Cancer Forums and News by PhD's


News | Forums Register

Go Back   Cancer Forums and News by PhD's > Breast Cancer Forum

Reply
 
Thread Tools Display Modes
  #1  
Old 11-21-2012, 07:08 AM
admin admin is offline
Administrator
 
Join Date: Nov 2006
Posts: 68
Default Diagnostic accuracy may be improved via 3D scanning technique

According to the results of a new multi-center study published in the journal Radiology, the use of three-dimensional breast imaging, known as tomosynthesis, could improve diagnostic accuracy.

"This is the first major advance in breast imaging and breast cancer screening since the development of breast MRI," said lead researcher Elizabeth A. Rafferty, M.D., director of Breast Imaging at the Avon Comprehensive Breast Center at Massachusetts General Hospital in Boston. "The beauty of tomosynthesis is that it addresses two major concerns with screening mammography: missed cancers and false positive rates."

According to the National Cancer Institute, there is convincing evidence that screening mammography reduces breast cancer mortality in women between the ages of 40 and 74. However, as many as 30 percent of breast cancers are not detected by mammography and an additional eight to 10 percent of women who undergo a screening mammogram are recalled for further testing when no cancer is present (called a false positive result).

Unlike a screening digital mammogram, which involves two X-ray images of each breast, breast tomosynthesis captures multiple, low-dose images from different angles around the breast. The images are then used to produce a three-dimensional reconstruction of the breast. Both digital mammography and breast tomosynthesis, which was approved by the United States Food and Drug Administration (FDA) in February of 2011, can be performed on the same mammography equipment in rapid succession.

Dr. Rafferty's study involved 1,192 women recruited from five sites, of whom 997, including 780 screening cases and 217 women who needed pre-biopsy breast imaging, had complete data sets. Each of the women underwent a standard digital mammogram followed by breast tomosynthesis. The total radiation dose for the combined procedure was less than 3 milligray, which is the FDA limit for a single mammogram.

Drawing from the eligible cases, the researchers then conducted two reader studies involving 312 and 310 cases, respectively. Twelve radiologists participated in the first reader study; 15 radiologists in the second. A total of 48 cancers were included in the first reader study; 51 cancers in the second.

Compared to digital mammography alone, the use of both standard mammogram and tomosynthesis resulted in increased diagnostic accuracy for all 27 radiologists. Additionally, the diagnostic sensitivity of the combined exam — or the rate at which cancer present in the breast was correctly identified — increased by 10.7 percent for radiologists in Reader Study 1 and 16 percent for radiologists in Reader Study 2.

"Almost all of the gains in diagnostic sensitivity with the combined modality were attributable to the improved detection and characterization of invasive cancers, which are the cancers we are most concerned about because of their potential to metastasize," Dr. Rafferty said.

With the addition of breast tomosynthesis to standard digital mammography, false positive recall rates also significantly decreased for all 27 of the radiologists. Absolute recall rate reductions of 38.6 percent and 17.1 percent were seen in Reader Studies 1 and 2, respectively.

"In the clinical setting, we would expect that type of reduction in recall rate to translate into a substantial number of unnecessary diagnostic tests being avoided," Dr. Rafferty said.

References:

"Assessing Radiologist Performance Using Combined Digital Mammography and Breast Tomosynthesis Compared to Digital Mammography Alone: Results of a Multicenter, Multireader Trial." Collaborating with Dr. Rafferty were Jeong Mi Park, M.D., Liane E. Philpotts, M.D., Steven P. Poplack, M.D., Jules H. Sumkin, M.D., Elkan F. Halpern, Ph.D., and Loren T. Niklason, Ph.D.

Radiological Society of North America

Last edited by gdpawel : 11-23-2012 at 12:38 PM. Reason: added references
Reply With Quote
  #2  
Old 11-21-2012, 12:44 PM
gdpawel gdpawel is offline
Moderator
 
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,082
Default

This is interesting! It seems to follow the observations of at least two other diagnostic techniques in cancer medicine.

Currently, there is no adequate diagnostic test for ovarian cancer. However, by using the combination of HE4 and CA125 tumor markers, physicians can better triage patients for care and refer them to the appropriate specialist whether at a community hospital or large academic institution.

It was only last year that results of a pilot study were published in the journal of Gynecologic Oncology that showed the combination of HE4 and CA125 provided the highest level of sensitivity and specificity out of all marker combinations for predicting the presence of ovarian cancer.

