Holiday 2004 Newsletter: New Directions in Systemic Treatments for Breast Cancer

By Dr. Gini Fleming Associate Professor of Clinical Medicine Department of Medicine Section of Hematology/Oncology

There has been steady improvement in the diagnosis and treatment of breast cancer. Although the numbers of breast cancers diagnosed in the U.S. is no smaller, the numbers of women dying from breast cancer in the U.S. has decreased. More types of therapy are available, and better supportive care, such as antinausea drugs and growth factors, is available to counteract some of the side effects of therapy. But there is still much progress to be made!

Newer Anti-hormonal Therapy for Young Women

Although it is chemotherapy that is more intense, in many cases it is anti-hormonal therapy that provides the most benefit to breast cancer patients. For many years in the United States, this was not appreciated. In particular, anti-hormonal therapy was not thought to work in premenopausal women. We now know this is false. Young women whose tumors express hormone receptors will do poorly if they do not get anti-hormonal therapy. Dr. Fleming is U.S. Study Chair of an ambitious multinational cooperation spearheaded by the International Breast Cancer Study Group (IBCSG) to try to speed up the lagging development of hormone therapy options in young women. This study, nicknamed the SOFT trial, randomizes premenopausal women to tamoxifen alone, ovarian function suppression plus tamoxifen, or ovarian function suppression plus exemestane (a newer anti-hormone therapy). More information about this trial, as well as many other cancer clinical trials can be found at the NCI website www.cancer.gov.

Individualized Cancer Therapy

The treatments we have are effective for some breast cancers and not others. Why can’t we figure out ahead of time which treatments will work on an individual patient’s cancer?

This is one of the important questions our breast cancer patients ask. It is a question researchers throughout the world and at the University of Chicago are working to answer. For breast cancer patients, some treatment choices are already based on the particular characteristics of a given cancer. Only tumors which have hormone receptors (Estrogen Receptor, known as ER, or Progesterone Receptor, known as PR) will shrink when treated with antihormonal therapies, such as tamoxifen or aromatase inhibitors. Only tumors which amplify the gene for Human Epidermal Growth Factor Receptor 2 (HER2) will shrink when treated with the monoclonal antibody trastuzumab (Herceptin®).

One way researchers have to learn about out how to predict what therapies will work for a specific patient’s cancer is to perform some tests on a biopsy of a breast cancer, then treat the cancer with chemotherapy before final surgery. Treatment with chemotherapy before surgery is frequently done in any case in order to shrink the tumor and make surgery easier (or possible at all), and is sometimes called “neoadjuvant therapy”.

Therapy for Young Women Whose Tumors do not have Hormone Receptors

Dr. Olopade is a researcher at the University of Chicago who has long had an interest in inherited breast cancer, and in the aggressive forms of hormone receptor negative breast cancer that often affects young black women both here in the United States, and in her native Nigeria. Some of these cancers may have defects in DNA repair making certain drugs that damage tumorDNA, such as cisplatin, particularly effective. Dr. Olopade is launching a revolutionary trial to treat large breast cancers with a chemotherapy containing cisplatin before surgery. Extensive tumor biopsies will be obtained prior to chemotherapy, and, with modern gene expression array technology, they will be tested for a multitude of factors to try to predict which ones benefit most from this therapy.

Importance of Steroids

Dr. Conzen is working on a related project here at the University of Chicago. Her laboratory published groundbreaking work showing that in breast cancer cell culture, corticosteroids can decrease the effectiveness of chemotherapy, although nobody knows if this is relevant to patients or not! Corticosteroids are routinely given prior to chemotherapy to prevent nausea or prevent allergic reactions. (These are, by the way, not the same sort of steroids that have been making Olympic news….) Dr. Conzen is looking at expression of genes related to cell death in tumors in a biopsy before treatment, and then a second small biopsy after chemotherapy (with or without steroids). The goal of the Breast Cancer Program at the University of Chicago is to get permission from patients for research biopsies on ALL patients getting neoadjuvant therapy, as part of the larger goal: to study tumors so that we can eventually predict which tumors will shrink!

Survivor Issues

As more women survive breast cancer, issues for survivors become ever more important. Can we preserve fertility in young women? Can we prevent second cancers, such as ovarian cancers, in those at high risk? Can we identify other family members who are at risk for cancers? Can we avoid premature osteoporosis? Do our treatments cause loss of memory or other higher function (“chemobrain”)? Can we improve screening with MRI for subsets of women? These are among the many issues that University of Chicago teams of researchers are tackling. We believe that, working with our patients, we can make breast cancer much less of a threat for future generations of women.