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Biomedical subjects

Catherine Van Poznak

Publications and source records attributed to Catherine Van Poznak.

15 recordsLinked to original sources
PubMed2026

Patient-reported outcomes from the TBCRC 022 study of neratinib and ado-trastuzumab emtansine for HER2-positive breast cancer brain metastases.

PURPOSE: In TBCRC 022 (NCT01494662), neratinib and ado-trastuzumab emtansine (T-DM1) demonstrated intracranial activity among patients with HER2-positive breast cancer brain metastases. However, gastrointestinal (GI) toxicities-particularly diarrhea-were common, potentially impacting quality of life. Clinician-reported adverse event (CTCAE) grading may underestimate the patient experience. We report GI toxicities using patient-reported outcomes (PROs) in TBCRC's neratinib-T-DM1 cohort. METHODS: Patients received neratinib (160&#x202f;mg daily) and T-DM1 (3.6&#x202f;mg/kg IV every 21 days). A pre-planned analysis assessed patient-reported GI toxicities during Cycles 1-4 using the Patient-reported Outcomes Measurement Information System (PROMIS) GI Diarrhea scale, Systemic Therapy-Induced Diarrhea Assessment Tool (STIDAT), and PRO-CTCAE. Descriptive statistics and linear mixed effects models evaluated symptom trajectories over time. We evaluated agreement for PRO and clinician-reported data. RESULTS: Forty-four patients enrolled; all completed &#x2265;1 PRO. GI symptom burden increased over Cycles 1-3. PROMIS scores worsened significantly by Cycle 2, with a peak mean increase of 6.62 (95% confidence interval (CI): 2.67-10.59; p&#x202f;=&#x202f;0.002) at Cycle 3. STIDAT scores also worsened by Cycle 3 (mean change 0.50; 95%CI: 0.11-0.90; p&#x202f;=&#x202f;0.015). Based on maximum PRO-CTCAE scores, moderate-to-severe symptoms were reported by 20.5% (diarrhea), 24.4% (appetite loss), and 41.0% (constipation). Agreement between PRO-CTCAE and clinician-reported CTCAE was low (kappa <0.2) with clinicians reporting less toxicity. PROMIS and STIDAT scores were significantly correlated. CONCLUSION: This GI-focused PRO analysis highlights the value of PROs in capturing patient-experienced toxicities that impact quality of life yet are underestimated by clinicians. Incorporating PROs into clinical trials can inform supportive care and prophylactic strategies.

Humans↗
PubMed2007

Increased dose density is feasible: a pilot study of adjuvant epirubicin and cyclophosphamide followed by paclitaxel, at 10- or 11-day intervals with filgrastim support in women with breast cancer.

PURPOSE: Because Cancer and Leukemia Group B 9741 trial showed a benefit for every 14-day administration of chemotherapy compared with every 21-day treatment, we hypothesized that even greater dose density would be more effective. We conducted a pilot trial to assess the feasibility of dose-dense chemotherapy consisting of a standard regime at 10- to 11-day intervals in the adjuvant/neoadjuvant setting. A 2-day window was allowed for scheduling logistics. EXPERIMENTAL DESIGN: Thirty-nine women with early-stage breast carcinoma were accrued from April 2004 to October 2004. Median age was 47 years (range, 26-67 years). Patients received therapy with 100 mg/m(2) epirubicin and 600 mg/m(2) cyclophosphamide (EC) q 10 to 11 days for four cycles followed by 175 mg/m(2) paclitaxel q 10 to 11 days for four cycles, all with filgrastim support (300 microg s.c. daily) from day 2 to 24 h before the next treatment. RESULTS: Thirty-five (90%) patients completed all planned therapy. The median intertreatment interval was 10 days (range, 8-28 days). Cycles (80.7%) were delivered at no more than 10- to 11-day intervals. There were five dose reductions of 25% for grade 3 nonhematologic toxicity in five patients. Six (16%) patients developed febrile neutropenia defined as temperature >38 degrees C with absolute neutrophil count <1,000/microL. All febrile neutropenia was during therapy with EC. Other grade 3 toxicities included bone pain, hand and foot syndrome, neuropathy, mucositis, nausea, and vomiting. CONCLUSIONS: Therapy with EC for four cycles followed by paclitaxel for four cycles at 10- to 11-day intervals is feasible. The approximately 30% reduction in intertreatment interval compared with every 14-day treatment could increase the efficacy of adjuvant chemotherapy.

