Breast Neoplasms: Brown P

Visvanathan K, Chlebowski RT, Hurley P, Col NF, Ropka M, Collyar D, Morrow M, Runowicz C, Pritchard KI, Hagerty K, Arun B, Garber J, Vogel VG, Wade JL, Brown P, Cuzick J, Kramer BS, Lippman SM, Anonymous00092. · Cancer Policy and Clinical Affairs, 2318 Mill Rd, Suite 800, Alexandria, VA 22314, USA. · J Clin Oncol. · Pubmed #19470930 No free full text.

Abstract: PURPOSE To update the 2002 American Society of Clinical Oncology guideline on pharmacologic interventions for breast cancer (BC) risk reduction. METHODS A literature search identified relevant randomized trials published since 2002. Primary outcome of interest was BC incidence (invasive and noninvasive). Secondary outcomes included BC mortality, adverse events, and net health benefits. An expert panel reviewed the literature and developed updated consensus guidelines. Results Seventeen articles met inclusion criteria. In premenopausal women, tamoxifen for 5 years reduces the risk of BC for at least 10 years, particularly estrogen receptor (ER) -positive invasive tumors. Women < or = 50 years of age experience fewer serious side effects. Vascular and vasomotor events do not persist post-treatment across all ages. In postmenopausal women, raloxifene and tamoxifen reduce the risk of ER-positive invasive BC with equal efficacy. Raloxifene is associated with a lower risk of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen in postmenopausal women. No evidence exists establishing whether a reduction in BC risk from either agent translates into reduced BC mortality. Recommendations In women at increased risk for BC, tamoxifen (20 mg/d for 5 years) may be offered to reduce the risk of invasive ER-positive BC, with benefits for at least 10 years. In postmenopausal women, raloxifene (60 mg/d for 5 years) may also be considered. Use of aromatase inhibitors, fenretinide, or other selective estrogen receptor modulators to lower BC risk is not recommended outside of a clinical trial. Discussion of risks and benefits of preventive agents by health providers is critical to patient decision making.

Speers C, Brown P. · No affiliation provided · J Natl Cancer Inst. · Pubmed #19001596 No free full text.

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Kalidas M, Hilsenbeck S, Brown P. · No affiliation provided · J Natl Cancer Inst. · Pubmed #15572750 links to  free full text

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Wu K, Brown P. · No affiliation provided · J Natl Cancer Inst. · Pubmed #12783921 links to  free full text

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Kalidas M, Brown P. · Breast Care Center, Baylor College of Medicine, Houston, TX 77030, USA. · Clin Breast Cancer. · Pubmed #15899070 No free full text.

Abstract: In a review of current information on aromatase inhibitors (AIs) and their use in breast cancer treatment and prevention, published reports were obtained through a Medline search. Tamoxifen, a selective estrogen receptor modulator, is approved for use in metastatic breast cancer (MBC), the adjuvant treatment of breast cancer, and the prevention of breast cancer in women at high risk. The 50% reduction in breast cancer incidence seen with tamoxifen is significant for women at increased risk but is accompanied by notable toxicities such as thrombotic events and endometrial cancer. Therefore, the development of other effective agents with less toxicity would be a major advance in breast cancer prevention. Aromatase inhibitors, recently approved for the treatment of MBC and in the adjuvant setting, are proving to be slightly more effective than tamoxifen therapy. These drugs, approved for use in only postmenopausal women, inhibit the enzyme aromatase and thereby lower circulating functional estrogen. To date, the most concerning side effect of these agents is an increase in fracture rate. Compared with tamoxifen, thrombotic events and endometrial cancer rates are much lower. Ongoing data from the Arimidex, Tamoxifen, Alone or in Combination trial continue to favor anastrozole over tamoxifen in the reduction of primary contralateral breast cancers. This information has prompted breast cancer chemoprevention trials with AIs. Although tamoxifen is the gold standard for prevention therapy, results of ongoing studies may indicate a role for AIs in the prevention of breast cancer.

Brown P. · Breast Center, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. · Breast J. · Pubmed #15725110 No free full text.

