Earlier this year Andrea Barish learned how new high-tech tools are  supplementing an old one—mammography, still the screening method of choice&mdash;in  detecting and diagnosing breast cancer. 

Barish, 45, strategic director of communications for Northern California at the American Cancer Society’s office in Oakland, underwent surgery in 2006 for removal of an early-stage invasive ductal carcinoma in her left breast, followed by radiation and chemotherapy. The centerpiece of her follow-up screening in February 2007 in San Francisco was digital, rather than film, mamography.

Digital mammography captures X-ray images in computer code instead of on  X-ray film, enabling the operator to adjust an image’s magnification,  orientation, brightness and contrast to get a clearer view. Unlike its film  counterpart, the digital device entails lower radiation doses and virtually no  wait for results.

“It was very interesting,” Barish says. “One of the things I wasn’t quite  prepared for was that they were able to give me my results immediately.” She  says not having to wait anxiously for the film to be developed and read, and for  the findings to arrive days later on a postcard, brought her some comfort but  also meant she might have to contend with distressing news that same day.  Fortunately, the digital mammogram did not detect signs of recurrent  disease.

One of the things I wasn't quite prepared for [with digital mammography] was  that they were able to give me my results immediately.

The goal of screening is not only to find more cancers, but to have that  result in improved survival for those patients. Experts attribute declines in  breast cancer deaths since 1990 to a combination of early detection, with the  aid of tools like mammography, and better therapies. Statistics show mammograms  reduce such deaths by 20 to 35 percent in women between ages 50 and 69, and by  about 20 percent in women in their 40s. The American Cancer Society now  recommends women undergo annual mammograms beginning at age 40 (the previous  recommendation was every year or two for ages 40 to 49) because earlier  detection means a greater chance of survival and more treatment options.

Clinicians are turning to state-of-the-art tools and techniques, or  combinations of them, to supplement mammography and in some cases ease the  impact of procedures on patients. Although mammography remains the only widely  accepted (and most widely available) imaging method for routine breast cancer  screening, various other techniques may be used.

In addition to improving the quality of images the radiologist sees and, as  Barish discovered, speeding the whole screening process, a study of about 50,000  women, published in the 

 in 2005,  suggested another potential advantage. Although overall diagnostic accuracy of  the two screening techniques was similar, investigators reported that digital  mammography was more accurate than film mammography as a screening tool for  women with dense breasts, those younger than 50 and who are premenopausal or  perimenopausal.

Often‚ digital mammography is paired with sophisticated software that can  bring suspicious areas to the radiologist’s attention. CAD‚ or computer-aided  detection‚ is pattern-recognition software that can flag suspicious lesions the  radiologist may have overlooked and that might warrant examination. It leverages  the notion that computer knowledge tends to be more consistent than human  knowledge in analyzing an image, says Gary Whitman, MD, a radiologist at M.D.  Anderson Cancer Center in Houston.

“Maybe one day the radiologist is distracted or just not focusing, and  performance drops off a bit,” he says. “With the computer, performance should be  relatively constant.” However, a new study published in 

 in April  found that use of CAD did not clearly improve the detection of breast cancer and  may instead make readings less accurate, leading to a higher number of false  positives.

This technique involves removing a tissue sample with a hollow needle instead  of surgically, which entails greater risk, discomfort and scarring. Minimally  invasive biopsies, such as fine needle aspiration (FNA), core biopsy and  vacuum-assisted biopsy, are commonly used and have the potential to spare up to  80 percent of women who otherwise might undergo open breast biopsy.

Danene Birtell has seen the payoffs of minimally invasive biopsy firsthand.  Daunting aspects of two surgeries back in 1998 and 2001—preoperative blood work,  general anesthesia, scalpel cuts and sutures&mdash;to excise a suspicious growth from  her right and then her left breast after core biopsies seem almost quaint  now.

That’s because in 2006, the 31-year-old veterinary nurse from Yardley,  Pennsylvania, had a third growth removed as an outpatient by means of a  vacuum-assisted biopsy. After a small incision and under local anesthesia, the  doctor pinpointed and removed the growth from surrounding tissue through a  pencil-sized needle. Doctors can withdraw larger segments of tissue with  vacuumassisted biopsy than with FNA or core biopsy.

In all three instances, the growths proved to be benign fibroadenomas. But  the third time, Birtell could watch the entire procedure on a nearby monitor  while interacting with the surgeon. Closure of the quarter-inch surgical cut  with tape strips rather than traditional sutures contributed to her quick  recovery, despite some minor bruising. She even attended kick-boxing camp in  Oregon the following week.

“I think the development of this procedure is just great,” Birtell says. “The  less [surgery], the better.”

Echoes from sound waves bounce off tissues and organs, producing distinct  images. Ultrasound, or sonogram, can distinguish between solid masses and  fluid-filled cysts, assess lumps that are difficult to see or inconclusive on a  mammogram, or guide a surgeon’s instrument to a precise location during  biopsy.

“The quality of the ultrasound image has improved, which makes it easier to  put the [biopsy] needle in the right place and to see lumps that are a bit  smaller than we used to be able to see—and see them accurately,” says Jack  Meyer, MD, a radiologist at Dana-Farber Cancer Institute and Brigham and Women’s  Hospital in Boston. Studies are ongoing to see if ultrasound can be useful as a  screening tool in addition to simply focusing on abnormalities picked up on  physical examination or mammogram.

What's been exciting is that we’ve discovered MRI can detect cancers invisible  on mammography, on ultrasound and on clinical breast exam.

A magnet linked to a computer yields detailed, threedimensional images of  tissue—enhanced by an intravenous contrast agent&mdash;without the radiation exposure  that comes with X-ray mammography.

MRI is versatile. Among other uses, it can investigate suspicious findings on  mammogram images, which are only two-dimensional; investigate abnormal tissue  that is felt but not visible on a mammogram or ultrasound; assess the extent of  diagnosed disease; and potentially find cancer that mammography overlooked in  the dense breasts of younger women, especially those at high genetic risk.

“What’s been exciting is that we’ve discovered MRI can detect cancers  invisible on mammography, on ultrasound and on clinical breast exam,” says  Constance Lehman, MD, PhD, director of breast imaging at the Seattle Cancer Care  Alliance. Breast MRI remains a difficult examination to perform and interpret  well, say experts, and requires highly experienced breast MRI clinicians. In  addition, MRI is currently used primarily in very high-risk situations, such as  individuals with a genetic predisposition—specifically, mutations in the BRCA1  or BRCA2 genes.

