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February 17, 2000


Given correct treatment, black breast cancer patients do as well as whites

Black and white women with same-stage breast cancer see largely similar outcomes when their treatment and follow-up care are appropriate for their individual disease conditions, suggesting that physiological responses to treatments are not responsible for poorer outcomes among blacks.

These findings are reported in a review paper by Pitt researcher James J. Dignam and published in the January-February issue of CA: A Cancer Journal for Clinicians, a journal of the American Cancer Society. Dignam is a research assistant professor in the University's Graduate School of Public Health and biostatistician for the National Surgical Adjuvant Breast and Bowel Project (NSABP).

The review covered historic and recent research on breast cancer prognosis among black and white women, including investigations of clinical, pathologic, social, economic and demographic factors that may contribute to poorer outcomes for blacks.

Dignam's review shows that the most important determinant of ultimate outcome in breast cancer patients is the stage of cancer at diagnosis, and blacks are more often diagnosed at a more advanced stage than are whites. Dignam suggested that possible reasons for this late diagnosis may be less access to, or utilization of, health care resources that would result in earlier detection, or more aggressive forms of the disease among black women.

When patients of the same stage are compared across racial lines, black women more often show characteristics associated with poorer prognosis, such as larger tumor size, greater nodal involvement and estrogen receptor negative tumors, the study shows. Even obesity, found to be more prevalent among black breast cancer patients, is associated with a more advanced stage, possibly due to obesity's effect on estrogen, which can accelerate disease progression.

When national guidelines are followed, such indicators of poorer prognosis might call for more aggressive treatments, such as chemotherapy in addition to, or instead of, tamoxifen, according to Dignam. But some studies show that black women with these indicators are not undergoing the appropriate therapies. Studies in some urban hospitals, which are likely to treat the bulk of black breast cancer patients, have a greater rate of late-stage diagnosis as well as a higher degree of nonstandard care, including less frequent post-surgical radiation therapy and diagnostic tests used to choose appropriate therapy.

"Certain aspects of care differed according to factors such as age and race, with older and black patients less frequently receiving treatment in accordance with recommended guidelines," Dignam said.

When treatment was administered, studies show, black women were much more likely to have received total mastectomy rather than lumpectomy with radiation therapy in cases where either procedure would have been acceptable.

"One study showed frequency of breast-conserving surgery to be related to higher income and education, but in fact the relationship between blacks and total mastectomy may have many causes, including an institution's lack of resources to provide adequate radiation therapy, and patient or physician preference," Dignam said.

Conversely, studies focusing on settings where national treatment guidelines were followed show similar outcomes between black and white patients at the same stage of disease, and roughly equal survival rates.

Dignam's project was funded by the National Cancer Institute and the American Cancer Society.


Pitt research may lead to new diabetes therapies

In research that may aid in developing new therapies for diabetes, Pitt researchers have developed transgenic mice that overexpress a protein, hepatocyte growth factor (HGF), inside pancreatic islet cells — thus fostering growth of this cell population, which is responsible for insulin, the sugar-regulating hormone.

The transgenic mice exhibited increased beta cell proliferation, enhanced islet mass, increased total insulin production, and decreased blood sugar levels when compared to control, non-transgenic mice. These combined effects resulted in the altered mice having sustained mild low blood sugar.

The research appeared in the Jan. 15 edition of The Journal of Biological Chemistry. "This is the first time that hypoglycemia and accelerated islet growth have been demonstrated in a trans-genic animal model," said Andrew F. Stewart, professor of medicine, chief of the division of endocrinology and metabolism and senior author of the paper. "These studies demonstrate that it is possible to bioengineer pancreatic islet cells so that they proliferate at a faster than normal rate over the long term in living animals, and that doing so can lead to overproduction of insulin and thereby lead to lower blood sugar levels."

Currently, the primary drug treatment for diabetes is to give drugs that increase pancreatic insulin production, or to give insulin itself. Both treatments require daily administration of oral or injectable drugs.

"This research suggests that it may some day be possible to engineer islets which can be given to patients with diabetes to allow them to simultaneously measure blood glucose and secrete the appropriate amount of insulin," Stewart said.

Diabetes occurs when the body cannot make use of the glucose in the blood for energy because either the pancreas cannot make enough insulin or the insulin that is available is not effective.

Islet cells, located in the pancreas, make and secrete hormones that help the body break down and use food. Beta cells are located in the islets and make and release insulin, which controls the level of glucose in the blood. Hypoglycemia is an indication that the level of glucose (sugar) in the blood is too low.

Others involved in the research are Karen K. Takane, Mushtaq A. Syed and Rupangi C. Vasavada, of Pitt's School of Medicine and William M. Philbrick, of Yale.

The National Institutes of Health funded the research.


Discovery of HIV "shedding" patterns, viral site to change research on AIDS vaccines, treatments

Pitt AIDS researchers have found that viral secretion in HIV-positive men follows one of three patterns, which are in turn related to different sources of HIV in the body.

This discovery, which has important implications for research on vaccines and retroviral therapies, was presented Jan. 30 in a poster session at the 7th Conference on Retroviruses and Opportunistic Infections.

"For the first time, we see that some HIV-positive men continuously produce, or shed, the virus, and that in this case the virus originates in the blood," said principal investigator Phalguni Gupta, professor of infectious diseases and microbiology at the Graduate School of Public Health (GSPH). "Other men shed intermittently, and in them the virus is produced in a genital organ, probably the prostate."

Another 28 percent of the participants were found to be non-shedders, meaning the virus was not detected in the semen but could be in the blood. While they are antibody-positive, non-shedders are less likely to infect their partners.

Previous research has shown that some men have the same strain of HIV in their blood and semen, while others exhibit differing strains. "Interestingly, we now see that those with the same strains in blood and semen are continuous shedders, while those with distinct virus populations are intermittent shedders," Gupta explained.

With this new knowledge about compartmentalization of HIV between blood and semen, researchers now know that any vaccine prepared from blood-borne HIV would not be effective against sexual transmission of HIV in all men. In addition, potent retroviral therapy may have a different effect on HIV in semen as compared to that in blood in men who shed the virus intermittently.

"Vaccines and retroviral therapies will need to address multiple HIV strains in intermittent shedders," Gupta said. Pitt researchers have begun testing patients who failed anti-retroviral therapy to determine if their seminal virus is different from that present in their blood.

Gupta's study also found that the compartmentalization of HIV is related to the number of sexual partners. Continuous shedders with blood-borne virus tend to be men who have multiple sex partners and resulting chronic inflammation of the male genital organ, according to Gupta. "This inflammation constitutes a leak in the system that allows virus or virus-infected cells in the blood to enter the genital organ, resulting in like strains in both blood and semen," he said.

On the other hand, all non-shedders had only one partner. Intermittent shedders in the study did not show a correlation between number of partners and shedding pattern. The fact that intermittent shedders have different strains of HIV in their semen and blood suggests that the secreted virus is produced by an organ, according to Gupta.

His study was a collaboration between GSPH's infectious diseases and microbiology department; the medical school's department of molecular genetics and biochemistry and department of pathology; and Northwestern University Medical School. The study was supported by the Public Health Service and by Pitt's Pathology Education and Research Foundation.

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