Progress Stalled in Metastatic Breast Cancer, Says Report

Linda Brookes, MSc


April 12, 2016

Recent advances in the detection and treatment of breast cancer have focused mainly on early-stage disease. Consequently, many women with advanced or metastatic breast cancer (MBC) feel that their needs are not adequately addressed and that fewer community resources are available to them, compared with those for women with early-stage disease.[1]

This view was reinforced by the latest findings in Global Status of Metastatic Breast Cancer (MBC): A 2005-2015 Decade Report, an international assessment of the scientific, societal, economic, and political landscape of advanced/metastatic breast cancer that was commissioned by Pfizer Oncology, working collaboratively with the European School of Oncology.[2] The report forms the basis for a global call to action for policy-makers, advocates, and the medical community to improve MBC outcomes by 2025.

The final report was presented in March at the European Breast Cancer Conference in Amsterdam by steering committee chair Dr Fatima Cardoso, MD, director of the Breast Unit of the Champalimaud Clinical Center in Lisbon, Portugal.[3] The report confirmed the findings of previous US and international surveys[4,5] that MBC "receives inadequate attention globally, and that information for patients is often lacking," Dr Cardoso said.

"Over the past decade there have been a few changes, particularly in the support groups, but little improvement in other areas," Dr Cardoso told congress delegates. "We, the breast cancer medical community, have not made the progress that we would have liked to have seen in treating this disease. There are major shortcomings in the treatment and management of metastatic breast cancer. Median survival has remained for many decades at 2 to 3 years after diagnosis. Our research strategies need a comprehensive overhaul if we are to make progress, with better international collaboration on large, well-designed clinical trials with truly meaningful endpoints/objectives, and smarter analysis of the large amount of biological data being gathered."

MBC Research Not Keeping Pace

Progress in the understanding and treatment of MBC appears to have stalled over the past 10 years, according to the report's findings. "We were the first to get many of the new technologies, molecular classification and subtyping, and the development of targeted therapies, but now we seemed to have reached a point where there is no more evolution and other fields are evolving more rapidly and outpacing us," Dr Cardoso said. She pointed to metastatic melanoma and metastatic lung cancer as fields where disease understanding; level of innovation; transformative approaches, such as immunotherapy; and advances in precision medicine have accelerated compared with MBC.

There must also be a commitment to continue to study the drug in the metastatic setting.

Speaking with Medscape, Dr Cardoso highlighted an important reason why new treatments for MBC lag behind those for early-stage breast cancer. "Almost every new treatment is first tested in the metastatic testing, but then very frequently, as soon as there is a positive result, the pharmaceutical company wants to move it to the early setting, because the market there is much bigger," she explained. "This is fine, because more people can benefit from the drug, but there must also be a commitment to continue to study the drug in the metastatic setting."

She cited two examples. "With paclitaxel, it took us 10 years to understand what was the best dose, the best regimen, and the best way of using it in metastatic disease, because as soon as it was seen to be efficacious, it was moved to the early setting and the metastatic setting was forgotten. The same happened with trastuzumab."

The report's call to action will include an appeal to request specific types of trials for breast cancer therapies.

The same trend is seen in the academic world, although there the motivation is career advancement, Dr Cardoso added. "Researchers want to be the principal investigator of a large, early-setting study that will change the lives of millions of women and are less interested in running a small trial that will help a smaller percentage of patients," she said.

The report's call to action will include an appeal to regulators, including the US Food and Drug Administration and the European Medicines Agency, to request specific types of trials for breast cancer therapies. "They must say, 'Okay, go and study it in the early setting, but you must commit to continue studying it in the metastatic setting,'" Dr Cardoso insisted.

Limited Improvement in Quality of Life

Probably the most surprising finding of the global report, according to Dr Cardoso, was a halt to a "substantial" improvement in quality of life (QOL) recorded in patients with MBC up to 2004. "There has not been any significant improvement over the past decade; in fact, there been a slight decrease in QOL as assessed by the EQ-5D [EuroQoL five-dimension] generic (non-cancer specific) health utility score," Dr Cardoso reported.

"We need to confirm whether this is really true," said Dr Cardoso. "But taking into account that in 2013, 8 out of 10 women felt that QOL was the biggest area in need of improvement in MBC care,[6] and the results that we have obtained from the past 10 years, there is a lot of work to be done," she commented. The report calls for more research to determine the approaches that create the greatest benefit in resolving QOL concerns—for example, access to referral services.