The American Cancer Society published new guidelines in March for breast  screening MRI to include women with a BRCA1 or BRCA2 mutation (the inherited  gene mutations that carry a high risk of breast cancer), a strong family history  of breast or ovarian cancer, a 20 percent or greater lifetime risk of breast  cancer and who had radiation therapy to the chest for treatment of Hodgkin’s  disease.

PET scans are more accurate in finding large, aggressive growths. Since tumor  tissue uses more glucose than normal breast tissue‚ PET scanning detects tumors  by determining sugar absorption in breast tissue. Clinicians may also use PET to  gauge the extent of disease—though the test may not be completely accurate&mdash;and  to monitor tumor shrinkage after treatment.

At first glance, breast cancer may appear no match against this impressive  arsenal. But, as clinicians are quick to point out, no individual tool is  appropriate for detecting all types of breast cancer. And each has strengths and  weaknesses— including high cost and, in some instances, false positives (results  that initially suggest cancer but in fact are benign, leading to needless  anxiety for patients and unnecessary surgery).

Take ultrasound, for example. While ultrasound is “very powerful,” its  sensitivity—the proportion of true positives it finds&mdash;in detecting breast  cancer isn’t as high as with MRI, says Dr. Lehman. High sensitivity may mean MRI  is particularly appropriate for high-risk women who are genetically predisposed  for breast cancer.

 in March that MRIs in women who were  diagnosed with cancer in one breast detected more than 90 percent of cancers  in the other breast that were missed by mammography and clinical exam at initial diagnosis. “We found that when we add screening MRI to the screening  mammography program, we can significantly increase the number of cancers we find  in this group,” says Dr. Lehman, who served as principal investigator of the  study. “It’s very exciting.”

The long-term hope of MRI’s ability to predict absence of a tumor, say  researchers, is to reduce the number of unnecessary double, or bilateral,  mastectomies at initial diagnosis. On the other hand, the heightened sensitivity  that makes MRI so valuable can result in low specificity—a high rate of false  positives. That may mean MRI is less appropriate for lower-risk women, and  experts caution MRI should not be substituted for mammography.

The future holds promise for even newer technologies and for refinement of  those available now. For example, researchers hope biomarkers—molecular or  cellular indicators of susceptibility to or the presence of disease&mdash;will one day  prove effective in detecting breast cancer earlier, perhaps in combination with  other screening methods. BRCA1 and BRCA2 serve as biomarkers. The goal is to  identify other cancer susceptibility genes and blood-borne indicators that would  reliably aid detection in much larger populations, says Jeffrey Marks, PhD, an  associate professor of surgery at Duke University Medical Center in Durham,  North Carolina, who is studying the molecular biology and genetics of breast  cancer.

To be of clinical value, he says, new biomarkers must demonstrate higher  sensitivity and specificity than mammography—that is, generate fewer false  negatives and false positives&mdash;or somehow work in tandem with mammography.  Marks’s research focuses on creating a so-called library of antibodies for  breast cancer-secreted glycoproteins that, in conjunction with mammography,  could be applied to help discriminate between cancerous and benign findings.

However, such breast cancer assays are years away, says Marks.“There’s no  shortage of biomarkers that have been proposed, but none of them have very good  performance in real-life specimens.”

While biomarker research may not produce immediate screening payoffs, it  along with refined technologies like digital mammography are expected to lead  clinicians closer to a common goal: earlier detection of breast cancer that  translates into more patients living longer.

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Patients benefit from ease and success of modern breast cancer screening.

To Catch a Cancer

Despite the high-tech tool chest available to clinicians these  days, routine followup screening of asymptomatic women for recurrent breast  cancer still comes down to three familiar mainstays recommended by the American  Society of Clinical Oncology: careful history taking, physical examination and  regular mammography.

Updated guidelines from ASCO in late 2006 for breast cancer  follow-up and management include breast exams every three to six months for the  first three years, every six to 12 months in the fourth and fifth years, and  annually thereafter for women who underwent mastectomies.

Patients who had breast-conserving surgery should get a mammogram  one year after the initial mammogram and at least six months after completing  radiation. Patients at high risk for familial breast cancer syndromes should be  referred for genetic counseling.

"Beyond history, physical exam and mammogram, there is no test of  any proven value in routine screening for the large majority of women with  breast cancer,” says Stephen Edge, MD, chief of breast surgery at Roswell Park  Cancer Institute in Buffalo, New York.

A number of new tools are available for predicting recurrent  breast cancer or for monitoring possible progression of disease. In February,  attention focused on the Food and Drug Administration’s approval of  MammaPrint

, the first molecular genetic profiling test for estimating whether breast cancer will spread or recur. However, experts say  clinicians are unlikely to use the gene-based test at this time in the United  States based on the difficulty of processing samples. A piece of the tumor  removed during surgery must be shipped to a lab in the Netherlands, making  the one- to three-week process impractical for everyday clinical use.

Although it received FDA approval in 2004 for predicting breast  cancer survival, a blood test called CellSearch™ gained an additional approval  in December 2006 for monitoring metastatic breast cancer. CellSearch detects  circulating tumor cells that have detached from a tumor and entered a patient’s  bloodstream.

Detecting recurrence at an early stage in asymptomatic women  is only half the battle; the other is pairing test results with specific  therapies known to improve outcomes.

Dr. Edge says such tests pose a thorny challenge. Detecting  recurrence at an early stage in asymptomatic women is only half the battle; the  other is pairing test results with specific therapies known to improve outcomes.  Detection alone, Dr. Edge says, may simply increase the length of time a  woman knows she faces a recurrence without any effective treatment options. The  development of better tests for recurrence and effective treatments that may  actually cure women at the very earliest signs of recurrence is a high  research priority. 

Content

The mainstays of screening for recurrent breast cancer remains physical exams and mammography, although researchers are looking for better ways to predict and find recurrences.  

Screening for Recurrent Breast Cancer

In a minute’s time, Kristine Kulowiec went from total despair to excitement.  Herceptin

 (trastuzumab) and chemotherapy had stopped working for her  recurrence of HER2-positive metastatic breast cancer, which meant the  49-year-old qualified for a clinical trial of a new targeted drug combination.  

“When the physician’s assistant told me the CT (computed tomography) scan  came back showing growth, I didn’t really hear anything else after that,”  Kulowiec says. She was barely listening to the information the assistant was  giving her about a clinical trial when her oncologist walked in.

“Now we can really get down to business,” Kulowiec remembers her doctor  saying with a big smile.

