Grace Makari-Judson

Longitudinal patterns of weight gain after breast cancer diagnosis: observations beyond the first year.

Abstract:  Many, but not all patients experience weight gain 1 year after a breast cancer diagnosis; clearly defined, clinically relevant groups at risk of weight gain have yet to be described. We set out to determine the factors associated with weight gain over time in patients with invasive breast cancer during a period of predominantly anthracycline‐based adjuvant chemotherapy and to identify groups with differing weight gain risks. Breast cancer patients (stage I–IIIB) were identified in a retrospective chart review. Evaluated parameters included weight at diagnosis and 1, 2, and 3 years later, height, body mass index (BMI), age, menopausal and change in menopausal status, as well as therapy and pathologic stage. Regression models identified significant independent predictors of weight change. Recursive partitioning analysis (RPA) was employed to divide the dataset into relevant and significant groups. In 185 identified patients, regression models and RPA demonstrated that weight gain at 1 year was associated with younger age, adjuvant chemotherapy, and lower BMI. Weight gain at 2 years (n = 176) was greater than at year 1, and in addition to weight gain at year 1, was associated with younger age and adjuvant chemotherapy in regression analysis; RPA found that anthracycline therapy, age, and BMI were important. Weights at 3 years were similar to those seen at 2 years. Early‐stage breast cancer patients treated with chemotherapy continue to gain weight 2 years after diagnosis, and this weight gain appears to be persistent at year 3. Observation beyond 1 year is needed to adequately evaluate weight gain in early‐stage breast cancer patients, particularly for those receiving contemporary adjuvant chemotherapy.

Sorafenib or Placebo with Either Gemcitabine or Capecitabine in Patients with HER-2–Negative Advanced Breast Cancer That Progressed during or after Bevacizumab

Purpose: We assessed adding the multikinase inhibitor sorafenib to gemcitabine or capecitabine in patients with advanced breast cancer whose disease progressed during/after bevacizumab. Experimental Design: This double-blind, randomized, placebo-controlled phase IIb study (ClinicalTrials.gov NCT00493636) enrolled patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)–negative breast cancer and prior bevacizumab treatment. Patients were randomized to chemotherapy with sorafenib (400 mg, twice daily) or matching placebo. Initially, chemotherapy was gemcitabine (1,000 mg/m2 i.v., days 1, 8/21), but later, capecitabine (1,000 mg/m2 orally twice daily, days 1–14/21) was allowed as an alternative. The primary endpoint was progression-free survival (PFS). Results: One hundred and sixty patients were randomized. More patients received gemcitabine (82.5%) than capecitabine (17.5%). Sorafenib plus gemcitabine/capecitabine was associated with a statistically significant prolongation in PFS versus placebo plus gemcitabine/capecitabine [3.4 vs. 2.7 months; HR = 0.65; 95% confidence interval (CI): 0.45–0.95; P = 0.02], time to progression was increased (median, 3.6 vs. 2.7 months; HR = 0.64; 95% CI: 0.44–0.93; P = 0.02), and overall response rate was 19.8% versus 12.7% (P = 0.23). Median survival was 13.4 versus 11.4 months for sorafenib versus placebo (HR = 1.01; 95% CI: 0.71−1.44; P = 0.95). Addition of sorafenib versus placebo increased grade 3/4 hand–foot skin reaction (39% vs. 5%), stomatitis (10% vs. 0%), fatigue (18% vs. 9%), and dose reductions that were more frequent (51.9% vs. 7.8%). Conclusion: The addition of sorafenib to gemcitabine/capecitabine provided a clinically small but statistically significant PFS benefit in HER2-negative advanced breast cancer patients whose disease progressed during/after bevacizumab. Combination treatment was associated with manageable toxicities but frequently required dose reductions. Clin Cancer Res; 19(10); 2745–54. ©2013 AACR.