Adult↗
PubMed2006

Effect of adjuvant breast cancer chemotherapy on cognitive function from the older patient's perspective.

PURPOSE: This longitudinal prospective study describes the older breast cancer patient's perception of the cognitive impact of adjuvant chemotherapy. METHODS: A total of 50 patients > or =age 65 with stage I to III breast cancer enrolled in this IRB-approved prospective study. Of the 50, 3 refused postchemotherapy testing and 2 had a cerebrovascular accident (CVA) during therapy, leaving 45 evaluable patients. The Squire Memory Self-Rating Questionnaire, given before and 6 months after chemotherapy, measured patients' perceptions of the ability to learn new information, of working memory, and of remote learning capabilities. RESULTS: Mean age was 70 years (range 65-84). Breast cancer stages were: I (33%), II (64%), III (2%). A 51% (23/45) of study participants perceived a decline in memory from before to 6 months after completion of chemotherapy. Patients who perceived a poorer memory than average before chemotherapy were more likely to report further memory deterioration after chemotherapy (19/30, 63%) than patients who perceived that their memory was average or better than average prior to chemotherapy (4/15, 27%). The memory domain most likely to be perceived as affected was the ability to learn new information (22/45, 49%) compared to remote memory (9/45, 20%) or working memory (13/45, 29%) capabilities. CONCLUSION: Approximately half of these older women perceived a decline in cognitive function from before to 6 months after chemotherapy. This perceived decline in cognitive function was most pronounced in patients with preexisting memory complaints. Further prospective study is needed to confirm these observations, correlate perceived memory changes with objective findings, and identify subgroups at special risk.

Aged↗
PubMed2006

Bone integrity and bone metastases in breast cancer.

Individuals with a history of early-stage breast cancer may be at increased risk of osteoporosis related to adjuvant therapy, and those with metastatic breast cancer may experience skeletal-related complications from the cancer affecting the bone. Maintaining bone strength is critical in the care of both early- and late-stage breast cancer patients because fractures are associated with morbidity and mortality. This article reviews the maintenance of bone integrity in women with breast cancer.

Bone Neoplasms↗
PubMed2006

C/EBPbeta at the core of the TGFbeta cytostatic response and its evasion in metastatic breast cancer cells.

Breast cancers may evade the growth-inhibitory action of TGFbeta by accumulating defects of unknown nature that selectively eliminate cytostatic gene responses. We found the transcription factor C/EBPbeta to be essential for TGFbeta induction of the cell cycle inhibitor p15INK4b by a FoxO-Smad complex and repression of c-MYC by an E2F4/5-Smad complex in human epithelial cells. These cytostatic responses are selectively missing in metastatic breast cancer cells from half of the patients that we tested. The basis for this loss was traced to an excess of the C/EBPbeta inhibitory isoform LIP. We suggest that C/EBPbeta plays a key role in the coordination of TGFbeta cytostatic gene responses, and its malfunction may trigger evasion of these responses in breast cancer.

Animals↗
PubMed2006

The phenomenon of osteonecrosis of the jaw in patients with metastatic breast cancer.

Osteonecrosis of the jaw (ONJ) has been noted to occur in patients with cancer receiving bisphosphonate therapy and may also be referred to as bisphosphonate associated osteonecrosis (BON). ONJ has come to attention through case reporting and the pathogenesis and true incidence of this condition are not yet defined. ONJ appears to be a relatively uncommon event, but it is of clinical significance; the evolving data on ONJ are discussed here.

Bone Density Conservation Agents↗
PubMed2006

Cognitive function of older patients receiving adjuvant chemotherapy for breast cancer: a pilot prospective longitudinal study.

