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The article reports on the debate and research spurred by decline in breast cancer due to decline in use of hormone. A study presented at a breast cancer symposium reported that the decline in incidence of breast cancer from 2002 to 2003 may have resulted form the fall in postmenopausal hormone use in the same period. Peter Ravdin of University of Texas and his colleagues have used data from the Surveillance, Epidemiology, and End Result (SEER) database.

The article discusses the possible link of the drop in hormone therapy (HT) use to declining breast cancer rates. Anderson Cancer Center researcher Peter Ravdin explained at the 2007 North American Medical Society conference that clinical trial evidence show that combined estrogen/progestin use pose a particular risk for breast cancer. Their study showed that while a 50% drop in HT use due to reports linking HT use to a higher breast cancer risk could be the cause for changes in breast cancer rates, other causes can not be excluded.

The classic treatises, as well as the latest studies regarding the breast neoplasms emphasize the importance of several favorable factors in the genesis of the breast neoplasm. The physiological personal history (age of the patient, age of first menstruation, late menopause, late-life sex, reduced breastfeeding, etc.), the personal pathological history, the heredocolateral history (breast, uterine neoplasia, other neoplasms) play a significant role, as well as the living and working conditions (stress, smoking, coffee, alcohol consumption), and dietary factors (hyper-lipidemic and hypoproteinemia regimens). In order to evaluate the impact of these factors in the etiopathogenesis of breast cancer, we fol-lowed their incidence in a prospective study performed on the cases of breast neoplasm hospital-ized and surgically performed in the period between 2012-2018 in the 1st Surgery Clinic. [ABSTRACT FROM AUTHOR]

Background: The discovery of nonsteroidal antiestrogens created a new group of medicines looking for an application; however, at the time, cytotoxic chemotherapy was the modality of choice to treat all cancers. Antiestrogens were orphan drugs until 1971, with the passing of the National Cancer Act. This enabled laboratory innovations to aid patient care. Methods: This article traces the strategic application of tamoxifen to treat breast cancer by targeting the estrogen receptor (ER), deploying long-term adjuvant tamoxifen therapy, and becoming the first chemopreventive for any cancer. Laboratory discoveries from the University of Wisconsin Comprehensive Cancer Center (UWCCC) are described that address a broad range of biological issues with tamoxifen. These translated to improvements in clinical care. Results: Tamoxifen was studied extensively at UWCCC in the 1980s for the development of acquired resistance to long-term therapy. Additionally, the long-term metabolism of tamoxifen and regulation of growth factors were also studied. A concern with tamoxifen use for chemoprevention was that an antiestrogen would increase bone loss and atherosclerosis. Laboratory studies with tamoxifen and keoxifene (subsequently named raloxifene) demonstrated that 'nonsteroidal antiestrogens' maintained bone density, and this translated into successful clinical trials with tamoxifen at UWCCC. However, tamoxifen also increased endometrial cancer growth; this discovery in the laboratory translated into changes in clinical care. Selective estrogen receptor modulators (SERMs) were born at UWCCC. Conclusions: There are now five US FDA-approved SERMs, all with discovery origins at UWCCC. Women's health was revolutionized as SERMs have the ability to treat multiple diseases by switching target sites around a woman's body on or off. [ABSTRACT FROM AUTHOR]

Early pregnancy in women by the age of 20 is known to have a profound effect on reduction of lifelong breast cancer risk as compared to their nulliparous counterparts. Additional pregnancies further enhance the protection against breast cancer development. Nationwide trend of delayed pregnancy may contribute to the recently reported increase in the incidence of advanced breast cancer among young women in this country. The underlying mechanism for the parity-associated reduction of breast cancer risk is not clearly understood. The purpose of the current study is to use whole-genome DNA methylation profiling to explore a potential association between parity and epigenetic changes in breast tissue from women with early parity and nulliparity. Breast tissue was collected from age-matched cancer-free women with early parity (age < 20; n = 15) or nulliparity ( n = 13). The methyl-CpG binding domain-based capture-sequencing technology was used for whole-genome DNA methylation profiling. Potential parity-associated hypermethylated genes were further verified by locus-specific pyrosequencing, using an expanded cohort of parous ( n = 19) and nulliparous ( n = 16) women that included the initial samples used in the global analysis. Our study identified six genes that are hypermethylated in the parous group ( P < 0.05). Pyrosequencing confirmed parity-associated hypermethylation at multiple CpG islands of the FOXA1 gene, which encodes a pioneer factor that facilitates chromatin binding of estrogen receptor α. Our work identifies several potential methylation biomarkers for parity-associated breast cancer risk assessment. In addition, the results are consistent with the notion that parity-associated epigenetic silencing of FOXA1 contributes to long-term attenuation of the estrogenic impact on breast cancer development. [ABSTRACT FROM AUTHOR]

