Publications
Insight, Summer 2005
The summer 2005 issue of Insight contains stories that will help you understand targeted therapies, provides updates on clinical trials from the 2005 meeting of the Annual Society of Clinical Oncology and describes post-traumatic growth, the idea that a breast cancer diagnosis can lead to positive personal change.
Table of Contents
Understanding Targeted Therapies: What They Mean for You
Until the mid-20th century, healthcare providers in the United States treated breast cancer uniformly. Most women with tumors of 1 centimeter or more received chemotherapy, sometimes with hormonal therapy, because of the belief everyone could benefit from it.
Although increased public awareness and improved screening methods led to more and earlier diagnoses, we continued to treat breast cancer the same. In Europe, however, oncologists who believed American physicians "overtreat" breast cancer began to explore the idea chemotherapy could benefit some women more than others. They spearheaded the study of targeted therapies (TT), which identify specific proteins, receptors or antibodies that may influence the potential for development or recurrence of breast cancer.
Unlike chemotherapy, which cannot distinguish healthy cells from malignant cells, TTs identify a specific therapeutic target in the biology of the cancer cell and use a particular agent to modify the activity or amount of this target. Since TTs are designed for individual sites, only those women who might benefit would receive a specific medication. And as researchers identify more targets, women can expect to receive more personalized therapy—and a variety of treatments for breast cancer.
Are They Really New?
Early TTs included surgical procedures to reduce or remove the body’s supply of estrogen. One example is removal of the ovaries (oopherectomy). In women who test positive for the BRCA1 or BRCA2 gene abnormality, a diagnosis of breast cancer may significantly increase the risk for ovarian cancer. An oopherectomy may be performed to reduce risk.
More recently, researchers have developed medications that block or inhibit estrogen without surgical intervention. These therapies are designed to modify hormone pathways, inhibit certain molecular binding necessary in cancer development, and reduce the number and activity of hormone receptors, thus blocking or eliminating the receptors, or lowering the level of hormones.
The Pathology Report
One of the most important tools in understanding your particular breast cancer is the pathology report. This report classifies or grades tumors using the TNM (Tumor, Node, Metastasis) staging system based on three factors: the size of the tumor; the number of positive lymph nodes, if any; and whether the tumor is confined to the breast and axillary lymph nodes or has spread to other areas.
You should ask your healthcare team the following questions:
• What is the size of my tumor? This information assists your healthcare team in determining the extent of disease.
• Is my cancer ductal or lobular? Ductal originates in the milk ducts; lobular originates in the lobules of the breast.
• Is it in situ or invasive? In situ refers to a tumor contained in the ducts or lobules; invasive refers to tumors that break through the ducts or lobules into the surrounding tissue.
• Were any lymph nodes removed for testing? Were any of the lymph nodes positive for cancer cells? Positive lymph nodes indicate the cancer has moved from the breast to another part of the body. This information is valuable in determining the aggressiveness of treatment needed.
• What is the stage of my tumor? The TNM staging helps your oncologist design an effective treatment plan.
• Is my tumor estrogen or progesterone-receptor positive or HER2/neu positive?
• What are all the options available for my treatment? Knowing all treatment options can help you participate in the decision-making process.
In addition, you should also have a complete physical examination, usually including x-rays, scan, and blood work. Let your healthcare team know about pre-existing medical conditions, especially heart, kidney, or lung diseases. This information will help determine which treatments would be the most effective and most appropriate for you.
You may also have tissue from your tumor analyzed using the new Oncotype DX 21-gene panel assay. In recent trials, this test successfully predicted the likelihood of recurrence for women with early-stage, estrogen receptor-positive breast cancer. Knowing your "recurrence score" could help your healthcare team determine whether you would benefit from chemotherapy treatment or hormonal treatment alone.