OBJECTIVES: To report on the longitudinal cognitive functioning of older women receiving adjuvant chemotherapy for breast cancer. DESIGN: Neuropsychological and functional status testing were performed before chemotherapy and 6 months after chemotherapy. SETTING: Cancer center. PARTICIPANTS: Thirty-one patients aged 65 and older with Stage I to III breast cancer. Of the 31 patients enrolled, three refused post-testing, and 28 were evaluable. MEASUREMENTS: The following domains of cognitive function were examined: attention; verbal memory; visual memory; and verbal, spatial, psychomotor, and executive functions. RESULTS: Participants had a mean age of 71 (range 65-84): 39% Stage I, 50% Stage II, and 11% Stage III. The number of scores 2 standard deviations (SDs) below the norm were calculated for each patient before and 6 months after chemotherapy; 14 (50%) had no change, 11 (39%) worsened, and three (11%) improved (P=.05). Seven patients (25%) experienced a decline in cognitive function, defined as a 1-SD decline from pre- to post-testing in two or more neuropsychological domains. Exploratory analyses revealed no significant difference between functional status, comorbidity, and depression scale scores and change in overall quality-of-life scores before and after chemotherapy. CONCLUSION: In this cohort of older women receiving adjuvant chemotherapy, a subset experienced a decline in cognitive function from before chemotherapy to 6 months after chemotherapy. Further prospective study is needed to confirm these observations and to identify the subgroup at special risk.

Age Factors↗
PubMed2006

Osteonecrosis of the jaw in cancer patients receiving IV bisphosphonates.

Cases of osteonecrosis of the jaw (ONJ) have been reported with an increasing frequency over the past few years. ONJ is most often identified in patients with cancer who are receiving intravenous bisphosphonate therapy but it has also been diagnosed in patients receiving oral bisphosphonates for nonmalignant conditions. The condition involves exposed bone of the maxilla or mandible. Although it is often associated with a recent dental surgical procedure, spontaneous ONJ can also occur. Patients commonly present with symptoms. Through case reporting and clinical experience, there is a suggestion that the incidence of ONJ in patients with cancer receiving intravenous bisphosphonates ranges between 1% and 10%. Management of ONJ focuses on maximizing oral health, conservative actions with mouth rinses, antibiotics, and avoidance of unnecessary invasive dental procedures. The currently available data on ONJ are reviewed here.

Bone Density Conservation Agents↗
PubMed2005

Clinical management of osteoporosis in women with a history of breast carcinoma.

Osteoporosis is a skeletal disorder that is characterized by low bone mass and compromised bone strength. Fractures are the clinically important consequence of osteoporosis and result not only in disability but also in excess mortality. Women who have a history of breast carcinoma may represent a unique population for whom screening and treatment for osteoporosis should be modified. A review of the English literature was performed that included original, review, consensus, and statement articles that were identified through Medline or National Institutes of Health-related links. According to the literature, osteoporosis constitutes a major public health problem. Approximately 55% of the U.S. population > or = 50 years of age has low bone mass (osteopenia or osteoporosis). Annually, > 200,000 women in the U.S. are diagnosed with breast carcinoma. Due to the high prevalence rates of both low bone mass and breast carcinoma in women, these two diseases commonly coexist in the same individuals. Women with a history of breast carcinoma may be at increased risk of developing bone loss and fragility fractures as a consequence of antineoplastic therapies. The majority of women treated for early-stage breast carcinoma do not develop recurrences, as a result of recent advances in therapy. Ensuring the diagnosis, prevention, and treatment of long-term toxicities and comorbid conditions like osteoporosis in breast carcinoma survivors is a serious concern and is of increasing importance. In this article, the authors address the evaluation and treatment of osteoporosis in women who have a history of early-stage breast carcinoma.

Antineoplastic Agents↗
PubMed2005

Phosphorylated/activated HER2 as a marker of clinical resistance to single agent taxane chemotherapy for metastatic breast cancer.

Purpose. To determine the association of phosphorylated/activated HER2 (P-HER2) and response to taxane chemotherapy in patients with metastatic breast cancer (MBC). Materials and Methods. Archived tumor specimens of patients with MBC treated on clinical trials with taxane monotherapy were analyzed by immunohistochemistry (IHC) for the presence of phosphorylated HER2 using the PN2A monoclonal antibody. Chi-squared analysis was performed to evaluate the association of P-HER2 status and efficacy of single agent taxane therapy. Results. One hundred twenty-six cases were identified as evaluable for both IHC and clinical outcome. Twelve cases (10 percent) were positive for P-HER2, of which 5 had evidence of clinical progression and 7 had evidence of clinical benefit with taxane therapy. Of the 114 cases that were negative for P-HER2, 20 demonstrated progression and 94 had clinical benefit. Chi-squared analysis revealed a significant correlation between the presence of P-HER2 and resistance to taxane therapy, chi2 = 3.9724 and p = 0.046. Conclusions. Phosphorylated/activated HER2 is associated with clinical resistance to single agent taxane therapy for MBC. The likelihood of direct progression of disease on taxane was greater in cases of PN2A-positive tumors (42 percent) as opposed to PN2A-negative ones (18 percent, p = 0.046). Functional assessment of HER2 status may provide unique predictive information not seen with conventional assessments.