There appears to be a broad consensus that estrogen is a cause of breast cancer. Proof of cause and effect in clinical medicine requires a different approach for an epidemiological exposure (a 'mosaic' approach) than for an infectious agent suspected of causing a particular disease (a 'chain of evidence' approach). This paper discusses the differences between these two approaches in determining the relationship between a risk factor and a disease, and assesses the strength of the data linking estrogen with breast cancer. Analysis of existing data, including findings from the Women's Health Initiative, finds that all nine of the criteria necessary for confirming the epidemiological strength of a risk factor are not met in the case of estrogen, raising serious questions about the validity of this widespread assumption. [ABSTRACT FROM AUTHOR]

The Oncotype DX Recurrence Score (RS) is a validated genomic predictor of outcome and response to adjuvant chemotherapy in ER-positive breast cancer. Adjuvant! was developed using SEER registry data and results from the Early Breast Cancer Clinical Trialists' overview analyses to estimate outcome and benefit from adjuvant hormonal therapy and chemotherapy. In this report we compare the prognostic and predictive utility of these two tools in node-negative, ER-positive breast cancer. RS and Adjuvant! results were available from 668 tamoxifen-treated NSABP B-14 patients, 227 tamoxifen-treated NSABP B-20 patients, and 424 chemotherapy plus tamoxifen-treated B-20 patients. Adjuvant! results were also available from 1952 B-20 patients. The primary endpoint was distant recurrence-free interval (DRFI). Cox proportional hazards models were used to compare the prognostic and predictive utility of RS and Adjuvant!. Both RS ( P < 0.001) and Adjuvant! ( P = 0.002) provided strong independent prognostic information in tamoxifen-treated patients. Combining RS and individual clinicopathologic characteristics provided greater prognostic discrimination than combining RS and the composite Adjuvant!. In the B-20 cohort with RS results ( n = 651), RS was significantly predictive of chemotherapy benefit (interaction P = 0.031 for DRFI, P = 0.011 for overall survival [OS], P = 0.082 for disease-free survival [DFS]), but Adjuvant! was not (interaction P = 0.99, P = 0.311, and P = 0.357, respectively). However, in the larger B-20 sub-cohort ( n = 1952), Adjuvant! was significantly predictive of chemotherapy benefit for OS (interaction P = 0.009) but not for DRFI ( P = 0.219) or DFS ( P = 0.099). Prognostic estimates can be optimized by combining RS and clinicopathologic information instead of simply combining RS and Adjuvant!. RS should be used for estimating relative chemotherapy benefit. [ABSTRACT FROM AUTHOR]

The author comments on the studies on neural networks and sensors. The author wonders on the possibility of the study to be applied in addressing medical applications such as breast cancer. He knows several applications of neural networks in breast cancer in such an instance when a developed website was created that offer predictions of survival probability among cancer patients. The author hopes for an artificial neural network (ANN) expert to investigate on ductal carcinoma in-situ (DCIS).

Background: Many oncologists consult the Adjuvant! prognostic model to communicate risk with breast cancer patients; however, little is known about how effective that communication is.Methods: The authors analyzed this small data set featuring 20 breast cancer patients' risk estimates, focusing on rankings or gist of the estimates.Results: Overall, there was no gain in the accuracy of patient rankings. The number of patients with more accurate estimates was matched by the number of patients with less accurate estimates after consultation.Conclusions: The current methods used by oncologists to present Adjuvant! risks were not effective in helping patients to get the gist of their risks. [ABSTRACT FROM AUTHOR]