Patients value the way they communicate with health professionals almost as much as they value quality of life.

Another issue identified as "crucial" for patients is the way that physicians and nurses communicate with them. "Our report mirrored the findings of a similar survey done in the United States by the MBC Alliance,[7] which found that patients value the way they communicate with health professionals almost as much as they value QOL," Dr Cardoso noted. The report records patient dissatisfaction with communication with healthcare professionals and underlines the need for "holistic, individualized and compassionate" exchanges about MBC.

"In the United States and around the world, there is very little training in communication skills in medical schools or during residency," Dr Cardoso pointed out. Among 582 oncologists and other healthcare practitioners surveyed in the United States, Europe, Latin America, and Australia, less than 50% reported having received training on how to deliver bad news to patients and families.

"We have charged ASCO [the American Society of Clinical Oncology] and ESMO [the European Society for Medical Oncology] to come together to do a global curriculum in medical oncology that now includes communication skills training,"[8] Dr Cardoso noted. Practicing physicians should also use online training sessions themselves. "Everyone can do something to improve the way [in which] they communicate with their patients," she said.

The report also stresses the need for patients to proactively seek involvement in treatment decision-making. "Healthcare professionals surveyed for the report said that only about one half of their patients voiced their treatment goals, so we need to investigate why this is happening," Dr Cardoso urged. She noted that end-of-life discussions in 65% of cases begin only after multiple changes in treatment have occurred, whereas "they should start very early on and be done in a subtle and progressive way."

Psychological support may be necessary for the staff involved in these discussions to avoid burnout, particularly among young oncologists, Dr Cardoso told Medscape. "Dealing with death regularly is hard on physicians and nurses, and they need support for that in our centers."

Impact of Societal Attitudes Toward MBC

Attitudes toward MBC among the public in the United States; Europe; and other parts of the world, particularly the developing countries, are still extreme, Dr Cardoso explained. "Either they believe that it is like early breast cancer and it is curable, or they believe that it is a hopeless situation and they are going to die, so it is useless to do anything."

"The most shocking finding": 18%-49% of the general population believe that patients with MBC should keep it secret.

According to a survey carried out for the report, 18%-49% of the general population believe that patients with MBC should keep it secret and not discuss it with anyone other than their physician. "This was for me the most shocking finding," Dr Cardoso admitted to Medscape. "We are in the 21st century, in the so-called developed world, and this is still the attitude."

These attitudes have a negative impact on patients, who can feel isolated and helpless because of a lack of understanding and the stigma associated with the disease. "There is a need to educate not just lay people, but everyone who is not directly involved with the disease," Dr Cardoso told Medscape. "People do not realize that there is a period, which we hope will become longer and longer, where a woman receiving treatment can live a more or less normal life.

Dr Cardoso recalled that one effect of the "pink" breast cancer awareness movement, which focused on a positive message of prevention and survival, was that patients with MBC were excluded, because people did not want to see patients who were going to die of their disease. She said that there were two consequences of this: Patients with MBC were marginalized and had no information or support, and they also felt guilty, thinking that perhaps the cancer returned because they did something wrong.

In the 1970s, we had to fight the taboo against talking about breast cancer; now we have to fight the taboo against talking about how breast cancer can kill.

Speaking to Medscape, Dr Cardoso said, "In the 1970s, we had to fight the taboo against talking about breast cancer; now we have to fight the taboo against talking about how breast cancer can kill. Unfortunately, there is not always a happy ending."

The lack of a guaranteed happy ending is why the media currently don't want to report on MBC, Dr Cardoso added. "It is important to educate the media to have them on our side," she said, adding that outside of professional journalism, social media can be very influential in opening up discussion about advanced cancer and death.

The Patent's Right -- and Need -- to Work

The global report found that many employers and healthcare providers are not educated about the extent to which MBC affects a woman's capacity to work. "Many women with MBC are able and want to work, yet in some countries,[9] they experience stress due to lack of job security, access to employee benefits, or the effect of being unable to meet contractual commitments, said Dr Cordoso."

Women with MBC face problems in the absence of legal protection for their right to work and the right to flexibility in their work in terms of schedules and responsibilities. "Although 43%-93% of breast cancer patients reenter the workplace,[10] it is very sad to see from one international study that about one half leave within 1 year of their return." Dr Cardoso said.