Chronic diarrhea associated with persistent norovirus excretion in patients with chronic lymphocytic leukemia: report of two cases

BackgroundChronic diarrhea in patients treated with immunosuppressive agents or suffering from immunosuppressive disease can represent a diagnostic and therapeutic challenge to the clinician. Norovirus infection, a major cause of acute epidemic diarrhea, has been described as a cause of chronic diarrhea in patients who are immunosuppressed, including transplant recipients and the very young.Case presentationsWe describe two patients, a 64 year-old man and a 59 year-old woman, both suffering from chronic lymphocytic leukemia and hypogammaglobulinemia, who developed chronic diarrhea resistant to therapy. In both cases, after months of symptoms, persistent norovirus infection--documented by repeatedly-positive high-sensitivity stool enzyme immunoassay--was found to be the cause. Both patients died with active diarrheal symptoms.ConclusionsWe describe the first cases of advanced chronic lymphocytic leukemia to suffer from chronic symptomatic norovirus infection. Clinicians caring for such patients, particularly those with concomitant hypogammaglobulinema, who have chronic unexplained diarrhea, should consider norovirus infection in the differential diagnosis.

Weight gain following breast cancer diagnosis: Implication and proposed mechanisms.

Weight gain occurs in the majority of women following breast cancer treatment. An overview of studies describing weight gain amongst women treated with early to modern chemotherapy regimens is included. Populations at higher risk include women who are younger, closer to ideal body weight and who have been treated with chemotherapy. Weight gain ranges between 1 to 5 kg, and may be associated with change in body composition with gain in fat mass and loss in lean body mass. Women are unlikely to return to pre-diagnosis weight. Possible mechanisms including inactivity and metabolic changes are explored. Potential interventions are reviewed including exercise, dietary changes and pharmacologic agents. Although breast cancer prognosis does not appear to be significantly impacted, weight gain has negative consequences on quality of life and overall health. Future studies should explore change in body composition, metabolism and insulin resistance. Avoiding weight gain in breast cancer survivors following initial diagnosis and treatment should be encouraged.

Expression of c-Kit in adenoid cystic carcinoma of the breast

Breast adenoid cystic carcinoma (BACC) is a biologically distinct tumor with morphologic mimickers, which might make accurate classification problematic. Because c-kit expression has been reported in adenoid cystic carcinoma of various anatomic sites, we evaluated BACC for c-kit by immunohistochemical analysis, comparing the findings to similarly stained mimickers. Tested cases included 6 BACCs, 15 low-grade infiltrating ductal carcinomas (LGIDCs) chosen as potential mimickers, and 15 head-neck adenoid cystic carcinomas (HNACCs). All BACCs showed plasma membranous and cytoplasmic staining equal to or greater than that of adjacent benign epithelium. Five BACCs (83%) expressed c-kit in more than 50% of tumor cells. Only 2 of 15 LGIDCs expressed low-intensity, focal c-kit staining. Of the 15 HNACCs, 10 (67%) expressed c-kit. Hormone receptors were consistently negative in BACCs. All BACCs expressed c-kit, whereas LGIDCs infrequently expressed low-intensity c-kit. Immunohistochemical evaluation for c-kit might aid in accurately classifying carcinomas with histologic features overlapping adenoid cystic carcinoma and LGIDC.

Contralateral Breast Cancer: Factors Associated with Stage and Size at Presentation

Abstract:  Few reports have evaluated factors associated with the stage at presentation of contralateral breast cancer and whether contralateral cancer presentation has changed in recent years, during which increased screening and enhanced adjuvant therapy of the initial tumor has been introduced. Patients with initial cancers staged 0–IIIB diagnosed between 1980 and 1999 who subsequently developed contralateral breast cancer were evaluated for stage, primary tumor size and histologic features, patient age and year of diagnosis, synchronous or metachronous presentation, and time from initial tumor to diagnosis of contralateral breast cancer. Tumor presentation was compared with contemporaneously diagnosed unilateral breast cancer patients. A total of 171 patients were diagnosed with contralateral breast cancer; 161 cases if lobular carcinoma in situ for either the initial or the contralateral tumor were excluded. Contralateral tumors were of significantly smaller size and of earlier stage than initial tumors. Contralateral cancers demonstrated earlier stage distributions with more recent year of diagnosis; initial tumors in contralateral patients did not. Earlier stage at presentation of contralateral tumors was associated in a multivariate model with more recent year of contralateral tumor diagnosis and earlier stage at presentation of the initial tumor; contralateral tumor size was associated with the size of the initial tumor. More recently diagnosed contralateral breast cancers are presenting with earlier stages of disease. The stages of initial tumors in these patients have not undergone such an improvement. Initial tumor size and stage is strongly associated with contralateral breast cancer size and stage; this association is independent of the year of diagnosis. Increased compliance with screening might be expected to improve both initial tumor stage and tumor size presentations in contralateral tumor patients, as well as the presentation of contralateral cancers. 

