Breast cancer online : BCO最新文献

{"title":"The 3rd InterAmerican Breast Cancer Conference Fiesta Americana Grand Coral Beach Hotel, Cancun, Mexico July 27–29, 2006","authors":"S. Glück","doi":"10.1017/S1470903106005682","DOIUrl":"https://doi.org/10.1017/S1470903106005682","url":null,"abstract":"The 3rd InterAmerican Breast Cancer Conference took place in Cancun, Mexico in the Fiesta Americana Grand Coral Beach Hotel from July 27–29, 2006. The meeting followed on from successful meetings which were held in 2002 and 2004. Over those years, the participation increased from 200 to over 450 active participants at the 2006 meeting. Delegates from 36 countries from the Americas, Europe and Asia participated. Not only oncologists (surgical, radiation and medical), but also nurses and support staff were present and enjoyed the wonderful environment and the high level of scientific and clinical meetings. The first day, Thursday July 27, the morning session was chaired by Dr. Hortobagyi from MD Anderson Cancer Center and Dr. Stefan Glück, University of Miami, Sylvester Cancer Center, Dr. Judy Garber presented on epidemiology of breast cancer as well as assessment of women who are on high risk of getting this dreadful disease. Modifying risk factors and management was also identified. Dr. Umberto Veronesi who has been called the father of modern breast cancer therapy, summarized the state of the art sentinel lymphnode biopsy of the axilla as well as internal mammary lymph nodes. We have learned over the last several decades that ‘more’ is not necessary ‘better’, which includes surgery, radiation and chemotherapy. This is also true for the surgery of the axilla. Sentinel lymphnode biopsy now is here to stay and clear guidelines can be established. Many questions remain unanswered, but these are all subject of well designed clinical trials. Dr. Stefan Glück, summarized all adjuvant trastuzumab trials. It is clear that all five studies published or presented thus far show a relative risk reduction of recurrences by adding trastuzumab [Herceptin®] to current adjuvant treatments by approximately 50–60%. This is the case after short period of observation (in 2 years) and translates into survival benefit. The only major side effect that needs special attention is the potential cardiotoxicity reported up to 40% of all cases. The highlight of the day was the presentation of the second Umberto Veronesi award for the future fight against breast cancer. Dr. Denis Slamon is the second awardee (after Dr. Hortobagyi in 2004). Consequently, Dr. Hortobagyi introduced Dr. Denis Slamon’s lifetime achievements regarding breast cancer and introduced the speaker. The keynote lecture of Dr. Slamon was ‘The future of breast cancer: a visionary view’. Dr. Slamon summarized the discovery and development of the proto-oncogene c-ERB-B2 in breast cancer, its protein HER2, and the development of targeted therapy which ultimately culminated in the adjuvant studies that Dr. Glück presented. Following Dr. Slamon’s lecture, the award was presented to him by Professor Veronesi, Dr. Silva, Dr. Hortobagyi and Dr. Glück. In the lunch break, questions from the audience and prepared cases were discussed in the adjuvant therapy of breast cancer with Drs. Hortobagyi, Slamon, Sartor and Bal","PeriodicalId":89901,"journal":{"name":"Breast cancer online : BCO","volume":"12 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2006-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S1470903106005682","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56920821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basic science (April 2006)","authors":"R. Sutherland, J. Scorer","doi":"10.1017/S1470903106005657","DOIUrl":"https://doi.org/10.1017/S1470903106005657","url":null,"abstract":"1. Amlal H, Faroqui S, Balasubramaniam A, Sheriff S. Estrogen up-regulates neuropeptide YY1 receptor expression in a human breast cancer cell line. Cancer Res 2006; 66: 3706–3714. 2. Aneja R, Lopus M, Zhou J, Vangapandu SN, Ghaleb A, Yao J, Nettles JH, Zhou BF, Gupta M, Panda D, Chandra R, Joshi HC. Rational design of the microtubule-targeting anti-breast cancer drug EM015. Cancer Res 2006; 66: 3782–3791. 3. Arendt LM, Rose-Hellekant TA, Sandgren EP, Schuler LA. Prolactin potentiates transforming growth factor alpha induction of mammary neoplasia in transgenic mice. Am J Pathol 2006; 168: 1365–1374. 4. Bramley M, Clarke RB, Howell A, Evans DGR, Armer T, Baildam AD, Anderson E. Effects of oestrogens and anti-oestrogens on normal breast tissue from women bearing BRCA1 and BRCA2 mutations. Br J Cancer 2006; 94: 1021–1028. 