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Breast Cancer Screening Recommendations:More evidence or more confusion?

By Gary H. Lyman, MD, MPH, FRCP(Edin)

In the current national healthcare reform debate, few issues have generated more opinions and greater confusion than the value of cancer screening such as for prostate and breast cancer. Breast cancer mortality has decreased by 27% since the early 1990s, likely the result of earlier diagnosis with screening and better treatment options. Nevertheless, skepticism has recently been voiced about the value of breast cancer screening, which, along with persistent financial and educational barriers, has led to a decline in mammography screening rates despite clear recommendations from the American Cancer Society and several medical professional organizations.* The federally funded US Preventive Services Task Force (USPSTF) has until now fully supported such recommendations. Mysteriously, and reading somewhat like a John Grisham or Dan Brown novel, the USPSTF has reversed several long-held key recommendations for breast cancer screening. Despite little new data and no change in estimates of benefit and harm, the USPSTF now recommends against screening in the 40- to 49-year age group, screening in older women only every other year instead of annually, and explicitly recommends against teaching women breast self-examination (BSE). So, why has the USPSTF reversed its positions on such important issues that fly in the face of other US recommendations including their own?

A few clinical trials have updated their results, and one new study in the 40- to 49-year age group from the United Kingdom reports an estimated reduction in the risk of breast cancer mortality at 10 years of 17%, virtually identical to that of earlier trials considered by the USPSTF. In fact, in the most recent trial, adjustment for incomplete adherence with screening led to an achievable reduction in breast cancer mortality in women aged 40 to 49 years of nearly 25%. After considering potential harm from false positive results and low-level radiation exposure, the net benefit was found to exceed any harm over a broad range of assumptions.

The USPSTF now considers this reduction in mortality to be “small” in this age group, which they balance against “moderate” potential harm from unnecessary biopsies. Most oncologists would consider a treatment reducing breast cancer mortality by 15% to 25% a breakthrough. While there is no evidence that occasional negative biopsies cost lives, failure to diagnose early-stage breast cancer does. While recent advances have focused on less surgery and a more personalized approach, we are not yet able to safely identify patients with breast cancer who do not require treatment. It is premature and somewhat reckless to suggest that some invasive breast cancers are not life threatening and do not require treatment. The USPSTF now recommends screening older women every 2 years rather than annually. While the clinical trials varied in the screening interval from every year to more than 2 years, it is not possible to directly compare the value or loss of benefit to less frequent screening in those trials. While such a change could save costs in the short term, the additional confusion and uncertainty may lead to further declines in screening rates, while even a small increase in more advanced disease may have an eventual adverse effect on both women’s lives and healthcare costs.

Perhaps the most puzzling change in recommendations from the USPSTF relates to BSE, which, despite no new data, they now explicitly recommend that women NOT be taught. While it is true that two large trials on this subject found no reduction in mortality, they were conducted in very different cultures and health systems and have questionable relevance to a US setting. While the potential for harm and costs are negligible, countless women have found their cancer through self-examination months or even years before it would have likely come to medical attention at a more advanced stage. Why would the USPSTF recommend against patients being taught a simple, safe, and inexpensive procedure that may be life saving? Go figure.

While some will conclude that these misguided recommendations are an early attempt to ration healthcare, they more likely reflect the need for input from practicing cancer specialists with expertise in the diagnosis and treatment of breast cancer. Whatever the cause, these new and conflicting recommendations are likely to lead to greater confusion and reduced breast cancer screening, reversing decades of effort to reduce the devastating impact of advanced breast cancer on the lives of tens of thousands of women in this country each year. Should the Center for Medicare and Medicaid Services and other insurers act on these new recommendations, reversing hard-fought reimbursement policies for breast cancer screening, it will be a major step backward, not forward, in the war against cancer. Efforts to improve the survival and quality of life for women with breast cancer require the rational application of all effective strategies in a cost-effective manner, including breast cancer screening.