“She was so excited about this trial and wanted to tell me,” says Kulowiec,  who lives in Wake Forest, North Carolina. “Seeing her excited made me really  excited about it. All of a sudden, I realized this was really important.”

Because Kulowiec’s cancer had progressed on Herceptin, she qualified for a  study examining a combination of Herceptin and Tykerb

  (lapatinib)—another targeted agent that inhibits HER2, but by a different  mechanism. She started the combination in September 2006, and by mid-March of  this year, Tykerb was approved for metastatic disease in combination with an  orally administered chemotherapy called Xeloda

 Herceptin ushered in the age of personalized breast  cancer therapy in the 1990s. Researchers found cancer cells that overexpress the  HER2 protein on their surface make good targets for the monoclonal antibody,  which was first approved for metastatic breast cancer in 1998. In 2005, an  analysis of two large phase III clinical trials showed Herceptin plus  chemotherapy cut the recurrence rate in early-stage breast cancer by half  compared with chemotherapy alone, and the Food and Drug Administration  consequently approved the drug for that indication in 2006. Side effects of  Herceptin include fever, nausea and, rarely, heart damage.

Newly approved Tykerb targets both HER2 and the epidermal growth factor  receptor (EGFR), also called HER1. The Tykerb/ Xeloda combination delayed  disease progression for 27.1 weeks compared with 18.6 weeks for patients taking  Xeloda alone. Researchers are still waiting to see if an overall survival  benefit results from the combination. Because Tykerb had such positive results  in advanced cancer, experts believe the benefit in early-stage cancer will be  even more dramatic, as was the case with Herceptin.

But that’s where the comparison ends, says Neil Spector, MD, director of the  Translational Research Oncology program at Duke Comprehensive Cancer Center, who  contributed to the development of Tykerb, which began nearly a decade ago. One  of the attributes that distinguishes Tykerb from Herceptin is its  administration—oral versus Herceptin’s intravenous delivery. But it also works  differently.

There are multiple benefits in assessing individual tumors in individual  patients instead of lumping everything together as breast cancer.

“The best analogy is if you looked at the tumor cell as a room with a bunch  of wall sockets, with the sockets providing power that promotes the growth and  survival of the room. Herceptin is the childproof cap,” Dr. Spector says,  whereas Tykerb “cuts the wire inside the wall.”

For 16 weeks, Kulowiec saw her tumors shrink on the Tykerb and Herceptin  combination, a response even her doctors didn’t expect. At 24 weeks, her cancer  has stabilized. “I feel so much better now than I did six months ago—to me,  that’s the miracle,” Kulowiec says, who no longer has to take naps because of  severe fatigue and can drive herself to treatment. Patients taking Tykerb may  experience diarrhea, vomiting and rash.

 Even before the approval of the anti-estrogen  therapy tamoxifen 30 years ago, scientists knew not all breast cancers behaved  the same way. Tamoxifen was the first drug approved for the type of breast  cancer fueled by hormones—namely estrogen. It works in about half of all women  with estrogen receptor-positive breast cancer by mimicking the hormone and  binding to its receptor to shut down cancer growth. At the time, it was  considered a huge success and is still the standard treatment for breast cancer  in premenopausal women. The drug may cause hot flashes and increased risk of  blood clots and uterine cancer, though this is rare.

Another type of anti-estrogen therapy called aromatase inhibitors (AIs),  which include Aromasin

 (letrozole), work by reducing estrogen  production, primarily from the adrenal glands and fat issue since the ovaries in  postmenopausal women no longer produce estrogen. AIs, which can cause  significant bone loss, have been found to be effective in early-stage and  advanced breast cancers, but are only used in postmenopausal women.

Although estrogen receptor-positive breast cancers have been studied for  decades, evidence shows these cancer cells may be “smarter” than previously  thought. Cancers sometimes develop resistance to drugs like tamoxifen,  especially in advanced-stage disease. “One of the frustrating aspects is you  often see very dramatic clinical responses where the tumor just melts away, but  unfortunately the tumor comes roaring back,” says Dr. Spector. “The question is  what is in the tumor that enables it to develop resistance?”

Scientists suspect some hardy tumor cells that use estrogen to fuel growth  change their growth pathway from estrogen to HER2 when flooded with  anti-estrogens. Likewise, while HER2-positive breast cancer cells may respond  tremendously to Tykerb or Herceptin at first, after a while some cells become  resistant. Therefore, researchers are pounding the cancer with multiple drugs  that target estrogen receptors and HER2 at the same time to destroy cancer cells  before they begin to alter their growth pathway. 

“We found that if we treated [cancer cells] upfront with Tykerb and an  anti-estrogen—the most effective being fulvestrant (Faslodex

),” says  Dr. Spector, “you could essentially prevent the development of resistance in  cell culture (laboratory tests).”

In a human study published in the journal Cancer in 2005, 240 patients with  no previous therapy for their estrogen-sensitive, HER2-negative cancer were  treated with either tamoxifen or Femara. At the time of disease progression, 26  percent of patients were found to have cancers that converted from HER2-negative  to HER2- positive disease.

“Does this mean we have the possibility of preventing all acquired resistance  in patients receiving these [therapies]? We certainly hope so,” Dr. Spector  says. “Clinical trials that are ongoing—combining aromatase inhibitors and  Tykerb, Faslodex and Tykerb, tamoxifen with Tykerb&mdash;will hopefully validate the  lab findings.”

View Illustration: Cross-Talking Receptors

You don't waste money, you don’t waste time and you don’t waste women’s lives.  People won’t have to wait a long time to see if a drug works or not. It’s very  innovative and it’s really going to revolutionize the way we test drugs.

 A target scientists have utilized to create several  new drugs is the VEGF protein. Avastin

 (bevacizumab) neutralizes  VEGF, thus inhibiting a process known as angiogenesis in which the tumor  secretes proteins to attract the growth of new blood vessels to deliver oxygen  and nutrients to the tumor. Approved for lung and colorectal cancers, Avastin  has been studied in breast cancer for a number of years in different  combinations and sequences. The drug showed benefit for metastatic disease  primarily when combined with chemotherapy, and current trials are studying the  antiangiogenic drug in early stage breast cancer. Patients taking Avastin  experienced high blood pressure and increased risk of blood clots.