Hormone-Based Targets
Approximately two-thirds of women with invasive breast cancer are ER+. Many are also progesterone receptor positive (PR+). Researchers recognized that if they developed certain hormonal medications to bind with these receptors, the influence of estrogen on breast tumors would be significantly impacted, resulting in a potential decrease in recurrence and increase in survival.
There are several classifications of hormonal therapies:
Selective Estrogen Receptor Modulators (SERMs) interfere with estrogen’s ability to bind to receptors. The first of these medications, and still the first choice for impacting estrogen binding, is tamoxifen (brand name: Nolvadex). Success rates are excellent with an almost 50 percent reduction in new tumor development. Many women report hot flashes and vaginal symptoms. Rare but serious risks include stroke, blood clots, uterine cancers and an increase in cataract development. Both pre- and post-menopausal women can take tamoxifen, so those who are pregnant or plan to become pregnant should not take it.
Fulvestrant (brand name: Faslodex) is a Selective Estrogen Receptor Down-Regulator (SERD), another type of hormone therapy. Fulvestrant is similar to tamoxifen in its actions, but while tamoxifen modifies the receptor’s ability to bind with estrogen, SERDs attach to, block and destroy receptors. Fulvestrant is indicated only for post-menopausal women because it has been tested only in this group of women. Common side effects are nausea, vomiting, constipation, diarrhea, headache, back pain, hot flashes and sore throats. Some women experience blood clots and joint aches, although very rarely.
Toremifene (brand names: Acapodene, Fareston) is a SERM that works like tamoxifen. It has the advantage of a decreased risk of uterine cancer.
Raloxifene (brand name: Evista) strengthens bones. The Food and Drug Administration (FDA) has approved it for use in osteoporosis in post-menopausal women. Raloxifene has been found to lower the risk of developing breast cancer in post-menopausal women who have concurrent osteoporosis. A National Surgical Adjuvant Breast and Bowel Project (NSABP) trial is comparing raloxifene to tamoxifen for women at high risk for developing breast cancer. Side effects include hot flashes and vaginal changes. Rare incidences of stroke and blood clots have been seen.
Goserelin (brand name: Zolodex) works to prevent the ovaries from producing estrogen. Pre-menopausal women will begin menopause if they take both goserelin and tamoxifen, which usually results in significant bone loss. If untreated, this may lead to osteoporosis. Speak with your physician about methods to prevent bone loss, such as taking calcium and Vitamin D supplements and doing weight-bearing exercise. A recent study showed zoledronate (brand name: Zometa) may stop bone loss, especially in pre-menopausal women.
Aromatase inhibitors (AIs) lower the body’s production of estrogen in muscle and fat tissue by targeting the enzyme that transforms certain hormones to estrogen. Since AIs have no effect on estrogen produced by the ovaries and other tissues, they should not be used in pre-menopausal women. Anastrozole (brand name: Arimidex), letrozole (brand name: Femara), and exemestane (brand name: Aromasin) are the three AIs now in use. In trials, women who took these medications had decreases in recurrence of breast cancer, especially in the unaffected breast, as well as an increase in survival compared to those who took tamoxifen. Common side effects with AIs include fatigue, joint pain, diarrhea, hot flashes and vaginal dryness/loss of sexual drive. Rare incidences of headache, dizziness, vaginal bleeding, skin rashes, nausea, thinning hair, elevated cholesterol, bone fractures, heart attacks and strokes have been reported.
Targeting HER2/neu
The HER2/neu oncogene (cancer gene protein) is one of several proteins that can malfunction and "overexpress" itself, meaning it provides an excess or abnormal amount of proteins, or receptors. HER2/neu cancers tend to be aggressive and more likely to recur.
ImmunoHistoChemistry (IHC) and Flourescence In Situ Hybridization (FISH) are the two most frequently used tissue studies to test for the HER2/neu receptor protein. The IHC is scored on a zero to 3+ scale. A negative test will register zero or 1+; a positive test, 2+ or 3+. The FISH test looks for abnormalities in the HER2/neu gene and is scored as either "positive" or "negative." It is the more accurate of the two, but it is not as readily available.
