Biomedical subjects

Bella Kaufman

Publications and source records attributed to Bella Kaufman.

13 recordsLinked to original sources

PubMed2006

Lapatinib plus capecitabine for HER2-positive advanced breast cancer.

BACKGROUND: Lapatinib, a tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 (HER2, also referred to as HER2/neu) and epidermal growth factor receptor (EGFR), is active in combination with capecitabine in women with HER2-positive metastatic breast cancer that has progressed after trastuzumab-based therapy. In this trial, we compared lapatinib plus capecitabine with capecitabine alone in such patients. METHODS: Women with HER2-positive, locally advanced or metastatic breast cancer that had progressed after treatment with regimens that included an anthracycline, a taxane, and trastuzumab were randomly assigned to receive either combination therapy (lapatinib at a dose of 1250 mg per day continuously plus capecitabine at a dose of 2000 mg per square meter of body-surface area on days 1 through 14 of a 21-day cycle) or monotherapy (capecitabine alone at a dose of 2500 mg per square meter on days 1 through 14 of a 21-day cycle). The primary end point was time to progression, based on an evaluation by independent reviewers under blinded conditions. RESULTS: The interim analysis of time to progression met specified criteria for early reporting on the basis of superiority in the combination-therapy group. The hazard ratio for the independently assessed time to progression was 0.49 (95% confidence interval, 0.34 to 0.71; P<0.001), with 49 events in the combination-therapy group and 72 events in the monotherapy group. The median time to progression was 8.4 months in the combination-therapy group as compared with 4.4 months in the monotherapy group. This improvement was achieved without an increase in serious toxic effects or symptomatic cardiac events. CONCLUSIONS: Lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline, a taxane, and trastuzumab. (ClinicalTrials.gov number, NCT00078572 [ClinicalTrials.gov].).

Adult↗

PubMed2006

Association between diabetes mellitus and adverse characteristics of breast cancer at presentation.

Type 2 diabetes mellitus is associated with increased incidence and inferior outcome of various malignancies. The aim of this study was to explore the impact of type 2 diabetes on breast cancer characteristics at presentation. The study population included 79 diabetic and 158 age-matched non-diabetic patients. Parity, country of birth, co-morbidity other than diabetes, and mode of diagnosis were similar in both groups. Mean body mass index (BMI) was higher among diabetic patients. Tumour stage and size were higher among diabetic patients and the differences remained significant after adjustment for BMI. Moreover, after adjustment for BMI, breast cancer among diabetic patients was more often hormone receptor negative. Our results show that diabetes mellitus is associated with negative prognostic factors at breast cancer presentation.

Adult↗

PubMed2006

Familial clustering of site-specific cancer risks associated with BRCA1 and BRCA2 mutations in the Ashkenazi Jewish population.

Inherited mutations in BRCA1 and BRCA2 lead to significantly increased risks of breast and ovarian cancer. We used epidemiologic methods to evaluate the relative risks of breast cancer vs. ovarian cancer among women of Ashkenazi Jewish ancestry with inherited mutations in BRCA1 or BRCA2. The cancer of a family's index case (i.e., breast cancer vs. ovarian cancer) was significantly associated with site-specific risks of cancer in relatives known to carry mutations in BRCA1 or BRCA2. Specifically, breast cancer risks were higher among relatives of breast cancer index cases compared with relatives of ovarian cancer index cases [hazard ratio (HR) = 3.0, P < 0.001 for BRCA1 carriers and HR = 4.8, P = 0.017 for BRCA2 carriers], and ovarian cancer risks were higher among relatives of ovarian cancer index cases compared with relatives of breast cancer index cases (HR = 7.2, P = 0.001 for BRCA1 carriers and HR = 15.8, P = 0.018 for BRCA2 carriers). Breast and ovarian cancer risks also increased with more recent year of birth. For each later decade of birth, risk increased 1.2-fold (P = 0.03). Effects of cancer site of the index case and of birth cohort were independent. These results suggest that both genetic and nongenetic factors modify cancer risks among BRCA1 and BRCA2 mutation carriers, and that genetic modifiers and other familial factors may influence risk specifically for either breast or ovarian cancer.

Breast Neoplasms↗

PubMed2006

Adiponectin, ghrelin, and leptin in cancer cachexia in breast and colon cancer patients.