Investigators hope to find successful breast cancer therapy regimens using  different combinations of targeted agents, including Avastin, Herceptin, Tykerb,  Xeloda and Sutent

 (sunitinib), another antiangiogenic drug recently  approved for kidney cancer.

  in 2005, Kathy Miller, MD, associate professor in the division of  hematology/oncology at the Indiana University School of Medicine, and colleagues  reported that adding Avastin to Xeloda in previously treated metastatic breast  cancer patients increased the response rate from 9 percent to nearly 20 percent,  but the combination didn’t significantly improve overall survival. (A response  was defined as tumor shrinkage of 30 percent or greater.)

Preliminary results from another Avastin/Xeloda study, a phase II trial known  as XCALIBr, were presented at the San Antonio Breast Cancer Symposium late last  year. Unlike the JCO study, the metastatic breast cancer patients enrolled in  XCALIBr are all HER2-negative and have received no prior treatment. Early data  show 34 percent of patients taking the combination have at least 30 percent  tumor shrinkage and another 38 percent have stable disease.

Dr. Miller has also combined Avastin with Taxol

 (paclitaxel) in  patients without prior chemotherapy for metastatic breast cancer, resulting in a  nearly doubled progression-free survival over Taxol alone (11 months compared  with 6.1 months). She’s now excited about a new trial comparing that combination  to Sutent/Taxol.

The Avastin/Taxol combination proved very effective for Terry Farrer, 54, of  Royal Center, Indiana. After a mastectomy, chemotherapy and tamoxifen to treat  her initial diagnosis in 1993, breast cancer was the last thing on Farrer’s mind  when doctors found a mass on her ovary in 2002. After removing her ovary and  testing the molecular make-up of the tumor, doctors confirmed it was breast  cancer that had probably spread from her first cancer (no cancer was ever  detected in her remaining breast).

“I know now that once you have cancer, there’s always the possibility of it  returning, but I had gone on with my life and thought it was behind me,” Farrer  says.

After Femara and then Faslodex failed to prevent the cancer from spreading,  she enrolled in the Avastin/Taxol trial. The tumor responded so well that she  continued with Avastin for another nine months after the trial ended. When the  cancer began growing again, her doctor switched her to another  combination—Herceptin/Taxol&mdash;because her tumor tested positive for HER2  overexpression. For nearly a year, Farrer has had no signs of cancer, but she  remains on Herceptin to keep the cancer at bay.

“I feel really good about the future and the prognosis, and I just heard that  Tykerb was approved for HER2-positive cancer and women can take it if the  Herceptin stops working,” Farrer says. “But I intend for the Herceptin to work  for a very long time.”

About 30 clinical trials examining breast cancer vaccines are in the works.  Based on the notion that vaccines can spur the body’s immune system to prevent  recurrence or destroy existing cancer, scientists have developed several  different types of experimental breast cancer vaccines, including those based on  HER2 or MUC1, another protein target.

By isolating and purifying a piece of the HER2 protein found on cancer cells  and giving it to patients along with immune-boosting factors once a month for  six months, breast cancer recurrence dropped by 50 percent, according to a study  presented at last year’s San Antonio Breast Cancer Symposium. Indeed, after two  years of follow-up, fewer than 6 percent of vaccinated patients had a recurrence  compared with nearly 15 percent of patients who did not receive the vaccine.  Although numerous vaccines with HER2 have been unsuccessful in treating breast  cancer, this study has given scientists the idea that perhaps these vaccines  would work best as a preventive measure.

“We’ve been working for decades on how to use our own immune system, but for  breast cancer we haven’t had anything close to a home run,” says Dr. Gralow, who  is hopeful researchers will find the right target for a breast cancer vaccine,  including MUC1. Dr. Gralow’s team is in talks with a number of companies to make  antibodies for the protein, which is found on a large percentage of breast  cancer cells. MUC1 can also be a useful marker of circulating tumor cells in the  bloodstream.

Scientists are even looking at old drugs to use in new ways, such as MPA  (medroxyprogesterone acetate), a dated steroid initially used as contraception  and then as anti-estrogen therapy, but fell out of favor once tamoxifen became  widely used. Scientists found MPA decreases the ability of cancer cells to  metastasize and may affect angiogenesis, and ironically “it’s able to do that in  cells that are completely insensitive to estrogen,” says Dr. Miller, who will  soon collaborate on a study involving MPA in hormone receptornegative breast  cancer. “It’s a fascinating story.”

The biggest advancement may not be one single drug at all, but how we test  certain therapies for effectiveness in breast cancer. “There is a shift in the  way we’re designing and looking at clinical trials,” says Ingrid Mayer, MD, an  oncologist at Vanderbilt-Ingram Cancer Center in Nashville.

Taking the tumor’s molecular make-up one step further, scientists are now  exploring how best to gauge the effectiveness of treatments on the cellular  level. Researchers would examine the tumor at the initial biopsy, give the  patient neoadjuvant therapy (treatment before surgery) and then examine a  follow-up biopsy sample before the tumor is removed. The process may help  investigators see if a new drug has any effect on the tumor at the molecular  level—essentially speeding up the process because you’re looking for molecular  changes, not survival or time to progression, which can take several years and  require hundreds or even thousands of patients to be enrolled in a trial.

“You don’t waste money, you don’t waste time and you don’t waste women’s  lives,” Dr. Mayer says. “People won’t have to wait a long time to see if a drug  works or not. It’s very innovative and it’s really going to revolutionize the  way we test drugs.”

Because breast cancer treatment has become individualized based on stage, hormone receptor sensitivity, genetics, menopausal status, protein overexpression and lifestyle, breast cancer is no longer “just” breast cancer.

“I think we’re entering a new era,” says Julie Gralow, MD, associate head of the Breast Cancer Program at the Fred Hutchinson Cancer Research Center in Seattle. “There are multiple benefits in assessing individual tumors in individual patients instead of lumping everything together as breast cancer.”

Currently, two traits pathologists primarily look for when diagnosing breast cancer are HER2 overexpression and estrogen status, which help doctors decide the best course of treatment—essentially eliminating therapies that would have little or no effect. But scientists are beginning to examine many other targets, including vascular endothelial growth factor, or VEGF, a substance cancer cells secrete to spur blood vessel growth to the tumor. Scientists are taking this rapidly growing arsenal of targeted agents, chemotherapies and anti-estrogens&mdash;even if they showed little benefit alone or lost benefit over time&mdash;and are finding that combining them can enhance their effects.

As data emerge from a surge of new therapies, doctors combine the best of the best.

A New Era

Peggy Plaisted recalls the day she was diagnosed with breast cancer in 2002  as one with lots of surprises and lots of paper. She had been tracking a cyst on  her ovary and had planned surgery to remove her ovaries when her doctor  recommended she have her annual mammogram, which was overdue. The doctor called  her later with the news that she had a noninvasive form of breast cancer and  they would remove her ovaries at the same time as a lumpectomy to remove the  tumor in her left breast. 