The combination performed well in both pre- and post-menopausal women, accurately stratifying 95% of patients with epithelial cancer as high risk and 75% of benign cases as low risk.

While some cell-death assay labs use singular endpoints (point of termination), functional cytometric profiling labs assess the activity of a drug upon combined effect of all cellular processes, using several metabolic (cell metabolism) and morphologic (structure) endpoints, at the cell "population" level rather than at the "single cell" level, measuring the interaction of the entire genome.

Just as using a combination of CA125 and HE4 makes identification more accurate, a combination of metabolic and morphologic endpoints makes functional cytometric profiling more accurate.

I like the idea that combining breast tomosynthesis to standard digital mammography, false positive recall rates are significantly decreased.
__________________
Gregory D. Pawelski
Reply With Quote
  #3  
Old 11-21-2012, 05:03 PM
gdpawel gdpawel is offline
Moderator
 
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,082
Default Is this study just in time?

(USA Today) - According to an analysis in the recent New England Journal of Medicine that's likely to reignite the running debate over the value of cancer screening, up to 70,000 American women a year are treated unnecessarily for breast cancer because they were screened with mammograms.

The study found that nearly one in three breast cancer patients (1.3 million women over the past three decades) have been treated for tumors that, although detectable with mammograms, would never have actually threatened their lives. The study lays bare the greatest risk of cancer screening, called "overdiagnosis."

The study's co-author H. Gilbert Welch of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H. says that overdiagnosis occurs when technology detects cancers that, although technically malignant, behave as if they're benign. Doctors have long known that some tumors aren't actually fatal. Instead, some remain dormant for years or even disappear on their own.

Doctors and public health campaigns typically emphasize the benefits of mammograms – such as the potential to detect cancers when they're smaller and more curable – but ignore the "huge human costs" of women who go through surgery, radiation and hormonal therapies for nothing, Welch says.

"We've suggested to women that having a mammogram is one of the most important things you can do for your health, and that's simply not true," Welch says. "I can't tell you the right thing to do, except to tell women the truth, tell them both sides of the story. We shouldn't be scaring women. This is a really close call."

Though policy experts are familiar with such tradeoffs, few others understand that, in any screening program, some women will be harmed while others are helped, says Fran Visco, president of the National Breast Cancer Coalition. Breast cancer therapies can be very toxic, leading to second cancers, heart failure and even death, Visco says.

"When you intervene in a healthy population, you better be sure you're helping them, because you can be sure you're harming them," says Visco, a breast cancer survivor, who wasn't involved in the new study. "If it were really clear mammograms saved a lot of lives, there wouldn't be this constant debate."

Authors acknowledge their paper doesn't offer any guidance to women diagnosed with cancer. Because doctors can't tell for sure which tumors are most dangerous, they treat all breast cancers — and even pre-cancers — as if they have the potential to kill, says co-author Archie Bleyer of St. Charles Health System in Bend, Ore.

In a statement, the American Cancer Society says "overdiagnosis is a matter deserving of attention," but it notes that other analyses have arrived at different estimates of the number of patients treated unnecessarily.

Len Lichtenfeld, the society's deputy chief medical officer, urged people to view the findings "with caution." Overall, "the benefits of screening mammography outweigh the risks and harms, which are an unavoidable part of breast cancer screening," Lichtenfeld says.

Rigorously designed clinical trials – the gold standard of medical evidence – have found that mammograms reduce the death rate from breast cancer by about 15% in women in their 40s and 50s and 30% for women in their 60s. More recent studies, though less rigorously designed, suggest the benefits could be even greater, says radiologist Barbara Monsees, speaking for the American College of Radiology.

"We know that overdiagnosis exists," Monsees says. Although doctors need better tools to differentiate lethal tumors from relatively harmless ones, Monsees says, "we should continue to screen, because we know we can save lives."

Eric Winer, head of breast medical oncology at Boston's Dana-Farber Cancer Institute, notes that the study found an 8% reduction in the number of women whose tumors were detected at more advanced stages. Even under a scenario in which mammograms led more than 1 million women to receive unnecessary treatment, the screenings would have prevented 410,000 diagnoses of late-stage cancer.

"We probably have to some degree oversold the benefits of mammography, but we still know that mammography is beneficial, certainly for women over the age of 50 and likely for some women under 50," Winer says. "I don't think we need to abandon mammography. It's still our best test, although we desperately need better tests."