BACKGROUND: The hormone ghrelin and the adipocytokines leptin and adiponectin participate in body weight regulation. In response to weight loss, ghrelin and adiponectin levels increase and leptin decreases. Cancer cachexia is a complex metabolic state, characterized by loss of muscle mass and adipose tissue together with anorexia. The authors hypothesized that responses of these hormones may be attenuated in cancer cachexia. METHODS: Fasting plasma ghrelin, adiponectin, and leptin levels, as well as weight loss, were determined in 40 cancer patients: 18 of them suffered from cancer-induced cachexia, and 22 served as a comparison group. Hormone levels were measured before administration of cancer therapy. RESULTS: A similar distribution of age, gender, and diagnosis was observed in both study groups, but the cachectic patients had higher rates of metastatic disease and lower albumin levels. No significant correlation was observed between plasma adiponectin levels and weight loss. Mean plasma ghrelin levels were higher among cachectic compared with noncachectic patients. Notably, the association between ghrelin levels and weight loss was only modest, and in a third of the cachectic patients, ghrelin levels were equal to or lower than those in the noncachectic group. Plasma leptin levels showed gender-dependent associations, and significantly lower levels were found among cachectic women but not among cachectic men. CONCLUSIONS: Results suggested a gender-dependent attenuation of expected physiologic responses to weight loss among cancer cachexia patients. Thus, impaired response of adiponectin, ghrelin, and leptin may play a role in the pathogenesis of cancer cachexia syndrome.

Adiponectin↗

PubMed2006

The P1812A and P25T BRCA1 and the 5164del4 BRCA2 mutations: occurrence in high-risk non-Ashkenazi Jews.

Founder mutations in the BRCA1 and BRCA2 genes have been discovered in the Ashkenazic Jewish population, but a founder mutation(s) has not been discovered among non-Ashkenazi Jews (NAJ). Two BRCA1 mutations (P1812A, P25T), and a BRCA2 mutation (5164del4) have been detected in NAJ high-risk families. We studied the prevalence of these three mutations in 270 high-risk NAJ families, including 85 from Iraq/Iran, 67 from North Africa, 27 from Yemen, 50 from the Balkan region, and 41 with mixed ancestry. The three mutations were detected only in individuals related to the original families. We conclude that the P1812A and P25T BRCA1 and 5164del4 BRCA2 mutations are not likely to be founder mutations in NAJ high-risk families. We also assessed the pathogenicity of the BRCA1 P1812A mutation in vitro using reporter gene assays in yeast and mammalian cells. We found that the BRCA1 P1812A variant activity assays yielded a slightly reduced reporter gene activity. Thus, there is some uncertainty as to the pathogenicity of BRCA1 P1812A.

Adult↗

PubMed2006

[Body weight, nutritional factors and physical activity--their influence on prognosis after breast cancer diagnosis].

Numerous studies have examined the association between body weight, nutritional factors, physical activity and the risk for primary breast cancer. Relatively few studies, however, have examined the associations between these issues and the recurrence of the disease and cure of the primary tumor. Today, three areas of focus are actively being researched for breast cancer survivors: body weight, diet composition and physical activity with specific emphasis on the risk for recurrence, survival and quality of life. Increased body weight or BMI (Body Mass Index) at diagnosis was found to be a significant risk factor for recurrent disease, decreased survival, or both. Overall obesity has been shown to adversely affect prognosis. Appropriate weight control may be particularly beneficial for breast cancer survivors. Breast cancer survivors should be encouraged to achieve and maintain a healthy weight. Limiting fat intake can reduce the risk of breast cancer recurrence. Increasing consumption of vegetables and fruits seems to have possible beneficial effects during and after treatments. To date physical activity after breast cancer diagnosis has been found to reduce the risk of death. The greatest benefit occurred in women who performed the equivalent of walking 3-5 hours per week at an average pace. Safe weight loss via increased physical activity and healthful food choices should be encouraged for normal, overweight or obese breast cancer survivors in order to improve survival and life quality.

Body Weight↗

PubMed2005

Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme.