Antibodies, Monoclonal↗
PubMed2003

Third North American Symposium on Skeletal Complications of Malignancy: summary of the scientific sessions.

The current introduction summarizes the five scientific sessions (bone marrow microenvironment and animal models of bone metastasis; prostate carcinoma; multiple myeloma; breast carcinoma; and preclinical and clinical studies on metastasis: future directions) and provides an overview of the proceedings of the Third North American Symposium on Skeletal Complications of Malignancy, Bethesda, Maryland, April 25-27, 2002.

Animals↗
PubMed2002

Assessment of molecular markers of clinical sensitivity to single-agent taxane therapy for metastatic breast cancer.

PURPOSE: The taxanes affect tubulin polymerization and interfere with mitotic transition. A checkpoint blockade at the G(1)-S boundary would be expected to promote taxane-induced apoptotic cell death through a mechanism that may involve p27. Other proposed determinants of clinical taxane sensitivity/resistance include p53, members of the epidermal growth factor receptor (EGFR) superfamily (e.g., HER2, EGFR), and estrogen receptors and progesterone receptors. These molecular markers and their correlation with clinical taxane sensitivity are investigated in this retrospective clinicopathologic study. PATIENTS AND METHODS: We performed immunohistochemistry (IHC) for estrogen receptors, progesterone receptors, HER2, EGFR, p53, and p27 on 144 breast tumor specimens from patients treated for metastatic breast cancer on a series of clinical trials of single-agent taxane chemotherapy for correlation with clinical response (complete or partial response). Patient characteristics that could influence response (i.e., performance status, extent of disease, and prior therapy) were also examined. RESULTS: In univariate analysis, Karnofsky performance status > or = 90% and no prior history of anthracycline therapy correlated with a good clinical response to single-agent taxane (P =.003 and P =.041, respectively). None of the IHC variables tested were predictive of clinical response to taxane therapy, although p27 negativity showed a trend toward significance (P =.075). Concordance between the polyclonal antibody with HercepTest (DAKO, Carpinteria, CA) and the monoclonal antibody CB-11 (BioGenex, San Ramon, CA) was noted (kappa = 0.943); however, neither univariate nor multivariate analysis demonstrated an association between HER2 status and response to taxane chemotherapy. CONCLUSION: The IHC biomarkers studied were not predictive of response to single-agent taxane chemotherapy in patients with metastatic breast cancer. Identification of molecular correlates of taxane response remains an important goal.

Antineoplastic Agents, Phytogenic↗
PubMed2002

Critical review of current treatment strategies for advanced hormone insensitive breast cancer.

Breast cancer is the most common cancer diagnosis in American women. Over the past several decades, there has been a steady increase in the incidence of this disease. Fortunately, the death rates in the last decade has showed a decrease. Patients with breast cancer now have more treatment options and a better chance of long term survival than ever before. Patients with metastatic disease are considered candidates for chemotherapy if they are symptomatic, have rapidly progressing or bulky disease, or if they are inappropriate candidates for hormonal therapy either because of negative hormonal receptor status or progression of disease on hormonal therapies. Patients are often treated with a chemotherapy regimen until progression of disease, or prohibitive toxicity, at which time the therapy is changed to a second or a third line therapy. This manuscript will provide a review of the current treatment strategies for advanced hormone insensitive breast cancer.

Antibodies, Monoclonal↗
PubMed2002

HER2 testing and correlation with efficacy of trastuzumab therapy.

The need for accurate detection of HER2 status is becoming more apparent, as therapeutic decisions are influenced by this information in both the adjuvant and advanced-stage setting. Since the US Food and Drug Administration approved trastuzumab (Herceptin) for the treatment of metastatic breast cancer, the urgency of accurately evaluating HER2 status of breast cancer specimens, in order to identify patients who might benefit from this therapy, has increased. A wide range of assay methods are available for determining HER2 status, but immunohistochemistry followed by fluorescence in situ hybridization (FISH) is the recommended approach for ambiguous cases. FISH is not as widely available and is more costly than immunohistochemistry, but economic modeling shows that it is the most effective (and cost-effective) option.

Animals↗