BREAST CANCER MONTH
Tips from Emory University's Breast Health Center

September, 1996

Media Contacts: Sarah Goodwin, 404/727-3366 - sgoodwi@emory.edu
Kathi Ovnic, 404/727-9371 - covnic@emory.edu

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BREAST CANCER IN BLACK WOMEN

African-American women with breast cancer are more than twice as likely to die of the disease than white women.

Now approximately three-fourths of that survival difference can be explained by known risk factors such as the stage at which a woman is diagnosed and tumor characteristics, said authors of a 1994 analysis of the phenomenon.

Researchers from Emory University's Rollins School of Public Health, the National Cancer Institute and other institutions published "Racial Differences in Survival from Breast Cancer: Results of the National Cancer Institute Black/White Cancer Survival Study" in the Sept. 28, 1994, issue of the Journal of the American Medical Association.

"We found large differences between the groups in social and economic circumstances and access to health care," said first author J. William Eley, M.D., of Emory University, in the analysis of 1,130 women diagnosed in 1985-86 with primary breast cancer in Atlanta, New Orleans and San Francisco/Oakland. "Sociodemographic variables appeared to act largely through stage at diagnosis. Stage at diagnosis accounts for 40 percent of the racial difference in survival, which is important since stage may be amenable to change through improved access to and use of screening of black women."

When the groups were compared only on the basis of race, it appeared that African-American women were more than twice (2.2 times) as likely to die from breast cancer.

"The good news about this analysis, which confirms similar studies, is that it appears many of the factors which put African-American women at higher risk for dying of breast cancer can be dealt with," said Dr. Eley, who is assistant professor of epidemiology and assistant professor of medicine (oncology) in the Winship Cancer Center. "Improved access to health care, better insurance, better public health education and screening interventions all could theoretically improve survival rates."

"Women with no health insurance had a risk of death from breast cancer 2.3 times greater than women with any private insurance..." the authors reported. Being divorced, separated or never married, or having an increased body mass index significantly decreased women's chances of survival when measured exclusive of other variables. Specific characteristics of the cancer itself, such as tumor stage, grade and size, the number of lymph nodes affected and estrogen receptor status, when measured individually, also appeared to affect survival. The study suggests that racial differences may be partly due to biologic factors such as the more aggressive tumors seen in many African-American women. Treatment for breast cancer, certainly a factor affecting survival, did not measurably affect racial differences in survival among study participants.

By the end of 1990, researchers noted that 350 study participants had died, including 242 African-American women and 108 white women.

"For most cancers, survival among blacks is poorer than that for whites in the United States," says Brenda K. Edwards, Ph.D., of the Division of Cancer Prevention and Control, National Cancer Institute. "Black women diagnosed with breast cancer experience a five-year relative survival of only 62 percent, compared with 79 percent for white women.

"Part of the poorer breast cancer survival for black women is due to more advanced stage of disease at presentation, but some analyses that have controlled or stratified for stage have still found black women's survival to be poorer than that of their white counterparts. Previous research concerning differences in breast cancer survival between black and white women suggests that the biological characteristics of tumors may differ between the races, thereby affecting survival...".

HEADING HOME AFTER BONE MARROW TRANSPLANT

Instead of spending the requisite four to six long weeks in the hospital after receiving high- dose chemotherapy and undergoing bone marrow transplantation (BMT), some breast cancer patients at the Winship Cancer Center of Emory University may now recover at home.

The outpatient procedure is available to Emory patients having an autologous transplant, in which the patient's own bone marrow is extracted, cleansed and reinfused to reconstitute the immune system.

Qualified patients receive high-dose chemotherapy in the hospital, then are discharged to the outpatient clinic for intensive daily support with antibiotics, pain medicine, growth factors or nutrition supplements, as needed.

Patients go home or to alternative sites near the hospital under the care of a specified caregiver such as a family member or friend.

Studies of the outpatient procedure at other centers have had promising results, including a decrease in mortality and morbidity, and a 50 percent savings in cost.

