Ipsogen SA (Alternext - FR0010626028 - ALIPS), a molecular
diagnostic company specialized in the development, manufacturing and
commercialization of diagnostic assays for breast cancer and leukemia, today
announces the European launch of the MapQuant Dx(TM) HR test. Running on an
Affymetrix microarray diagnostic platform, this new genomic test will
improve
the identification of endocrine-responsive tumors by measuring the
expression
of genes related to oestrogen and progesterone biology in breast cancer.

Current issues with endocrine-responsiveness determination in
breast cancer

Determining endocrine-responsiveness of breast cancer is
essential as it guides the use of hormonotherapy, based primarily on
tamoxifen and aromatase inhibitors such as letrozole and anastrozole.
Currently, endocrine-responsiveness is routinely assessed by
immunohistochemistry (IHC), a semi-quantitative method measuring the
expression of hormone receptors (HR) for estrogen (ER) and progesterone (PR)
on tissue sections. However, and despite constant efforts toward technical
standardisation, IHC reproducibility and accuracy is not satisfactory, with
as much as 15% of cases reported as equivocal. This may lead to
inappropriate
treatment decisions.

Beyond the technical and standardisation issues, two
biological problems are unsolved:
(i) do ER-/PR+ tumors exist, or should
they
be considered as technical artifacts?
(ii) how to define the threshold for
receptor positivity (which is different in US and EU pathology practices)?

MapQuant Dx(TM) Genomic HR

The Genomic HR test measures the hormone receptor status of
invasive breast tumors. It has been developed on a training set of 137
tumors
with unequivoqual receptor expression by IHC. It was validated in 7
independent datasets totalling 691 tumors. It measures, by microarray
technology, the expression profile of genes selected to best discriminate
tumors expressing ER and/or PR proteins. These genes, selected on a
statistical rationale, are known to be related to the estrogen and
progesterone biology, adding a strong pathological rationale to the
selection
process.

Through this micro-array technique, an objective and
biologically-relevant cutoff for receptor positivity could be identified.
Over 97% of tumors could be given an unequivocal result. Moreover, no tumor
expressing PR but nor ER could be identified, supporting the current
hypothesis that such PR+/ER- tumors could be artifacts of the IHC technique.

Multi-testing with MapQuant Dx (TM)

Together with the Genomic Grade test and the Genomic HER2
test, the Genomic HR test provides a complete genomic testing panel for
breast cancer that will help pathologists to better determine tumor grade,
HR
and HER2 status, and, ultimately, allow a more individualised treatment
decision in breast cancer patients.

The Genomic HR test is made available for diagnostic use in
Europe through an ISO-17025/CLIA Lab Service performed by DNAVision SA
(Gosselies, Belgium). It can also be performed directly by cancer care
centers equipped with the CE-marked, FDA-cleared Affymetrix GeneChip(R)
3000Dx2 (GCS3000Dx2) system.

The MapQuant Dx(TM) testing solution for routine micro-array
profiling of breast tumors also includes: a Path Kit, CE-marked, ensuring
easy sampling, RNA-preservation and sample shipping at ambient temperature;
and CE-compliant software, ensuring highly reliable quality controls, data
processing and genomic test computation.

MapQuant Dx(TM) testing solution is developed under the
Innovation Support Programme of the French Health Products Safety Agency
(Afssaps).

About IPSOGEN

Ipsogen, Cancer Profiler, develops and markets molecular
diagnostic tests designed to map diseases in order to guide patients and
oncologists’ decisions along their complex therapeutic path.

With more than 70 references already used routinely worldwide
for the diagnosis, prognosis and follow-up of thousands of patients with
leukemia, Ipsogen is now also targeting breast cancer. Its initial goal will
be to provide diagnostic information that was not availble until now.
Ipsogen
is also a partner of choice for biopharmaceutical companies committed to the
development of ‘companion diagnostic’ tests.

Strengthened by its first-rate scientific, clinical and
technological partnerships, in addition to its highly skilled
multidisciplinary team in France and the USA, Ipsogen is striving to become
the leader in molecular profiling of cancers. It continues its efforts to
indentify, develop and commercialise diagnostic tests that will become
standard references and will have a significant impact on patients, medical
professionals and society.

Ipsogen employed 51 people as of March 31, 2009. Its
headquarters are located in Marseille, France. The company also has a
subsidiary, Ipsogen Inc., in New Haven, CT, USA.

Source
Ipsogen SA

HOUSTON, May 13 — Older women with early-stage breast cancer fared better with conventional adjuvant chemotherapy than with the newer agent capecitabine (Xeloda) in a large multicenter clinical trial.

• Explain to patients that this study showed that older, injectable forms of chemotherapy reduced the risk of relapse and improved survival compared with a newer drug in older women with early breast cancer.

Patients treated with capecitabine had almost twice the risk of relapse or death compared with those who received an older combination regimen, Hyman Muss, M.D., of the University of North Carolina in Chapel Hill, and colleagues reported in the May 14 issue of the New England Journal of Medicine.

After three years of follow-up, patients assigned to conventional adjuvant chemotherapy had better disease-free and overall survival.

“Our data are part of a developing body of evidence that the choice of adjuvant chemotherapy really matters in older women with breast cancer and that standard chemotherapy is superior to the oral agent capecitabine,” the authors concluded.

Age is the major risk factor for breast cancer in the U.S., and most breast cancer deaths involve women 65 or older. Ironically, older patients have been underrepresented in clinical trials of adjuvant chemotherapy, and patients do not always receive guideline-supported treatment, the authors said.

Moreover, older women tolerate adjuvant chemotherapy about as well as their younger counterparts, and more severe toxicity has not had a meaningful impact on the benefits, they added.

To examine the benefits of adjuvant chemotherapy in older women, investigators in Cancer and Leukemia Group B conducted a trial to compare oral capecitabine to standard therapy in women ages 65 and older.

Standard therapy was either cyclophosphamide, methotrexate, and 5-fluorouracil, or cyclophosphamide plus doxorubicin.

Patients with hormone receptor-positive cancer also received endocrine therapy.

The trial’s statistical design allowed for a patient population of 600 to 1,800 patients. The trial was stopped after enrollment of the 600th patient when an interim analysis showed that capecitabine was likely to be inferior to the conventional regimens with longer follow-up.

With follow-up for one year beyond enrollment of the last patient, patients randomized to capecitabine had a hazard ratio for recurrence or death of 2.09 versus conventional therapy (95% CI 1.38 to 3.17, P<0.001).

Capecitabine-treated patients had a mortality hazard ratio of 1.85 versus standard adjuvant therapy (P=0.02).

The three-year relapse-free survival was 68% with capecitabine and 85% in women assigned to standard therapy. Overall survival was 86% with capecitabine and 91% with standard chemotherapy.

Capecitabine was associated with almost twice the incidence of moderate-to-severe toxicity (64% versus 33%).

The study was supported by the National Cancer Institute, the National Institute on Aging, the Breast Cancer Research Foundation, the Coalition of Cancer Cooperative Groups, and Roche Biomedical Laboratories. Dr. Muss and co-authors Donald A. Berry, Clifford A. Hudis, Larry Norton, Julie Gralow, Edith Perez, and Antonio C. Wolff disclosed relationships with Hoffman-La Roche.

Primary source: New England Journal of Medicine

Source reference:
Muss HB, et al “Adjuvant chemotherapy in older women with early-stage breast cancer” N Engl J Med 2009; 360(20): 2055-65.