Abstract: With the current understanding of sporadic and familial breast cancer, it is now possible to identify individuals who have a moderate or high risk of breast cancer. For these individuals, it is useful to perform formal cancer risk assessment and develop an individualized risk reduction plan, including a tailored plan for cancer screening, preventive therapy, and/or prophylactic surgery. Assessment using a predictive model such as the Gail model is particularly useful in individuals at increased risk for sporadic breast cancer. In addition, assessment of risk based on histologic appearance of benign or premalignant breast lesions can be used to identify individuals for whom more aggressive risk reduction strategies are warranted. For individuals who are at risk for familial cancer syndromes, other predictive models are more appropriate. For this extremely high-risk group, genetic testing for mutations in familial cancer susceptibility genes is helpful to identify individuals who would benefit from even more aggressive cancer risk reduction strategies. Strategies to identify the levels of risk for breast cancer, including the identification of moderate, high, or very high risk groups are discussed. Management options for these groups are presented, including who to consider for more aggressive screening, chemoprevention, or prophylactic surgery. Current recommendations for screening, chemoprevention, and surgery for each risk group are presented. The ability to identify individuals at high risk for breast cancer now enables clinicians to intervene to reduce the risk of breast cancer. Aggressive screening, preventive therapy, and prophylactic surgery in moderate- to high-risk individuals should, in the future, significantly reduce the incidence of invasive breast cancer.

McCormick S, Brody J, Brown P, Polk R. · Department of Sociology, Brown University, Providence, RI 02912, USA. · Int J Health Serv. · Pubmed #15560426 No free full text.

Abstract: Public involvement in health program planning has been taking place for many years, and has provided a precedent for the emergence of public involvement in research conducted since the early 1990s. Such involvement is now widely seen in breast cancer research, due to the large public concern and major social movement activity. This article reviews current practices and general models of public involvement in research and constructs a prototype. The authors interviewed researchers, program officers, and laypeople in order to understand the obstacles, processes, and benefits. They conclude that public involvement has major ramifications for the democratization of science and the construction of knowledge by teaching lay people about science and sensitizing researchers to concerns of the public. There is growing support on the part of scientists and government agents for public involvement.

Allred DC, Brown P, Medina D. · Breast Center/Department of Pathology, Baylor College of Medicine, Houston, Texas, USA. · Breast Cancer Res. · Pubmed #15535853 links to  free full text

Abstract: Current hormonal therapies have benefited millions of patients with breast cancer. Their success, however, is often temporary and limited to a subset of patients whose tumors express estrogen receptor alpha (ER). The therapies are entirely ineffective in ER-negative disease. Recent studies suggest that there are many biological pathways and alterations involved in determining whether ER is expressed and how it is regulated during breast cancer evolution. Improving hormonal therapies, in addition to perfecting current strategies, will also target these newly discovered pathways and alterations, and others yet to be found. The present commentary will briefly highlight a few important observations and unanswered questions regarding ER status and growth regulation during breast cancer evolution, which hopefully will help to stimulate new thinking and progress in this important area of medial research.

Kramer R, Brown P. · Breast Center, Baylor College of Medicine and the Methodist Hospital, Houston, Texas 77030, USA. · Drug Saf. · Pubmed #15471505 No free full text.

Abstract: Breast cancer is the most commonly diagnosed cancer in women. The risk of developing breast cancer can be lowered by maintaining a healthy bodyweight and avoiding long-term use of combined estrogen and progestogen replacement after menopause. However, many women are at an increased risk of developing breast cancer secondary to age, early menarche, a family history of breast cancer or a personal history of benign breast disease. These women may now be offered tamoxifen as a chemoprevention therapy. Five years of tamoxifen treatment results in a reduction in the relative risk of developing estrogen receptor-positive breast cancer of 48%. This benefit outweighs the risk of tamoxifen-related adverse events for many healthy women. However, the benefit-risk ratio of tamoxifen chemoprevention varies for individual women. The randomized clinical trials evaluating standard-dose tamoxifen versus placebo as chemoprevention therapy are reviewed and analyzed to determine which particular women are most likely to benefit and least likely to experience a tamoxifen-related adverse event. Tamoxifen decreases the risk of breast cancer associated with aging, having a first-degree relative with disease, and a personal diagnosis of atypical ductal hyperplasia or lobular carcinoma in situ. Women who have had a hysterectomy and are at low risk of a thromboembolic event have a decreased risk of adverse effects associated with tamoxifen therapy. The strengths and weaknesses of the Gail model (frequently used to assess an individual's risk of developing invasive breast cancer over the next 5 years) are highlighted. A method for assessing the benefit-risk ratio for an individual woman is presented. Alternative breast cancer chemoprevention strategies are considered, including the use of aromatase inhibitors. This article discusses the pros and cons of these various preventive therapies and concludes that at this time, tamoxifen remains the gold standard for breast cancer prevention.