Touch-preparation cytologic examination of breast core biopsy specimens: Accuracy in predicting benign or malignant core histologic results

RATIONALE AND OBJECTIVES The purpose of this study was to determine the accuracy of touch-preparation cytologic examination of breast core biopsy specimens in predicting benign or malignant core histologic results. MATERIALS AND METHODS One hundred two core biopsies were performed on 88 women with stereotactic or ultrasonographic (US) guidance. Slides were prepared by smearing one core sample on each slide, spraying the slides with fixative, and staining them with the Papanicolaou technique. Slides were blindly reviewed by a cytopathologist. Cytologic results were categorized as positive for malignancy, not diagnostic for malignancy, or insufficient for diagnosis. Results were correlated with histologic results from all specimens obtained during the core biopsy. RESULTS Imaging depicted the lesions sampled for biopsy as masses (n = 70), clustered calcifications (n = 29), focal asymmetries (n = 2), or architectural distortion (n = 1). Touch-preparation slides of 87 (85%) lesions contained sufficient material for diagnosis. Cytologic results correctly identified 12 of 16 (three of five intraductal and nine of 11 invasive) malignancies in 10 of 13 masses and two of three clusters of calcifications. Two false-positive results occurred, both with fibroadenomas. Overall, touch-preparation studies produced 69 true-negative and four false-negative results. Excluding slides with insufficient material, the sensitivity, specificity, and accuracy of touch-preparation results were 75%, 97%, and 93%, respectively. Including insufficient samples, accuracy was 79%. CONCLUSION Although touch-preparation cytologic examination of breast core biopsy specimens is fairly accurate in prediction of benign or malignant core histologic results, its correlation with histologic results is not sufficient to justify routine use in immediate counseling and treatment planning.

Spectrum of breast disease encountered in HIV-positive patients at a community teaching hospital

INTRODUCTION HIV infection directly and indirectly affects breast tissue. This study describes the spectrum of HIV-related breast disease encountered at a community teaching hospital. METHODS A 9 year retrospective review was performed of HIV-positive patients with a breast-related diagnosis seen at our institution. Patient demographics, HIV status, comorbid disease, medications, clinical findings, diagnostic procedure, pathology, treatment and outcome were recorded. RESULTS A total of 46 individuals were included with a median age of 47 years (range 24-64 years) and male:female ratio of 1:3 (12 men and 34 women). Mean duration of HIV infection was 7 years during which time 46% of patients had an AIDS defining illness. Median CD4 cell count was 437 cells/mm(3) (range 2 to ≥500 cells/mm(3)) at the time of the breast diagnosis. Breast disease identified included benign conditions (59% total: 92% for men, 47% for women), infection (17% total: 8% for men, 21% for women), cancer (22% total: 0% for men, 29% for women), and atypia (2% total: 0% for men, 3% for women). Patients with a breast infection had a lower median CD4 cell count than those with breast cancer or benign conditions. Gynecomastia was detected in seven out of 12 (58%) men. In these men, antiretroviral therapy (ART) of all drug classes was associated with gynecomastia. Breast cancer occurred only in women and included patients with invasive ductal carcinoma (n = 7), ductal carcinoma in situ (n = 2), and liposarcoma diagnosed in one individual. Specific risk factors for breast cancer in this setting were not identified. Five (11%) patients died, only one from breast disease during the study period. CONCLUSION These data indicate that increased longevity in patients with chronic HIV infection may be associated with the occurrence of breast conditions in both men and women. A broad spectrum of breast disease should be anticipated in HIV-infected persons living longer with effective ART.