The antibody trastuzumab (brand name: Herceptin) blocks HER2/neu receptors, slowing the growth of cancer. It has shown great success in metastatic breast cancer and is being tested on women with early-stage disease. Common side effects include flu-like symptoms, low white or red blood cell counts, diarrhea and infections.
Tell your healthcare team if you have a history of heart or lung problems. In rare but serious cases, trastuzumab has damaged the heart’s ability to pump blood. This can lead to stroke or congestive heart failure. Prior to beginning the medication and during therapy, your doctor will probably order tests on your heart to determine its pumping ability. Sometimes people develop allergic reactions, lung dysfunction, low blood pressure and fluid buildup around the lungs.
Promising New Targets
Lapatinib (GW572016) inhibits growth and induces death of breast cancer cells. It also affects HER2/neu receptors, and clinical trials have shown it benefits women whose tumors do not respond to trastuzumab. In a Phase I clinical trial, the primary side effects reported in about 10 percent of participants were diarrhea, rash and fatigue. The FDA has not yet approved lapatinib for any use, so it is available only through clinical trials.
Bevacizumab (brand name: Avastin), originally approved for the treatment of colon cancer, has shown promising results in clinical trials for breast cancer. Bevacizumab works by blocking blood-vessel growth. Researchers theorize that by impeding the tumor’s blood supply, the cancer cells will begin to die. Side effects, while serious, are uncommon, and include lung hemorrhages, blood clots, stroke and heart attacks.
There is much ongoing study in targeted therapies for breast cancer. If you are in treatment, you should ask your healthcare team for information about any new studies or clinical trials.
Susan M. Coles, RN, MSN, AOCN, APRN-BC works at the Jeanette Rudy School of Nursing at Cumberland University, Lebanon, TN. She has worked in nursing since 1972 and in oncology since 1987. She is a board certified acute care nurse practitioner and certified as an advance-practice oncology nurse. She is approaching the second anniversary of her diagnosis of invasive breast cancer.
Cheryl Dudley: Inspired by Faith, Motivated by Change
Cheryl F. Dudley, 47, has lived her life guided by faith.
The daughter of a minister, Cheryl left her hometown of Phoenix, Arizona, to become an ordained minister in the American Baptist Church. During her years in Peoria, Illinois, she advocated for the poor as a pastor and community organizer. And when her path led her to Pennsylvania, Cheryl joined a national effort to promote racial understanding and reconciliation. She provides people with tools to better communicate across cultures.
"God continues to call, and that yearning was deep within me," Cheryl says. "I grew up in an ethnically diverse setting, so [this job] is a natural for me. When there’s diversity, that feels right."
Change came calling in April 2002, when Cheryl was diagnosed with breast cancer. Doctors discovered her disease as a result of her annual mammogram. Six weeks later, Cheryl had her first surgery, a lumpectomy and sentinel lymph node biopsy. Her pathology report showed the cancer was limited to her breast. Cheryl and her healthcare team decided upon a course of chemotherapy and radiation treatment.
Cheryl had faced seemingly intractable challenges before, but breast cancer tested her faith in a personal way.
"In ministry, you counsel and teach that God does not punish people by giving them disease," Cheryl recalls. "I said, ‘God, I wasn’t a smoker. I didn’t eat fatty foods every day. My lifestyle had been careful. I’ve been faithful all my life.’ I just didn’t understand."
Cheryl says people often blame God for their troubles. Her anger, however, dissipated quickly. "It was cathartic and helpful to rage a while. Then you receive the lessons and the blessings that are yours to receive through the experience," she says.
Among the blessings Cheryl received was her network of friends and family. People from different parts of her life traveled cross-country during her chemotherapy treatments. Those who could not make the trip sent mail-order meals. Her neighbors helped out, and her friends sent cards and called. Their message was simple, Cheryl says, "You are one of us. We are going to be with you through this."
