THE BLOG
10/24/2013 11:49 am ET Updated Jan 23, 2014

Safely Avoid Chemotherapy in Breast Cancer With New Genetic Test

One in eight women in the U.S. will develop breast cancer. It is the most commonly diagnosed cancer in women and their second most common cause of cancer death. Once the diagnosis is made, a complex series of tests help determine the best course of action. For some it is neoadjuvant therapy (chemotherapy first followed by surgery), for others adjuvant therapy (surgery first followed by chemotherapy). Some need radiation, most need hormonal therapy. Yet there is a significant proportion of patients that do not need chemotherapy at all after surgery. In order to decide what group a woman falls into there are tumor characteristics defined by pathologists that determine the size, type, and grade of the tumor, involvement of lymph nodes, and presence of hormone receptors to estrogen, progesterone and HER2 protein (human epidermal growth receptor 2).

Once these are established a team of doctors composed of surgical, medical and radiation oncologists advice on how to best treat patients to decrease the risk of recurrence as much as possible without incurring unnecessary or unwanted side effects from the treatment. There are statistical tools and blood tests that help guide these decisions. However, many err on the side of caution, with the end result that most people get chemotherapy.

There is now a tumor-based test that can help both doctors and patients figure out who can safely avoid chemotherapy. The Mammaprint test was developed at the Netherlands Cancer Institute Antoni van Leeuwenhoek; which has a vast tumor sample bank with follow-up data on most patients for decades. This relatively new test, commercially called Mammaprint, is a 70-gene prognosis signature that helps categorize patients into low risk vs. high risk for distant metastasis and breast cancer survival over a 10-year interval. Agendia, the developers of the Mammaprint test, were able to genetically analyze the entire 25,000-gene human genome in 35,000 tumor samples and found particular patterns of gene expression that tended to correlate with "high risk" and "low risk" groups for recurrence during a follow period of 13 years. The test has been further validated in 12,000 patients in more than 60 publications worldwide. Many of the genes found by computer analysis to correlate with higher risk were genes known to have relationships with breast cancer development, invasion and spread. Others were new and unknown, but further study of these genes has led to eventual discovery of new pathways for cancer development.

According to the RASTER study, when the results of this test were incorporated into the treatment decisions of 427 women with newly-diagnosed breast cancer, 51 percent of patients had a result that indicated that they could safely avoid chemotherapy. In the RASTER study, those with a "low risk" test result had a 97 percent chance of being cancer-free after five years without using any chemotherapy. By contrast, those with a "high risk" test result had a historical chance of only 71 percent of being cancer-free at five years without treatment and therefore would highly benefit from chemotherapy. According to the RASTER study, when those high risk patients largely chose to receive chemotherapy, their chances of being cancer-free at five years improved to 91 percent. Multiple other studies have further analyzed this test with different follow-up periods ranging from 5-10 years; results vary mostly within the range described. For specific percentages please see original articles.

Mammaprint is the foundation of a battery of tests called the "Symphony Suite" of personalized Breast Cancer Genomic Profile. This suite of genetic tests can help with multiple other therapeutic choices. The Blueprint test can subtype breast cancer tumors into Luminal, Basal and Her2 and help determine the best therapy options. The Targetrint test can help determine hormone receptor status more accurately than other assays, and the Theraprint test can help determine the best therapy options for endocrine, chemotherapy and targeted therapy, in case of metastasis. All are commercially available tests that can be ordered by oncologists and surgeons.

As a primary care physician and an integrative medicine specialist, I know that most of my patients would be very interested in getting a test that can provide personalized, genotyped prognosis and treatment recommendations, especially if this means they may have a better chance of avoiding chemotherapy altogether. Rare would be the patient that would not like to know if they can safely avoid the typical side effects of hair loss, nausea, vomiting, fatigue and the general schedule disruptions that having to get chemotherapy for extended periods of time can entail. Medical genomics are changing the way we bring precision medicine to our patients. Women need to be aware of this technology to support their breast cancer treatment decisions so they can not only extend their life, but also retain their wellness.

References:
1. Int J Cancer. 2013 Aug 15;133(4):929-36. doi: 10.1002/ijc.28082. Epub 2013 Mar 4. A prospective evaluation of a breast cancer prognosis signature in the observational RASTER study. Drukker CA, Bueno-de-Mesquita JM, Retèl VP, van Harten WH, van Tinteren H, Wesseling J, Roumen RM, Knauer M, van 't Veer LJ, Sonke GS, Rutgers EJ, van de Vijver MJ, Linn SC. Source Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

2. Use of 70-gene signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER).
Bueno-de-Mesquita JM, van Harten WH, Retel VP, van't Veer LJ, van Dam FS, Karsenberg K, Douma KF, van Tinteren H, Peterse JL, Wesseling J, et al. Lancet Oncol. 2007 Dec; 8(12):1079-87. Epub 2007 Nov 26.

3. Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. Buyse M, Loi S, van't Veer L, Viale G, Delorenzi M, Glas AM, d'Assignies MS, Bergh J, Lidereau R, Ellis P, et al. J Natl Cancer Inst. 2006 Sep 6; 98(17):1183-92.

4. Gene expression profiling for guiding adjuvant chemotherapy decisions in women with early breast cancer: an evidence-based and economic analysis. Health Quality Ontario. Ont Health Technol Assess Ser. 2010; 10(23):1-57. Epub 2010 Dec 1.

5. Breast Cancer Res Treat. 2009 Jul;116(2):295-302. doi: 10.1007/s10549-008-0130-2. Epub 2008 Jul 27. The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1-3 positive lymph nodes in an independent validation study. Mook S, Schmidt MK, Viale G, Pruneri G, Eekhout I, Floore A, Glas AM, Bogaerts J, Cardoso F, Piccart-Gebhart MJ, Rutgers ET, Van't Veer LJ; TRANSBIG Consortium.

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