"We believe insurance companies will be less likely to balk at covering the procedure if its cost were significantly decreased, thereby making the procedure available for more patients," says Andrew Yeager, M.D., head of Emory's BMT Program.

Emory doctors are collecting the first available data on quality of life after outpatient discharge for chemotherapy/BMT.

DESPITE TOXICITY, HIGHER CHEMOTHERAPEUTIC DOSES BETTER FOR MANAGING BREAST CANCER

Dosage levels of chemotherapy used to treat breast cancer patients must be at least moderately high to be most effective, and should not be lowered to reduce toxicity, says William Wood, M.D., chairman of the Department of Surgery at Emory University School of Medicine, and principal investigator of a multicenter study on chemotherapeutic dosing.

The investigators found that women who received moderate or high doses of a three-drug regimen of chemotherapy following primary surgical treatment had fewer recurrences of their cancer and a greater overall survival rate than did women who received lower doses of chemotherapy. The study was designed to test the hypothesis that increasing the dose and dose-intensity (dose over time) of chemotherapy would improve treatment outcome.

Beginning in 1985 the investigators conducted a prospective clinical trial at 26 institutions of 1,572 women with Stage II, node-positive breast carcinoma. Although chemotherapy is known to extend survival in breast cancer, some physicians believe that a higher dose and higher dose intensity are more effective, while others use a lower dose and lower dose intensity to reduce toxicity. Conflicting data from other studies have left it unclear whether variations in the dose and intensity affect the outcome of the treatment.

"Even though some breast cancer patients may experience serious side effects from treatment, women's lives can be extended significantly by giving moderately high doses of chemotherapy," Dr. Wood says.

ENDOSCOPY FOR BREAST RECONSTRUCTION

Plastic surgeons worldwide are traveling to Emory to master a technique to take back to their own breast cancer patients. It is called endoscopic latissimus reconstruction, and it is a state-of-the-art breast reconstruction technique pioneered by plastic surgeons at Emory's Winship Cancer Center. It leaves the breast looking so natural, and with so little scarring, that most people have a hard time discerning the reconstructed breast from its unadulterated mate.

The beauty of the endoscopic procedure is that it requires just two or three very small surgical incisions, which leave only tiny, unobtrusive scars. Conventional open surgery leaves a scar on a woman's back about 6-to 9-inches long. The smaller, endoscopic incisions also limit damage to nerve and muscle tissue. Because the procedure is less invasive, it hastens recovery time, reduces the need for pain medications, decreases the risk of infection and shortens the length of hospital stay.

Plastic surgeons Foad Nahai, M.D., and John Bostwick, M.D., have performed the endoscopic surgery on more than 40 patients. Their success rate has been so impressive from the beginning that they started teaching a special course to board-certified, practicing plastic surgeons.

Dr. Nahai explains, "Not every woman with breast cancer is a candidate for this procedure. The ones who are, however, will come away with excellent results and minimal or no new scars."

The procedure is so named for the viewing instrument, an endoscope, which consists of a long tube fitted with a tiny camera and a bright light that is inserted through a small incision. Images of the body's internal structures are magnified and projected onto a large TV-sized viewing screen. Surgeons watch the screen to maneuver other instruments, such as a scalpel or scissors, through a second incision without having to cut away large folds of skin and muscle. A section of tissue is cut from the patient's latissimus dorsi muscle, a large, flat, triangular muscle that originates in the lower spine and stretches up and over toward the shoulder. Surgeons slide the section of muscle from the back around to the breast. In this way, cancerous breast tissue that has been removed is "replaced" with healthy tissue.

The endoscopic technique has been used for years in many surgical specialties, but is still relatively new in plastic surgery. Until now, plastic surgeons have used it only for aesthetic procedures. It is technically difficult to perform and requires intense training.

HIGH EXPOSURE TO ONE'S OWN BREAST CANCER APPEARS TO INCREASE BREAST CANCER RISK

The more female mice are exposed to the female hormone estrogen produced by their own body, the greater their risk for breast cancer, report researchers from the Emory University School of Medicine in the July 15 issue of Cancer Research.