5. Burkhardt M, Mayordomo E, Winzer KJ, Fritzsche F, Gansukh T, Pahl S, Weichert W, Denkert C, Guski H, Dietel M, Kristiansen G. Cytoplasmic overexpression of ALCAM is prognostic of disease progression in breast cancer. J Clin Pathol 2006; 59: 403–409. 6. Callagy GM, Pharoah PD, Pinder SE, Hsu FD, Nielsen TO, Ragaz J, Ellis IO, Huntsman D, Caldas C. Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham Prognostic Index. Clin Cancer Res 2006; 12: 2468–2475. 7. Chakraborty G, Rangaswami H, Jain S, Kundu GC. Hypoxia regulates cross-talk between Syk and Lck leading to breast cancer progression and angiogenesis. J Biol Chem 2006; 281: 11322–11331. 8. Charafe-Jauffret E, Ginestier C, Monville F, Finetti P, Adelaide J, Cervera N, Fekairi S, Xerri L, Jacquemier J, Birnbaum D, Bertucci F. Gene expression profiling of breast cell lines identifies potential new basal markers. Oncogene 2006; 25: 2273–2284. 9. Christensen LA, Finch RA, Booker AJ, Vasquez KM. Targeting oncogenes to improve breast cancer chemotherapy. Cancer Res 2006; 66: 4089–4094. 10. Cohen I, Pappo O, Elkin M, San T, Bar-Shavit R, Hazan R, Peretz T, Vlodavsky I, Abramovitch R. Heparanase promotes growth, angiogenesis and survival of primary breast tumors. Int J Cancer 2006; 118: 1609–1617. 11. Creighton CJ, Hilger AM, Murthy S, Rae JM, Chinnaiyan AM, El-Ashry D. Activation of mitogenactivated protein kinase in estrogen receptor alpha-positive breast cancer cells in vitro induces an in vivo molecular phenotype of estrogen receptor alpha-negative human breast tumors. Cancer Res 2006; 66: 3903–3911. 12. Ding L, Erdmann C, Chinnaiyan AM, Merajver SD, Kleer CG. Identification of EZH2 as a molecular marker for a precancerous state in morphologically normal breast tissues. Cancer Res 2006; 66: 4095–4099. 13. Eliassen AH, Missmer SA, Tworoger SS, Hankinson SE. Endogenous steroid hormone concentrations and risk of breast cancer: does the association vary by a woman’s predicted breast cancer risk? J Clin Oncol 2006; 24: 1823–1830. 14. Fernandez SV, Russo IH, Russo J. Estradiol and its metabolites 4-hydroxyestradiol and 2hydroxyestradiol induce mutations in human ","PeriodicalId":89901,"journal":{"name":"Breast cancer online : BCO","volume":"9 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2006-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S1470903106005657","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56920754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Should positive sentinel node cases have a further axillary dissection","authors":"B. Cady","doi":"10.1017/S1470903106005049","DOIUrl":"https://doi.org/10.1017/S1470903106005049","url":null,"abstract":"The treatment of lymph node metastasis in human cancers has been a source of controversy for many years. Several contemporary randomized trials indicate no survival advantage to performing axillary dissection in contrast to merely observing the axilla after invasive breast cancer. This assumption is confirmed since survival advantages cannot be demonstrated when comparing greater or lesser lymph node dissections or dissection vs. observation of regional lymph nodes in melanoma and breast cancer and all other epithelial cancers. Many recent studies indicate that axillary metastases, when they do occur in this era of mammographic screening and small invasive cancers, demonstrate metastases in the axillary sentinel nodes only in from 20% to almost 100% depending on primary cancer size. For instance, in T1a and T1b cancers, 50–100% of lymph node metastases, infrequently discovered, are contained entirely within the sentinel nodes. In T2 cancers, this proportion is roughly 25–50%, and in T3 cancers it ranges from 20% to 40%. A number of recent articles have demonstrated no difference in survival and very little nodal recurrence when patients with positive sentinel nodes are not followed by axillary dissection although the axillary disease tends to be less advanced in observed compared to treated patients with axillary dissection. Nevertheless, basic principles have been reconfirmed in these reports. grow in other metastatic sites; this has been demonstrated clinically in clinical trials previously mentioned. Therefore, there is no benefit in performing subsequent axillary dissections even when the sentinel node biopsy is positive, because of: (1) very low risk ( (cid:1) 2%) of recurrent clinical nodal metastases, (2) the lack of impact on disease specific or overall survival, (3) most lymph node metastases are limited to the sentinel nodes, and (4) lymph node metastases are only indicators not governors of the