Support also came from unexpected places. After surgery and chemotherapy, Cheryl was exhausted. But she still had 37 daily radiation treatments ahead. As she and a technician sat in the radiation oncologist’s office planning the treatments, she broke down and cried. The technician looked her in the eye and told her she had gone through the worst part already. "She was right. And because you see those folk every day, they feel like family. They are your touchstone," Cheryl said.
As she has throughout her life, Cheryl relied on her faith. She met with a prayer group that practiced visualization techniques. In her prayers, the Catholic nun who ran the group saw Cheryl in a white healing light. Eventually the light was replaced by a red flame, representing the spirit of life coming through her.
This image became important to Cheryl. It reminded her of a saying from the scriptures: "Your fear will melt away like wax." She created her own healing rituals, including burning red and heart-shaped candles.
Cheryl’s long hair fell out during chemotherapy. The experience was traumatic but she took it in stride. She jokes that she experimented with her "5,000 scarves, 57,000 hats and 800 bald caps because one of the advantages of being African-American is that you can do funky things to your head and feel like that’s OK."
She also bought a wig, but she never wore it. "I didn’t recognize myself," she says. "I recognized myself a little better without it."
Cheryl, who is unmarried, socialized throughout treatment. She spent time with a man who shaved his head and they compared notes. She also says she learned an important lesson about intimate relationships.
"We define our sensuality around our hair," she says. "I found out you still have your sensuality without it. It’s about who you perceive yourself to be and how people respond to you."
Cheryl worked during much of her treatment. She cut back to an eight-hour day and curtailed long-distance travel. She discovered, however, that treatment had caused severe dryness in her throat. This side effect made it difficult for her to do public speaking, a major part of her job. She lost self-confidence.
She decided to reframe her gifts by "giving birth to more artistic endeavors." She returned to writing, a favorite pastime of her youth. She also walked a labyrinth. Labyrinths have existed for centuries and may be structures—paths separated by hedges—or designs on paper that people trace with their fingertips. The labyrinth gave Cheryl energy and helped her feel God’s presence in her life.
Last March, Cheryl began designing her own labyrinth, which she plans to make available online. "It is a prayer, a meditation tool," she says. "It integrates reconciliation, my other passion. This is one of the most significant things I’ve done in my life."
Cheryl also took up yoga after attending LBBC’s Yoga Unites for Living Beyond Breast Cancer in June 2003. She enjoyed doing yoga outdoors and learned methods to strengthen areas of her body impacted by treatment.
Several months after her treatment ended, Cheryl rediscovered her voice. Now she is back on the road, helping people cross the racial divide and do the spiritual work necessary for change. Her voice has changed.
"A shift happened inside—now I speak about something that comes out of my heart rather than my head," she says. "I’m revealing more of my insights than I did before. I’m not afraid to be out of the mold."
One reason Cheryl agreed to share her story is to help others. Wherever she goes, she feels surprised by the number of women she meets with similar stories: "We’re everywhere, but we fade into the background. If my own experience is helpful to someone, then I am glad to share it."
Would you like to be considered for a Survivors’ Profile? Send a 250-word description of your experience to .
Diet Impacts Risk for Recurrence
Results from a phase III clinical study showed a low-fat diet may reduce the risk of recurrence for post-menopausal women with early-stage breast cancer, particularly those with estrogen-receptor negative disease.
Between 1994 and 2001, 2,437 women participated in the Women’s Intervention Nutrition Study. Participation was limited to post-menopausal women who received treatment during the previous year.
Women in this prospective study were randomly assigned to two dietary groups. The first made no significant changes to their standard diet but met periodically with a nutritional counselor. They ate, on average, 51 grams of fat per day. The second group of women modified their diet so that dietary fat composed 20 percent of their total daily calories. The women on the low-fat diet reduced fat intake by using less cooking oil, eating more fruits and vegetables and managing portion size. They received one-on-one dietary counseling once every two weeks for 16 weeks, and then once every three months for the remainder of the study. These women ate an average of 33 grams of fat per day and lost, on average, four pounds.