The human epidermal growth factor receptor (HER-2) oncogene encodes a transmembrane tyrosine kinase receptor that has evolved as a major classifier of invasive breast cancer and target of therapy for the disease. The validation of the general prognostic significance of HER-2 gene amplification and protein overexpression in the absence of anti-HER-2 targeted therapy is discussed in a study of 107 published studies involving 39,730 patients, which produced an overall HER-2-positive rate of 22.2% and a mean relative risk for overall survival (OS) of 2.74. The issue of HER-2 status in primary versus metastatic breast cancer is considered along with a section on the features of metastatic HER-2-positive disease. The major marketed slide-based HER-2 testing approaches, immunohistochemistry, fluorescence in situ hybridization, and chromogenic in situ hybridization, are presented and contrasted in detail against the background of the published American Society of Clinical Oncology--College of American Pathologists guidelines for HER-2 testing. Testing issues, such as the impact of chromosome 17 polysomy and local versus central HER-2 testing, are also discussed. Emerging novel HER-2 testing techniques, including mRNA-based testing by real-time polymerase chain reaction and DNA microarray methods, HER-2 receptor dimerization, phosphorylated HER-2 receptors, and HER-2 status in circulating tumor cells, are also considered. A series of biomarkers potentially associated with resistance to trastuzumab is discussed with emphasis on the phosphatase and tensin homologue deleted on chromosome ten/Akt and insulin-like growth factor receptor pathways. The efficacy results for the more recently approved small molecule HER- 1/HER-2 kinase inhibitor lapatinib are also presented along with a more limited review of markers of resistance for this agent. Additional topics in this section include combinations of both anti-HER-2 targeted therapies together as well as with novel agents including bevacizumab, everolimus, and tenespimycin. A series of novel HER-2-targeting agents is also presented, including pertuzumab, ertumaxomab, HER-2 vaccines, and recently discovered tyrosine kinase inhibitors. Biomarkers predictive of HER-2 targeted therapy toxicity are included, and the review concludes with a consideration of HER-2 status in the prediction of response to non-HER-2 targeted treatments including hormonal therapy, anthracyclines, and taxanes. [ABSTRACT FROM AUTHOR]

The table of contents for the December 2007 issue of the journal "Clinical Cancer Update: 2007 in Review" is presented.

This section presents comments on studies published in "Science" on the discovery of a BRCA1-binding protein named RAP80, which directs BRCA1 to the site of double-stranded DNA (dsDNA) breaks. The editors claim that RAP80 contains a tandem ubiquitin-interacting motif, and both research groups showed that binding of ubiquitin is necessary for the location of RAP80 to the damage-induce foci.

This section presents comments on several studies on the risks associated with primary disease. The editor argues that it seems highly unlikely that the observed reduction in breast cancer incidence in the U.S. represents a direct effect of the change in hormone replacement therapy (HRT) use only one or two years before on malignancy initiation. He adds that the relationship between ever-use of progestagen and breast cancer risk did not vary by previous use of oral contraceptives.

Although patients diagnosed with axillary node-negative estrogen receptor-positive breast cancer have an excellent prognosis, about 15% of them fail after 5 years of tamoxifen treatment. Clinical trials have provided evidence that there is a significant benefit from chemotherapy for these patients, but it would be significant overtreatment if all of them were treated with chemotherapy. Therefore, context-specific prognostic assays that can identify those who need chemotherapy in addition to tamoxifen, or those who are essentially cured by tamoxifen alone, and can be performed using routinely processed tumor biopsy tissue would be clinically useful. Using a stepwise approach of going through independent model-building and validation sets, a 21-gene recurrence score (RS), based on monitoring of mRNA expression levels of 16 cancer-related genes in relation to five reference genes, has been developed. The RS identified approximately 50% of the patients who had excellent prognosis after tamoxifen alone. Subsequent study suggested that high-risk patients identified with the RS preferentially benefit from chemotherapy. Ideally the RS should be used as a continuous variable. A prospective study--the Trial Assigning Individualized Options for Treatment (Rx) (TAILORx)--to examine whether chemotherapy is required for the intermediate-risk group defined by the RS is accruing in North America. [ABSTRACT FROM AUTHOR]

Background: To determine whether a dose-dense regimen improves outcome in early breast cancer patients, we compared outcomes with the same fluorouracil, epirubicin, and cyclophosphamide (FEC) chemotherapeutic regimen administered every 3 weeks (FEC21) or administered every 2 weeks (FEC14 including support with filgrastim, a granulocyte colony-stimulating factor) in a multicenter phase III randomized trial. Methods: A total of 1214 patients with early-stage breast cancer were randomly assigned to receive six cycles of FEC14 (604 patients) or of FEC21 (610 patients). Study endpoints were overall survival and event-free survival. Associations were assessed by multivariable analysis with adjustment for age; tumor size; grade; proliferative rate; and menopausal, lymph node, estrogen receptor, and progesterone receptor status. All statistical tests were two-sided. Results: Patients in the FEC14 arm had fewer dose reductions or treatment delays or discontinuation (26%) than those in the FEC21 arm (33%) (difference = 7%, 95% confidence interval [CI] = 2% to 12%; P = .008). FEC14 therapy, compared with FEC21 therapy, was associated with more asthenia (36% versus 29%, difference = 7%, 95% CI = 2% to 12%; P = .01), bone pain (33% versus 4%, difference = 29%, 95% CI = 25% to 33%; P<.001), anemia (38% versus 19%, difference = 19%, 95% CI = 14% to 24%; P<.001), and thrombocytopenia (8% versus 2%, difference = 6%, 95% CI = 4% to 9%; P<.001), but with less leukopenia (12% versus 45%, difference =33%, 95% CI = 28% to 37%; P<.001). No acute myelogenous leukemia or myelodysplastic syndrome was observed. At a median follow-up of 10.4 years, no statistically significant difference in the hazard of death (hazard ratio [HR] =0.87,95% CI = 0.67 to 1.13) or recurrence (HR =0.88,95% CI = 0.71 to 1.08) was found between FEC14 and FEC21 groups after adjustment by multivariable analysis. Although the study was underpowered for subset analysis, we found no evidence that the effect of the treatment type was associated with any of the potential prognostic factors. Conclusion: Our results support the long-term safety of FEC14 chemotherapy as an adjuvant treatment of breast cancer. However, this therapy wits not associated with improved outcome, but because of the limited statistical power of our study, we cannot rule out a modest improvement in outcome associated with FEC14 therapy. [ABSTRACT FROM AUTHOR]