Experts offer different recommendations about the frequency and timing of mammograms. The American College of Radiology and American Cancer Society both recommend women get annual mammograms beginning at age 40. The U.S. Preventive Services Task Force recommends that women be screened every other year beginning at age 50, but they should make up their own minds about whether or not to have mammograms before that.

Given the test's limitations, Winer says, women may choose to have fewer screenings to reduce their risk. "It certainly suggests that a woman who chooses to wait until she's 50 to have mammograms, or who chooses to have mammograms every other year, is making a rational decision," Winer says.

Barry Kramer, director of the National Cancer Institute's division of cancer prevention, says women should be presented with the full picture of mammography's risks and benefits.

Though women have been instructed that "early detection saves lives," relatively few are told that screenings also have costs, including the risk of undergoing surgery, radiation and drug therapy that doesn't help them, Kramer says. "The risks of overdiagnosis are real, and women ought to know about it," Kramer says.

One comment I've read about Welch's study is the one important additional point on mammography: 600,000 women have been enrolled in randomized trials of screening mammography and no overall mortality benefit is apparent after more than a decade of follow-up. Overall mortality is the only scientifically trustworthy outcome in such data. In other words, randomized clinical trials have shown that mammography doesn't save lives, and Dr. Gil Welch knows this. The science on mammography is that it doesn't work.

[url]http://summaries.cochrane.org/CD001877/screening-for-breast-cancer-with-mammography
[url]http://cancerfocus.org/forum/showthread.php?t=3008
__________________
Gregory D. Pawelski

Last edited by gdpawel : 11-26-2012 at 12:05 PM. Reason: corrected url addresses
Reply With Quote
Sponsored Links
Advertisement
  #4  
Old 11-21-2012, 05:06 PM
gdpawel gdpawel is offline
Moderator
 
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,082
Default Effect of Three Decades of Screening Mammography on Breast-Cancer Incidence

Effect of Three Decades of Screening Mammography on Breast-Cancer Incidence

Archie Bleyer, M.D., and H. Gilbert Welch, M.D., M.P.H.

N Engl J Med 2012; 367:1998-2005November 22, 2012 DOI:10.1056/NEJMoa1206809

BACKGROUND

To reduce mortality, screening must detect life-threatening disease at an earlier, more curable stage. Effective cancer-screening programs therefore both increase the incidence of cancer detected at an early stage and decrease the incidence of cancer presenting at a late stage.

METHODS

We used Surveillance, Epidemiology, and End Results data to examine trends from 1976 through 2008 in the incidence of early-stage breast cancer (ductal carcinoma in situ and localized disease) and late-stage breast cancer (regional and distant disease) among women 40 years of age or older.

RESULTS

The introduction of screening mammography in the United States has been associated with a doubling in the number of cases of early-stage breast cancer that are detected each year, from 112 to 234 cases per 100,000 women — an absolute increase of 122 cases per 100,000 women. Concomitantly, the rate at which women present with late-stage cancer has decreased by 8%, from 102 to 94 cases per 100,000 women — an absolute decrease of 8 cases per 100,000 women. With the assumption of a constant underlying disease burden, only 8 of the 122 additional early-stage cancers diagnosed were expected to progress to advanced disease. After excluding the transient excess incidence associated with hormone-replacement therapy and adjusting for trends in the incidence of breast cancer among women younger than 40 years of age, we estimated that breast cancer was overdiagnosed (i.e., tumors were detected on screening that would never have led to clinical symptoms) in 1.3 million U.S. women in the past 30 years. We estimated that in 2008, breast cancer was overdiagnosed in more than 70,000 women; this accounted for 31% of all breast cancers diagnosed.

CONCLUSIONS

Despite substantial increases in the number of cases of early-stage breast cancer detected, screening mammography has only marginally reduced the rate at which women present with advanced cancer. Although it is not certain which women have been affected, the imbalance suggests that there is substantial overdiagnosis, accounting for nearly a third of all newly diagnosed breast cancers, and that screening is having, at best, only a small effect on the rate of death from breast cancer.