distant metastases. The American College of Surgeons Oncology Group (ACOSOG) Z-11 Trial was designed to specifically address this point, but unfor-tunately was closed early because of poor accrual; nevertheless, 900 patients were enrolled and will be analyzed over time to address this point. https://www.cambridge.org/core.","PeriodicalId":89901,"journal":{"name":"Breast cancer online : BCO","volume":"9 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2006-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S1470903106005049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56920792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of surgery for pulmonary metastases in breast cancer patients","authors":"D. Hess, H. Klomp","doi":"10.1017/S1470903106002288","DOIUrl":"https://doi.org/10.1017/S1470903106002288","url":null,"abstract":"","PeriodicalId":89901,"journal":{"name":"Breast cancer online : BCO","volume":"9 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2006-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S1470903106002288","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56920088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth factor pathway switching: implications for the use of gefitinib and trastuzumab","authors":"H. E. Jones, J. Gee, I. Hutcheson, R. Nicholson","doi":"10.1017/S1470903106005451","DOIUrl":"https://doi.org/10.1017/S1470903106005451","url":null,"abstract":"Over-expression or aberrant signalling of the erbB family members epidermal growth factor receptor (EGFR) and HER2 (erbB2/neu) have been associated with the pathogenesis of the malignant phenotype. In addition, high levels of EGFR and HER2 expression have been shown to correlate with poor prognosis and also implicated in disease progression. Signal transduction inhibitors (STIs) have been developed with specifically target these receptors and include the small molecule tyrosine kinase inhibitor gefitinib (IressaTM) which targets the EGFR and the humanised monoclonal antibody trastuzumab (HerceptinTM), which has anti-tumour activity against HER2. Studies however, have indicated that de novo or acquired resistance to these agents is a major clinical problem. Cancer cells are highly adaptive and can readily switch from one receptor signalling pathway to another in order to maintain growth or cell survival, a process paradoxically, that in many instances is induced by the anti-tumour agents themselves, ultimately limiting their activity and promoting resistance. Evidence is accumulating which demonstrates that signalling interplay occurs between the EGFR/HER2 and the insulin-like growth factor -1 receptor (IGF-1R) and the article will focus on the growth factor pathway switching that occurs between these receptors which can influence the effectiveness gefitinib and trastuzumab.","PeriodicalId":89901,"journal":{"name":"Breast cancer online : BCO","volume":"9 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2006-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S1470903106005451","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56920886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modest benefits of adjuvant chemotherapy in hormone receptor-positive breast cancer","authors":"T. Svahn, R. Carlson","doi":"10.1017/S1470903106004378","DOIUrl":"https://doi.org/10.1017/S1470903106004378","url":null,"abstract":"The benefits of adjuvant chemotherapy, endocrine therapy, and trastuzumab therapy are well-established in patients with early breast cancer. Further, there are patient and tumor characteristics that can assist in predicting which patients are more likely to benefit from specific adjuvant therapies. For example, patients whose tumors express estrogen and/or progesterone receptors (ER/PR) derive significant benefit from adjuvant endocrine therapy, whereas those whose tumors do not express these receptors derive very little or no benefit from endocrine therapy [1]. Patients whose tumors overexpress HER2 experience profound benefits from treatment with adjuvant trastuzumab [2,3]. We have recently begun to understand that ER/PR-positive breast cancer also responds differently to chemotherapy than its hormone receptor-negative counterpart. This is not, however, entirely new information. As early as 1978, it was retrospectively observed that ER-positive metastatic breast cancer had lower response rates to a variety of older chemotherapy regimens than did ER-negative disease [4]. In 2001, an analysis of IBCSG, SWOG, and NSABP trial data examined disease-free survival (DFS) and relapse-free survival (RFS) for ER-positive