News from ASCO 2011

The American Society for Clinical Oncology (ASCO) held its annual meeting in Chicago from June 2-7, an extraordinary gathering of over 35,000 cancer experts and advocates from around the world. This year, according to TNBCF Medical Advisory Board Member, Eric Winer, MD, there was no study presented on TNBC that represents a major step forward or will have a significant immediate impact on clinical practice. That statement is true for the meeting as a whole in which the majority of studies were focused on incremental advances, especially in the area of targeted therapies.

Iniparib Phase III Study fails to show an Improvement in Survival
The biggest news for TNBC patients actually relates to a study that failed to meet its two primary endpoints. In 2010, data from the Phase II study that added iniparib to the standard chemotherapy regimen of gemcitabine and carboplatin suggested a real advantage to the iniparib arm—and generated a surge of excitement. The buzz died quickly in January when the Phase III trial results didn’t showed no statistically significant advantage in either overall survival or progression free survival when iniparib was added to the standard regimen.

In a special briefing for breast cancer advocates, Charles Hugh-Jones, VP of US medical operations for Sanofi-aventis which makes iniparib conceded that overall the trial had been disappointing. He also pointed out that the data do appear to indicate an advantage to for TNBC patients receiving who get the iniparib/gemcitabine/carboplatin after failing one or more previous chemotherapy regimens. He also noted that laboratory research now indicates that while iniparib has anti-cancer activity, it is not as previously believed a PARP inhibitor. PARP inhibitors are a relatively new group of anti-cancer agents that work by interfering with a cancer cell’s ability to repair damage to its DNA—thus potentially greatly enhancing the effect of chemotherapy and radiation therapy. Hugh-Jones told the advocates that Sanofi is committed to ongoing work with iniparib both to understand its exact mechanism of activity and to determine the subsets of TNBC patients for whom it is effective.

From Eric Winer’s perspective, the iniparib trial is a strong testament to the value of rigorous clinical trials. He notes that, as in usually the case, the Phase II trial was small, enrolling a total of 122 patients in both arms. Phase II trials are used to generate data to drive the much larger Phase III studies—but smaller sample sizes, shorter time frames and the lack of stratification among the patients on the trial can in some instances lead to results that are not borne out in future studies.

“It’s all about expectations,” he says. “All of us—patients, doctors and the pharmaceutical companies—were excited by the Phase II results, and disappointed by the Phase III negative trial. But that’s why we it is so important to do these randomized trials.”

Study shows advantage for regional node radiation
Women with node positive or high risk node negative breast usually receive whole breast radiation therapy following their surgery. A Canadian study indicates that expanding the area irradiated to include regional lymph nodes improves disease free survival, reducing cancer recurrences both near the tumor site and in other part of the body. Regional node irradiation also improved overall survival but not a level that reached statistical significance. Women who received the RNI did have a low but statistically significant increase in grade II lymphedema .

“These results will encourage physicians to offer all women with node-positive disease the option of receiving regional node irradiation,” said Timothy J. Whelan, BM, BCh, lead investigator of the trial.

Prevention study significantly reduces risk of invasive breast cancer
For women who are already confronting a diagnosis of TNBC positive results from a prevention study may seem too late and too little—but for all of us the real hope for the future is no one will have to hear the words “you have breast cancer.” A study presented at ASCO offers the real possibility of reducing the risk of invasive breast cancer using the aromatase inhibitor exemestane. In this large randomized, double-blind trial, (MAP.3 conducted by the National Cancer Institute of Canada), post-menopausal women who were at high risk of getting breast cancer who took exemestane had a 65% reduced risk of developing invasive breast cancer compared to the group receiving a placebo. Women receiving the exemestane reported more symptoms, including hot flashes, fatigue, sweating, insomnia and arthralgia—all known effects of aromatase inhibitors—but according to the study leaders, these did not affect overall health-related quality of life.

While the results were highly significant and the potentially impact on public health is enormous, some experts expressed doubt as to whether women and their doctors would begin using an aromatase inhibitor as a preventive measure.

“It’s an important study,” said Winer, “but we know that a percentage of women being treated for breast cancer discontinue aromatase inhibitors because of the side effects, so it may be difficult to persuade healthy women to take these drugs. It’s not for everyone but for women who are truly at high risk for getting breast cancer, it could be very significant.”

Focus on TNBC and the future
There is no question that researchers are increasingly recognizing the importance of TNBC as an entity and focusing their efforts on several key areas, including:

• Defining exactly what comprises TNBC and developing more sensitive biomarkers for identifying which patients have this disease.
• Within the TNBC patient population, identifying which subsets of patients will benefit from specific targeted therapies
• Identifying new agents and combinations of existing agents that improve the treatment outcomes for TNBC patients.

It was notable at this year’s meeting that TNBC was the topic of a number of international presentations focusing on patient characteristics and treatment approaches in countries around the world. The key to progress is to having the best minds—both in the lab and the clinic—focused on understanding the biology of TNBC and using that knowledge to develop effective, targeted therapies.

Link to ASCO abstracts relating to TNBC:
http://abstractsearch.asco.org/?index=442064&calln=5&lastq=&nolog=1&sortsel=rel&opt=ANY&doc0=0&query=triple%20negative%20breast%20cancer

Pink Ribbon Fatigue

By BARRON H. LERNER, M.D.
From The New York Times Health Blog “Well” by Tara Parker-Pope

Another Breast Cancer Awareness Month is upon us, which will mean lots of pink ribbons.