Yang LM, Tin-U C, Wu K, Brown P. · Department of Medicine, The University of Texas Health Science Center at San Antonio, 78284, USA. · J Mammary Gland Biol Neoplasia. · Pubmed #10705921 No free full text.

Abstract: Retinoids are vitamin A-related compounds that have been found to prevent cancer in animals and humans. In this review, we discuss the role of retinoids and their receptors in the treatment and prevention of breast cancer. The retinoid receptors are expressed in normal and malignant breast cells, and are critical for normal development. In breast cells, when bound by retinoid hormones, these proteins regulate proliferation, apoptosis, and differentiation. The mechanism by which retinoids inhibit breast cell growth has not been completely elucidated, however, retinoids have been shown to affect multiple signal transduction pathways, including IGF-, TGFbeta-, and AP-1-dependent pathways. Retinoids have also been shown to suppress the growth and prevent the development of breast cancer in animals. These agents suppress tumorigenesis in carcinogen-treated rats and in transgenic mice, and inhibit the growth of transplanted breast tumors. These promising preclinical results have provided the rationale to test retinoids in clinical trials for the treatment and prevention of breast cancer. Several retinoids, including all trans retinoic acid and 9-cis retinoic acid, have been shown to have modest activity in the treatment of breast cancer, and these agents are now in clinical trials in combination with cytotoxic agents and anti-estrogens. Another retinoid, 4-HPR, is currently being tested in a human cancer prevention trial. Preliminary results suggest that 4-HPR may suppress breast cancer development in premenopausal women. Future clinical trials will focus on testing new synthetic retinoids that have reduced toxicity and enhanced therapeutic and preventive efficacy.

Brody JG, Morello-Frosch R, Brown P, Rudel RA, Altman RG, Frye M, Osimo CA, Pérez C, Seryak LM. · Silent Spring Institute, Newton, MA 0245, USA. · Am J Public Health. · Pubmed #17666695 No free full text.

Abstract: The recent flood of research concerning pollutants in personal environmental and biological samples-blood, urine, breastmilk, household dust and air, umbilical cord blood, and other media-raises questions about whether and how to report results to individual study participants. Clinical medicine provides an expert-driven framework, whereas community-based participatory research emphasizes participants' right to know and the potential to inform action even when health effects are uncertain. Activist efforts offer other models. We consider ethical issues involved in the decision to report individual results in exposure studies and what information should be included. Our discussion is informed by our experience with 120 women in a study of 89 pollutants in homes and by interviews with other researchers and institutional review board staff.

Liby K, Rendi M, Suh N, Royce DB, Risingsong R, Williams CR, Lamph W, Labrie F, Krajewski S, Xu X, Kim H, Brown P, Sporn MB. · Dartmouth Medical School, Hanover, NH 03755, USA. · Clin Cancer Res. · Pubmed #17020999 links to  free full text