vs. ERnegative cohorts separately for younger ( 35 years old) and older ( 35 years old) premenopausal women enrolled in chemotherapy-only treatment groups. This study demonstrated a consistent pattern that chemotherapy was of less benefit for young patients with ER-positive vs. ER-negative tumors when treated with chemotherapy alone [5]. In 2002, the International Breast Cancer Study Group (IBCSG) reported the results of Trial IX, which randomized postmenopausal patients with axillary lymph nodenegative breast cancer to cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) followed by tamoxifen vs. tamoxifen alone [6]. The added benefit of CMF followed by tamoxifen over tamoxifen alone was dependent on ER status. For ER-negative tumors, the addition of CMF improved DFS (5-year DFS risk ratio 0.52, 95% CI 0.34–0.79; P 0.003) and overall survival (OS) (5-year OS risk ratio 0.51, 95% CI 0.30–0.87; P 0.01), but for patients with ER-positive tumors, addition of CMF provided no benefit in terms of DFS or OS (5-year DFS risk ratio 0.99, 95% CI 0.75–1.3 and 5-year OS risk ratio 0.95, 95% CI 0.64–1.4). Further analysis examining quantitative ER values demonstrated a strong treatment effect associated with adding chemotherapy for patients with tumors expressing no or low levels of ER compared with virtually no improvement in DFS for patients with tumors having higher values of ER. NSABP B-20 randomized 1577 patients with ERpositive, axillary lymph node-negative tumors to tamoxifen alone vs. CMF followed by tamoxifen [7]. The study demonstrated that the overall population derived benefit from the addition of chemotherapy to tamoxifen in RFS and OS. When the same endpoints were assessed according to age, patients aged 49 years or younger had signi","PeriodicalId":89901,"journal":{"name":"Breast cancer online : BCO","volume":"9 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2006-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S1470903106004378","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56920418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional characterization of PIK3CA as a breast cancer oncogene. Review of: 1. Breast cancer-associated PIK3CA mutations are oncogenic in mammary epithelial cells 2. The oncogenic properties of mutant p110 alpha and p110 beta phosphatidylinositol 3-kinases in human mammary epithelial cells","authors":"Haley L. Bennett, R. Daly","doi":"10.1017/S1470903106005591","DOIUrl":"https://doi.org/10.1017/S1470903106005591","url":null,"abstract":"Citation of original article 1: S. J. Isakoff, J. A. Engelman, H. Y. Irie, J. Luo, S. M. Brachmann, R. V. Pearline, L. C. Cantley, J. S. Brugge. Cancer Research 2005; 65 : 10 992–11 000. Abstract of the original article 1: Activation of the phosphoinositide 3-kinase (PI3K) pathway has been implicated in the pathogenesis of a variety of cancers. Recently, mutations in the gene encoding the p110 catalytic subunit of PI3K ( PIK3CA ) have been identified in several human cancers. The mutations primarily result in single amino acid substitutions, with >85% of the mutations in either exon 9 or 20. Multiple studies have shown that these mutations are observed in 18% to 40% of breast cancers. However, the phenotypic effects of these PIK3CA mutations have not been examined in breast epithelial cells. Herein, we examine the activity of the two most common variants, E545K and H1047R, in the MCF-10A immortalized breast epithelial cell line. Both variants display higher PI3K activity than wild-type p110 yet remain sensitive to pharmacologic PI3K inhibition. In addition, expression of p110 mutants in mammary epithelial cells induces multiple phenotypic alterations characteristic of breast tumor cells, including anchorage-independent proliferation in soft agar, growth factor-independent proliferation, and protection from anoikis. Expression of these mutant p110 isoforms also confers increased resistance to paclitaxel and induces abnormal mammary acinar morphogenesis in three-dimensional basement membrane cultures. Together, these data support the notion that the cancer-associated mutations in PIK3CA may significantly contribute to breast cancer pathogenesis and represent attractive targets for therapeutic inhibition. Citation of original article 2: J. J. Zhao, Z. N. Liu, L. Wang, E. Shin, M. F. Loda, T. M. Roberts. Proceedings of the National Academy of Sciences of the United States of America 2005; 102 : 18 443–18 448. Abstract of the original article 2: The PIK3CA gene encoding the p110α subunit of Class IA phosphatidylinositol 3-kinases (PI3Ks) is frequently mutated in