[url]http://www.nejm.org/doi/full/10.1056/NEJMoa1206809?query=featured_home
[url]http://www.nejm.org/doi/full/10.1056/NEJMclde1212888?query=featured_home
[url]http://www.kaiserhealthnews.org/Stories/2012/November/21/annual-mammogram-breast-cancer-study.aspx?utm_source=feedburner&utm_medium=feed&u tm_campaign=Feed%3A+khn%2Ffulltext+%28All+Kaiser+H ealth+News+%28Full+Text%29%29
__________________
Gregory D. Pawelski

Last edited by gdpawel : 11-24-2012 at 09:35 AM. Reason: additional url
Reply With Quote
  #5  
Old 11-24-2012, 04:09 PM
gdpawel gdpawel is offline
Moderator
 
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,082
Default 3D Mammography Ups Detection, Lowers False Recall?

(Medscape Oncology) - The addition of breast tomosynthesis, also known as 3-dimensional (3D) mammography, to standard digital mammography "offers the dual benefit of significantly increased diagnostic accuracy and significantly reduced recall rates for noncancer cases," researchers report in a study published online November 20, 2012 in Radiology.

As a result, patients can avoid unnecessary additional testing and decrease "attendant anxiety, inconvenience, and cost", write principal investigator Elizabeth Rafferty, MD, director of breast imaging at the Avon Comprehensive Breast Center, Massachusetts General Hospital, in Boston, and colleagues.

"It's actually pretty remarkable because with most technologies, any kind of gain in sensitivity will come at a cost in specificity," Dr. Rafferty told Medscape Medical News. "It's very, very rare to have improvements in both sensitivity and specificity," she added, calling breast tomosynthesis "the first major advance in breast imaging and breast cancer screening since the development of breast MRI."

Unlike conventional mammography, which involves 2 x-ray images of each breast, tomosynthesis captures multiple images from different angles, which are then used to make a 3D reconstruction of the breast, Dr. Rafferty explained. Radiologists still use standard 2-dimensional mammographic imaging for interpretation.

This combination of tomosynthesis and standard mammography can be integrated into the same piece of equipment. That approach was approved by the US Food and Drug Administration (FDA) in February 2011 (Selenia Dimensions, Hologic).

Dr. Rafferty explained that the strength of tomosynthesis is that it overcomes the source of standard mammography's limitations: overlapping tissue.

The limitations of mammogram sensitivity and specificity are related to overlapping tissue either "obscuring lesions or mimicking abnormalities and generating false-positive results. Because tomosynthesis minimizes the impact of overlapping structures, it's able to positively affect both sensitivity and specificity," she noted.

Study Results

The study, which was supported by Hologic, recruited 1192 women from 5 sites who presented for either screening mammography or prebiopsy breast imaging.

Participants underwent same-day digital mammography and tomosynthesis imaging of both breasts in the mediolateral oblique and craniocaudal positions.

The total radiation dose for the combined studies was less than 3 mGy, which is 2 times that of digital mammography alone but less than the limit for a single mammogram set by the FDA.

Two groups of radiologists who were experienced in mammogram interpretation but not tomosynthesis interpretation were trained by an experienced tomosynthesis reader to interpret the images.

Of the 997 women eligible for analysis (780 presenting for screening and 217 presenting for prebiopsy imaging), the images of 312 (including 48 cases of biopsy-proven cancer) were assigned to the first group of readers and 310 (including 51 cases of biopsy-proven cancer) were assigned to the second group of readers.

The readers first scored the digital mammograms alone and then scored the combined mammogram and tomosynthesis images. The accuracy of their interpretation was measured against the pathology results.

Training for the first group of 14 readers consisted of a review of approximately 150 cases. However, a few of those radiologists ignored "lesions that were what we call circumscribed or very well demarcated, but lobulated in shape," Dr. Rafferty explained. "It seemed clear from the types of lesions they were choosing to ignore that they were trying to translate some of their impressions from standard mammography over to tomosynthesis, despite having been trained not to do that."

Therefore, training for the second group of 15 readers was slightly different; it was reinforced with written material and included 3 additional examples. "Also, in the first [group], we did not ask the readers to actually mark the lesions they were recalling, so there was no way to confirm they had actually seen the cancer. In the second [group], we had the radiologists actually mark the lesions they were recalling rather than just describing them," she said.

For both sets of readers, diagnostic accuracy with the combined approach was significantly better than that with mammography alone ( P < .001).

Combined imaging improved diagnostic sensitivity by 11% (from 65.5% to 76.2%) with the first group of readers and by 16% (from 62.7% to 78.7%) with the second group.