Abstract: PURPOSE: We tested whether a selective estrogen receptor modulator (SERM) and a rexinoid are active for prevention and treatment in the mouse mammary tumor virus-neu mouse model of estrogen receptor-negative breast cancer. EXPERIMENTAL DESIGN: For prevention, mice were fed a powdered control diet, the SERM arzoxifene (Arz, 20 mg/kg diet), the rexinoid LG100268 (268, 30 mg/kg diet), or the combination for 60 weeks. In a second prevention study, mice were fed Arz (6 mg/kg diet), 268 (30 mg/kg diet), the combination of Arz and 268, the SERM acolbifene (Acol, 3 mg/kg diet), or the combination of Acol and 268 for 52 weeks. For the treatment studies, mice with tumors were fed combinations of a SERM and 268 for 4 weeks. RESULTS: The rexinoid 268 and the SERMs Arz and Acol, as individual drugs, delayed the development of estrogen receptor-negative tumors. Moreover, the combination of a SERM and 268 was strikingly synergistic, as no tumors developed in any mouse fed the combination of 268 and a SERM. Moreover, this drug combination also induced significant tumor regression when used therapeutically. These drugs did not inhibit transgene expression in vitro or in vivo, and the combination of Arz and 268 inhibited proliferation and induced apoptosis in the tumors. CONCLUSION: The combination of a rexinoid and SERM should be considered for future clinical trials.

Medina D, Kittrell FS, Hill J, Shepard A, Thordarson G, Brown P. · Baylor College of Medicine, Houston, TX 77030, USA. · Cancer Res. · Pubmed #15833886 links to  free full text

Abstract: Tamoxifen reduces the relative risk of breast cancer developing from specific premalignant lesions. Many breast cancers that arise after tamoxifen treatment are estrogen receptor-alpha (ER-alpha)-negative, although premalignant lesions such as atypical ductal hyperplasia are highly ER-alpha-positive. The p53 null mouse mammary epithelial transplant model is characterized by ER-alpha-positive premalignant lesions that give rise to both ER-alpha-positive and ER-alpha-negative tumors. Given this progression from ER-alpha-positive to ER-alpha-negative lesions, we tested the ability of tamoxifen to block or delay mammary tumorigenesis in several versions of this model. In groups 1 and 2, p53 null normal mammary epithelial transplants were maintained in virgin mice. In groups 3 to 5, the p53 null and mammary transplants were maintained in mice continuously exposed to high levels of progesterone. In groups 6 and 7, transplants of the premalignant outgrowth line PN8a were maintained in virgin mice. Tamoxifen blocked estrogen signaling in these mice as evidenced by decreases in progesterone-induced lateral branching and epithelial proliferation in the mammary epithelium. Tamoxifen did not alter the elevated levels of progesterone in the blood while significantly reducing the circulating level of prolactin. Tamoxifen reduced tumor incidence in p53 null normal mammary epithelial transplants maintained in virgin mice from 55% to 5% and in progesterone-stimulated mice from 81% to 21%. The majority of the resultant tumors were ER-alpha-negative. Tamoxifen also significantly delayed tumorigenesis in the ER-alpha-positive high premalignant line PN8a from 100% to 75%. These results show that tamoxifen delays the emergence of ER-alpha-negative tumors if given early in premalignant progression.

Ellsworth RE, Ellsworth DL, Neatrour DM, Deyarmin B, Lubert SM, Sarachine MJ, Brown P, Hooke JA, Shriver CD. · Clinical Breast Care Project, Windber Research Institute, Windber, PA 15963, USA. · Mol Cancer Res. · Pubmed #15755873 links to  free full text

Abstract: Axillary lymph node status is the most important prognostic factor in predicting disease outcome in women with breast cancer. A number of chromosomal aberrations in primary breast tumors have been correlated with lymph node status and clinical outcome, but chromosomal changes particular to metastatic lymph node tumors have not been well studied. DNA samples isolated from laser-microdissected primary breast and metastatic axillary lymph node tumors from 25 women with invasive breast cancer were amplified using 52 microsatellite markers defining 26 chromosomal regions commonly deleted in breast cancer. Levels and patterns of allelic imbalance (AI) within and between breast and lymph node tumors were assessed to identify chromosomal alterations unique to primary or metastatic tumors and to examine the timing of metastatic potential. The overall frequency of AI in primary breast tumors (0.24) was significantly greater (P < 0.001) than that in lymph node tumors (0.10), and congruent AI events were observed for < 20% of informative markers. AI at chromosomes 11q23.3 and 17p13.3 occurred significantly more frequently (P < 0.05) in primary breast tumors alone; no chromosomal regions showed a significantly higher AI frequency in lymph nodes. Higher rates of AI in primary versus metastatic lymph node tumors suggest that acquisition of metastatic potential may be an early event in carcinogenesis, occurring before significant levels of AI accumulate in the primary tumor. In addition, patterns of AI were highly discordant between tumor types, suggesting that additional genetic alterations accumulated independently in the two cell populations.