human tumors. Mutations in the PIK3CB gene encoding p110β, the only other widely expressed Class IA PI3K, have not been reported. We compared the biochemical activity and transforming potential of mutant forms of p110α and p110β in a human mammary epithelial cell system. The two most common tumor-derived alleles of p110α, H1047R and E545K , potently activated PI3K signaling. Human mammary epithelial cells expressing these alleles grew efficiently in soft agar and as orthotopic tumors in nude mice. We also examined a third class of mutations in p110α, those in the p85-binding domain. A representative tumor-derived p85-binding-domain mutant R38H showed modestly reduced p85 binding and weakly activated PI3K/Akt signaling. In contrast, a deletion mutant lacking the entire p85-binding domain efficiently activated PI3K signaling. When we constructed in p110β a mutation homologous to the E545K allele","PeriodicalId":89901,"journal":{"name":"Breast cancer online : BCO","volume":"9 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2006-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S1470903106005591","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56920501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basic science (February 2006)","authors":"R. Sutherland, J. Scorer","doi":"10.1017/S1470903106005633","DOIUrl":"https://doi.org/10.1017/S1470903106005633","url":null,"abstract":"1. Abdelrahim M, Ariazi E, Kim K, Khan S, Barhoumi R, Burghardt R, Liu SX, Hill D, Finnell R, Wlodarczyk B, Jordan VC, Safe S. 3-Methylcholanthrene and other aryl hydrocarbon receptor agonists directly activate estrogen receptor alpha. Cancer Res 2006; 66: 2459–2467. 2. Bernstein JL, Teraoka SN, John EM, Andrulis IL, Knight JA, Lapinski R, Olson ER, Wolitzer AL, Seminara D, Whittemore AS, Concannon P. The CHEK2*1100de/C allelic variant and risk of breast cancer: screening results from the breast cancer family registry. Cancer Epidemiol Biomark Prevent 2006; 15: 348–352. 3. Besada V, Diaz M, Becker M, Ramos Y, CastellanosSerra L, Fichtner I. Proteomics of xenografted human breast cancer indicates novel targets related to tamoxifen resistance. Proteomics 2006; 6: 1038–1048. 4. Bose S, Chandran S, Mirocha JM, Bose N. The Akt pathway in human breast cancer: a tissue-array-based analysis. Modern Pathol 2006; 19: 238–245. 5. Brew CT, Aronchik I, Hsu JC, Sheen JH, Dickson RB, Bjeldanes LF, Firestone GL. Indole-3-carbinol activates the ATM signaling pathway independent of DNA damage to stabilize p53 and induce G1 arrest of human mammary epithelial cells. Int J Cancer 2006; 118: 857–868. 6. Buttitta F, Felicioni L, Barassi F, Martella C, Paolizzi D, Fresu G, Salvatore S, Cuccurullo F, Mezzetti A, Campani D, Marchetti A. PIK3CA mutation and histological type in breast carcinoma: high frequency of mutations in lobular carcinoma. J Pathol 2006; 208: 350–355. 7. Chen SN, Iversen ES, Friebel T, Finkelstein D, Weber BL, Eisen A, Peterson LE, Schildkraut JM, Isaacs C, Peshkin BN, Corio C, Leondaridis L, Tomlinson G, Dutsm D, Kerber R, Amos CI, Strong LC, Berry DA, Euthus DM, Parmigiani G. Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol 2006; 24: 863–871. 8. Chenevix-Trench G, Healey S, Lakhani S, Waring P, Cummings M, Brinkworth R, Deffenbaugh AM, Burbidge LA, Pruss D, Judkins T, Scholl T, Bekessy A, Marsh A, Lovelock P, Wong M, Tesoriero A, Renard H, Southey M, Hopper JL, Yannoukakos K, Brown M, Easton D, Tavtigian SV, Goldgars D, Spurdle ABGAkI. Genetic and histopathologic evaluation of BRCA1 and BRCA2 DNA sequence variants of unknown clinical significance. Cancer Res 2006; 66: 2019–2027. 9. Cheng ASL, Jin VX, Fan MY, Smith LT, Liyanarachchi S, Yan PS, Leu YW, Chan MWY, Plass C, Nephew KP, Davuluri RV, Huang THM. Combinatorial analysis of transcription factor partners reveals recruitment of c-MYC to estrogen receptor-alpha responsive promoters. Mol Cell 2006; 21: 393–404. 10. Chooniedass-Kothari S, Hamedani MK, Troup S, Hube F, Leygue E. The steroid receptor RNA activator protein is expressed in breast tumor tissues. Int J Cancer 2006; 118: 1054–1059. 