“They were giving me brochure after brochure about all the services offered  for breast cancer. It was overwhelming,” she recalls. All the information left  her head spinning, Plaisted says.

“I called my oncologist and told him I couldn’t get out of bed. He gave me  the name of the coordinator for the support group and a prescription for an  antidepressant. I called and it turned out they were meeting that night—and I  was there.”

Plaisted, who was 47 when she was diagnosed, returned to the group sessions  twice a month for a year because it helped her to talk about what she was going  through. She still attends, but now she takes newly diagnosed women from her  community, something she does to give back. She also goes to check in with the  women in the group who have become her friends.

Twice she has attended an all-day breast cancer symposium at Gilda’s Club  North Texas, a free support community named for comedian Gilda Radner that has  numerous support groups, classes, speakers and workshops on topics that include  nutrition, pain, yoga, meditation and journaling, among others.

Just two decades ago, Plaisted’s doctors probably would have told her not to  talk to other women because they might give her wrong information. Or, as  happened to one woman, be told by her surgeon to “stop crying” because she  wasn’t going to die.

Today, thanks to insightful medical professionals and demanding breast cancer  patients, the need to include emotional and social issues in the resolution of a  breast cancer diagnosis has been accepted.

Research studies in the psychosocial aspects of breast cancer, which only  began in earnest in the mid-1980s, have shed light on a complicated area that  encompasses not only emotional and social issues, including family matters,  spirituality, employment and insurance, but also supportive care issues, such as  pain management, and a vast array of complementary therapies, such as exercise  and nutrition.

Today, support for women with breast cancer ranges from cancer center  programs that might be a support group to others where patients might find  enough options to bring them to the hospital every day doing art therapy, music  therapy, an exercise class, a nutrition class or meditation. Nationwide  community programs include Gilda’s Club and The Wellness Community, among many  others.

Research in psychosocial areas explore myriad variables, including what  constitutes a psychosocial issue, how to determine who needs interventions, the  best solutions and when the solutions should be presented. The studies also look  at why some women still do not receive adequate interventions despite their  demonstrated benefit and what types of intervention are most effective for  specific subgroups of patients.

Mary Jane Massie, MD, attending psychiatrist at The Breast Center at Memorial  Sloan-Kettering Cancer Center in New York City, has been working in the area of  psychosocial support for women with breast cancer for more than 30 years. She  experienced the medical community’s acceptance that treating a woman for cancer  should encompass the whole person, including her mental health needs and the  core issues that can cause disruption.

Dr. Massie, who recalls a time when patients weren’t even told they had  cancer, says in addition to medical professionals who recognized the need, it  was the women themselves who demanded information and participation in what was  happening to them.

“We never saw men back when I started,” she says.“Women brought their mother  or friend or sister. The first time I saw a husband, I ran out to the waiting  area to ask if he wanted to join us. He said no, and right then decided he  needed to go put money in the meter. He ran out of there. Now, there are men and  the whole family, and the men want to know how it works.”

Today, many women meet with support persons immediately after diagnosis and  are introduced to the range of options provided by the facility. These  interventions may be as casual as handing the woman a brochure or as formal as  an interview to gather extensive information on her emotional and social  environment.

“It’s assessing what is there for patients—family, religion, community and  their cultural and professional community,” Dr. Massie says. “We need to  identify those who are most vulnerable and determine how this person best  receives help.”

A 2004 report from the Institute of Medicine of the National Academies  presented an overview of psychosocial help for women with breast cancer. One  study in the report identified women of younger age as those most likely to  experience distress as well as those with a history of depression, physical  health issues or inadequate social support.

Patricia Ganz, MD, director of UCLA’s LIVESTRONG Cancer Survivorship Center  of Excellence and head of the division of cancer prevention and control research  at Jonsson Comprehensive Cancer Center in Los Angeles, says screening of a  patient’s emotional status should occur before treatment to understand the  patient’s needs. “Then special attention needs to be paid at transition points:  starting treatment, ending treatment. If you haven’t already assessed once, you  won’t know where the patient started,” says Dr. Ganz, who contributed to the IOM  report.

It’s a matter of paying attention to patients and their needs because there  are no universal reactions, says Dr. Ganz, offering as an example the results of  a recent study in women at the end of treatment that didn’t show the distress  researchers anticipated. Instead, physical issues, such as sleep disorders and  pain, were of more concern.

Dr. Ganz’s patient assessment process begins by exploring intrapersonal  issues and the patient’s life history, such as how she coped with difficulty in  the past and how she feels about body changes and, if appropriate, being  disfigured. Then there are the interpersonal issues of relationships and work  followed by discussion of physical issues like chronic pain, fatigue and sexual  dysfunction.

We want to help them find a way to normalize symptoms and know that these issues  go along with a diagnosis. They may not have difficulties immediately, but when  we have introduced the idea that they may experience something later, they know  they have a place to go.

Once the patient’s history has been assessed, Dr. Ganz helps the patient  understand that there will be a variety of issues associated with the cancer  journey and offers tools for coping. “We want to help them find a way to  normalize symptoms and know that these issues go along with a diagnosis. They  may not have difficulties immediately, but when we have introduced the idea that  they may experience something later, they know they have a place to go.”

It’s a process, Dr. Ganz says. No one can handle it all on the first visit.  For example, if a woman is going to be thrown into menopause, she should know  what symptoms to expect and where to get help.

Dr. Ganz, like many medical professionals, takes advantage of  well-established programs already in place. And, for women who can’t or won’t be  involved with people, she recommends online resources, which a 2005 study  conducted by the University of Missouri at Columbia showed could provide  numerous psychosocial benefits. The study analyzed 33,000 postings to an online  community and showed benefits such as increased skill or ability to cope with  the disease, improved mood, decreased psychological distress and strategies to  manage stress. The longer women belonged to the online community, the more they  reflected a positive well-being—and the more they began to share information  with the group. Indeed, the study showed the longer women belonged to the group,  the more time they spent online offering information to newly diagnosed women  who joined the community.

Although psychosocial support services have come a long way, Dr. Ganz says  they are still not on par with medical services. The breast cancer journey is  individualized, and women must continue to demand support and take control of  how to get support—and what that support should look like.

Women need [and are now getting] more than medical care to heal from breast cancer.

