Women & living with breast cancer today.

When Arlene Dobren's mother was diagnosed with breast cancer 30 years ago, the cancer had already spread to her liver. She died a year later at age 62. Conversely, when Ms. Dobren herself was diagnosed with breast cancer in 1995 during a routine mammogram, she underwent a breast-conserving lumpectomy followed by chemotherapy and radiation and remained cancer-free for nine years.

When the cancer recurred last year--picked up during a routine chest X-ray--doctors quickly eased Ms. Dobren's panic, telling her that these days, metastatic breast cancer can be treated as a chronic disease. While she would have cancer for the rest of her life, they said, life could be expected to go on for many years.

"That was quite a concept for me," recalls Ms. Dobren, 58, a retired New York City guidance counselor. "They talk about partial remissions and full remissions, and all I could think about was that remissions had to do with leukemia. Now that a year has passed, I'm beginning to understand it. I'm still being treated, and I'll always be treated. But I still feel good."

"Things have progressed drastically in the last 20 years," says Margaret C. Kirk, CEO of the support and advocacy group, Y-ME National Breast Cancer Organization. One example: When her organization was created by two breast cancer survivors in 1978, "cancer" was known as the "big C," and no one ever said the words "breast cancer" out loud, she says.

Today, millions of Americans proudly display pink ribbons on their cars, women's magazines devote entire sections to breast cancer coverage during October, and breast cancer research receives more government funding than any other cancer. (1), (2)

New treatment options, solid research and women willing to participate in clinical trials to identify better ways of screening, diagnosing and treating the disease have led to a significant drop in the breast cancer death rate in recent years, even though the incidence remains about the same.

Specifically, while the death rate increased by 0.4 percent a year between 1975 and 1990, it dropped 2.3 percent a year between 1990 and 2002. (3)

Women also are surviving longer with breast cancer, with 88 percent of women still alive five years after their diagnosis, and 63 percent still alive 20 years after their diagnosis. Those figures are undoubtedly higher now, notes the American Cancer Society, since they were based on women diagnosed before more recent treatment advances. (3)

However, the disease is still the most common cancer in women, and the second most common cause of cancer death in women (behind lung cancer). This year, breast cancer is expected to affect an estimated 270,000 women, killing about 40,410, according to the American Cancer Society. (3)

"There are still tremendous challenges around diagnosis and screening tools," says Ms. Kirk. "Other challenges include more effective, less toxic treatments, better translation of science into the clinic and ensuring that all women with breast cancer receive quality care based upon accepted medical guidelines and standards," she adds.

Targeted Treatments

Every time Ms. Dobren pops another chemotherapy pill into her mouth or spends a couple of hours at the oncologist's getting a Herceptin infusion, she's aware of just how far breast cancer treatment has come since she was first diagnosed 10 years ago.

The drug she swallows used to be given only by time-consuming injection. And Herceptin (trastuzumab), a biological drug that targets a specific protein on breast cancer cells, didn't even exist outside the laboratory.

Today, both keep her cancer at bay while enabling her to live a full life, complete with trips to Las Vegas with her husband, an evening glass of wine, weekends at her country home in the mountains of Pennsylvania, and regular workouts.

Indeed, breast cancer treatments have become not only more targeted, but easier to bear, says Funmi Olopade, MD, a breast cancer specialist and professor of medicine at the University of Chicago Medical Center. "We've come a long way since I started in oncology," says Dr. Olopade. "Today, we're all about having people live well, have a good quality of life and be able to manage a normal lifestyle even when they're in the midst of treatment."

For instance, she says, many of her patients receive chemotherapy along with drugs to minimize nausea or receive oral chemotherapy or hormone treatment with very few side effects and are able to work during treatment. She and her peers also have new tools to treat the low blood counts and fatigue that come with chemotherapy, such as erythropoietin to treat or prevent anemia, and hormone growth factors to stimulate the production of immune system cells.

Plus, newer chemotherapies like capecitabine (Xeloda) can be taken as a pill alleviating the need to come to the hospital for an intravenous infusion, says Toni K. Choueiri, MD, a hematology and medical oncology fellow at the Cleveland Clinic Foundation in Ohio, reducing the risk of infection.

Doctors also are getting better at treating hormone-receptive cancers, which make up the majority of breast cancers. These cancers rely on estrogen to grow, so anti-estrogen therapies aim to cut off their fuel supply. The oldest anti-estrogen, tamoxifen, has been used for more than 20 years to treat and, more recently, prevent breast cancer. Today a new class of anti-estrogen drugs called aromatase inhibitors seems to work even better. (4), (5), (6)

Unlike tamoxifen, which works by blocking estrogen receptors on cells, the aromatase inhibitors anastrazole (Arimidex), exemestane (Aromasin) and letrozole (Femara) work by preventing androgen hormones from turning into estrogen in the first place.