We are calling for protective laws for women with MBC in the workplace.

Maintaining employment is important in providing psychological, economic, and societal benefits to patients with cancer and to their caregivers. "If they keep up their professional activity, it has a positive impact in terms of avoiding depression," she said. "Unfortunately, we are living in a period when unemployment rates are quite high, and these patients are among the first people to suffer. But these women can still be extremely productive, and given their median age, they are in the prime of their lives and careers. We are calling for protective laws for women with MBC in the workplace, similar to those that protect people with disabilities and women who are pregnant."

Remaining in the workforce can be seen as an economic necessity for women with MBC. Studies have demonstrated that the costs associated with treating MBC effectively are greater than those incurred by management of early-stage breast cancer. One study estimated the cost-effectiveness of treating early-stage breast cancer (stages I, II, and II) at $6550 per disability-adjusted life-year (DALY) averted, compared with $70,400 per DALY averted for treating stage IV disease.[11] The corresponding figures for treatment in Africa/Asia were < $390 vs < $3500.

The financial burden for patients and their families can be severe; a link between direct costs of advanced cancer treatment and bankruptcy has been demonstrated among patients in the United States, Europe, and Australia, Dr Cardoso noted. Indirect costs of MBC can account for more than 50% of the total cost of care.[12] These include time without work; travel to the hospital and back; and, in the majority of cases, supportive therapy, such as pain and nausea medication and other medications that help the patient tolerate treatment. They also include loss of work by the caregiver who accompanies the patient to hospital.

"We know that the quality of interpersonal relationships with caregivers and those close to patients is critical," Dr Cardoso said. Although caregivers provide critical support for MBC patients, their own needs are often neglected. "The report records that caregivers can face economic, psychological, and marital/family strains—the psychologic impact for some being equal to or greater than those of the patients. Frequently, the emotional or mental health of loved ones is not routinely discussed between patients and their healthcare providers and the family." The survey found that among 50 breast cancer centers around the world, only one half offered caregiver services. "In this respect, the United States is far more advanced in providing specific programs for support to the caregivers." Dr Cardoso noted.

A Goal of Doubling Overall Survival

"This report[2] has given us a bird's-eye view of what is happening around the world in MBC, but patients cannot live on our good intentions," Dr Cardoso said. "The second step, which we have already started working on, is our call to action, which has tangible objectives that will be reviewed annually at the Advanced Breast Cancer (ABC) conference." These objectives will include changes in such areas as employment protection laws and education about MBC.

"We also aim to attract more media attention, using social media, and to bring together the scientific and advocacy groups, Dr Cardoso told Medscape. "The past decade has seen changes in the advocacy world, so that there now are specific advocacy groups for advanced breast cancer, such as the Metastatic Breast Cancer Network and METAvivor."

"There are also specific groups for advanced breast cancer patients within large advocacy organizations, such as Susan G. Komen and the European Breast Cancer Coalition (EUROPA DONNA). In 2015, EUROPA DONNA successfully lobbied the European Parliament for a declaration requiring that patients with MBC be treated and receive support services coordinated in a single specialist breast unit,"[13] Dr Cardoso noted. She announced that a global alliance is now being set up that will incorporate all the members of the MBC Alliance in the United States and the ABC network. "I believe that this will be very powerful in terms of advocacy and lobbying," she said.

I hope in the next decade, we will see that breakthrough and really change the median overall survival.

For Dr Cardoso, the most important objective for MBC over the next 10 years is to double the median overall survival. "Everybody tells me that I am asking too much," she told Medscape. "But median overall survival now is 2-3 years, so if it gets to be 4-6 years, do you really think that that is a lot? I say that it is too little. I think we can do it, because we have already done so for HER2-positive disease, and we are on our way to doing it for luminal cancers. Where we need a breakthrough is in triple-negative disease, because that is pulling the median down. But I hope in the next decade, we will see that breakthrough and really change the median overall survival. That is my goal before I retire!"

Dr Cardoso has disclosed relevant financial relationships with: Astellas/Medivation; AstraZeneca; Celgene; Daiichi Sankyo; Eisai; GE Oncology; Genentech; GlaxoSmithKline; Merck & Co; Merus BV; Novartis; Pfizer; Pierre Fabre; Roche; Sanofi; Teva Pharmaceutical Industries