New Test May Predict Breast Cancer Metastasis

March 30, 2009

Researchers at NewYork-Presbyterian Hospital/Weill Cornell Medical Center have identified a new marker for breast cancer metastasis called TMEM, for Tumor Microenvironment of Metastasis. As reported in the March 24 online edition of the journal Clinical Cancer Research, density of TMEM was associated with the development of distant organ metastasis via the bloodstream - the most common cause of death from breast cancer.

The National Cancer Institute (NCI)-funded translational study could lead to the first test to predict the likelihood of breast cancer metastasis via the bloodstream - a development that could change the way breast cancer is treated.

An estimated 40 percent of breast cancer patients relapse and develop metastatic disease. About 40,000 women die of metastatic breast cancer every year.

"Currently, anyone with a breast cancer diagnosis fears the worst - that the cancer will spread and threaten their lives. A tissue test for metastatic risk could alleviate those worries, and prevent toxic and costly measures like radiation and chemotherapy," says senior author Dr. Joan G. Jones, professor of clinical pathology and laboratory medicine at Weill Cornell Medical College and director of Anatomic Pathology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

"If patients can be better classified as either low risk or high risk for metastasis, therapies can be custom tailored to patients, preventing over-treatment or under-treatment of the disease," adds first author Dr. Brian D. Robinson, resident in Anatomic Pathology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

The Weill Cornell investigators set out to build on previous research by co-author Dr. John S. Condeelis of the Albert Einstein College of Medicine. Working in animal models, he identified a link between blood-borne or systemic metastasis and a three-part association between invasive carcinoma cells, perivascular white blood cells (macrophages) and the endothelial cells that line vessel walls. To confirm this finding in humans, Drs. Jones and Robinson developed a triple immunostain for human breast cancer samples that simultaneously labels the three cell types that together they named TMEM (Tumor Microenvironment of Metastasis).

In a case-control study, they performed a retrospective analysis of tissue samples from 30 patients with invasive ductal carcinoma of the breast who developed systemic, distant-organ metastases. These samples were compared to matched controls that had only localized disease (i.e., invasive ductal carcinoma limited to the breast or with regional lymph node metastasis only). All patients were female and underwent primary resection of their breast cancer at NewYork-Presbyterian Hospital/Weill Cornell Medical Center between 1992 and 2003.

They found that TMEM density was more than double in the group of patients who developed systemic metastases compared with the patients with only localized breast cancer (median of 105 vs. 50, respectively). Offering further evidence in support of the TMEM concept, they found that in well-differentiated tumors, where the outcome is generally good, the TMEM count was low.

Notably, TMEM density was associated with the development of distant-organ metastasis, independent of lymph node status and tumor grade.

"Traditionally, the likelihood of breast cancer metastasis is estimated based on tumor size, tumor differentiation - how similar or dissimilar the tumor is compared to normal breast tissue - and whether it has spread to the lymph nodes. While these are useful measures, TMEM density directly reflects the blood-borne mechanism of metastasis, and therefore may prove to be more specific and directly relevant," says Dr. Jones.

The researchers say the next step will be to validate the findings in a larger sample group. Also on the agenda is identifying a threshold TMEM density for metastasis risk, and streamlining the process for measuring TMEM.

Breast cancer is the most prevalent malignant disease of women in the developed world, apart from non-melanoma skin cancers, with approximately one in eight women in the United States being diagnosed with breast cancer at some time in their lives. While an estimated 10 percent to 15 percent of patients have an aggressive form of the disease that metastasizes within three years after initial diagnosis, metastasis can take 10 years or longer to occur. To decrease the risk for the emergence of metastatic tumors, approximately 80 percent of breast cancer patients are treated with adjuvant chemotherapy. The clinical benefit is a 3 percent to 10 percent increase in 15-year survival, depending upon the age of the patient at diagnosis.

Study co-authors include Drs. Gabriel L. Sica and Yi-Fang Liu of NewYork-Presbyterian/Weill Cornell; Dr. Thomas E. Rohan of the Department of Epidemiology and Population Health at Albert Einstein College of Medicine; Dr. Frank B. Gertler of the Department of Biology, Koch Institute for Integrative Cancer Biology at Massachusetts Institute of Technology; and Dr. John S. Condeelis of the Department of Anatomy & Structural Biology, Program in Tumor Microenvironment and Metastasis, Albert Einstein Cancer Center at the Albert Einstein College of Medicine.

The study was funded by the Integrative Cancer Biology Program (ICBP) of the National Cancer Institute (NCI).

