Breast SPORE Projects

Designed to meet the fundamental requirements of the National Cancer Institute for translational research, the Breast SPORE projects capitalize on pre-existing research to find the most innovative ways to generate advances in our understanding of breast cancer biology and reflect Mayo's strengths in basic, translational, clinical and clinical trials research in breast cancer. The investigative teams are interdisciplinary, and include both breast cancer researchers and clinicians who are experienced in patient-oriented cancer research.

Project #1: Chfr in Tumorigenesis and Paclitaxel Sensitivity in Breast Cancer
Investigators: Junjie Chen, Ph.D., Yale University School of Medicine; Scott Kaufmann, M.D., Ph.D., and Edith Perez, M.D., Mayo Clinic Cancer Center

Drugs known as taxanes (including paclitaxel and docetaxel) are widely used in treating breast cancer. Cells, whether they're healthy or cancerous, pass through many steps or checkpoints as they divide. Taxanes slow or stop cancer cell division by targeting microtubules, the parts of a cell that help pull chromosomes apart before cells divide. Unfortunately, these drugs are effective in treating only 30 percent to 50 percent of breast cancer patients.

Over the past 20 years, researchers have identified multiple potential mechanisms that cause some breast cancers to be resistant to the efficacy of taxanes. Project #1 focuses on a recently discovered gene called Chfr and examines the role this gene plays in cancer cell division (and attendant breast cancer development) and the sensitivity of cancer cells to taxane therapy. Chfr controls production of a small protein (polypeptide) that drives cell division.

Read More

Project #2: BRCA2 missense mutations and breast cancer
Investigators: Fergus Couch, Ph.D.; Noralene Lindor, M.D.

Between 5 percent and 10 percent of breast cancers are a direct result of inherited mutations in predisposition genes. Defects in the BRCA1 or BRCA2 genes put women at greater risk of developing breast, ovarian and pancreatic cancers. Usually these genes help prevent cancer by making proteins that allow the cell to check for any damage in its DNA and make repairs before dividing again. Mutations in these genes allow genetic changes to accumulate in cells. The cells may then continue dividing and pass damage to future generations of new cells, which increases the likelihood that the cells will become cancerous.

Several kinds of mutations have been observed in the BRCA1 and BRCA2 genes. Those that result in a failure to make a complete BRCA1 or BRCA2 protein uniformly increase a person's chances of developing cancer. However, many other mutations (called missense mutations) only change single amino acids (the building blocks of proteins) within BRCA1 and BRCA2. It is currently unclear whether the majority of these mutations increase risk of cancer, or whether they actually have no role in cancer and represent random unimportant changes.

The goal of Project #2 is to study a large group of these missense mutations, also called variants of uncertain significance (VUS), to determine which mutations increase breast and ovarian cancer risk and which mutations have no effect.

Read More

Project #3: Preclinical and Clinical Studies of MUC1 Glycopeptide Vaccine Strategies in Breast Cancer
Investigators: Mayo Clinic Cancer Center - Sandra Gendler, Ph.D.; Svetomir Markovic, M.D., Ph.D.; Pinku Mukherjee, Ph.D.; James Ingle, M.D.; Timothy Hobday, M.D.; and Daniel McCormick, Ph.D.

The term cancer vaccine is often used to describe a substance that triggers a person's immune system to recognize and destroy cancer cells without harming normal cells. The goal of Project #3 is to develop a vaccine that attacks tumors which have started or prevents them from starting. Mayo researchers will first attempt to identify the most effective antigen--something that causes the body to produce a type of white blood cell that can kill tumors, called tumor-specific cytotoxic T lymphocytes (CTLs).

MUC1 is a tumor-associated antigen that is present on nearly all cases of breast adenocarcinoma. In laboratory animal experiments, treatment of tumor-bearing mice with MUC1 (peptide) vaccines has resulted in tumor regression. Likewise, immunization of mice for MUC1 has reduced the development of breast cancer, suggesting the importance of MUC1 as a candidate immune target in the quest for an effective breast cancer vaccine.

Dr. Markovic's work on human cancer vaccines evaluating molecules that enhance the ability of vaccines to generate an immune response in combination with Dr. Gendler's and Dr. Mukherjee's work on the MUC1 vaccine has already led to the development of the first Mayo Clinic breast cancer vaccine study that will be activated in the near future. In this clinical trial the MUC1 vaccine will be combined with a Her-2 vaccine, administered in conjunction with one of three different cocktails of immune boosting molecules (adjuvants). The vaccine will be administered to patients with completely-treated early breast cancer with no current evidence of disease.

Read More

Project #4: Aromatase Inhibitors, Mammographic Density, and Plasma Steroid Hormones
Co-Principal Investigators: Celine Vachon, Ph.D., Mayo Clinic Cancer Center; Paul Goss, F.R.C.P., M.B.B.Ch., Ph.D., Dana-Farber/Harvard Cancer Center

Estrogen, the principal female hormone, is known to influence the growth and development of certain breast tumors. Normal breast tissue cells contain receptors for estrogen and progesterone, another female hormone. Receptors are cell proteins that bind to specific substances in the bloodstream, such as hormones. Receptors and hormones function as a lock and key. If the hormone fits with the receptor, it binds to the cell, opens the door and fuels cell growth.

Many breast cancer cells have hormone receptors for estrogen, progesterone or both. These cancers are called hormone receptor positive. Hormone receptor positive cancers may shrink with hormone therapy, a treatment that blocks the effects of estrogen. Although a woman's ovaries are the main source of estrogen, women produce the hormone in other ways, even after menopause. The adrenal glands produce several hormones (such as androgens) that are converted into estrogens in other parts of the body, including the breast. This conversion of androgens to estrogens is brought about by an enzyme called aromatase. Medications called aromatase inhibitors work by keeping aromatase from creating estrogen.

Numerous studies have established aromatase inhibitors as an important part of optimal therapy in postmenopausal women following removal of an early stage breast cancer that is hormone receptor positive. However, questions remain about how best to use these medications. More research is needed to better identify which women will benefit most from the medication.

The ultimate goal of Project #4 is to examine whether variations in breast tissue and hormone levels will help identify women early in their therapy who will respond to aromatase inhibitors.

Read More