Fox SB, Brown P, Han C, Ashe S, Leek RD, Harris AL, Banham AH. · Nuffield Department Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, UK. · Clin Cancer Res. · Pubmed #15161711 links to  free full text

Abstract: PURPOSE: The FOXP1 protein belongs to a functionally diverse family of winged-helix or forkhead transcription factors that have diverse roles in cellular proliferation, differentiation, and neoplastic transformation. The FOXP1 gene, which maps to 3p14, shows common loss of heterozygosity in breast tumors and is a candidate tumor suppressor gene. However, its role in breast cancer is unknown. EXPERIMENTAL DESIGN: We have therefore investigated the pattern of FOXP1 expression in whole sections from normal (n = 16) and neoplastic (n = 90) breast tissues and correlated the level of expression in 283 invasive breast carcinomas on tissue microarrays with clinicopathological factors and survival. Because a relationship with estrogen receptor (ER) was identified, estrogen (17beta-estradiol) regulation and ER/FOXP1 colocalization was also investigated. RESULTS: Expression of FOXP1 was significantly positively associated with ER (P = 0.03) and negatively with epidermal growth factor receptor (P = 0.01) but no association with age (P = 0.91), lymph node status (P = 0.94), size (P = 0.76), or grade (P = 0.22). In a multivariate analysis of survival, FOXP1 expression was associated with a significantly improved relapse-free (P = 0.03) and borderline overall (P = 0.09) survival. Unlike normal breast, there was common coexpression of FOXP1 and ER in cell lines and tumors, but no 17beta-estradiol (10(-9) m) regulation of FOXP1 in MCF-7 cells was demonstrated. CONCLUSIONS: Our findings support a role for FOXP1 as a potential ER coregulator in human breast carcinoma and suggest that it may also independently regulate additional important pathways that control the progression of breast cancer.

Brown P, Zavestoski S, McCormick S, Mayer B, Morello-Frosch R, Gasior Altman R. · Department of Sociology, Brown University, Providence, RI 02912, USA. · Sociol Health Illn. · Pubmed #15027990 No free full text.

Abstract: Social movements organised around health-related issues have been studied for almost as long as they have existed, yet social movement theory has not yet been applied to these movements. Health social movements (HSMs) are centrally organised around health, and address: (a) access to or provision of health care services; (b) health inequality and inequity based on race, ethnicity, gender, class and/or sexuality; and/or (c) disease, illness experience, disability and contested illness. HSMs can be subdivided into three categories: health access movements seek equitable access to health care and improved provision of health care services; constituency-based health movements address health inequality and health inequity based on race, ethnicity, gender, class and/or sexuality differences; and embodied health movements (EHMs) address disease, disability or illness experience by challenging science on etiology, diagnosis, treatment and prevention. These groups address disproportionate outcomes and oversight by the scientific community and/or weak science. This article focuses on embodied health movements, primarily in the US. These are unique in three ways: 1) they introduce the biological body to social movements, especially with regard to the embodied experience of people with the disease; 2) they typically include challenges to existing medical/scientific knowledge and practice; and 3) they often involve activists collaborating with scientists and health professionals in pursuing treatment, prevention, research and expanded funding. This article employs various elements of social movement theory to offer an approach to understanding embodied health movements, and provides a capsule example of one such movement, the environmental breast cancer movement.

Ip C, Brown P. · Dept. of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. · J Mammary Gland Biol Neoplasia. · Pubmed #14587859 No free full text.

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Brown P, Allen AR. · Cancer Prevention and Control, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, USA. · W V Med J. · Pubmed #12645281 No free full text.