The Comforts of Help

Few women get a more dramatic introduction to breast cancer prevention than  Sharon Anderson. Nearly 15 years ago her identical twin Karen was nursing her  fourth child when she noticed a lump in her breast. Karen’s doctor thought it  was a blocked milk duct, but after a few visits scheduled a mammogram. At the  time doctors excised the lump, cancer had spread to 17 of 21 lymph nodes. 

Karen lived in west Kansas but sought further treatment at the University of  Kansas Medical Center, near her sister Sharon. After Carol Fabian, MD, director  of the hospital’s Breast Cancer Prevention Center, finished her first visit with  Karen, she turned to Sharon. “Be here tomorrow at 8,” she said firmly. “You are  having your first mammogram.”

Sharon Anderson was only 35 at the time, and no one had ever mentioned  mammograms before. Now the veteran of four clinical trials, she’s helping her  daughter’s generation fight cancer before it happens. One trial told her she  carried the BRCA2 gene (a genetic mutation that markedly increases a woman’s  risk of breast and ovarian cancers), and she had the recommended oophorectomy  (removal of the ovaries). She took the osteoporosis drug Evista

  (raloxifene) for five years in the STAR (Study of Tamoxifen And Raloxifene)  trial, which compared the effects of two breast cancer risk-reducing drugs. Now  she’s in a trial testing the aromatase inhibitor Aromasin

With time, we will hopefully come up with a combination of medical and lifestyle  interventions that reduce the risk of breast cancer. It will be similar to  treatment, so that an individual woman walks in and, depending on her profile,  there are various options for her.

Despite four trials testing drugs known for side effects, she has never had a  problem. “I never did like taking medicine. I guess I just think my body should  be able to take care of itself,” says Anderson, who also exercises regularly and  watches her diet.

In this new era, complex cancers like breast cancer probably won’t decrease  as dramatically as cervical cancer, which may be practically eliminated with the  new human papillomavirus vaccine. But the puzzling tangle of genetic and  lifestyle factors that lead to breast cancer is finally starting to loosen. And  the search for chemoprevention—drugs or nutrients that could slow down cancer or  even prevent it altogether&mdash;is beginning to yield fruit.

Last year, leading British cancer epidemiologist Jack Cuzick, PhD, argued in  the journal 

 that it was time for oncologists “to catch  up with the cardiologists,” who have cut deaths from heart disease in the United  States by half using drugs like statins and a prevention mindset.

"Across the board it’s better to prevent a disease," argues Worta  McCaskill-Stevens, MD, of the Division of Cancer Prevention at the National  Cancer Institute. “With time, we will hopefully come up with a combination of  medical and lifestyle interventions that reduce the risk of breast cancer. It  will be similar to treatment, so that an individual woman walks in and,  depending on her profile, there are various options for her.”

Cancer prevention begins with figuring out your risk. You may have taken  available online tests (

) that ask your age, how many  immediate relatives have had breast cancer, age at menarche and age at first  childbirth. Your answers get plugged into a complex equation developed by NCI  biostatistics guru Mitchell Gail, MD, PhD, and out pops your likelihood of  developing breast cancer in the next five years.

The strength of the Gail model is that it’s accurate with very little  information. (It works better for white women; the model is still being  calibrated for other ethnic groups.) But if it tells you that five out of 100  women may develop breast cancer, it can’t tell you which 5. Defining high risk  is complex, but one commonly accepted measure of being at high risk of  developing breast cancer in the next five years is a Gail score of 1.67 percent  or greater. The Gail risk score is used in some prevention studies to determine  eligibility.

After tamoxifen was released in the 1970s, doctors noticed breast cancer  patients who took the drug, which inhibits estrogen activity, were less likely  to develop a second cancer in the opposite breast. Research among high-risk  women eventually revealed tamoxifen cut the risk of breast cancer in half over a  period of five years. The well-known Breast Cancer Prevention Trial reported by  the National Surgical Adjuvant Breast and Bowel Project found that of 13,175  high-risk women, 244 women in the placebo group developed breast cancer compared  with 124 women taking tamoxifen.

In 1998, tamoxifen was approved for breast cancer prevention in high-risk  women, though its main use has been to prevent recurrence of breast cancer.  Serious possible side effects—blood clots in older patients and a slightly  increased risk of uterine cancer&mdash;alarmed high-risk, but otherwise healthy,  women. In fact, for women over 65 with an only somewhat elevated breast cancer  risk compared with the general population, the risk of side effects may actually  outweigh the benefit.

[The FDA’s approval decision for Evista in breast cancer prevention] is moving  at the pace of government. It’s regrettable that we aren’t using the agents that  we do have. There are half a million women taking Evista for osteoporosis, so  they and their doctors are obviously comfortable with it.

Evista works a lot like tamoxifen, so a massive comparison of the two began  in 1999 involving nearly 20,000 high-risk women without a personal history of  invasive cancer. The results of the STAR trial were released last year and  showed Evista gave comparable protection with fewer blood clots and uterine  cancers. Eli Lilly and Company submitted an application to the Food and Drug  Administration in December 2006 for an additional approval of Evista for the  reduction of breast cancer risk in postmenopausal women. The FDA’s decision is  expected before the end of the year.

"It’s moving at the pace of government,” says Victor G. Vogel, MD, director  of the Breast Cancer Prevention Program at Magee-Womens Hospital in Pittsburgh.  “It’s regrettable that we aren’t using the agents that we do have. There are a  half million women taking Evista for osteoporosis, so they and their doctors are  obviously comfortable with it."

Dr. Fabian says the STAR trial resulted in a draw. While Evista has fewer  side effects overall, it doesn’t seem to be as good as tamoxifen in reducing  noninvasive breast cancer (ductal carcinoma in situ and lobular carcinoma in  situ). “When you get a mixed message like this, it’s very difficult to explain  that to patients,” she says.

Cheryl Pilate illustrates the problem. When her mother was diagnosed with  breast cancer at an early age, Pilate was referred to Dr. Fabian’s clinic for  high-risk patients. At first everything looked clear, but then they began to see  alarming changes in Pilate’s breast tissue with a sampling procedure called  random periareolar fine needle aspiration. The test results suggested she had 10  times the risk of her peers, which “broke through the little shell of denial  that we all keep,” says Pilate. “It really scared me.”

Removing her ovaries was an option, but Pilate wanted to go through menopause  naturally. She also considered tamoxifen. The side effects worried her, but her  biggest concern was efficacy. “My lifetime risk was astronomically high. How  does it help me to cut it in half?” She finally decided on a bilateral  prophylactic mastectomy.“It was the best thing I’ve ever done in my whole life.  I woke up in a state of elation and euphoria. It might seem radical to some, but  to me it seemed the least invasive.”