Specificity improved by 5.1% (from 84.1% to 89.2%) with the first group of readers but dropped by 1.7% (from 86.2% to 84.5%) with the second group of readers.

Positive and negative predictive values increased by 13% and 2%, respectively, with the first group of readers, and by 3% and 3%, respectively, with the second group of readers.

Almost all of the gains in diagnostic sensitivity with the combined approach were attributable to an improvement in the detection of invasive cancers — by 14.8% with the first group of readers and by 21.7% with the second group of readers.

There was also a statistically significant decrease in the mean false-positive recall rate with the combined imaging, compared with mammography alone, with the first group of readers (16.7% vs 55.1%; P < .001) and with the second group of readers (30.1% vs 48.8%; P < .001).

"Clinically, such a reduction in recall rate can be expected to translate to a substantial number of unnecessary diagnostic tests being avoided," write the authors.

Although the reduction in false-positive recalls "represents a clear advantage," the authors point out that the addition of tomosynthesis to standard mammography requires particular attention to the interpretation of the images.

"Care must be taken to avoid misclassification of malignant lesions," they write. With the first group of readers, "it was apparent that cancers manifesting as certain finding types, in particular circumscribed lobulated masses, were being inappropriately dismissed by some readers. In mammographic interpretation, radiologists often associate circumscribed masses with a benign or probably benign process. In tomosynthesis imaging, however, circumscribed margins, particularly when associated with lobulated lesions, may be an indication of malignancy. This is important to emphasize as clinical radiologists transition to interpreting tomosynthesis studies," the authors explain.

Radiation Dose Details

Although not reported in the study, Dr. Rafferty told Medscape Medical News that women with large breasts or implants or who had undergone breast surgery or biopsy were excluded from the study. Some have suggested that this might limit the generalizability of the results. However, she explained that such exclusions were necessary.

"Women with breasts too large to be imaged in 1 exposure were excluded because institutional review boards didn't want them exposed to too much radiation in the investigational phase, which is completely reasonable," she explained. "Women with implants were excluded for the same reason, because they routinely need twice the number of images." Women who had undergone previous surgery or biopsy were excluded because the readers were not provided with patient histories and scars can generate false-positive results, she said.

She emphasized that the findings do not suggest that tomosynthesis is inappropriate for such patients; in fact, the technique has been approved with no restrictions.

"Anywhere it is appropriate to perform a standard mammogram, it is acceptable to do this combination imaging. In the clinical setting, we haven't had any problem implementing the technology on women who have undergone previous surgery or who have a history of cancer," Dr. Rafferty said.

Adding tomosynthesis exposes patients to more radiation than standard mammography alone, although the dose is still within recommended limits, she said. "The whole mammography machine was redesigned to generate an x-ray beam that would allow this combined exposure to be below the limit for a single mammographic exposure."

This increased radiation concern might be short-lived because the FDA Medical Devices Advisory Committee recently endorsed a modification of the equipment that enables the generation of synthesized mammograms directly from the tomosynthesis data, as reported at the time by Medscape Medical News. "The key was to give the radiologist some 2-dimensional depiction of the breast while still getting the benefits of the 3-dimensional technology and cutting the radiation dose essentially in half," said Dr. Rafferty, who investigated and presented data on the modified Hologic technique to the FDA, but emphasized that she was not paid by the company for her time or expenses.

Mammography review workstations, as well as a grant for image collection and equipment, were provided to each of the 5 participating sites by Hologic. Dr. Rafferty reports receiving research support from Hologic. Coauthor Loren T. Niklason, PhD, is an employee of Hologic. Coauthor Elkan F. Halpern, PhD, from the Department of Radiology at the Massachusetts General Hospital, reports being a consultant and statistician for Hologic.

Citation: 3D Mammography Ups Detection, Lowers False Recall. Medscape. Nov 21, 2012.