*American College of Physicians, the National Comprehensive Cancer Network, the American Medical Association, the American Academy of Family Physicians, the American College of Obstetrics and Gynecology, the Canadian Task Force on Preventive Health Care.

Prevention and Treatment of Venous Thromboembolism in Patients with Cancer

Cancer Investigation

Journal of Oncology Practice

Oncology NetGuide

Contemporary Oncology

Oncology & Biotech News

Gary H. Lyman MD, MPH, FRCP (Edin) is Professor of Medicine and Director of Health Services, Effectiveness and Outcomes Research in Oncology at Duke University and the Duke Comprehensive Cancer Center, where he is also Senior Fellow at the Duke Center for Clinical Health Policy Research. Dr Lyman serves as a member of both the ASCO Cancer Education and Health Services Committees, chairing the Methodology Subcommittee as well leading several clinical practice guideline panels, including the recent ASCO Guideline on . Dr Lyman is a member of the Oncology Drug Advisory Committee (ODAC) to the US Food and Drug Administration. He is Editor-In-Chief of and the Peer Review Editor for ASCO’s . He is also on the editorial advisory board of , , and . The recent media coverage of the United States Preventive Services Taskforce (USPST) mammography guidelines alludes to the “controversy” within the medical community regarding the value of mammography in screening women in the 40- to 50-year age range. First, there is no controversy; second, this is not a political issue. The subject places well-informed physicians in a better position to address their patients’ needs by explaining the nature of the debate to inquiring patients.

West's PointsOur Role in How the Mass Media Covers Cancer Stories

By H. Jack West, MD

There was a time when oncologists learned the latest information about potential risks of cancer and new treatment ideas at major cancer meetings. Nowadays, we’re likely to first learn about these issues from a news report—and often in the business section!—or from patients directly. What is particularly challenging is that these stories are often reported in extreme terms: Coffee Prevents Cancer! Coffee is Poisonous! Miracle Cancer Treatment Discovered! In fact, if you only watched the headlines, you might think a new miracle cancer treatment was ready to hit the shelves just about every week.

60 Minutes

This leaves oncologists with the unenviable task of needing to apply context when our patients respond breathlessly to the typically unjustified promises or fears these stories generate. Oprah, the network news science correspondent, or even a report may lead our patients to believe that the next big breakthrough is right around the corner, forcing us to act as that wet blanket reminding them of the big difference between encouraging early lab-based work in cell cultures or mice and validated clinical research in real human cancer patients.

Journal of the National Cancer Institute

I give credit to the authors of a recent editorial in the by Woloshin and colleagues (2009;101(23):1595) for highlighting the problems with how the media handle reporting about cancer. It describes reasons why far too much new information is presented in such sensationalized terms. The authors note that willful misrepresentation in hopes of generating viewership/readership is part of the issue; another is the fact that many journalists lack the knowledge required to place the findings in the proper context.

Many of our research reports only reference the relative risk or benefit (ie, 30% higher risk of developing cancer or 20% improvement in survival) without noting the effects in absolute terms. If a press release is deliberately ambiguous, it’s the fault of the investigators or those writing the press release if journalists merely echo what they see, highlighting a “20% improvement” without noting the limitation that this difference may amount to only 3 weeks in absolute terms or that a doubling of risk of developing a rare cancer may mean that the risk escalates from 0.1% to 0.2% over a person’s lifetime.

Another common media practice is to obtain a quote or two, often from the person who led the research effort. When you think about it, it would be hard to find anyone more likely to be biased about the importance of the work than the person who led the study. I consider it particularly frustrating and potentially unethical for an investigator involved in very early research that is years away from being vetted in appropriate clinical trials to declare that the work represents a breakthrough for cancer patients. This may just be a case of investigators who cannot be objective because it is their research (just as most of us think our own children are smart and beautiful), or it may be motivated by the desire to leverage the attention into more research funding and an opportunity to achieve greater recognition in the field. If an opinion is sought from someone unlikely to be impartial, it makes sense to corroborate or counterbalance the investigator’s self-congratulatory commentary with an alternative view from another expert in the field.