Fulvestrant ("Faslodex") is a new oestrogen receptor (ER) antagonist with no agonist effects that is licensed in the USA, Brazil, Europe and elsewhere for the treatment of advanced breast cancer (ABC) in postmenopausal women following progression on other endocrine agents. This report consolidates clinical experience from the "Faslodex" Compassionate Use Programme, including a total of 339 patients treated at eight cancer centres. Patients received fulvestrant as first- (n=22), second- (n=125), third- (n=105), fourth- (n=58), fifth- (n=22) or sixth-line (n=5) hormonal treatment for ABC, with two patients receiving fulvestrant after more than six other endocrine therapies. Objective response was achieved by 40 patients and stable disease lasting 6 months by 92 patients, giving overall clinical benefit (CB) in 132/339 patients (39%). The CB rate decreased as fulvestrant was used later in the sequence of endocrine treatments, from 46% (10/22) with first-line fulvestrant to 27% (6/22) with fifth-line fulvestrant. Increased benefit was found in patients with tumours expressing both ER and progesterone receptor (PgR) compared with other combinations, although good activity was reported in patients expressing either ER or PgR as well as in tumours expressing human epidermal growth factor receptor 2. Fulvestrant was well tolerated; adverse events were noted in 18/339 patients (5%). These findings concur with data from the clinical-trial setting and further support the assertion that greater benefit is derived when fulvestrant is used early in the treatment sequence.

Adult↗

PubMed2005

Breast conservation after neoadjuvant chemotherapy.

BACKGROUND: Tumor downstaging by preoperative neoadjuvant chemotherapy in patients with locally advanced breast tumors allows breast conservation in women who were previously candidates for mastectomy. Nevertheless, lumpectomy success in such cases cannot be fully achieved. The aim of this study was to create a quantitative tool for preoperative evaluation of the success of breast conservation in such patients. METHODS: The study population included 100 consecutive patients with stage II and III breast cancer who were designated for lumpectomy and 19 patients who were designated for mastectomy. All patients received neoadjuvant therapy. Breast-conserving surgery was offered in accordance with clinical and esthetic criteria. Demographic details and clinical, imaging, and pathologic information were collected from medical files. A decision protocol for classifying patients to lumpectomy or mastectomy was built by using the Classification and Regression Trees procedure based on preoperative characteristics. RESULTS: Three factors were found to be the main predictors for successful breast conservation: absence of diffuse microcalcifications as seen in the pretreatment mammogram, a postchemotherapy tumor size of < 25 mm, and the existence of a circumscribed lesion on mammography. CONCLUSIONS: The use of these criteria as a basis for decision on the type of surgery may decrease the performance of unnecessary procedures.

Adult↗

PubMed2005

Motivation for giving birth after breast cancer.

BACKGROUND: Breast cancer at a young age threatens the natural developmental tasks that characterize this phase in life including parenthood. The dilemma of whether to give birth arises due to the potential medical, psychological and social implications of pregnancy, birth and child rearing after breast cancer. The purpose of this study was to investigate the positive and negative motivations toward childbirth of breast cancer survivors and their husbands. METHOD: Thirty breast cancer survivors and 13 husbands were compared to 29 healthy women and 15 husbands. The study included qualitative questions and quantitative measures including: a demographic and medical questionnaire, the Parenthood Motivation Questionnaire--Revised, the ENRICH Marital Satisfaction Scale, the Brief Symptom Inventory, the Impact of Events Scale, and the Mental Adjustment to Cancer Questionnaire. RESULTS: The experience of having breast cancer did not hinder overall positive motivations toward childbirth, nor did it increase overall negative motivations toward childbirth, among women and their husbands. However, there were several differences between the groups, which may reflect the illness experience. For example, breast cancer survivors and their husbands reported more negative motivations toward childbirth due to health concerns than did healthy women and their husbands.

Adult↗

PubMed2005

Diabetes mellitus and breast cancer.

Type 2 diabetes is a serious health problem that affects more than 7% of adults in developed countries. Up to 16% of patients with breast cancer have diabetes, and two major risk factors for type 2 diabetes-old age and obesity-are also associated with breast cancer. Three mechanisms have been postulated to associate diabetes with breast cancer: activation of the insulin pathway, activation of the insulin-like-growth-factor pathway, and regulation of endogenous sex hormones. Comparative cohort studies and case-control studies suggest that type 2 diabetes may be associated with 10-20% excess relative risk of breast cancer. Gestational diabetes mellitus, but not type 1 diabetes, might also be associated with excess risk of breast cancer. Moreover, diabetes and its complications can adversely affect cancer therapy and the use of screening, which will thus affect the outcome of patients with breast cancer.

Breast Neoplasms↗

PubMed2004

[Hormone replacement therapy in breast cancer survivors: the Israeli Society for Clinical Oncology and Radiotherapy policy letter].