Next on the prevention horizon is a class of drugs called aromatase  inhibitors, or AIs, which include Aromasin, Arimidex

 (letrozole), for use in postmenopausal women who get  estrogen not from their ovaries but as a byproduct of other processes in the  adrenal gland and fat tissue (such as the breast). AIs interrupt this estrogen  production, and based on how well they work with chemotherapy could provide an  additional reduction in risk over tamoxifen and Evista.

The IBIS-2 prevention trial is an international study testing Arimidex for  breast cancer prevention, and the ExCel trial in Spain, Canada and the United  States is looking at Aromasin. STELLAR, a large-scale U.S. study comparing  Femara and Evista, was expected to start recruiting in April. But the trial,  expected to cost $100 million, is currently on hold because of budget cuts to  the National Cancer Institute.

“I don’t think there is any question but that the AIs are going to be more  active than tamoxifen,” says Dr. Fabian. But she also wonders if enough  high-risk women will be willing to live with potential side effects, such as  bone loss and reduced libido or vaginal dryness.“That’s even worse than hot  flashes,” she says. Designing drugs with fewer side effects, or that can be  taken for shorter periods of time, is a significant challenge. The long-term  effects of AIs are not yet known since they have not been in use as long as  tamoxifen.

Using clues called biomarkers, scientists hope to improve their powers of  prediction. Single genes like BRCA1 and BRCA2 are clear biomarkers. Others that  suggest breast cancer risk include mammographic density (how much of the image  is white) and the level of hormones, such as testosterone, estradiol and the  growth hormone IGF-1. High-risk clinics also perform biopsies that look for  what’s called atypical hyperplasia—essentially too many cells&mdash;which can be a  precursor to breast cancer.

A less-invasive biomarker would be welcomed, but what’s really needed is one  that reliably indicates risk and response to treatment. Dr. Fabian is confident  we’re within a few years of being able to use biomarkers like atypical  hyperplasia to reduce the participant number, time and cost of breast cancer  prevention trials. “We have this vast array of things that are promising,” she  says, but “you can’t spend $200 million on each one.”

And the roster of potential agents for breast cancer prevention alone is  huge. Among those working their way through clinical trials are arzoxifene  (works like tamoxifen); the statin Zocor (simvastatin);  anti-inflammatory agent Clinoril (sulindac); and all three AIs.  Dozens more have caught investigators’ eyes. And many potential prevention  regimens combine several compounds and may even work in combination with  modified hormone replacement therapy.

It's just a matter of translating what we already do and know for cardiovascular  disease into what we can do and know now for preventive oncology.

“I think it’s all about the agent,” says Dr. Vogel. “We’re on our way to  finding the optimal agent, but we haven’t found it yet.”

From a public health perspective, Dr. McCaskill-Stevens says prevention is  extremely important and physicians must have a medical intervention. Prevention  also means oncologists and their patients need to occasionally pull back from  the relentless pursuit of malignancy and see the whole patient.

“More than 75 percent of women who get breast cancer today will never die  from their disease,” says Dr. Fabian. “We have to seriously think about  prevention of other diseases that we might induce with treatment. Prevention and  survivorship are part of the same continuum.”

Researchers have established that the prevention paradigm works with early  detection, screening interventions and reducing risk factors, says Dr. Vogel.  “It’s just a matter of translating what we already do and know for  cardiovascular disease into what we can do and know now for preventive  oncology.”

Part of the challenge is getting the medical finance industry to pay for  preventive services. “As soon as you start paying for these services, doctors  will start providing them,” says Dr. Vogel. “The pressure for mammographic  screening to be used across the board did not come from the medical community.  It came from the advocate community.”

Breast cancer prevention meets success with new agents and a new thinking.

Eluding Cancer

For some women across the country, a breast cancer diagnosis  brings with it a patient navigator, a former patient or hospital patient  educator who has been trained to serve as a personal guide through the  psychological, emotional and financial challenges of cancer.

Started in 1990 by Harold Freeman, MD, founder and medical  director of Harlem’s Ralph Lauren Center for Cancer Care and Prevention, the  patient navigator program has expanded to 60 sites across the country through  the American Cancer Society, which launched a program in 2005 to specifically  reach underserved populations. In early 2007, the drug company AstraZeneca  donated $10 million to the ACS to add at least another 50 patient navigator  sites over the next five years. In other settings, psychosocial support may be  provided by an oncology social worker, oncology nurse, nurse practitioner or  chaplain.

In Denver, Sandra Walters, RN, left her hospital position to open  the Andre Center for Breast Cancer Education and Navigation, a community-based  outreach program. Serving as an educator and care coordinator to help guide  women through breast cancer, Walters sees her role as critical in providing  women with an educated medical professional who is not providing treatment but  has an in-depth understanding of breast cancer and treatment.

"The biggest hindrance to getting through a breast cancer  diagnosis intact is anxiety and fear,” she says. “You address those issues by  reaching out and saying, ‘I am going to help you understand and get through  this."

The biggest hinderance to getting through a breast cancer diagnosis intact is  anxiety and fear. You address those issues by reaching out and saying, ‘I am  going to help you understand and get through this.'

In the eight years before beginning the Andre Center, Walters  helped develop two hospital-based breast cancer programs, where she worked  with hundreds of patients. “I know the value of timely, upfront education and  the benefit it brings in decreasing anxiety through one-on-one education and  compassion,” she says.

Walters also knows the challenges of creating and maintaining a  patient navigator position in hospitals because of the pressures of  managed care and time, but “if it’s done right, it will pay for itself  through downstream revenue. It’s making the commitment to the process that has  to happen.” 

Some breast cancer patients are finding help with their diagnosis in patient navigators&mdash;a person who has been trained to serve as a personal guide through cancer. 

Navigation As Support

Potentially harmful side effects restrict chemoprevention  agents to women with a high risk of breast cancer. But in terms of sheer number,  more average-risk women ultimately get breast cancer.

For these women , changes in exercise and diet may be the best  prevention bet. “We need to look further than synthesized drugs,” says Carol  Fabian, MD. “Behavioral modifications may be just as effective.”

Diet and exercise certainly affect breast cancer risk. For  example, studies show women who eat a Mediterranean diet rich in fruits and  vegetables throughout their lives have a reduced risk of breast cancer. A direct  relationship between breast cancer and alcohol use has been made, with the risk  being slightly raised even with one to two drinks a day. This absolute risk  increase is very small and possibly offset by a small protective effect on the  heart from light to moderate alcohol use. Research has also demonstrated an  association between moderate to vigorous exercise and decreased breast cancer  risk among premenopausal and postmenopausal women.