The pink ribbon has been a spectacular success in terms of bringing recognition and funding to the breast cancer cause. But now there is a growing impatience about what some critics have termed “pink ribbon culture.” Medical sociologist Gayle A. Sulik, author of the new book “Pink Ribbon Blues: How Breast Cancer Culture Undermines Women’s Health” (Oxford University Press), calls it “the rise of pink October.”

“Pink ribbon paraphernalia saturate shopping malls, billboards, magazines, television and other entertainment venues,” she writes on her Web site. “The pervasiveness of the pink ribbon campaign leads many people to believe that the fight against breast cancer is progressing, when in truth it’s barely begun.”

The National Breast Cancer Coalition, a highly visible activist group based in Washington, D.C., has also taken a swipe at pink culture as it tries to reconfigure breast cancer activism through a highly ambitious plan to eradicate the disease by 2020. “Peel back the pink,” the group urges its advocates, “and go beyond awareness into action to end breast cancer.”

So what’s a breast cancer survivor, or an interested citizen, supposed to think when encountering the ubiquitous pink ribbons on everything from yogurt to bathrobes? It helps to know a little of the history of breast cancer activism.

The first breast cancer activists were a series of women in the early and mid-1970s who challenged the routine use of the radical mastectomy, a highly disfiguring operation that involved removal of both the affected breast and the nearby chest wall muscles, for treating breast cancer. Building on the work of a few renegade surgeons plus the era’s feminism, these women gradually got the medical profession to rethink radical surgery. Data eventually showed that smaller operations, such as lumpectomies, accompanied by local radiation were equally effective.

Among the most persistent and effective activists was Rose Kushner, a breast cancer survivor who took on not only the radical mastectomy but also the practice in which doctors decided whether or not to remove cancerous breasts while women were under anesthesia, effectively silenced.

But even Ms. Kushner knew the next steps in breast cancer activism would be even harder. Beginning in the 1980s, she forged alliances with prominent physician-researchers in the field, such as Bernard Fisher. She also informally reviewed grant applications for the National Cancer Institute, a momentous acknowledgment by a scientific organization about the value of lay opinion. Ms. Kushner, who had taken the anti-estrogen drug tamoxifen to treat her breast cancer but who ultimately died of the disease in 1990, even forged a working relationship with Imperial Chemical Industries, the manufacturer of the drug. The company would later merge with the Zeneca Group to form a huge drug conglomerate, AstraZeneca.

This latter connection is particularly telling, as the AstraZeneca Healthcare Foundation is now the major sponsor of the annual Breast Cancer Awareness Month. Pink activities are hardly restricted to October, but they are particularly prominent during the month: billboards promoting breast cancer awareness; media coverage of the latest advances in breast cancer detection and treatment; and races, walks, climbs and other events for breast cancer survivors that provide emotional uplift, a sense of community and an opportunity to raise money for the cause.

So how can the pink ribbon be objectionable? Among the first salvos against the pink ribbon was a 2001 article in Harper’s magazine entitled “Welcome to Cancerland,” written by the well-known feminist author Barbara Ehrenreich. Herself a breast cancer patient, Ms. Ehrenreich delivered a scathing attack on the kitsch and sentimentality that she believed pervaded breast cancer activism.

Others added to Ms. Ehrenreich’s arguments, notably the San Francisco-based group Breast Cancer Action, which in 2002 initiated a “Think Before You Pink” campaign. The organization’s main concern was that pharmaceutical companies that manufactured breast cancer treatments, plus other industries that promoted the pink ribbon for publicity purposes, produced toxic waste that poisoned the earth — and actually promoted breast cancer. Rather than being used to study the causes of breast cancer and how to prevent the disease, a large proportion of pink money, the group argued, has been used to pay for local screening and treatment programs and research into new, expensive biological agents that have had little impact on women’s survival from breast cancer.

The head of the National Breast Cancer Coalition, Fran Visco, in a recent e-mail to her membership, called for a “solution,” such as the development of a breast cancer vaccine, rather than just more hope. “We have to stop celebrating breast cancer awareness months and begin pushing for the end,” she wrote.

In “Pink Ribbon Blues,” Ms. Sulik offers three main objections to the pink ribbon. First, she worries that pink ribbon campaigns impose a model of optimism and uplift on women with breast cancer, although many such women actually feel cynicism, anger and similar emotions.

And like Ms. Ehrenreich, Ms. Sulik worries that the color pink reinforces stereotypical notions of gender — for example, that recovery from breast cancer necessarily entails having breast reconstruction, wearing makeup and “restoring the feminine body.”

Finally, Ms. Sulik closely examines what she calls the “financial incentives that keep the war on breast cancer profitable.” She reports that the Susan G. Komen Foundation, which annually sponsors over 125 annual Races for the Cure and more than a dozen three-day, 60-mile walks, has close to 200 corporate partners, including many drug companies. These associations, she warns, are a potential conflict of interest.

So should women start boycotting these very corporate events, which Ms. Sulik admits raise billions of dollars each year, and in which participants receive make-up and other pink-ribbon products in honor of their achievements? I’m not so sure. It is hard not be moved by these types of gatherings, in which survivors demonstrate their perseverance, altruism and endurance.

But one does hope that books like “Pink Ribbon Blues” and campaigns like Breast Cancer 2020 encourage all of us to examine the facts anew. Over 40,000 women still die from breast cancer annually in the United States, and strategies for preventing the disease have received inadequate attention and funding.

It is great to celebrate one’s survivorship from breast cancer, but it would be better not to have to be a survivor in the first place.

Barron H. Lerner, a physician and medical historian at Columbia University Medical Center, is the author of “The Breast Cancer Wars: Hope, Fear and the Pursuit of a Cure in Twentieth-Century America.”