Another recommendation included in the editorial is that journals demand that investigators describe the limitations of their own work and/or that the journal offer some context for the data. The Annals of Internal Medicine has recently started to pursue such a policy, but they are ahead of the curve in this respect. There are certainly some journalists who demonstrate the sophistication and dedication to cover the gray areas of a topic and highlight the limitations of early research. We should strive to educate journalists on how to vet a story and provide greater balance. Meanwhile, medical researchers could generate coverage that is more evenhanded by offering more context and less grandstanding. We need to convey to the general public the need to be wary of simplistic spoon-fed solutions, whether they represent fear-mongering or tout this week’s miracle cancer treatment. Dispelling the myth of the definitive, easy answer in oncology is about as much fun as telling kids that there really isn’t a Santa Claus. But these are our patients, and it is our responsibility to treat them with something other than magical wishes.

H. Jack West, MD is a medical oncologist and medical director of the Thoracic Oncology Program at the Swedish Cancer Institute in Seattle, Washington. He also serves as president of the nonprofit organization Global Resource for Advancing Cancer Education (GRACE), http://cancergrace.org.

Breast Density & Not Age the Best Predictor of Mammography’s Usefulness

By Edibaldo Silva, MD, PhD, FACS

The recent media coverage of the United States Preventive Services Taskforce (USPST) mammography guidelines alludes to the “controversy” within the medical community regarding the value of mammography in screening women in the 40- to 50-year age range. First, there is no controversy; second, this is not a political issue. The subject places well-informed physicians in a better position to address their patients’ needs by explaining the nature of the debate to inquiring patients.

We know that data-driven studies show mammography can prevent death from breast cancer in 25% to 30% of appropriately screened women. We also know that mammography is not infallible and misses 1 in 5 of even palpable breast cancers. Most missed cancers are in women under age 50. To that end, the shift in screening from film mammography to digital mammography best improved the detection rate of breast cancers in this age group. However, when the population benefit of screening mammography is addressed in an impartial, data-driven manner, the information revealed by the USPST is correct: mammography, as we have always known, is not as reliable in women under age 50 as it is in women older than age 50. The question for well-informed physicians is how to use this information wisely.

The limitations of mammography have less to do with age than with the density of the woman’s breast. Until recently, when research has begun to elucidate the primacy of breast density on the risk of breast cancer, age alone was used to define the risk of breast cancer. Yet, because dense breast tissue is more often noted in women under 50, the accuracy of mammograms in younger women is inferior to that seen in older woman, whose dense breast tissue has undergone the typical postmenopausal changes that make the breast more fatty, less dense, and therefore easier to “see through.”

Many women under age 50 have fatty breast tissue, and mammography in these women proves as reliable and accurate as it tends to be in older women. The converse may also be true. A 60-year-old woman on hormone replacement therapy may have such dense breast tissue that her mammogram may not be very accurate compared with other women her age. Yet her exceptional examination does not render screening mammography useless for other women in her age group.

Physicians must be aware of the limitations of mammography and design a screening strategy that best suits an individual woman’s risk of breast cancer. Once a risk assessment is obtained, the physician can decide whether mammography is useful as part of her overall preventive strategy, regardless of age. If a patient’s mammogram shows fatty, easy-to-see-through breast tissue, mammography should be part of her individual risk prevention strategy. If she has a very dense breast and mammograms add little benefit, she needs a better strategy that perhaps uses mammograms every 2 years or longer or involves other ancillary examinations until the mammogram’s informative value improves with age-related declines in breast density. The USPST recommendations are cost-effective population studies that must be used as one more piece of data available to physicians who must then make screening recommendations for the individual patient.

