February 2013, Vol 2, No 1

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Molecular Subtyping Reclassifies Early Breast Cancer in a Proportion of Patients

Phoebe Starr

Uncategorized

Molecular subtyping of early breast cancers using MammaPrint and BluePrint allows precise and accurate prediction of the molecular phenotype of the disease, which has the potential to guide selection of personalized therapy if the tests are used prospectively. A retrospective study of 208 tumor samples found that molecular subtyping with these 2 platforms led to reclassification of 25% of the tumors, which would have been treated differently had the tests been applied prospectively. These findings have important therapeutic and prognostic implications.

Retrospective classification showed that 39% of breast cancer classified clinically as HER2 disease should actually have been treated with therapies for luminal-type breast cancer (eg, endocrine therapy); and 20% of breast cancer classified clinically as triple- negative breast cancer could have been treated with therapies for luminal- and HER2-type disease, such as endocrine therapy and trastuzumab-based regimens.

“The use of MammaPrint and BluePrint should be implemented in the management of primary breast cancer for the selection of adjuvant therapy in the era of personalized care,” stated lead author Massimo Cristofanilli, MD, Fox Chase Cancer Center, Philadelphia, PA, and coauthors.

The study used frozen tumor samples from 208 patients treated at 2 US institutions according to National Comprehensive Cancer Network standard guidelines between 1992 and 2010. Median follow-up was 11.3 years. Median age was 56 years (range, 28-89 years); 59% were hormone receptor positive (ER+/PR+), 20% were HER2+, and 24% were triple negative by locally assessed immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). All patients underwent lumpectomy or mastectomy with axillary staging.

The microarray-based assays were as follows: BluePrint, an 80-gene assay that discriminates between luminal-type, basal-type, and HER2-type breast cancer. Luminal type is substratified by the 70-gene Mamma-
Print assay into low-risk luminal A and high-risk luminal B breast cancer.

Breaking down results of molecular subtyping showed that 13 of 188 tumors that were ER+/PR+/HER2– are not classified as luminal type by BluePrint; 24 of 41 clinical HER2+ patients are not classified as HER2 type by BluePrint; and 10 of 49 triple-negative tumors are not classified as basal type by BluePrint.

Fifty-one patients were reclassified as a result of molecular subtyping. Of these, 28 were reassessed centrally for ER/PR/HER2 status by IHC and FISH.

Patients with luminal-type early breast cancer identified by BluePrint have an excellent relapse-free survival: 97% for luminal A–type patients and 98% for luminal B–type patients.

Interview with the Innovators - February 20, 2013

Next-Generation Sequencing:

An Interview with Michael J. Pellini, MD, of Foundation Medicine

As the molecular drivers of cancer are better understood and targeted therapies are developed against those drivers, there is a growing need to perform comprehensive molecular analysis of tumors to determine the optimal treatment strategy for each patient. To this end, Foundation Medicine was founded in April 2010 by leaders [ Read More ]

Uncategorized - February 20, 2013

The Drawn Out Process of the Medical Lawsuit

She was one of the most highly sought radiologists in her hospital, a doctor with the uncanny ability to divine the source of maladies from the shadows of black and white X-ray films. But one afternoon my colleague revealed that she had been named in a lawsuit, accused of overlooking [ Read More ]