The study provides the first biologic evidence to support epidemiologic and clinical hypotheses associating early exposure to circulating, endogenous (produced by one's own body) estrogen and breast cancer risk.

The researchers developed a line (model) of transgenic mice whose genetic make up had been altered to overexpress an enzyme aromatase (int-5/aromatase) which catalyzes the conversion of androgens (male sex hormones) to estrogen -- the rate limiting step in creating estrogen. Signs of precancerous and cancerous activity were apparent in the breast (mammary) tissue of every mouse in which this gene overexpressed; none of their nontransgenic litter mates showed precancerous activity, reports first author Rajeshwar Rao Tekmal, Ph.D., assistant professor at Emory's Winship Cancer Center and Department of Gynecology and Obstetrics.

"...no studies have demonstrated the direct involvement of aromatase in the initiation of preneoplastic (precancerous) and/or neoplastic (cancerous) changes in mammary epithelium (tissue)," the authors say. "The study reported here addressed this question directly, presenting evidence for the first time that the overproduction of int-5/aromatase in mammary glands of transgenic females leads to a range of morphological abnormalities... which are all indicative of preneoplastic changes. plastic changes in mammary tissue.

"These changes may in turn increase the risk of developing breast neoplasia and increase susceptibility to environmental carcinogens."

BREAST CANCER SUPPORT GROUPS AT EMORY

Breast Cancer Support for the Newly Diagnosed. Meets every Thursday from 6-7:30 p.m., Decatur Plaza, 101 W. Ponce de Leon, Decatur. Call 404-778-4335 for information.

Breast Cancer Support for Women with Recurrent Cancer. Meets every Thursday from 4:30-6 p.m., The Emory Clinic, Bldg. B, First Floor, 1365 Clifton Rd., NE, Atlanta. Call 404-778-4335 for information.

VOLUNTEERS NEEDED FOR BREAST CANCER STUDIES AT EMORY

Women's Health Initiative: Women of color, particularly African-American women in the metropolitan Atlanta area, are invited to participate in a large dietary and hormone replacement study at Emory University. Researchers are studying breast cancer, heart disease and osteoporosis. Volunteers must be between 50-79 years of age and should already have undergone menopause &emdash;the change of life. Qualified participants will receive clinic visits, blood pressure and EKG screenings, body measurements, breast exams, mammograms and nutrition information free-of-charge.

The Women's Health Initiative, which is sponsored by the National Institutes of Health, will last eight to 12 years and will include 3,600 Atlanta women. Call 404-473-8600.

Tamoxifen Breast Cancer Prevention Trial: Women age 35 and older are eligible to volunteer for a nationwide clinical trial to determine whether the anti-estrogen drug tamoxifen is effective in preventing breast cancer in women at high risk for developing the disease. Participants should have a strong family history of the disease or a medical history that includes multiple breast biopsies because of suspected breast disease. Women 60 and older are eligible for the study regardless of a family history of breast cancer or past biopsies. Call 404-778-5377.

EMORY BREAST CANCER INFORMATION LINE

Emory's CancerWise Information Line: 778-7777 or 1-800-446-5566

The Emory University System of Health Care provides the toll-free CancerWise Information Line as a service to the public. A registered nurse is on duty from 8:30 a.m.-5 p.m. weekdays to provide specific information about various cancers (including breast cancer), standard therapies, and to suggest questions patients may ask their doctors. Patients may learn about Emory physicians who specialize in the research and treatment of breast cancer. Printed material is available upon request.

PRIMITIVE PUBERTY

Fewer periods -- that is the factor cancer researchers believe may help explain current differences in worldwide breast cancer incidence -- and what Emory's Boyd Eaton, M.D., believes may help explain why Stone Age women had far less breast cancer.

"For our Stone Age ultra-grandmothers, menarche (puberty) was later and first birth earlier," Dr. Eaton says. "They had more pregnancies after which they nursed their babies longer and more intensely, they had fewer lifetime ovulations and their menopause occurred earlier. All these lifestyle and reproductive differences meant that over her lifetime, a cavewoman had fewer years of high circulating estrogen levels and low average rates of reproductive cell turnover -- factors researchers are beginning to link to cancer initiation."