Weill Cornell Medical College

---

---

	Fight Now: Eat & Live Proactively Against Breast Cancer by Aaron Tabor, MD Dr. Tabor’s FIGHT NOW book provides information on lifestyle choices that might improve breast health and overall health. The purpose of Dr. Tabor’s medical research is to empower you to become proactive against breast cancer now with specific food and lifestyle choices. We can make specific food and lifestyle choices to lower the risk of getting breast cancer, risk of recurrence, and risk of dying from breast cancer. The only alternative is to be reactive after you get breast cancer or have a recurrence of breast cancer. The choice is clear Whether you are currently fighting breast cancer; are a survivor; or, simply trying to lower your risk, Dr. Tabor’s FIGHT NOW book will give you concise, critical information that you can start using today. You don’t have to read...
	Just Get Me Through This!: A Practical Guide to Coping with Breast Cancer by Deborah A. Cohen (Author), Robert M. Gelfand (Author)
	The Breast Cancer Companion: A Guide for the Newly Diagnosed by Nancy Sokolowski (Author), Valerie Rossi (Author), Richard Zelkowitz (Foreword) Named a 2010 Best Consumer Health by the American Journal of Nursing The Breast Cancer Companion is a step-by-step guide through treatment for the 2 million women living with breast cancer in the United States. It provides ample space and encouragement to record questions, thoughts and feelings, doctor's appointments, medications, and contact information for the oncology team and others. The book also covers myriad other details that are often lost in the trauma and emotion of diagnosis and illness. The book helps women to be well-organized, well-informed, and have peace of mind so that, even in the midst of their breast cancer treatment they remain focused on what matters most: becoming well and achieving a healthy outcome. Special features include a calendar to help with...
	Chicken Soup for the Breast Cancer Survivor's Soul: Stories to Inspire, Support and Heal (Chicken Soup for the Soul) by Jack Canfield (Author), Mark Victor Hansen (Author), Mary Olsen Kelly (Author) Your support group in a book, filled with boundless strength and profound hope - until the fight is won. Along with the shock, fear and loss many women face upon a breast cancer diagnosis comes unexpected strength, wisdom, and strong networks of sharing, support and healing. In Chicken Soup for the Breast Cancer Survivor's Soul, survivors and their family members talk openly about how difficult their fight with breast cancer has been and how they made it through the dark times with a belief in a higher power and the support of those closest to them. Find strength in the encouraging stories of how family members confront their fears and show genuine affection for one another through gestures such as a granddaughter cutting the hair off of all her dolls so that they will look more like...
	Breast Cancer: 50 Essential Things to Do by Greg Anderson (Author), Erica A. Harvey (Introduction), Christine Northrup MD (Introduction) 2.5 million women in the U.S. have had a breast cancer diagnosis; more than 200,000 women are diagnosed each year. While recovery and survival rates have improved, selecting a treatment plan can be confusing and overwhelming.Breast Cancer: 50 Essential Things You Can Do offers a roadmap for women facing breast cancer. Cancer-survivor Greg Anderson, a recognized pioneer in the field of integrated cancer care, has guided tens-of-thousands of cancer patients to health and healing over the past 25 years, through his books and his Cancer Recovery Foundation. In this new book he offers critical information about the major issues patients face following a breast cancer diagnosis, and shows how to implement a comprehensive recovery plan that maximizes opportunity for healing and recovery.This is...
	Uplift: Secrets from the Sisterhood of Breast Cancer Survivors by Barbara Delinsky (Author) Barbara Delinsky's 1998 bestseller, COAST ROAD, featured a heroine who was a breast cancer survivor. To this day, it is the book that generates more mail than any of her others. That fact, combined with Barbara's ongoing commitment to breast cancer research, led her to her first book of nonfiction. Not a medical book -- there is no discussion of the pros and cons of a particular treatment or hospital or doctor -- UPLIFT is rather a collection of hundreds of pieces of practical and inspiring tidbits collected from survivors and their on everything from what kind of deodorant to use during radiation treatment to the best kinds of exercise aftloved ones. Think of it as "The Girlfriends' Guide" to breast cancer, with hints on everything from what kind of deodorant to use during radiation...
	Breast Cancer Survival Manual, Fourth Edition: A Step-by-Step Guide for the Woman With Newly Diagnosed Breast Cancer by John Link (Author) A completely updated edition of the definitive guide for patients with breast cancer The new fourth edition of The Breast Cancer Survival Manual provides essential updates on treatment and care, enhancing the basic information that has made this the most trusted guide for women diagnosed with breast cancer for the past decade. This edition includes the most current advice on • getting a second opinion: why it's important, what questions    to ask, and how to decide which team of doctors is best for you • updates on genetic testing and how doctors are using    the results to tailor care for each patient • navigating new types of radiation, the herceptin    breakthrough, and improved reconstruction surgeries Conscious of the rapidly evolving spectrum of...
	Dr. Susan Love's Breast Book, 5th Edition (A Merloyd Lawrence Book) by Susan M. Love MD (Author), Karen Lindsey (Contributor) Dr. Susan Love’s Breast Book has long been the bible for the newly diagnosed. In this completely revised fifth edition, it also becomes a guide for those at risk of getting breast cancer, survivors interested in the consequences of their treatment, and anyone who wants to understand the new research about how the local environment influences the manifestations and treatments of many different kinds of breast cancer. Major advances being made in genetic research today mean that prevention and treatment can work not only to get rid of mutated cells (through chemo or surgery), but also to change the environment around the cells (through hormone therapy, exercise, and stress reduction). Among other promising developments discussed are advances in imaging, recognition of breast density as a...
	Dancing With Fear: Tips and Wisdom from Breast Cancer Survivors by Leila Peltosaari (Author) Tips and wisdom from breast cancer survivors. 125 women share their real-life experience through treatments, recovery, aftermath, and reclaiming life after breast cancer. Sections include: > Finding the tumor > Dealing with doctors and surgeries > Lymphedema > Chemotherapy and radiation > Tamoxifen and aromatase inhibitors > Fear of recurrence > Complementary and alternative treatments > Optimism and pessimism > Support and humor > Spirituality and facing death
	The Breast Cancer Caregiver's Survival Guide: Practical Tips for Supporting Your Wife through Breast Cancer by Rick and Becky Kraemer One of the worst possible things has happened to you. You’ve gotten the bad news from your wife’s doctor, and the two of you are either facing breast cancer treatments, or are in the middle of them now. We’re here to help. In 2000, Becky was diagnosed with breast cancer, and completed extensive treatments (surgery, chemotherapy, radiation, hormone therapy). She is currently in remission and leading a normal, healthy, and athletic lifestyle. This booklet is in response to the questions we’ve received from men looking for practical advice on supporting their wives through this difficult time.