Edibaldo Silva, MD, PhD, FACS is an associate professor with the Division of Surgical Oncology, Department of Surgery, and an attending surgeon at the Olson Women’s Center at the University of Nebraska Medical Center in Omaha. He is also a member of the editorial advisory board for Oncology & Biotech News and Oncology NetGuide.

CT Scans Increase Patients’ Risk of Cancer

Imaging specialists with the University of California in San Francisco (UCSF) say routine computed tomography (CT) scanning is associated with a 1 in 80 chance of developing cancer in certain groups. According to the investigators, radiation doses from CT scanning are higher than previously thought and vary between procedures.

“In day-to-day clinical practice, we found signifi- cant variation in the radiation doses for the same type of CT procedures within institutions and across institutions,” said lead investigator Rebecca Smith- Bindman, MD, professor of radiology at UCSF.

According to the researchers, approximately 70 million CT procedures are performed annually, up from 3 million in 1980. The process is typically much faster than it used to be, but Dr Smith- Bindman described this as a “double-edged sword.” She explained, “Because the images can be obtained so quickly, it has been very tempting to do multiphase studies...increas[ing] the radiation dose.”

The UCSF team looked at the 11 most frequently ordered CT procedures and assessed radiation exposure associated with each. Then they calculated the potential risk of cancer related to each procedure. The review involved 1119 patients treated at four institutions in the San Francisco Bay Area in a 5-month period. All the procedures involved the head and neck, chest, or abdomen and pelvis.

They measured a mean 13-fold variation between the lowest and highest radiation doses delivered with one CT procedure. The number of CT scans required to cause cancer was greater for women than for men, which Dr Smith- Bindman said was what the investigators had expected. Age was also a factor.

The estimated cancer incidence for women was 1 in 270 for a CT coronary angiogram at age 40 years; in men, the same procedure was associated with an estimated 1 in 600 incidence. CT scans of the head were associated with far lower rates of cancer, at 1 in 8100 for 40-year-old women and 1 in 11,080 for men of the same age. Patients less than age 20, however, had nearly double the risk. “The risk associated with obtaining a CT is routinely quoted as around 1 in 1000 patients who undergo CT will get cancer,” Dr Smith-Bindman said. “In our study, the risk of getting cancer in certain groups of patients for certain kinds of scans was as high as 1 in 80.”

Archives of Internal Medicine

The dose of radiation delivered with a single CT scan was as high as 74 mammograms or 442 chest radiographs. To minimize patients’ exposure, the investigators recommended reducing unnecessary studies or those not likely to affect clinical decision-making. They suggested standardization for CT scanners regarding low-dose and lower-dose protocols and the adoption of federal standards for radiation doses across patients and facilities, as well as FDA oversight on the performance of CT scans. The study was published in the .

Medroxyprogesterone Decreases Hot Flushes in Prostate Cancer

Researchers from University Hospital in Poitiers, France, published a study online at the Lancet Oncology Website that says medroxyprogesterone helps reduce hot flushes in men receiving androgen suppression for prostate cancer.

In a double-blind trial, 919 men were treated for 6 months with 11.25 mg of leuprorelin, an androgen suppressor, for prostate cancer. In the sixth month, the 311 men who requested treatment for hot flushes or reported experiencing 14 or more hot flushes during the preceding week were randomized to receive daily treatment with 75 mg of venlafaxine (n = 102), 20 mg of medroxyprogesterone acetate (n = 108), or 100 mg of cyproterone acetate (n = 101).

To assess the number of hot flushes, patients were asked to record them in a diary for 1 week before randomization. They also completed a quality-of-life questionnaire before each visit. Data were compared to baseline evaluations and assessments at 4 weeks, 8 weeks, and 12 weeks post-randomization. Patients who received at least 1 dose of the study treatment were included in the efficacy analysis; 2 patients were excluded from the efficacy analysis for deviating from protocol.