Women living today in primitive hunter-gatherer societies such as the Kung San people of Africa (who Dr. Eaton has visited and studied) and in some Asian societies, have a reproductive lifestyle similar to that of Stone Age women, and hence, they have lower incidence of women's cancers. Teenagers in many parts of China, for instance, do not experience puberty until they are 17 years of age, Dr. Eaton says.

BREAST STUDY EVALUATES TOXICITY OF FEAR

You notice a lump in your breast that wasn't there before. You schedule a mammography, just to be sure. It shows a tiny, granular looking spot, smaller than a pea. You are told you need a breast biopsy. You are terrified it might be cancerous.

It is well-documented that women who face the prospect of a breast biopsy experience heightened emotional distress. The distress has been severe enough to compromise immune function. Some research indicates that suppression of the immune system associated with distress has a very significant, adverse effect on health.

Decrease in immunologic function has been noted in a variety of life situations, such as divorce, unemployment or graduate school exams.

A study at Winship Cancer Center is looking at the specific psychological and immunological characteristics of women who require breast biopsy, as compared with those who do not.

The women receiving biopsies will be compared: those with a low degree of suspicion for cancer versus those with a high degree of suspicion. Measures of emotional distress, coping behavior, hormonal and immunologic activity will be taken.

Results will help researchers understand the mechanisms by which emotional distress and coping behavior affect the immune system.

EMORY STUDY FURTHER VALIDATES MAMMOGRAPHY'S LIFESAVING CAPABILITIES

Mammography works -- so why don't more women over 40 have mammograms?

Breast imaging experts at Emory found that mammographically-discovered cancers in women in this age group have a lower stage than the cancers found by physical exam. Results are from a study of newly discovered breast cancers at Emory University Hospital and Grady Memorial Hospital, the public hospital affiliated with Emory.

Of the cancers seen at Emory, 38 percent were discovered via mammogram, and 62 percent were found either by patient or physician during physical exam. All mammographically-detected cases revealed less advanced tumors than did clinical cases.

At Grady, 26 percent of the cancers were found with mammography and 75 percent were found clinically or by the woman herself. Again, the women in the first group had less advanced disease and were more easily treated.

Previous screening mammography studies have similarly demonstrated improved survival for earlier discovery.

The fact remains, however, that the overwhelming majority of cancers are detected by the patient herself. By then, it is often too late. Thus, despite proven benefits and the efforts of national organizations, screening mammography remains underused, says Emory study investigator Debra Monticciolo, M.D.

IMAGING BREAST TUMORS

One of the few radiologists in the South fellowship-trained in breast imaging is conducting research on imaging systems that go beyond mammography to provide valuable information about the breast.

In some cases, says Debra Monticciolo, M.D., director of the Emory Breast Health Center, the techniques she and her colleagues are investigating eliminate the need for surgical breast biopsy.

STEREOTACTIC CORE BIOPSY is one such technique. Since Dr. Monticciolo began offering the technique at Emory a few years ago, many women have been able to forego open surgical procedures requiring general anesthesia. Instead, a specially designed X-ray machine pinpoints the precise location of a suspected tumor. Using digital imaging, a cylindrical core of tissue is obtained through a guided needle, in a minimally invasive procedure requiring only local anesthesia. An accurate diagnosis can be made by examining the core of tissue. The Emory team is part of a national study of core biopsy versus surgical biopsy.

PET -- Dr. Monticciolo and Emory radiologist John Vansant, M.D., are among the first researchers applying positron emission tomography (PET) to breast cancer diagnosis. Access to Emory's PET Center, considered one of the best equipped in the world, has given Dr. Monticciolo the opportunity to use PET to specifically determine lymph node involvement.

MRI & GADOLINIUM --While PET provides superior "functional" insights into internal chemical activity, magnetic resonance imaging (MRI) offers superb "structural" insights. Dr. Monticciolo is using the contrast agent gadolinium to enhance MRI and help distinguish benign from malignant cancer.

