Using Immuno-Therapy to Prevent the Spread of Ovarian Cancer

Francine Foss, M.D.

Francine Foss, M.D., Professor in the Yale Cancer Center

More than 25,000 women develop ovarian cancer each year in the United States, yet available chemotherapy treatments that stem the progression of the disease often are not effective in preventing recurrence. Dr. Foss study focused on immunotherapy (stimulation of the immune system to fight tumor cells) as a potentially promising new way of treating advanced or recurrent ovarian cancer.

Highlighted Study Findings

Dr. Foss has isolated and characterized the nature of the immune cells from the ascites, or fluid which builds up in the abdomen of ovarian cancer patients. She and her team investigated the nature of these immune cells in patients. Dr. Foss found that only one in three patients had evidence of an active response by killer T-cells that attack and destroy tumor cells, whereas the other patients had predominately immunoregulatory or suppressive T-cells. This discovery supported her view of the importance of increasing the killer T-cell response in the immune system. She then isolated other cells, called dendritic cells, from the abdominal fluid and exposed them to a novel process developed to provide “instructions” on how to attack harmful cancer cells. The results showed that over half the cells became activated and, thus, capable of stimulating T-cells. Dr. Foss is using this new information to develop drug immunotherapies to increase and harness the power of individual patients’ killer T-cells to combat ovarian cancer.

Aromatase Inhibitors in Older Women with Breast Cancer

Cary P. Gross, M.D.

Cary P. Gross, M.D., Associate Professor of Internal Medicine (Primary Care)

Approximately 80,000 women over the age of 65 years are diagnosed with breast cancer in the United States annually, and Aromatase Inhibitor (AI) therapy is rapidly becoming the standard of care for adjuvant therapy in preventing recurrence in the majority of these patients. AI therapy appears to be more effective than previous therapies at preventing recurrence of cancer yet, in practice, is causing adverse effects that lead to reduced medication adherence. AIs, which are supposed to be taken daily for five years for full beneficial effect, can cause muscle aches, and joint stiffness and pain, thus prompting patients to stop their therapy early. Women who participated in the clinical trials that led to FDA approval of AIs tended to be younger patients than those with breast cancer in the typical community setting. Gross and his interdisciplinary colleagues have enrolled older post-menopausal women with breast cancer in this study to evaluate their experiences in a community setting.

Highlighted Study Findings

Dr. Gross’s ongoing study focuses on the musculoskeletal effects of AI therapy in women over age 65, which represents the larger proportion of women diagnosed with breast cancer. Gross and his interdisciplinary colleagues have enrolled older post-menopausal women with breast cancer in this study with follow-up over 2 years in order to evaluate physical functioning and mobility, musculoskeletal symptoms, and the relationship of these side effects to adherence with AI therapy in a typical community health care practice. Information from this study is expected to inform clinicians and patients about potential interventions that could be designed to help patients better tolerate and manage their AI therapy, and adhere to their AI therapy for the full five years.

Developing a Molecular Analysis for Early Onset Breast Cancer

Bruce G. Haffty, M.D.

Bruce Haffty, M.D., Professor, Department of Therapeutic Radiology

Breast cancer initially occurring in those at a young age (less than 42 years old) has unique biological characteristics compared to later onset disease. However, the genetic and molecular characteristics of early onset breast cancer that set it apart from later onset breast cancer have not been extensively examined. In an attempt to understand the genetic contribution to early onset disease, Dr. Haffty previously tested patients for the breast cancer susceptibility genes, BRCA1 and BRCA2, and found that these genes do incur increased risk for recurrence of cancer in the untreated breast. In this follow-up study, he expanded on that work by analyzing the primary tumor specimens of patients with early stage, early onset breast cancer. These tissues were examined for several molecular markers commonly expressed in breast tumors and associated with the biological activity of the cancer cells.

Highlighted Study Findings

This study found that specific molecular markers in the tumors of young women with breast cancer were related to BRCA1 and BRCA2 status. This relationship was even stronger in young women with a particular type of cancer (intraductal cancer) compared to older women. Additional research then found a surprisingly high frequency of BRCA1 and BRCA2 mutations in Korean women.  Yet, despite the high frequency of mutations found, the rate of breast cancer was much lower in Korean women than in American women. Furthermore, family members of the women with mutations had a low frequency of breast and ovarian cancer. This suggests that another factor (genetic or environmental) may account for the onset of the disease in American populations.  Work in this area continues, building on the findings of Dr. Haffty’s initial studies.

Pilot Project Study was funded in 2001, Dr. Haffty is now at Robert Wood Johnson Medical School in New Jersey

Developing Early Detection for Breast Cancer

Bonnie L. King, Ph.D., Associate Research Scientist in Therapeutic Radiology

The benefits of early breast cancer detection are clearly illustrated by reduced mortality associated with mammographic screening in postmenopausal women. However, women at high risk for breast cancer, particularly breast cancer recurrence, would benefit from more sensitive measures of detection. Research by Dr. King focused on the development of a new approach for breast cancer screening that involves the analysis of cells regularly shed from the breast. 

Highlighted Study Findings

Dr. King’s research focused on the use of ductal lavage, a minimally invasive procedure, as a method of collecting routinely shed breast duct cells to detect early changes associated with the development of breast cancer. Her results showed that this procedure holds the promise of early detection of cell abnormalities that indicate risk for breast cancer. Her previous work showed that the method is safe, well tolerated, and able to detect early abnormalities in high-risk women. Building upon this initial research, Dr. King’s Program-funded investigation resulted in preliminary identification of genetic abnormalities that may indicate an increased probability of a cell becoming cancerous. The study showed that the intraductal approach offered a new dimension for early detection of breast cancer and risk assessment for breast cancer.

Pilot Project Study was funded in 2000, Dr. King is now at Stamford University, CA

Employing Psychologically Tailored Messages to Increase Mammography Use

Peter Salovey, Ph.D., Professor of Psychology and Epidemiology and Public Health

Breast cancer is the second leading cause of cancer death among American women. Although mammography is generally regarded as the most effective tool for detecting breast cancer early and preventing cancer death, many women do not obtain regular mammograms. To motivate women to use routine mammography screening, more effective public health messages are needed. Dr. Salovey’s work focuses on the persuasiveness of health messages, and has shown that a standardized health message does not generate the same response in every listener. In the current work, he examined the type of health messages that encourage women to obtain mammography.

Highlighted Study Findings

Dr. Salovey found that recommendations about health behaviors, such as mammography, are most effective in changing behavior when customized to an individual’s preferred way of gaining new information. Dr. Salovey and his research team examined the persuasiveness of health messages, specifically “gain-frame” (e.g., if you get a mammogram, you will live to see your grandchildren) versus “loss-frame” (e.g., if you do not get a mammogram, you will not live to see your grandchildren) health messages, when they are matched to individuals’ information-processing styles, specifically one’s health locus of control (i.e., willingness to attribute the responsibility for maintaining good health to self or to health professionals). Overall, results demonstrated that women who received messages consistent with their health locus of control information –processing style, they were more likely to obtain a mammogram as assessed at 6 and 12 month follow-up than women who received messages that were not consistent with their health locus of control information –processing style. These findings have been incorporated into message framing for mammography, and used in a variety of health promotion messages.