here we go again: How inexact ER status testing is!!!

[Hopeful]

In a post above, I mentioned an article that described a mechanism of Tamoxifen resistance which resulted from Her2 signalling displacing the ER receptor from the nucleus of the cell to the cell membrane. Well, looking for something else (as always!) I found it. Here is the link: http://clincancerres.aacrjournals.or...ull/10/11/3621

Hopeful

[Lani]

was methylene blue dye used to locate your surgery or your lymph nodes?

It causes false negative results in ER testing (I posted this about 8 weeks ago)--go to the search function on this site and put in "dye"

I attended a meeting on the biologic basis of breast cancer in July and a famous pathologist got up and discussed the need to improve ER testing with some practical suggestions.

Many cancer centers do second pathologic opinions--some of your slides get sent from the pathology department of the hospital where your surgery was done and the pathologists at the institution you send them to evaluate them. MD Anderson does it, Stanford does it, I would guess that MSK and Dana-Farber do it. I helped arrange for a second pathologic opinion of a friend of a friend from Denmark with triple negative bc done at MD Anderson. I remember scouring their website to find the info on how it was to be requested and the Danish hospital sent the slides and it was quite easy all around.

If I remember the name of the pathologist who gave the talk I will post it.
Hope this helps!

[Lani]

Jeffrey Ross, MD Albany Medical College, Dept. of Pathology

Clinical Cancer Research 13, 2831-2835, May 15, 2007. doi: 10.1158/1078-0432.CCR-06-2522
© 2007 American Association for Cancer Research


Standardizing Slide-Based Assays in Breast Cancer: Hormone Receptors, HER2, and Sentinel Lymph Nodes

Jeffrey S. Ross1, W. Fraser Symmans2, Lajos Pusztai3 and Gabriel N. Hortobagyi3
Authors' Affiliations: 1 Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, and Divisions of 2 Pathology and 3 Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Jeffrey S. Ross, Department of Pathology and Laboratory Medicine, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208. Phone: 518-262-5461; Fax: 518-262-8092; E-mail: rossj@mail.amc.edu.

Despite the rapid expansion of novel diagnostics designed to personalize breast cancer care, there remain several significant unmet needs for improving the accuracy and reliability of tests that are already in common daily clinical practice. For example, although immunohistochemistry has been the predominant method for measuring estrogen receptor and progesterone receptor status for over 15 years, this assay remains unstandardized and there is a widespread concern that inaccuracy in immunohistochemistry technique and interpretation is leading to an unacceptably high error rate in determining the true hormone receptor status. Similarly, there is considerable concern that both false-negative and false-positive result rates for testing for HER2 status are unacceptably high in current clinical practice. This commentary considers a variety of factors, including preanalytic conditions and slide-scoring procedures, and other variables that may be contributing to current testing error rates and why there is a great need for the standardization of these biomarker assay procedures to further enable the highest possible quality of care for newly diagnosed breast cancer patients.

[Lani]

for example, the study by Arpino that those tumors that are ER+PR- are more resistant to tamoxifen and better treated by AIs--they went back and did the hormone receptor testing in "central laboratories" and got a different result:

1: J Clin Oncol. 2007 Aug 6; [Epub ahead of print]
Prognostic and Predictive Value of Centrally Reviewed Expression of Estrogen and Progesterone Receptors in a Randomized Trial Comparing Letrozole and Tamoxifen Adjuvant Therapy for Postmenopausal Women With Early Breast Cancer: Results From the BIG 1-98 Collaborative Groups.

Viale G, Regan MM, Maiorano E, Mastropasqua MG, Dell'orto P, Bruun Rasmussen B, Raffoul J, Neven P, Orosz Z, Braye S, Ohlschlegel C, Thürlimann B, Gelber RD, Castiglione-Gertsch M, Price KN, Goldhirsch A, Gusterson BA, Coates AS.
Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy; International Breast Cancer Study Group (IBCSG) Statistical Center, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, MA; Department of Pathological Anatomy, University of Bari, Bari, Italy; Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy; Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy; Department of Pathology, Nordsjaellands Hospital, Hilleroed, Denmark; Service d'Anatomie et de Cytologie Pathologiques, Centre Hospitalier-site-Belfort-Montbéliard, Montbéliard, France; Department of Gyn Oncol and Multidisciplinary Breast Centre, UZ-KULeuven, Leuven, Belgium; Department of Pathology, National Institute of Oncology, Budapest, Hungary; Australian New Zealand Breast Cancer Trials Group, University of Newcastle and Anatomical Pathology, Hunter Area Pathology Service, John Hunter Hospital, New Lambton Heights, NSW, Australia; Kantonsspital, St Gallen, Swiss Group for Clinical Cancer Research, Bern, Switzerland; Senology Center of Eastern Switzerland, Kantonsspital, St Gallen, Switzerland, Swiss Group for Clinical Cancer Research; IBCSG Statistical Center, Dana-Farber Cancer Institute, Frontier Science and Technology Research Foundation, Harvard School of Public Health, Boston, MA; IBCSG Coordinating Center, Bern, Switzerland; IBCSG Statistical Center and Frontier Science and Technology Research Foundation, Boston, MA; European Institute of Oncology, Milan, Italy; Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; Division of Cancer Sciences and Molecular Pathology, Western Infirmary, University of Glasgow, UK; International Breast Cancer Study Group, Bern, Switzerland and University of Sydney, Australia.
PURPOSE: To evaluate locally versus centrally assessed estrogen (ER) and progesterone (PgR) receptor status and the impact of PgR on letrozole adjuvant therapy compared with tamoxifen in postmenopausal women with early breast cancer. PATIENTS AND METHODS: Breast International Group (BIG) 1-98 randomly assigned 8,010 patients to four arms comparing letrozole and tamoxifen with sequences of each agent. The Central Pathology Office received material for 6,549 patients (82%), of which 79% were assessable (6,291 patients). Prognostic and predictive value of both local and central hormone receptor expression on disease-free survival (DFS) were evaluated among 3,650 assessable patients assigned to the monotherapy arms. Prognostic value and the treatment effect were estimated for centrally assessed ER and PgR expression levels using the Subpopulation Treatment Effect Pattern Plot. RESULTS: Central review confirmed 97% of tumors as hormone receptor-positive (ER and/or PgR >/=10%). Of 105 tumors locally ER-negative, 73 were found to have more than 10% positive cells, and eight had 1% to 9%. Of 6,100 tumors locally ER positive, 66 were found to have no staining, and 54 had only 1% to 9%. Discordance was more marked for PgR than ER. Patients with tumors reclassified centrally as ER-negative, or as hormone receptor-negative, had poor DFS. Centrally assessed ER and PgR showed prognostic value. Among patients with centrally assessed ER-expressing tumors, letrozole showed better DFS than tamoxifen, irrespective of PgR expression level. CONCLUSION: Central review changed the assessment of receptor status in a substantial proportion of patients, and should be performed whenever possible in similar trials. PgR expression did not affect the relative efficacy of letrozole over tamoxifen.
PMID: 17679725 [PubMed - as supplied by publisher]