Data from several large adjuvant breast cancer chemotherapy trials suggest that anthracycline-based chemotherapies relative to non-anthracycline-based adjuvant therapies are particularly effective in patients whose tumors overexpress Her2. Most trials show some evidence of this effect, but the interaction generally has not been confirmed statistically, perhaps because the trials are underpowered. In addition, there have been a multiplicity of Her2 immunohistochemistry techniques used in these studies, which are clearly not of equivalent utility in detecting this effect. Thus, while there is good evidence that further work in this area will be of value, at this time the results are inconclusive and not ready for clinical application. [ABSTRACT FROM AUTHOR]

Objective: Our goal was to provide health-care providers, patients, and the general public with an assessment of currently available data regarding the use of adjuvant therapy for breast cancer. Participants: The participants included a non-Federal, non-advocate, 14-member panel representing the fields of oncology, radiology, surgery, pathology, statistics, public health, and health policy as well as patient repro resentatives. In addition, 30 experts in medical oncology, radiation oncology, biostatistics, epidemiology, surgical oncology, and clinical trials presented data to the panel and to a conference audience of 1000. Evidence: The literature was searched with the use of MEDLINE® for January 1995 through July 2000, and an extensive bibliography of 2230 references was provided to the panel. Experts prepared abstracts for their conference presentations with relevant citations from the literature. Evidence from randomized clinical trials and evidence from prospective studies were given precedence over clinical anecdotal experience. Consensus Process: The panel, answering predefined questions, developed its conclusions based on the evidence presented in open forum and the scientific literature. The panel composed a draft statement, which was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately after its release at the conference and was updated with the panel's final revisions. The statement is available at http://consensus.nih.gov. Conclusions: The panel concludes that decisions regarding adjuvant hormonal therapy should be based on the presence of hormone receptor protein in tumor tissues. Adjuvant hormonal therapy should be offered only to women whose tumors... [ABSTRACT FROM AUTHOR]

Focuses on the conference statement on the use of adjuvant therapy for breast cancer in the United States. Aims of the National Institutes of Health Consensus Development conference; Availability of adjuvant therapy to women with tumors expressing hormone receptor protein; Inclusion of anthracyclines in the adjuvant chemotherapy regimens.

Objective To identify variables within the patient-oncologist communication pattern that impact overall patient comprehension and satisfaction within the breast cancer adjuvant therapy (AT) setting. Setting and participants Fifty patients were recruited from a number of academic and community-based oncology practices. Fifteen oncologists participated. Main variables Three communication variables were identified: percentage of total utterances spoken by the patient, percentage of total physician utterances that were coded as affective (i.e. emotional), and total number of questions asked by the patient during the consultation. Knowledge and satisfaction were assessed by a variety of outcome measures, including knowledge items and satisfaction as measured by VASs, the satisfaction with decision scale and the decisional conflict scale. Results The level of patient knowledge about breast cancer and satisfaction with the clinical encounter showed a tendency to correlate with the variables measuring aspects of patient-physician communication style. Patients who spoke more or asked more questions tended to be more knowledgeable whilst patients whose physicians used more affective language tended to know less but to be more satisfied with their clinical encounter. Conclusions In order to optimize patients’ degree of comprehension and satisfaction with their breast cancer adjuvant therapy, physicians need to increase their affective participation in clinical encounters whilst encouraging patients to ask questions and to actively participate in the decision-making process. [ABSTRACT FROM AUTHOR]