Investigators reported a 47% drop in median daily hot flushes 1 month after randomization. Cyproterone and medroxyprogesterone were associated with significantly larger declines in the incidence of hot flushes compared with venlafaxine (P <.001). There was no significant difference in the occurrence of hot flushes between the cyproterone and medroxyprogesterone groups, but the authors noted that “cyproterone is a recognized treatment in prostate cancer and its use could interfere with hormonal therapy.” Thus, they suggested medroxyprogesterone be considered as a “standard treatment for men undergoing androgen suppression for prostate cancer.”

Five patients in the medroxyprogesterone group experienced serious adverse effects compared with 4 in the venlafaxine group and 7 in the cyproterone group. They noted that the short follow-up in the study and the potential effect of steroidal antiandrogens on prostate cancer were limitations to this study.

FDA Weighs Erlotinib as Maintenance Therapy in NSCLC

The FDA has decided to convene a panel of outside experts to assess the effectiveness of erlotinib (Tarceva) as a maintenance therapy for patients with non—small cell lung cancer (NSCLC) compared with currently available treatments. In an FDA review, regulators agreed that erlotinib, manufactured by OSI Pharmaceuticals, slows lung cancer progression and prolongs survival when used after chemotherapy.

OSI has petitioned the FDA to approve erlotinib as a maintenance therapy or to stop the spread of cancer in patients who are responsive to their chemotherapy regimen. It is currently approved as a second-line treatment for progressive NSCLC following chemotherapy.

The FDA reviewed data from a study of 889 patients who started erlotinib or placebo immediately after chemotherapy. Those taking erlotinib experienced stable disease for at least 3 months. This was a 1-month improvement compared with the patients who received placebo.

According to the FDA, “The main issue concerns other available treatment options,” such as pemetrexed (Alimta), which was approved earlier this year as maintenance therapy for NSCLC; and docetaxel (Taxotere), which has been shown to improve survival in lung cancer by 3 months when treatment is initiated after signs of progression following stable disease on chemotherapy. Erlotinib has also demonstrated similar efficacy when initiated after disease has resumed progression, which means overall survival (OS) appears to be longer with delayed erlotinib than with immediate erlotinib.

The FDA also said that patients with EGFR-negative tumors had poorer OS rates in the erlotinib arm. The reviewers said this might be a consideration in any approval decision. In addition, erlotinib was less effective in patients with squamous histology.

Cancer Patients Report Insomnia

The Duke Clinical Research Institute published data from a study that found patients with a new cancer diagnosis have problems sleeping. Kevin Weinfurt, PhD, associate professor in the departments of psychiatry and behavioral sciences and psychology and neuroscience at Duke said, “Our study found that when it comes to overall impact upon quality of life, sleep disruption is highly significant.” According to the investigators, earlier studies suggest that nearly half of all people with cancer report sleep disruption and that the problem often persists after treatment has concluded.

Dr Weinfurt and colleagues mailed invitations to patients listed in the University’s tumor registry, inviting them to participate in focus groups. The study included 10 focus groups with 6 to 12 participants in each one. Seven groups included only patients in active treatment; the remaining 3 comprised patients who had finished treatment.

Many patients considered sleep disruption to be a major problem. Notable causes included hot flashes and night sweats. Others had difficulty finding a comfortable sleeping position due to tenderness from a surgical site, radiation burns, or medical devices (eg, ports, tubing, or ostomy). Anxiety was another factor.

Psycho-Oncology

The investigators said some of the treatments for cancer, including hormonal therapies and chemotherapy, have side effects associated with insomnia and fatigue. Being immunocompromised is also related to insomnia. The patients said lack of sleep at night contributed to daytime tiredness and difficulty with concentration. The researchers concluded by saying there is not enough evidence to “guide the management of insomnia in patients with cancer,” and they recommended more attention be devoted to this issue. Results were published in .