What isn’t known is whether mid-life course corrections can make a  difference. “Will an exercise program taken up by a middle-age at-risk woman  markedly reduce her risk of breast cancer? As a scientist, I don’t know  that,” says Victor G. Vogel, MD. While the data for exercise is encouraging but  inconclusive, the American Cancer Society recommends moderate to vigorous  exercise for 45 to 60 minutes five or more days per week.

Mediterranean, low-fat and high-produce diets are all under  clinical investigation. The Women’s Intervention Nutrition Study (WINS) reduced  fat content in the diets of postmenopausal women with breast cancer, and  concluded it may reduce the risk of recurrence. The Women’s Healthy Eating and  Living, or WHEL, study is currently looking at a similar  population, but  features a diet rich in fruits and vegetables. Investigators are crunching  numbers and plan to release findings later this year.

“If it does nothing for breast cancer it still does an awful lot  for heart and bones and mental health,” says Dr. Vogel. “It’s still a very  prudent recommendation for people, as much as possible, to try to maintain or  achieve ideal body weight.”

On the horizon could be interventions that start at age 15 instead  of 45. “Phytoestrogens—soy and flaxseed&mdash;probably work best when we start around  adolescence,” says Dr. Fabian. 

Changes in lifestyle can impact cancer prevention.

The Lifestyle Approach

Marisa Acocella Marchetto lives in New York City and is a cartoonist for  

Readers' Forum

Cartoonist Marisa Acocella Marchetto, author of Cancer Vixen, shares her journey through breast cancer through her drawings.

The Law of Distraction

Breast cancer is staged based on the size of the  tumor and if and where it has spread, including nearby lymph nodes or distant  organs of the body. Staging is defined as TNM: T for tumor size (0 to 4); N for  lymph node involvement (0 to 3); M for whether the cancer has spread, or  metastasized, to distant organs (0 or 1). Once these attributes have been  determined, an overall stage of 0, 1, 2, 3 or 4 (also written as Roman numerals)  is assigned.

 About 62,000 women will be diagnosed this year with  what is called in situ breast cancer—abnormal cells that have not spread from  the milk ducts or lobules. Ductal carcinoma in situ is cancerous cells contained  within the milk ducts, usually treated with breast-conserving surgery and  radiation, or mastectomy. Lobular carcinoma in situ is when precancerous cells  are contained in the lobes. Women with LCIS are at high risk for invasive cancer  and may be prescribed tamoxifen to prevent further development of the abnormal  cells and are advised to increase the frequency of clinical exams.

 The tumor measures less than 2 centimeters.  Although cancer cells have invaded the fatty or connective tissue, the cancer  has not spread outside the breast. Breast-conserving surgery or mastectomy,  along with an examination of nearby lymph nodes for errant cancer cells is  recommended treatment.

 Tumors can be as large as 5 centimeters without  lymph node involvement or less than 2 centimeters but has spread to nearby lymph  nodes underneath the arm (called axillary nodes).

 The tumor is between 2 and 5 centimeters and  cancer cells have invaded one to three nearby nodes. The tumor can be larger  than 5 centimeters as long as it has not invaded axillary nodes.

 The tumor is smaller than 5 centimeters, but has  spread to four to nine axillary nodes, which have grown together or into other  nearby structures; or the cancer is larger than 5 centimeters and has spread to  one to nine axillary nodes.

 The tumor has extended into the chest wall, skin  or the ribs and may have spread to no lymph nodes or to as many as nine axillary  nodes. It may have spread to internal mammary lymph nodes found on the inside of  the chest along the breast bone.

 The cancer has spread to the lymph nodes located  above the collarbone and at the base of the neck, or to 10 or more axillary  nodes. Inflammatory breast cancer is classified as stage 3 unless it has spread  to distant sites, which moves its classification to stage 4.

 Cancer cells have traveled to distant nodes and  organs of the body, including the brain, lung or liver; considered metastatic  breast cancer.

Web Exclusives

A guide to how breast cancers are staged, from in situ (stage 0) to metastatic (stage IV).

What Stage Is Your Breast Cancer?

Inflammatory breast cancer, or IBC, is considered the most aggressive type of  breast cancer and tends to mimic the appearance of a breast infection. The  breast may be sore, tender, swollen and red—a consequence of cancer cells  clogging up the lymph vessels. IBC is rare in the United States with about 3,500  people diagnosed with the disease each year, and researchers are finding it’s on  the rise. 

Women with IBC are usually prescribed the gamut of cancer therapies,  including chemotherapy, radiation, hormone therapy, surgery and targeted  therapies, including Herceptin

 (lapatinib) may also be added to the list.

Neil Spector, MD, at Duke Comprehensive Cancer Center, says the power of  Tykerb in IBC was found by chance—researchers weren’t actively selecting IBC  patients for a phase I trial, but a handful were treated with Tykerb alone or in  combination with chemotherapy and showed a dramatic response to the drug.

“We saw five out of six incredibly dramatic responses, and when we looked at  those tumors more carefully, we found just incredible overexpression of HER2,”  Dr. Spector says. Tykerb inhibits HER2 (the target of Herceptin), as well as  HER1. In those initial studies, researchers were able to conduct tumor biopsies  before treating patients with Tykerb and during therapy to better understand  what was going on in the tumors. Investigators hoped to find biomarkers,  including HER2, which they could then correlate with clinical response.

"Three years ago when I tried to convince people that conducting studies in  inflammatory breast cancer with Tykerb was worthwhile, people looked at me like  I was crazy,” Dr. Spector says. But now at least three phase II trials are  studying the drug in IBC.

Early results of a phase II trial were presented at the American Society of  Clinical Oncology last summer. Of 24 patients with relapsed or refractory  HER2-positive IBC, 15, or 62.5 percent, had their cancer stabilize or shrink in  response to Tykerb. Side effects seen in the trial included skin rash and  gastrointestinal issues.

“You have to step back and realize these are women that have one of the worst  prognoses, most aggressive types of breast cancer,” Dr. Spector says, including  women who had at least four or five prior treatments. “I think it’s incredibly  exciting. It gives a snapshot of what is it about IBC that makes it sensitive to  a drug like Tykerb?”

A once frightening diagnosis, inflammatory breast cancer now has treatment options.

Special Issue 2007 | CURE