Assessing Radiologist Performance Using Combined Digital Mammography and Breast Tomosynthesis Compared with Digital Mammography Alone: Results of a Multicenter, Multireader Trial

[url]http://radiology.rsna.org/content/early/2012/11/09/radiol.12120674.abstract

About Mammography and Tomosynthesis

[url]http://www.acrin.org/PATIENTS/ABOUTIMAGINGEXAMSANDAGENTS/ABOUTMAMMOGRAPHYANDTOMOSYNTHESIS.aspx
__________________
Gregory D. Pawelski

Last edited by gdpawel : 02-17-2014 at 12:20 AM. Reason: additional info
Reply With Quote
Sponsored Links
Advertisement
  #6  
Old 11-29-2012, 12:10 AM
gdpawel gdpawel is offline
Moderator
 
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,082
Default Study: 1.3 Million Overdiagnosed Breast Cancers in 30 Years

(Medscape Oncology) - In the past 30 years, an estimated 1.3 million American women had breast cancers that were "overdiagnosed," which means their screening-detected tumors would never have led to clinical symptoms, according to a study published in the November 22 issue of the New England Journal of Medicine.

In 2008 alone, breast cancer was overdiagnosed in an estimated 70,000-plus women, which was 31% of all breast cancers diagnosed that year, assert the study authors, Archie Bleyer, MD, from the Oregon Health and Science University in Portland, and H. Gilbert Welch, MD, MPH, from the Geisel School of Medicine at Dartmouth College in Hanover, New Hampshire.

Overall, about one third of all breast cancers detected in the United States are overdiagnosed, they say.

The authors point out that the advent of widespread mammography screening in the United States led to a "substantial increase" in early-stage breast cancer, but only "marginally reduced" the rate of advanced cancers detected. "The imbalance suggests that there is substantial overdiagnosis."

However, breast screening expert Daniel B. Kopans, MD, from Harvard Medical School in Boston, Massachusetts, believes the study is "outrageous" and "should have never passed peer review."

Mammography does not cause 'overdiagnosis'.

"The paper...is another in a long line of scientifically unsupportable attacks on mammography," he told Medscape Medical News.

Dr. Kopans questioned the authors' methodology in his critique of the study. He also dismissed one of its central findings and ideas. "Mammography does not cause 'overdiagnosis'," said Dr. Kopans. "Unfortunately, pathologists are not yet able to distinguish cancers that will be lethal if left untreated from those that do not need treatment."

First Prerequisite Not Met

In their study, Drs. Bleyer and Welch state that "effective" cancer screening programs must increase the incidence of early cancers detected and decrease the incidence of late cancers detected. But mammography screening has not done the latter substantially, they say.

They used Surveillance, Epidemiology, and End Results (SEER) data to examine trends in the incidence of early-stage breast cancer (ductal carcinoma in situ [DCIS] and localized disease) and late-stage breast cancer (regional and distant disease) in women 40 years and older from 1976 to 2008.

They found that the introduction of screening doubled the number of early breast cancers detected annually.

Specifically, the incidence jumped from 112 to 234 cases per 100,000 women — an absolute increase of 122 cases per 100,000 women over the study period.

At the same time, the rate at which women present with late-stage cancer decreased by only a small amount (8%), from 102 to 94 cases per 100,000 women — an absolute decrease of 8 cases per 100,000 women.

However, only 8 of the 122 additional early-stage cancers diagnosed were expected to progress to advanced disease, say Drs. Bleyer and Welch, leaving a large imbalance between detected early-stage and late-stage cancers.

The data suggest that "mammography has largely not met the first prerequisite for screening to reduce cancer-specific mortality — a reduction in the number of women who present with late-stage cancer," the authors state.

The findings suggest that "screening is having, at best, only a small effect on the rate of death from breast cancer," they conclude.

Our study raises serious questions about the value of screening mammography.

"Our study raises serious questions about the value of screening mammography," say Drs. Bleyer Dr. Welch. However, they note that their study does not answer a common question that women ask: "Should I be screened for breast cancer?"

Dr. Kopans suggests that the study delivers the message that screening is not worthwhile. And he sees Dr. Welch as part of a "small group of highly vocal individuals who have decided that they wish to end all screening for breast cancer."

"All responsible groups agree that mammography screening saves lives," said Dr. Kopans, referring to guidelines that recommend screening from major groups such as the US Preventive Services Task Force and the American College of Physicians.

Assumptions Questioned

Drs. Bleyer and Welch chose the 3-year period from 1976 to 1978 to obtain their estimate of the baseline incidence of breast cancer detected without mammography. "During this period, the incidence of breast cancer was stable and few cases of DCIS were detected," they write.

For each year after 1978, the authors calculated the absolute change in the incidence of early- and late-stage cancer relative to the baseline incidence. They then summed the data across the 3 decades.