Use of Survivorship Care Plans to Re-Engineer Breast Cancer Follow-Up

Background: Optimal strategies for quality care of breast cancer survivors include providing value in each visit and appropriately utilizing resources. The purpose of this study was to demonstrate the use of Survivorship Care Plans (SCPs) to coordinate follow-up in a multidisciplinary practice and improve access to breast surgeons. Methods: In 2009, our breast surgeons, medical oncologists and nurse practitioners agreed upon guidelines for follow up of breast cancer patients, developed a Survivorship Care Program to follow active treatment and implemented use of SCPs. To improve access to two part-time breast surgeons, guidelines were established to shift follow-up to medical oncologists and nurse practitioners. After diagnosis, patients were given comprehensive SCPs which included recommended follow up visits and testing. Wait times and numbers of new surgical patients were measured before and after use of SCPs. Results: Wait times were measured from call to first appointment. New patients included both benign and malignant breast disease. Implementation of SCPs occurred during 2009. In 2007 and 2008, average wait times were 43.5 days and 28.5 days respectively. Following implementation of SCPs, wait times in 2010 and 2011 were 10 and 9 days respectively. Numbers of new patients seen were 573 and 486 in 2007 and 2008; 571 and 650 new patients were seen in 2010 and 2011. Conclusions: SCPs were useful in re-engineering follow-up habits of clinicians, adding value to each visit and gaining acceptance from established patients regarding recommended surveillance. SCPs contributed to reduced wait times and increase in volume of new patients seen by breast surgeons. Future studies should assess contribution of SCPs to reducing unnecessary tests and improving compliance with ASCO guidelines.

Deleterious Effect of Chemotherapy on Measures of Insulin Resistance in Patients with Newly-Diagnosed Invasive Breast Cancer.

Background: Women treated with early stage breast cancer often gain weight in the two years following diagnosis, with adjuvant chemotherapy, younger age, lower body mass index (BMI) and pretreatment menopausal status being associated factors (Breast J 2007; 13:258). The effect of insulin resistance on treatment-related weight gain, and of treatment on measures of insulin resistance, are unclear.Purpose: To prospectively study weight gain in women receiving adjuvant therapy for early stage breast cancer and assess changes in body mass index, body composition, and explore the relationship between markers of insulin resistance, cancer therapy, exercise and weight gain.Methods: Prospective, observational study of non-diabetic women with early-stage breast cancer receiving adjuvant chemotherapy and/or hormonal therapy. Fasting insulin, glucose, and triglycerides, weight, BMI, waist and hip circumference were obtained at baseline before adjuvant therapy, and at 6, and 12 months. Patients completed nutrition and exercise logs using the Nutritionist-Pro program. Insulin resistance was calculated using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Waist/hip ratio (WHR) was used as a surrogate for percent body fat.Results: Complete data available for 95 patients are reported regarding weight change at 6 months (mean 0.4 kg, 95%CI -0.3, 1.0; p=.23 compared to baseline) and 12 months (0.9 kg, 95%CI 0.4, 1.8, p=.04 compared with baseline). Mean baseline HOMA-IR was 2.3 (95%CI 1.9, 2.7); mean baseline WHR was 0.82 (95%CI 0.81, 0.84). Six-month HOMA-IR tended to increase (by mean 0.34, p=.06) as did glucose/insulin ratio (p=.05). Waist measurement (p=.96) and WHR (p=.52) were unchanged. Chemotherapy-treated patients exhibited adverse changes compared with others (mean change for chemotherapy-treated and no chemotherapy for HOMA-IR: 0.53 vs. -0.64, p=.005; glucose/insulin: -2.1 vs. 2.7, p=.003; waist: 0.37 vs. -1.94 cm, p=.08; WHR: 0.001 vs. -0.024, p=.06). Age, BMI, hormonal therapy, or types of breast surgery were not associated with significant changes. Exercising patients demonstrated lower HOMA-IR and WHR, and greater glucose/insulin ratios at baseline, but exercise (aerobic, strength, or any exercise) was not associated with significant change at 6 and 12 months for any of these variables. While differences disappeared at 12 months despite further weight gain repeated measures analysis of variance confirmed the effect of chemotherapy over time for HOMA-IR (p=.048), glucose/insulin (p=.038) and WHR (p=.050).Conclusions: These preliminary data suggest that patients completing chemotherapy within 6 months of baseline appear to experience at least short-term changes in metabolism suggestive of insulin resistance. These adverse changes may help explain weight gain associated with adjuvant chemotherapy, and merit further prospective study. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1054.