“The potential public health impact of these findings is important,” said Paul E. Goss, lead study author and professor of medicine at Harvard Medical School and Massachusetts General Hospital. “Worldwide it is estimated that 1.3 million women are diagnosed with breast cancer each year, and nearly 500,000 women die of the disease. Results from the MAP.3 (Mammary Prevention Trial-.3) indicate that exemestane is a promising new way to prevent breast cancer in menopausal women most commonly affected with breast cancer.”
UC Davis was the only Northern California site participating in the research and one of only two sites in California.
Goss said that the reduction in breast cancers of 65 percent was in line with expectations. “The numbers of tumors are small, but there also appeared to be fewer of the more aggressive tumors on exemestane,” he said. “Our study not only showed an impressive reduction in breast cancers, but also an excellent side-effect profile, although my cautionary note is that average followup to date has been only three years.”
Results of the study are being presented today at the American Society of Clinical Oncology meeting.
John Robbins, professor of medicine and principal investigator of the study at UC Davis, emphasized that while the findings confirm that the drug works well, it is too early to know whether the drug will now be used routinely in women who have never had breast cancer.
Use of the drug in that population will likely depend on an individual woman’s breast cancer risks, personal preference and other factors yet to be determined, he said.
“If your mother and sister both had breast cancer, I would think seriously about taking it,” he said. “It will also depend on how the drug is priced, and if insurance companies are willing to pay for it.”
Robbins added that the study period was too short and the number of participants too small to identify significant side effects that may not be obvious until well after the drug has gone to market.
Study participant Beverly Pimentel, a 74-year-old retired physical therapist who lives in Davis, joined the trial hoping that the findings would lead to fewer cases of the disease in the future. She said several friends and two aunts were diagnosed with breast cancer and a young cousin died from the disease.
“I felt this was something I could do,” she said. “If in the long term it helps someone else, that’s good.”
Although Pimentel doesn’t know whether she has been taking the drug or a placebo, she said she would be willing to start or stay on the medication if her doctor recommends it.
“I am not considered high risk, but if a year down the road they said that because my cousin and aunts had breast cancer I am at significant risk, that would certainly make me consider it.”
Estrogens have been implicated in causing breast cancer. The anti-estrogens tamoxifen and raloxifene are FDA-approved breast cancer preventatives for women at high risk for the disease. However, it has been estimated that rare but serious uterine cancer and blood clots, which can be fatal, have limited the acceptance of tamoxifen to only 4 percent of high-risk women and 0.08 percent of all women in the U.S. There is a need for highly effective and safer options for breast cancer prevention.
Aromatase inhibitors (AIs) powerfully prevent estrogen synthesis and are distinct from tamoxifen in the way they counteract estrogen. AIs are superior to tamoxifen in preventing recurrences in early breast cancer patients, including the prevention of new breast cancers. The investigators predicted from laboratory experiments and clinical results that AIs would prevent breast cancer without the serious toxicities seen with tamoxifen.
The MAP.3 study, led and coordinated by the National Cancer Institute of Canada’s clinical trials group, is the first randomized trial to assess an aromatase inhibitor as a breast cancer preventative in healthy women. Exemestane is an AI approved by the FDA for use in early breast cancer patients. The trial enrolled 4,560 women from the U.S., Canada, Spain and France.
Women eligible for the study were postmenopausal and also had at least one other risk factor including being over age 60, having had non-cancerous abnormal breast tissue growth or ductal carcinoma in situ (DCIS) treated with mastectomy or score above 1.66 on the Gail Model breast cancer risk assessment tool, which takes into consideration additional risk factors such as a family history of breast cancer, race, time of first menstrual period and age of first live birth.
At a median followup of three years, the group receiving exemestane had a 65 percent reduction in invasive cancers (11 invasive breast cancers in the exemestane group compared to 32 in the placebo group). There was also a 60 percent reduction of invasive breast cancer and pre-invasive DCIS among the 66 cases in women participating in the trial. Importantly, there were fewer cases of cancer precursor lesions such as atypical ductal and atypical lobular hyperplasia in the group receiving exemestane.
The investigators reported symptoms such as hot flashes, fatigue, sweating, insomnia and joint pain were frequent in all women on study but predictably slightly more common on exemestane. However these symptoms did not appear to affect self-reports of overall health-related quality of life on exemestane.
More serious adverse events including bone fractures, osteoporosis, hypercholesterolemia, adverse cardiovascular events and other non-breast cancers were equal in both groups.
Goss said that after participants are informed whether they were on the drug or a placebo, women on active therapy will be offered exemestane to complete five years, and MAP.3 sites will have the option of offering five years of exemestane to those initially allocated to placebo.
“We and others are conducting placebo-controlled trials in healthy women and early breast cancer patients of aromatase inhibitors in menopausal women of similar age, and results from these ongoing trials will contribute to our understanding of long-term efficacies and toxicities of the drugs,” Goss said. “Long-term results in women with early breast cancer show durable long-term reductions in new breast cancers with exemestane without accumulation of late toxicities. So we are hopeful and optimistic that this will be the case in this prevention setting.”
About the National Cancer Institute of Canada Clinical Trials Group
The NCIC Clinical Trials Group (NCIC CTG) is a cancer clinical trials cooperative group that conducts phase I-III trials testing anti-cancer and supportive therapies across Canada and internationally. It is one of the national programs and networks of the Canadian Cancer Society. The NCIC CTG’s Central Office is located at Queen’s University in Kingston, Ontario, Canada.
UC Davis Cancer Center is the only National Cancer Institute- designated center serving the Central Valley and inland Northern California, a region of more than 6 million people. Its top specialists provide compassionate, comprehensive care for more than 9,000 adults and children every year, and offer patients access to more than 150 clinical trials at any given time. Its innovative research program includes more than 280 scientists at UC Davis and Lawrence Livermore National Laboratory. The unique partnership, the first between a major cancer center and national laboratory, has resulted in the discovery of new tools to diagnose and treat cancer. Through the Cancer Care Network, UC Davis is collaborating with a number of hospitals and clinical centers throughout the Central Valley and Northern California regions to offer the latest cancer-care services. For more information, visit cancer.ucdavis.edu.