However, they had a challenge for the years 1990 to 2005, during which many women used breast cancer-causing hormone replacement therapy. To remove the excess breast cancer incidence from that period, they "truncated" or lowered the incidence of the various types of breast cancers.

They estimated the current incidence of breast cancer on the basis of the 3-year period from 2006 to 2008. This was deemed a good time period because it is believed that the effect of hormone-replacement therapy ended at 2006.

Drs. Bleyer and Welch calculated 4 different estimates of the excess detection or "overdiagnosis" of breast cancer for the 30-year period. The estimates varied with regard to the "underlying incidence" of breast cancer, which is an estimate of the number of cases that would be found without mammography detection.

They calculated that the underlying incidence of breast cancer was increasing by 0.25% with each passing year. They describe this as a "best-guess" estimate, and used it as the basis for their conclusion that 1.3 million women had overdetected/overdiagnosed breast cancer. They also had an "extreme-assumption" estimate that assumed a 0.5% annual increase, resulting in an estimated 1.2 million overdiagnosed cases.

Dr. Kopans said that both of these estimates are too low. He explained that there has been an "underlying 1% per year increase in breast cancer incidence...that has been going on since at least 1940."

He also criticized other elements of the calculations. "They also underestimated the effects of lead time and ignored prevalence screening, which adds to incidence every year as new women begin screening. They also combined DCIS with early-invasive lesions in an effort to dilute the results," he noted.

Drs. Bleyer and Welch anticipated most of these criticisms.

"There has been plenty of time for the surplus of diagnoses of early-stage cancer to translate into a reduction in diagnoses of late-stage cancer — thus eliminating concern about lead time," they write.

They acknowledge that their best-guess estimate of the frequency of overdiagnosis — 31% of all breast cancers — did not distinguish between DCIS and invasive breast cancer. However, they say that invasive disease accounted for about half the overdiagnoses in their estimates, and that about 20% of invasive breast cancers were overdiagnosed. "These findings replicate those of other studies," they write.

They state that reliable estimates of overdiagnosis would "ideally" come from long-term follow-up after a randomized trial. One such trial from Sweden with that long-term follow-up supports these new findings, say the authors. "Among the 9 randomized trials of mammography, the lone example of this is the 15-year follow-up after the end of the Malmö Trial, which showed that about a quarter of mammographically detected cancers were overdiagnosed," they write.

Treatment Deserves Credit Too

Over the study period, "the rate of death from breast cancer decreased considerably," they note, citing other research.

They also cite other research to assert that among women 40 years or older, deaths from breast cancer decreased from 71 to 51 deaths per 100,000 women — a 28% decrease.

But screening is not the sole reason for this drop in the death rate, Drs. Bleyer and Welch note.

"This reduction in mortality is probably due to some combination of the effects of screening mammography and better treatment," they write.

The math suggests that early detection from screening is not the biggest reason for the reduction in disease-specific death, they say.

"Because the absolute reduction in deaths (20 deaths per 100,000 women) is larger than the absolute reduction in the number of cases of late-stage cancer (8 cases per 100,000 women), the contribution of early detection to decreasing numbers of deaths must be small," they write, combining incidence data from their study with those from a death rate study.

Better treatment for breast cancer lessens the need for screening, they suggest.

"Ironically, improvements in treatment tend to deteriorate the benefit of screening. As treatment of clinically detected disease (detected by means other than screening) improves, the benefit of screening diminishes. For example, since pneumonia can be treated successfully, no one would suggest that we screen for pneumonia," they argue.

Dr. Kopans also addressed this issue, saying that "early detection is the main reason that the death rate from breast cancer has declined by over 30% since screening became widely available." He noted that "therapy has improved, but therapy saves lives when cancers are found earlier."

The authors have disclosed no relevant financial relationships. Dr. Kopans reports receiving research support from GE Healthcare.

Citation: Study:1.3 Million Overdiagnosed Breast Cancers in 30 Years. Medscape. Nov 21, 2012.

N Engl J Med. 2012;367:1998-2005.
__________________
Gregory D. Pawelski
Reply With Quote
  #7  
Old 11-29-2012, 12:19 AM
gdpawel gdpawel is offline
Moderator
 
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,082
Default Screening Mammograms Overdiagnosed More Than 1 Million Women

(OncologySTAT) - Over the past 3 decades, screening mammography may have overdiagnosed more than a million clinically insignificant breast tumors, while having virtually no impact on the incidence of metastatic disease.

