladie bodies of endothelial cells, the alpha granules of platelets, and the plasma of patients with TTP, is present in the fetal circulation, at birth, and shortly after delivery.

Quantitative DNA Fingerprinting May Distinguish New Primary Breast Cancer From Disease Recurrence

PURPOSE Approximately 10% of women with breast cancer develop a second breast tumor, either a new primary or a recurrence. Differentiating between these entities using standard clinical and pathologic criteria remains challenging. Ambiguous cases arise, and misclassifications may occur. We investigated whether quantitative DNA fingerprinting, based on allele imbalance (AI) or loss of heterozygosity (LOH), could evaluate clonality and distinguish second primary breast cancer from recurrence. METHODS We developed a scoring system based on the AI/LOH fingerprints of 20 independent breast tumors and generated a decision rule to classify any breast tumor pair as related or unrelated. We validated this approach on eight related tumors (cancers and synchronous positive lymph nodes). Finally, we analyzed paired tumors from 13 women (bilateral cancers, primary tumors and contralateral positive axillary lymph nodes, or two ipsilateral tumors). Each pairs genetic classification was compared with their clinical diagnosis and outcome. RESULTS Each independent cancer had a unique fingerprint. Every tumor pairs relationship was quantifiable. Six of eight related tumor pairs were genetically classified correctly, two were indeterminate, and none were misclassified. Among the 13 women with two cancers, four of five clinically indeterminate pairs could be classified genetically. In three of 13 women, the pairs classification contradicted the clinical diagnosis. These women had bilateral cancers genetically classified as related and disease progression. This challenges the paradigm that bilateral cancers represent independent tumors. Overall, women with tumors genetically classified as related had poorer outcomes. CONCLUSION Quantitative AI/LOH fingerprinting is a potentially valuable tool to improve diagnosis and optimize treatment for the growing number of second breast malignancies.

Prevalence of vitamin D deficiency in patients attending an outpatient cancer care clinic in Boston.

Vitamin D is the prehormone important for maintaining normal calcium homeostasis andmineralization of the skeleton. Epidemiologic studies and prospective studies havesuggested that vitamin D may also be protective against many common cancers in humans,including prostate, breast, and colon cancer (1). Furthermore, studies in which cancer cellcultures and animal models of cancer were used have supported the protective role ofvitamin D in inhibiting the growth of many types of cancer cells (2,3). Therefore,maintenance of adequate vitamin D nutrition in patients with cancer is important—not onlyfor good bone health but also for its potential anticancer activity. In addition, patients withcancer frequently complain of muscle aches and bone pain, which may be symptoms ofvitamin D deficiency (4,5).We conducted a study to determine the prevalence of vitamin D deficiency in an outpatientcancer care clinic at Boston University Medical Center. After approval of the study by ourinstitutional review board, patients who attended an outpatient cancer care clinic during themonths of July, August, and September were enrolled in our study. A control group ofhealthy adults without cancer who were older than 40 years had been recruited the previousyear during the same months. Study participants gave written informed consent fordetermination of 25-hydroxyvitamin D [25(OH)D] and completed a dietary questionnaire.The 25(OH)D assay was performed as previously described by Chen et al (6) and confirmedby the Nichols Advantage chemiluminescent assay. Vitamin D deficiency was defined as a25(OH)D level of 20 ng/mL or less (7).The mean ages of the two study groups were 59 ± 10 years for the patients with cancer incomparison with 51 ± 10 years for the healthy control subjects (

Loss of heterozygosity in serial plasma DNA samples during follow-up of women with breast cancer