After a median of five years follow-up, 12.4 percent of the women on the standard diet experienced a recurrence, versus only 9.8 percent of those on the low-fat diet. This difference amounts to a 24 percent reduction in the risk of recurrence for women on the low-fat diet. The most pronounced risk reduction, 42 percent, occurred among women with ER- breast cancers.
More research is necessary to determine whether these women’s rates of recurrence may be because of other factors; for example, weight loss, increased consumption of fruits and vegetables, or the inclusion of chemotherapy in initial treatment. But the results suggest post-menopausal women, particularly those with ER- breast cancer, may want to discuss a low-fat diet with their healthcare team.
R.T. Chlebowski, et. al., Dietary fat reduction in postmenopausal women with primary breast cancer. Abstract 10. 2005 ASCO Annual Meeting.
Combating Bone Loss
Recent results from a multi-center trial suggest that women who take a bisphosphonate upfront with an aromatase inhibitor (AI) experience an increase in bone mineral density over those who start bisphosphonate treatment later.
Researchers have strong interest in combating treatment-related bone loss with bisphosphonates, which are used to build bone in people with osteoporosis. Women who take AIs are at risk for bone loss because estrogen has a protective effect on the bones.
The Z-FAST, or Zometa-Femara Adjuvant Synergy Trial, enrolled 602 women with Stage I-IIIa, ER+ breast cancer who underwent surgery to remove cancerous cells. Women with metastatic disease could not take part.
Participants were randomized into two groups. The first received an infusion of 4 mg of zoledronic acid (brand name: Zometa) upfront every six months beginning the first day of treatment with letrozole (brand name: Femara). The second group received the same treatments and dosages but with a delayed start of the Zometa.
After 12 months of follow-up, women who received the upfront Zometa with letrozole showed a mean increase of bone mineral density in the lower back of 1.9 percent versus a decrease of 2.4 percent in the other group. The upfront group also showed stronger bone mineral density in the hip area. About one-third of participants reported joint pain; other side effects reported include hot flashes, fatigue, and muscle and bone pain.
If you are considering an AI, this study suggests you may want to discuss taking a bisphosphonate before you begin treatment.
Studies Examine Differences in Treatment for African-Americans
Two studies presented at the American Society of Clinical Oncology (ASCO) Annual Meeting support the importance of LBBC’s outreach efforts.
One study reported that African-American women are more likely than other women to experience delays in the diagnosis and treatment of breast cancer. Delays are significant because postponing treatment for three months or more can decrease the five-year survival rate by 12 percent.
In this study, African-American women were 89 percent more likely than other women to have a diagnostic delay of more than one month, 58 percent more likely to have a treatment delay of more than one month and 81 percent more likely to have a total clinical delay (diagnosis plus treatment). Researchers attributed the differences to biological and genetic factors, cultural differences and healthcare access issues.
A second study examined whether African-American women die more often from breast cancer than other women because they receive lower doses of chemotherapy. Previous research showed that African-Americans sometimes have lower numbers of white blood cells (WBCs) than Caucasians. Since some chemotherapy treatments further reduce the number of WBCs, which protect the body from infections, researchers thought doctors might be giving African-American women lower doses of chemotherapy. The study showed that chemotherapy dosing is equal for Caucasian and African-American women and suggested more research is needed to understand the differing mortality rates.
LBBC is committed to reaching out to African-Americans with meaningful educational materials to encourage timely diagnosis and treatment. LBBC wrote and distributes a 40-page, consumer-focused book, Getting Connected: African-Americans Living Beyond Breast Cancer. This book is available free of charge to women affected by breast cancer and at low cost to healthcare professionals.
LBBC will continue to explore partnership opportunities and new vehicles to reach African-Americans. For more information, contact Gerda Gallop-Goodman at the LBBC office or .