The Israeli Society for Clinical Oncology and Radiotherapy appointed experts in breast cancer therapy to assess the Society's policy regarding hormone replacement therapy (HRT) in breast cancer survivors with menopausal symptoms. The first policy letter was published in November 2002, and referred to available literature at that time which included retrospective data alone. The professional literature suggested no increased risk in breast cancer recurrence or cancer specific mortality, and no effect on overall survival with the use of HRT for a limited period (up to 3 years). This data served as the rationale for international prospective studies. Former committee recommendations and precautions are detailed in the original publication. In February 2004, the interim analysis of a prospective trial, the HABIT (Hormonal replacement therapy after breast cancer--is it safe?) was published. In that trial, breast cancer survivors with menopausal symptoms were randomized to HRT (estrogens with or without progestins) or no therapy for 2 years. A total of 434 women were recruited from centers in Scandinavia who participated with the International Breast Cancer and the European Organization for Research and Treatment groups. Analysis was restricted to 345 women with at least one follow up report; median follow-up period was 2.1 years. The relative risk for breast cancer event was 3.5 (95% C.I. 1.5-8.1) in HRT users as compared with the non-HRT group and the HABIT trial was terminated. Study limitations are discussed. Thereby, at this time HRT can no longer be considered safe in breast cancer survivors. Physicians treating breast cancer survivors for severe menopausal symptoms should present study results and alternative non-hormonal treatment options to allow patients optimized consented treatment decisions.

Breast Neoplasms↗

PubMed2002

Male breast carcinoma in Israel: higher incident but possibly prognosis in Ashkenazi Jews.

BACKGROUND: Little information is available regarding male breast carcinoma. However, cumulative data have suggested a propensity for the disease among Ashkenazi Jews. Because Ashkenazi Jews comprise one of the major ethnic groups in Israel, the authors conducted a local study to shed more light on the features of this rare disease. METHODS: From 1960 to 2000, 131 men with breast carcinoma were treated at the Rabin Medical Center or the Rambam Medical Center, and, from 1980 to 1997, 470 patients with this diagnosis were recorded in the Israel Cancer Registry. These two data bases were used to analyze the epidemiologic and clinicopathologic characteristics of male breast carcinoma in Israel. RESULTS: Seventy-eight percent of the 131 Jewish patients were Ashkenazi. Most of their clinical characteristics were similar to those of their Sephardic counterparts. However, there was a statistically significant difference in the pattern of comorbidity between these groups (P = 0.000), and there was a trend toward a younger age at onset and more advanced tumor stage at the time of diagnosis for the Sephardim. It also was found that Sephardic origin was associated with poorer outcome (P = 0.03). Analysis of the Cancer Registry data base revealed an 80% increase in the risk of the disease for Ashkenazi Jews compared with Sephardic Jews (odds ratio, 1.8; 95% confidence interval, 1.4-2.3; P = 0.001). Survival analysis from this source suggested a poorer outcome for Sephardic Jews compared with Ashkenazi Jews (62% vs. 64.3% estimated 5-year survival rates, respectively; P = 0.08). CONCLUSIONS: Analyses of two independent data bases, patient charts, and a cancer registry indicate that breast carcinoma seems to be more prevalent among Ashkenazi Jewish men. At the same time, affected Ashkenazi patients may have a more favorable outcome than their Sephardic counterparts.

Adenocarcinoma↗

PubMed2002

[Hormone replacement therapy in breast cancer survivors: the Israeli Society for Clinical Oncology and Radiotherapy policy letter].

The Israeli Society for Clinical Oncology and Radiotherapy requested that experts in breast cancer therapy assess the Society's policy regarding the use of hormone replacement therapy (HRT) in breast cancer survivors. The following recommendations are based on updated literature, which is limited since it summarizes only retrospective data. There is currently no evidence of an increased risk of breast cancer recurrence, death attributable to cancer, or overall mortality among breast cancer survivors who use HRT. We therefore recommend that there is no need to avoid HRT in women with menopausal symptoms who are interested in receiving such treatment, as long as ovarian ablation does not play a major role in their adjuvant therapy. Women should be informed about the limitations of available data. There are some concerns regarding the use of HRT in patients whose tumors developed while undergoing HRT and in such cases treatment should be reserved only for those with severe menopausal symptoms. For women with milder symptoms or those who are not interested in HRT, other treatment options should be outlined. The policy should be updated according to future publication of results from ongoing randomized prospective studies.

Breast Neoplasms↗