We evaluated the potential utility of occult circulating tumor DNA as a molecular marker of disease in subjects previously diagnosed with breast cancer. Using 24 microsatellite markers located at sites of frequent loss of heterozygosity (LOH) or allele imbalance in breast cancer, we analyzed DNA from 16 primary tumors (Stage IIA or more advanced) and 30 longitudinally collected plasma specimens. Clinical data at the time of plasma collection were obtained. All 16 tumors were characterized by an individual pattern of LOH. LOH was detected in 12 of 30 (40%) plasma samples, taken from 8 of 14 (57%) subjects. However, the number of LOH in plasma was small (n = 15), and the mean proportion of LOH was much lower than in the tumors (0.05 vs. 0.52). Although infrequent, 12 of 15 (80%) plasma LOH were concordant with abnormalities in the paired tumors, and the mean percent LOH was higher than in normal plasmas, suggesting that they were authentic tumor‐derived abnormalities. We found, despite this, no association, between plasma LOH and tumor stage or clinical status at time of blood collection (i.e., LOH was as common in subjects with no evident disease as in those with evident disease). In addition, detection of LOH was not consistent between serial samples from 5 of 11 subjects (45%), despite stable clinical conditions. No association with clinical outcome was evident, although the sample size was small. Microsatellite instability in plasma was infrequent, nonconcordant with paired tumor and inconsistent in serial samples. This pilot study suggests that identifying tumor‐specific LOH in the plasma of breast cancer subjects may not be useful for detecting occult metastases or for monitoring disease. Other detection techniques may be more promising, but circulating tumor DNA may not be a sufficiently accurate reflection of breast cancer clinical status or tumor activity.

Is hands-on experience more effective than didactic workshops in postgraduate cancer pain education?

BACKGROUND This study examined the nurse outcomes of a cancer pain education program for nurses of patients from 11 different ethnic groups. METHODS Four hundred ninety six home, hospital, and hospice nurses participated in a one-day workshop or two half-day workshops on cancer pain assessment and management. Of these, 116 were randomized to participate in a bedside-precepted visit with an oncology nurse specialist with pain specialization and a focus group to discuss attitudinal issues. Eighty-six nurses served as controls. Pre-, post- and one-year follow-up tests were administered. RESULTS Attitudes, knowledge, and application skills significantly improved for workshop-only and enriched-model nurses relative to controls. CONCLUSION For postgraduate nurses, daylong cancer pain education workshops were, in the group studied, as effective as hands-on experience in improving cancer pain knowledge and changing attitudes. Both the workshop-only and the enriched-model nurses relative to controls had significantly improved knowledge and changed attitudes towards optimal pain management.

Treatment of advanced non-small cell lung cancer with very high-dose cisplatin combined with etoposide and mitomycin C

Background. Treatment options for advanced non‐small‐cell lung cancer are inadequate. There remains a critical need for more effective systemic therapies.

Epidermotropic metastatic mucoepidermoid carcinoma.

Mucoepidermoid carcinoma (MEC), an invasive malignant neoplasm composed of mucus-secreting, epidermoid, and intermediate cells in varying proportions, is the commonest malignant salivary gland neoplasm in adults. Cutaneous metastases from the same, although not entirely common, has been previously reported but are typically confined to dermis. In this report, we present a case of MEC presenting as a cutaneous metastasis. A histologic feature unique to this case was epidermotropism, previously not noted in either metastatic or primary MEC.

Discrepant Cytogenetic and Fluorescence In Situ Hybridization Results in a 26-Year-Old Male with Early T-Cell Acute Lymphocytic Leukemia

Analyzable G-banded metaphases were normal in bone marrow from a 26-year-old male having 80% blasts. Fluorescence in situ hybridization (FISH) using the centromeric probe, D7Z1, revealed 85% of interphase cells with one signal for chromosome 7. Chromosome painting revealed a chromosome 7 rearrangement in a few metaphases that were otherwise unanalyzable. A repeat bone marrow confirmed 3 of 20 metaphases, by G-banding, to have multiple rearrangements and aneuploidy, including a large derivative chromosome involving a complex rearrangement of chromosomes 5, 7, and 9; that is, der(5)t(5;9)(q31;q13)ins(5;7)(p15;q?31q?34), with loss of most of chromosome 7 (7 pter-->7q?31); one normal 7 was present. Immunophenotyping characterized the patients condition as an early T-cell acute lymphocytic leukemia (ALL), with a population of cells suggesting biphenotypic leukemia. He attained a complete clinical remission with chemotherapy. Six months after the initial presentation he received an allogeneic bone marrow transplant. Three months later a CNS relapse was followed by a bone marrow relapse. At this time, eight months after transplant, repeat study of his bone marrow revealed the majority of metaphases had structural and numerical chromosome abnormalities similar to the small clone in the earlier study, including der(5)t(5;9)ins(5;7), but with two normal 7s. FISH showed two 7-centromere signals in interphase. The patient expired one month later.