MRI TO SCREEN FOR SILICONE LEAKAGE -- Emory is also one of the few medical centers in the world using MRI to screen for leakage from silicone breast implants. Dr. Monticciolo and her colleagues have developed the means to image implants, so that everything in a scan is blacked out except for the silicone. Women who received silicone implants during breast reconstruction after breast cancer surgery &emdash;or for augmentation &emdash;are being screened regularly at Emory.

Dr. Monticciolo says that one of her main reasons for conducting this research are to catch breast tumors as early as possible &emdash;to keep breast health center patients out of the operating room or at least minimize their time there.

SKIN-SPARING MASTECTOMY IMPROVES COSMETIC OUTCOME

A surgical technique for removing cancerous breast tissue with minimal disfigurement is being refined by Grant Carlson, M.D., assistant professor of surgery at the Winship Cancer Center of Emory University -- one of a handful of surgeons performing the technique. Called skin-sparing mastectomy, the procedure preserves most breast skin, markedly improving the cosmetic results of reconstruction. When a patient returns home following mastectomy, her breast will look virtually intact.

"This is the single greatest advancement in breast reconstruction in the last five years," says Dr. Carlson, who describes in an early 1996 issue of The American Surgeon his adaptation of the procedure for early breast cancer patients.

The surgery involves making inconspicuous incisions to remove cancerous tissue yet preserving skin covering the breast as well as the inframammary fold, the "underneath" part of the breast that meets the chest wall and is removed during traditional mastectomy. This fold, says Dr. Carlson, "is what defines the shape of the breast. It's an anatomic landmark that has even been observed in 7-month-old fetuses."

During the procedure, surgeons also remove the nipple, scars from biopsy incisions and skin overlying superficial cancers. Once malignant tissue has been removed, use of the "abundant skin envelope" as well as the inframammary fold greatly improves immediate reconstruction, Dr. Carlson says. It also means less abdominal tissue is needed to "build up" the breast -- and the reduced scarring means less recovery time. Cancer recurrences in the remaining tissue are rare. In one clinical study involving 100 patients who underwent the skin-sparing procedure, only one recurrence was noted nearly two years after surgery. In Dr. Carlson's research at Winship over the past five years involving 280 patients, local recurrence was only five percent for patients with invasive cancer.

The best candidates for the new surgery are breast cancer patients with Stage I and II disease, Dr. Carlson says.

IMAGE REBORN: Support for the Reconstructed

When several breast cancer patients at the Winship Cancer Center asked nurse Lynne McCain to refer them to a support group for women undergoing breast reconstruction, she discovered there were none. So she started one herself.

The group, called Image Reborn, is now in its ninth year. Oncologists, researchers and plastic surgeons discuss at meetings the latest research on breast cancer treatment, control and rehabilitation. In addition to an educational seminar, the monthly meeting also serves as a forum for women to share their stories. Some have finished reconstruction while others are just beginning the process, which can take up to a year. They ask each other honest questions, compare results with the different surgical methods and describe the pain associated with different choices.

"It helps reduce anxiety for those who have not yet been through the process," Ms. McCain says.

Discussion topics range from self-image and sexuality to the brutal reality of recurrence and death. The group also has a government relations committee, whose goal is to alert government officials to the need for breast cancer research.

Image Reborn meets each second Thursday from 6-8 p.m. in the Glenn Building, Crawford Long Hospital, 25 Prescott St., Atlanta. Call 404/778-3454.

MULTIDRUG RESISTANCE

Dr. Kapil Bhalla of Emory's Winship Cancer Center is examining multidrug resistance in breast cancer and acute leukemia.

Anticancer drugs trigger a final pathway of cell death called apoptosis, which is regulated by a family of genes. Dr. Bhalla had demonstrated that specific changes in the behavior of these genes are what make cancer cells resistant to various anticancer drugs. This may explain why cancers at relapse exhibit multidrug resistance. Dr. Bhalla's current studies are defining the precise role of these genes in the molecular "execut