Down the road are new and existing drugs packaged as nanoparticles, microscopic materials that hitch a ride on the back of common proteins in the blood to target cancer cells. One laboratory study evaluating nanoparticles loaded with paclitaxel (Taxol), found the particles worked better at killing cancer cells than Taxol alone. (7)

Researchers are also working on vaccines to supercharge the immune system so it can destroy cancer cells. One such vaccine for metastatic breast cancer currently in clinical trials at the University of Pennsylvania and at Johns Hopkins University stimulates the immune system to create special white blood cells that target an enzyme found in more than 90 percent of breast cancer tumors. When the white blood cells go after this enzyme and destroy it, they also destroy the cancer cells. (8)

Genetic Screening Important

Doctors are also getting better at targeting therapies to a woman's individual tumor. For instance, Herceptin doesn't work for everyone; only the 20 to 30 percent of women whose tumors over-express the HER2 gene. But thanks to genetic testing of women's tumors, doctors can tell if the drug should be used.

That's particularly important with Herceptin. Currently approved only for metastatic breast cancer, it's expected to become a first-line treatment after surgery for women with primary breast cancer since studies presented at this year's American Society of Clinical Oncology meeting showed adding it to chemotherapy during adjuvant treatment could halve the risk of recurrence. (9)

Doctors also can use a screening test called Oncotype DX to identify 21 genes the tumor expresses. This enables them to predict the risk of recurrence in women with newly diagnosed, early stage invasive breast cancer and, in turn, determine if chemotherapy is needed, said Dr. Choueiri.

Of course, medicine is also getting better at predicting a woman's risk for breast cancer, particularly if she had a close relative with the disease. Researchers already know that mutations on two genes, called the BRCA1 and BRCA2, significantly increase a woman's risk of the disease. Now they're learning how to take that knowledge a step further, ensuring the cancer is caught early with advanced screening techniques like MRI, or preventing it altogether with prophylactic mastectomy.

But those genetic mutations account for only a tiny percentage of breast cancers. The vast majority occur with no evidence of family history, prompting researchers to look for other clues to a woman's individual risk.

One tool is called the Gail model, a computer program that uses personal and family history to estimate a woman's chance of developing breast cancer. It takes into account such things as when a woman started menstruating, how many children she's had and how early she had them, whether or not she breastfed, her race, age, weight and family history--all factors that play into a woman's risk of developing the disease. The Gail model does not, however, recognize certain risk factors that may influence the degree of risk in some women.

Better Radiation Therapy

Radiation treatment has changed too, notes Carol L. Kornmehl, MD, a radiation oncologist at Valley Hospital in Ridgewood, NJ, and author of The Best News about Radiation Therapy.

Nearly anyone who's had ductal carcinoma in situ (DCIS) or invasive cancer will need radiation, she notes. Why? How about a 30 percent risk of a local recurrence without it versus less than a 10 percent risk of recurrence with it? Not only that, she notes, but if you choose not to receive radiation, any recurrence could be much more serious and invasive than the original cancer. "So it's a risky business not to treat breast cancer with radiation," she says.

The good news? "We're so much better at targeting the radiation to just the tiny area of the breast that has the cancer," she says, using CT scans to exclude as much normal tissue as possible.

Doctors and radiation oncology nurses are also much more aware of how to manage and even reduce skin-related side effects, like redness, tenderness, blistering and ulcers.

"We give patients a break about halfway through their treatment to help minimize or even prevent a nasty reaction," explains Dr. Kornmehl. In the past, radiation oncologists might have continued to treat until the reaction occurred. There are also creams available to help protect the skin during treatment.

Plus, today women can receive internal radiation, also called brachytherapy, as well as external radiation. Brachytherapy involves placing radioactive tubes or even a wire within a balloon (called Mammosite) within your breast in the same spot as the tumor to supplement or instead of regular external radiation treatment.

Some institutions also offer accelerated radiation delivered through external beam, which is completed in two to three weeks.

Radiation therapy can also be an important part of any treatment for metastatic cancer, as Ms. Dobren learned when an MRI revealed the cancer had spread to her brain. She underwent a gamma knife treatment, also called sterotactic radiosurgery, in which a special form of radiation therapy delivers high-energy radiation rays directly to the cancer in the brain. The results, she says four months after the treatment, "look promising."

Hoping for the Best

Mention the word "cure" around cancer doctors, and they cringe just a bit. The word is politically incorrect in the medical field; instead of a cure, doctors talk about survival rates and long-term remission, pointing to the ways in which most cancers are being treated as chronic diseases like diabetes.

"Cure is very important but it is difficult to prove," says Dr. Choueiri. "Cancer can return 10 or 20 years after an initial occurrence. For instance, if a woman diagnosed with breast cancer at age 50 lives without any symptoms of recurrence until she dies of a heart attack at age 80, and then an autopsy finds signs of a recurrence that never bothered her while she was alive, was she really cured? We would rather speak about long-term remissions."