Advanced Care Planning Associated with More Practical Coping Skills inPatients with Hematologic Malignancies

By Christin Melton

Advanced care planning has become something of a controversial issue. Opponents of healthcare insurance reform have misbranded end-of-life discussions as “death panels.” The Catholic Church recently weighed in, with the U.S. Conference of Bishops ruling that Catholic hospitals should ignore advanced care directives that refuse medically assisted nutrition and hydration for patients who are not “imminently dying.” Some medical and psychological experts oppose advanced care planning out of concerns that discussing death will increase stress levels in patients with a terminal illness. A study presented at the 51st ASH Annual Meeting, however, found that patients with hematologic malignancies who participate in advanced care planning are no more likely to have psychosocial problems than their counterparts who lack an advanced care plan.

Only 10% of Americans have an advanced care plan, a document that address end-of-life choices and typically includes a living will and designates a healthcare proxy (the person authorized to make healthcare choices for the patient should he or she become incapacitated). An advanced care plan might describe the patient’s wishes regarding resuscitation or other life-sustaining measures.

According to researchers from the University of Nebraska Medical Center in Omaha and Fred Hutchinson Cancer Research Center in Seattle, previous studies suggest only 50% of patients with a hematologic cancer create an advanced care plan prior to a high-risk procedure like stem cell transplantation. Earlier data also show that those most likely to die are least likely to have a plan in place.

Researchers analyzed data for 293 patients with blood cancers in the HEMA-COMM (Hematology Communications) study, which evaluated communication between physicians and their patients. Patients were considered to have an advanced care plan if they had a living will and a designated healthcare proxy; those lacking one or both of these provisions were considered not to have an advanced care plan. Based on self-reporting, 149 (51%) were found to have an advanced care plan. Patients with advanced care plans tended to be older (a median of 56 years vs 52 years for those without plans) and have higher incomes. They were more likely to have a leukemia or myelodysplastic syndrome diagnosis and to have undergone prior cancer treatment.

In addition to comparing the psychosocial wellbeing (ie, coping, depression/anxiety, denial, social support, and quality of life) of patients with and without advanced care plans, the retrospective study also sought to uncover ways to encourage patients to engage in advanced care planning. Depression and anxiety were measured with the Hospital Anxiety and Depression Scale (HADS), coping was assessed with the BRIEF-COPE scale, social support was evaluated using the MOS-SS scale, and quality of life was assessed with the MOS-SF36 scale. Researchers also looked at denial.

Psychosocial wellbeing was found to be relatively equal between the two groups, except for coping. Patients that had advanced care plans were more likely to practice problem-focused coping methods, such as taking advice, seeking moral support from or talking about their feelings with others, maintaining a positive outlook, and actively working to address the problem. The authors defined “problem-focused coping” as actions taken to alter the source of stress, which they said “predominates when a person feels that something constructive can be done to affect the outcome of events.” Patients without advanced care plans often resorted to emotion-focused coping patterns, including denial, behavioral or mental disengagement, turning to religion, self-blame, and substance abuse.

Based on estimates of life expectancy and cure rates from their physicians, patients anticipated to have a worse prognosis were more likely to have an advanced care plan and discuss end-of-life wishes with a physician. Nearly one-third (30%) of those with a plan discussed their end-of-life wishes with a physician, 62% discussed wishes for life support use with family, and 8% did not discuss their wishes with anyone.

The researchers concluded that patients with problem-focused coping patterns were more likely to engage in advanced care planning, possibly reflecting a “realistic or pragmatic view of clinical outcomes.” They may be more likely to recognize the need for an advanced care plan because of an unfavorable prognosis.

Lead author Fausto R. Loberiza Jr, MD, associate professor at the University of Nebraska Medical Center, said he believes this practicality may be one avenue for increasing patient participation in advanced care planning. In a press release, Dr Loberiza said, “In order to increase engagement in advanced care planning, it is important to focus on the practical importance of advanced care planning regardless of prognosis, and deemphasize the emotional aspects of advanced care planning.” He suggested such an approach might be more appealing to patients “regardless of coping style.” He added that advanced care planning is important for all individuals. “We hope that more people engage in this important process,” he concluded.