These tumors lack hormone receptors that make ideal treatment targets, researchers say
By Alan Mozes
MONDAY, March 26 (HealthDay News) -- U.S. breast cancer patients with a particularly deadly form of the disease are more likely to be poor, black or Hispanic, and under 40 years of age, new research shows.
Patients diagnosed with "triple-negative" breast cancer lack three key hormonal cancer markers that are present in most other forms of the disease, experts explain.
The absence of these cell receptors deprives doctors and patients of critical diagnostic information and prime targets for treatment, reducing a patient's therapeutic options and undercutting her expected survival.
"The paradox is that while African-American and Hispanic women have a lower overall risk for breast cancer, they have a higher mortality, which is probably due to the higher incidence of triple-negative [disease]," said study co-author Dr. Vincent Caggiano, research medical director of the Sutter Cancer Center at the Cancer Surveillance Program in Sacramento, Calif.
"So, in addition to the usual surgery that all women undergo, these triple-negative women are not eligible to receive any hormonal therapy," he added. "This leaves them with only chemotherapy to treat a very aggressive form of breast cancer. And although triple-negative patients respond well to chemotherapy, they relapse and their survival is shortened."
The findings are published in the May 1 issue of Cancer.
According to the American Cancer Society, breast cancer is the second most common cancer among women, after nonmelanoma skin cancer. Women living in North America are subject to the highest rate of breast cancer in the world, and nearly 180,000 new cases of breast cancer will be diagnosed in the United States this year alone.
In most cases of breast cancer, the presence of hormonal receptors in tumor tissue allows for the use of highly effective and narrowly targeted endocrine treatments --collectively known as "hormone adjuvant therapy" -- which have been developed in recent years as an alternative to systemic chemotherapy.
Hormone receptors are specialized protein molecules that can be located outside or inside either normal or cancerous cells. Such receptors attract and draw in particular hormones, such as estrogen or progesterone. As hormones "lock up" with hormone receptors, the effect is like flicking on a switch for certain cellular activities, including cancer cell growth.
Recognizing that no two cancers are alike, newer drugs -- including aromatase inhibitors and herceptin -- target hormone receptors specific to the patient's cancer cells.
But about 15 percent of patients have so-called "basal-like" breast cancer, which includes all triple-negative cases. In such instances the tumor lacks hormone receptors for either estrogen (ER), progesterone (PR), or human epidermal growth factor receptor 2 (HER2).
To identify those women at highest risk for basal-like breast cancer, Caggiono and his team analyzed the demographics of 6,370 California women diagnosed with a primary case of triple-negative breast cancer between 1999 and 2003. The women were identified through the California Cancer Registry.
They next compared outcomes for women with triple-negative disease against those of more than 44,700 patients with breast cancers that carried the hormonal markers.
Triple-negative patients were significantly younger at the time of their diagnosis than were other breast cancer patients, the researchers found. Whereas about 63 percent of triple-negative cases were uncovered before the age of 60, less than half of other breast cancers were diagnosed in women under 60.
Women 40 years of age or under were over one-and-a-half times more likely to have triple negative breast cancer than were patients between the ages of 60 and 69, the team found.
Race was also a major risk factor. While nearly 25 percent of the black patients had triple-negative malignancies, only about 11 percent of whites, 12 percent of Asians, and 17 percent of Hispanics were similarly diagnosed.
In terms of income, richer patients were less likely to be triple-negative than poorer breast cancer patients, although the very poorest did not appear to have a significantly greater risk, the team says.
Triple-negative patients were also more likely to be diagnosed with larger tumors and at a more advanced stage of disease, the study found.
As suspected, survival was worse for triple-negative patients than for other patients. Three out of four (77 percent) of patients with triple-negative cancers survived five years post-diagnosis compared with 93 percent of other breast cancer patients.
Non-Hispanic black patients with triple-negative disease fared worst of all, having just a 14 percent five-year survival rate. By comparison, patients with other forms of late stage disease had five-year survival rates of between 36 and 49 percent.
Why such disparities? Caggiano's team say biological differences probably play a big role. But they also suggested that other factors, such as lack of health-care access and resulting differences in treatment could pay a role in the higher incidence of triple-negative cases among non-white patients and the poor.
"What's important to note is that breast cancer is not a single disease and even young women can get it," said Caggiano. "Why African-American and Hispanic women get this very aggressive form more often we really don't know. It may be due to genetics, socioeconomic status, or in part due to barriers to treatment. It's probably an interaction of all of them. It's clearly an area for further research."
Emily White, a researcher with the Fred Hutchinson Cancer Center in Seattle, said that "studies like this are worthwhile, and help us understand risk factors more clearly. But it's also an issue of debate whether estrogen and progesterone receptors and HER2 are fundamental [unchanging] characteristics of a tumor, or whether their status actually changes and they lose their ability to respond over time."
The notion of cancer cell change could help explain the socioeconomic disparities uncovered in this study, she said.
"If you say some tumors are simply destined to be negative from the start then you have to point to some genetic predisposition to explain it," said White, who is also professor of epidemiology at the University of Washington. "But, if you think tumors can change with time then it could be that certain socioeconomic groups get diagnosed with a more aggressive type of cancer simply because of diagnosis delays, due to health-care barriers. Whether or not this is so is not yet really understood."
For more on triple-negative breast cancer, head to Breastcancer.org.
SOURCES: Vincent Caggiano, M.D., research medical director, Sutter Cancer Center, Cancer Surveillance Program, and Sutter Institute for Medical Research, Sacramento, Calif.; Emily White, Ph.D., researcher, Fred Hutchinson Cancer Center, and professor, epidemiology, University of Washington, Seattle; May 1, 2007, Cancer