Ms. Dobren no longer thinks about a cure. Instead, she thinks ahead to the next MRI, the next CT scan, the next Herceptin treatment. And she focuses on the fact that, despite the rogue cancer cells in her body, she feels really good. She never stops counting her blessings--like great doctors and nurses and great health insurance. And she focuses on what she can control, rather than what she can't.

"You either live the rest of your life being miserable and being negative and berating your doctors and all the healthy people in the world and moaning, 'why me, why me,'" she says, "or you just say, 'look on the bright side and at all the things you're so lucky to have.'"

Resources

American Cancer Society

1-800-227-2345

www.cancer.org

The American Cancer Society offers vast resources on diagnosis, treatment and prevention for a wide range of cancers, as well as support and advocacy for the disease.

Breastcancer.org

www.breastcancer.org

Web site provides in-depth, easy-to-understand information about breast cancer screening, detection, treatment and living with cancer.

National Cancer Institute

1-800-422-6237

www.cancer.gov

Government agency devoted to research and providing information on cancer. Offers information on clinical trials.

Y-ME National Breast Cancer Organization

1-800-221-2141

www.y-me.org

Advocacy and support organization for women coping with breast cancer. Offers toll-free hotline 24 hours a day staffed by breast cancer survivors and print and online information.

References

(1) Estimates of Funding for Various Diseases, Conditions, Research Areas. National Institutes of Health. September 21, 2005. www.nih.gov.

(2) Defense Health Program, Fiscal Year 2006/FY 2007 Budget Estimates. Department of Defense. www.dod.gov.

(3) Breast Cancer Facts & Figures 2005-2006. American Cancer Society.

(4) Gross PE et al. A Randomized Trial of Letrozole in Postmenopausal Women after Five Years of Tamoxifen Therapy for Early-Stage Breast Cancer. N Engl J Med. 2003. 340:1793-1802.

(5) Howell A, Cuzick J, Baum M, et al. ATAC Trialists' Group. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005;365(9453):60-2.

(6) Coombes R, Hall E, Gibson L, et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004;350:1081-1092.

(7) Prabha S, Labhasetwar V. Nanoparticle-mediated wild-type p53 gene delivery results in sustained antiproliferative activity in breast cancer cells. Mol Pharm. 2004;1(3):211-9.

(8) Study Evaluates Immune Response to Telomerase Tumor Antigen as Possible Vaccine. [Press release]. Philadelphia, Pa. February 9, 2004.

(9) Early Herceptin Use a Breast Cancer Breakthrough. American Cancer Society News Center. May 17, 2005. www.cancer.org.

(10) Chlebowski RT, Chen Z, Anderson GL, et al. Ethnicity and breast cancer: factors influencing differences in incidence and outcome. J Natl Cancer Inst. 2005;97(6):439-48.

RELATED ARTICLE: Breast Cancer Glossary

* Adjuvant therapy. Chemotherapy and/or radiation given after surgery to prevent cancer recurrence.

* Ductal carcinoma in situ (DCIS). A noninvasive form of breast cancer in which cancer cells are found in the lining of a breast duct and limited to only this area. In some cases, it may become invasive and spread to other tissues.

* Metastatic disease. Cancer that has spread to another part of the body.

* Mammogram. X-ray of the breast to screen for breast cancer.

* Mastectomy. Removal of the breast to treat known breast cancer or prevent breast cancer in high-risk women.

* Prophylactic mastectomy. Removal of the breasts in high-risk women to prevent future breast cancer.

RELATED ARTICLE: Racial Disparities in Breast Cancer

At first glance, the declining death rate for breast cancer looks great--until you break it out by rate. While the death rate dropped 2.4 percent in Caucasian women between 1990 and 2002, it only dropped 1.8 percent in Hispanic women and one percent in African-American women. (3)

In fact, overall death rates are 37 percent higher in African-American women than in Caucasian women, even though the incidence of breast cancer in African-American women is lower than in Caucasian women (141 cases per 100,000 Caucasian women compared to 122 per 100,000 African-American women). (10)

Overall, just 76 percent of African-American women survive five years after diagnosis, compared to 90 percent of Caucasian women.

What's going on? Numerous factors, say experts. For one, African-American women are more likely to be diagnosed with more advanced, larger tumors, and their cancer is more likely to be estrogen-receptor negative, a classification that means that many of today's most effective drugs don't work. (10)

They are also less likely than Caucasians to get mammograms and less likely to have health insurance, and more likely to have lower incomes, unequal access to medical care and disparities in their treatment. (10)

"Racial disparities are always an issue in any cancer, whether it is breast cancer, leukemia or other cancers," says Toni K. Choueiri, MD, a hematology and medical oncology fellow at the Cleveland Clinic Foundation in Ohio. "Future research needs to more specifically target the area of cancer and race."