11. Collett K, Eide GE, Arnes J, Stefansson IM, Eide J, Braaten A, Aas T, Otte AP, Akslen LA. Expression of enhancer of zeste homologue 2 is significantly associated with increased tumor cell proliferation and is a marker of aggressive breast cancer. Clin Cancer Res 200","PeriodicalId":89901,"journal":{"name":"Breast cancer online : BCO","volume":"9 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2006-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S1470903106005633","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56920704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of: Proliferation of estrogen receptor-alpha-positive mammary epithelial cells is restrained by transforming growth factor-beta1 in adult mice","authors":"H. Kalirai, R. Clarke","doi":"10.1017/S1470903106005086","DOIUrl":"https://doi.org/10.1017/S1470903106005086","url":null,"abstract":"of the original article: Transforming growth factor (TGF)-beta1 is a potent inhibitor of mammary epithelial proliferation. In human breast, estrogen receptor (ER)-alpha cells rarely co-localize with markers of proliferation, but their increased frequency correlates with breast cancer risk. To determine whether TGF-beta1 is necessary for the quiescence of ER-alpha-positive populations, we examined mouse mammary epithelial glands at estrus. Approximately, 35% of epithelial cells showed TGF-beta1 activation, which co-localized with nuclear receptor-phosphorylated Smad 2/3, indicating that TGF-beta signaling is autocrine. Nuclear Smad co-localized with nuclear ER-alpha. To test whether TGF-beta inhibits proliferation, we examined genetically engineered mice with different levels of TGF-beta1. ER-alpha co-localization with markers of proliferation (i.e., Ki-67 or bromodeoxyuridine) at estrus was significantly increased in the mammary glands of TGF-beta1 C57/bl/129SV heterozygote mice. This relationship was maintained after pregnancy but was absent at puberty. Conversely, mammary epithelial expression of constitutively active TGF-beta1 via the MMTV promoter suppressed proliferation of ER-alpha-positive cells. Thus, TGF-beta1 activation functionally restrains ER-alpha-positive cells from proliferating in adult mammary gland. Accordingly, we propose that TGF-beta1 dysregulation may promote proliferation of ER-alphapositive cells associated with breast cancer risk in humans. Journals Club Correspondence to: Robert Clarke, Breast Biology Group, Division of Cancer Studies, University of Manchester, Christie Hospital, Manchester M20 4BX, UK. E-mail: rclarke@picr.man.ac.uk; Tel: 16 1446 3210; Fax: 16 1446 3218. Received: 10/11/05 Accepted: 31/03/06 First published online 12/05/06 BCO/508/2006/JC https://doi.org/10.1017/S1470903106005086 Downloaded from https://www.cambridge.org/core. IP address: 54.70.40.11, on 02 Jul 2021 at 01:38:57, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. Page 2 of 3 Journals Club Review inhibitor of ductal elongation and branching. Oestrogen and progesterone, on the other hand, are critical for promoting mammary epithelial proliferation, although it is clear that mammary epithelial cells differ in their ability to respond to these signals. Furthermore, observations in the human breast epithelium that oestrogen receptor (ER )/progesterone receptor (PR) positive cells rarely co-localise with markers of proliferation [8,9] led several groups to propose that the steroid receptor positive cells act as sensors for adjacent proliferating cells but are themselves actively prevented from proliferating by a growth inhibitor. In this article the authors hypothesise that this growth inhibitor is TGF 1 and that the difference in sensitivity to oestrogen or progesterone is due to the ability of TGF 1 to restrain the proliferative response of epithelial cell populations in response to ovarian steroi","PeriodicalId":89901,"journal":{"name":"Breast cancer online : BCO","volume":"9 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2006-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S1470903106005086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56920842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-operative endocrine therapy: focus on the clinical and biological results of the IMPACT trial","authors":"R. Jones, I. Smith","doi":"10.1017/S1470903106002549","DOIUrl":"https://doi.org/10.1017/S1470903106002549","url":null,"abstract":"randomised to the anastrozole alone group; 108 to the tamoxifen alone; and 109 to the combination group. All had confirmed oestrogen receptor (ER) positive, invasive breast carcinoma and the median age was 73 years. Post-menopausal patients with small breast carcinomas, not necessar-ily requiring mastectomy, were also eligible for trial entry and the median tumour size was 4 cm for each treatment group.","PeriodicalId":89901,"journal":{"name":"Breast cancer online : BCO","volume":"36 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2006-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S1470903106002549","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56920118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}