Abstract: Researchers have found a consistent relationship between a number of diseases, including diabetes, heart disease, high blood pressure and stroke. Although study results related to cancer have been conflicting, with some showing an increased risk and others not showing such an association, obesity does appear to increase the risk of cancers of the breast, colon, prostate, endometrium, cervix, ovary, kidney and gallbladder. Studies have also found an increased risk for cancers of the liver, pancreas, rectum and esophagus. Although there are many theories about how obesity increases cancer risk, the exact mechanisms are not known. They may be different for different types of cancer. In addition, because obesity develops through a complex interaction of heredity and lifestyle factors, researchers may not be able to tell whether the obesity or something else led to the development of cancer.

van de Rijn M, Perou CM, Tibshirani R, Haas P, Kallioniemi O, Kononen J, Torhorst J, Sauter G, Zuber M, Köchli OR, Mross F, Dieterich H, Seitz R, Ross D, Botstein D, Brown P. · L235 Department of Pathology, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA. · Am J Pathol. · Pubmed #12466114 links to  free full text

Abstract: While several prognostic factors have been identified in breast carcinoma, the clinical outcome remains hard to predict for individual patients. Better predictive markers are needed to help guide difficult treatment decisions. In a previous study of 78 breast carcinoma specimens, we noted an association between poor clinical outcome and the expression of cytokeratin 17 and/or cytokeratin 5 mRNAs. Here we describe the results of immunohistochemistry studies using monoclonal antibodies against these markers to analyze more than 600 paraffin-embedded breast tumors in tissue microarrays. We found that expression of cytokeratin 17 and/or cytokeratin 5/6 in tumor cells was associated with a poor clinical outcome. Moreover, multivariate analysis showed that in node-negative breast carcinoma, expression of these cytokeratins was a prognostic factor independent of tumor size and tumor grade.

Friedell GH, Rubio A, Maretzki A, Garland B, Brown P, Crane M, Hickman P. · Markey Cancer Center, Cancer Control Program, University of Kentucky, 2365 Harrodsburg Road, Suite A230, Lexington, KY 40504, USA. · J Health Care Poor Underserved. · Pubmed #11217227 No free full text.

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Bush NE, Wooldridge J, Foster V, Shaw K, Brown P. · Fred Hutchinson Cancer Research Center, Seattle, WA, USA. · Oncol Nurs Forum. · Pubmed #10382184 No free full text.

Abstract: PURPOSE/OBJECTIVES: To explore the development of a customized Web site to assist Breast and Cervical Health Program (BCHP) outreach staff in a community screening program and to evaluate the Internet knowledge and access issues and barriers of outreach staff during a two-year period using the Web site. DESIGN: Knowledge, access issues and barriers, and descriptive questionnaires. SETTINGS: Comprehensive cancer center in Seattle, WA, workshops, and presentations around the state. SAMPLE: BCHP outreach workers, screening coordinators, and almost exclusively public health nurses from regional health districts and program-contracted clinics. METHOD: Web site development was based on continuous input from sample. Detailed descriptions of computer and Internet resources and opinions about the use and usefulness of the BCHP Web site came from a 1996 evaluation and 1998 follow-up conducted using mailed and online Web questionnaires. "Hits" to the Web site were monitored monthly. MAIN RESEARCH VARIABLES: Computer and Internet resources were used along with monthly Web site traffic and opinions about the use and usefulness of the BCHP Web site in the outreach program. FINDINGS: Use of the BCHP Web site has risen steadily over two years to reach a stable plateau. User evaluations show a marked increase in the adoption of the Internet as a working tool. Users believe the Internet is becoming increasingly important to their work. More training and familiarization with the Web is needed. CONCLUSIONS: The Web is an efficient medium for improving communication and providing easy access to resources within the BCHP program. IMPLICATIONS FOR NURSING PRACTICE: Public health programs with meager resources can benefit from the relatively inexpensive use of customized and versatile Web sites.

Brown P. · No affiliation provided · BMJ. · Pubmed #11021849 links to  free full text

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