Compared with the premammography era, routine screening now picks up 122 additional cases of early cancer per 100,000 women - just eight of which would likely have progressed to distant disease, Dr. Archie Bleyer and Dr. Gilbert Welch wrote in the Nov. 22 issue of the New England Journal of Medicine.

Looking at the results in light of a corresponding 28% decrease in breast cancer mortality puts screening mammography in perspective, the authors said: "Our data show that the true contribution of mammography to decreasing mortality must be at the low end of this range. They suggest that mammography has largely not met the first prerequisite for screening to reduce cancer-specific mortality - a reduction in the number of women who present with late-stage cancer."

Population cancer screening is a doubled-edged sword, wrote Dr. Bleyer of Oregon Health and Science University in Portland, and Dr. Welch of Geisel School of Medicine at Dartmouth in Hanover, N.H. While it's impossible to say which screen-detected cancers would have caused serious disease or death, "there is certainty about what happens to [these women]. They undergo surgery, radiation therapy, hormonal therapy for 5 years or more, chemotherapy, or (usually) a combination of these treatments for abnormalities that otherwise would not have caused illness."

The authors used the Surveillance , Epidemiology, and End Results (SEER) database to examine screening mammography and breast cancer incidence data from 1976-2008. They considered the incidence baseline to be the number of cancers reported from 1976-1978, and compared it with incidence in 2006-2008. All of the models in the study controlled for an upswing of breast cancer from 1990 to 2005, which was associated with hormone-replacement therapy.

Screening mammography increased from about 30% of women aged 40 or older in the mid-80s to almost 70% by 2008. This was mirrored by an increase in the diagnosis of early-stage breast cancers diagnosed, from 112/100,000 to 234/100,000 per year - representing an absolute increase of 122/100,000 (N. Engl. J. Med. 2012;367:1998-2005 [doi:10.1056/NEJMoa1206809].

"[This] reflects both the detection of more cases of localized disease and the advent of the detection of [ductal carcinoma in situ] (which was virtually not detected before mammography was available)," the authors said.

There was a much smaller concomitant decrease in late-stage cancers, which fell from 102/100,000 to 94 /100,000 women. This was almost entirely driven by a drop in regional disease, from about 85/100,000 in 1976 to 78/100,000 in 2008. The incidence of distant disease was almost entirely unchanged, hovering around 17/100,000 for the entire study period.

"If a constant underlying disease burden is assumed, only 8 of the 122 additional early diagnoses were destined to progress to advanced disease, implying a detection of 114 excess cases per 100,000 women" - a total of more than 1.5 million over the study period.

The incidence of overdiagnosis held when the authors used other models designed to favor mammography's impact.

In a "best-guess estimate," they assumed that breast cancer incidence increased by 0.25% over the study period. "This approach suggests that the excess detection attributable to mammography ... involved more than 1.3 million women in the past 30 years."

The "extreme" model assumed that incidence increased by 0.5% each year, an estimate that minimized surplus diagnoses of early-stage disease and maximized the deficit of late-stage cancer. This model found that screening mammography detected an excess of 1.2 million cancers over the study period.

The "very extreme assumption" model assumed that incidence increased by 0.5% each year, and that the baseline incidence of late-stage disease was the highest ever observed (113 cases per 100,000 women, in 1985). Even with this model - the most favorable toward mammography - the authors estimated overdiagnosis of slightly more than 1 million women.

"Our analysis suggests that whatever the mortality benefit, breast-cancer screening involved substantial harm of excess detection of additional early-stage cancers that was not matched by a reduction in late-stage cancers. This imbalance indicates a considerable amount of overdiagnosis involving more than 1 million women in the past 3 decades - and, according to our best-guess estimate, more than 70,000 women in 2008."

SEER breast cancer mortality data help put the findings into perspective, the authors said. There has been a substantial reduction in mortality, which fell from 71/100,000 to 51/100,000 over the study period. "This reduction in mortality is probably due to some combination of the effects of screening mammography and better treatment," they said. But because the absolute reduction in deaths (20/100,000) was larger than the absolute reduction in late-stage cancer (8/100,000), screening mammography can't be the main driver of change.

"Furthermore ... the small reduction in cases of late-stage cancer that has occurred has been confined to regional (largely node-positive) disease - a stage that can now often be treated successfully, with an expected 5-year survival rate of 85% among women 40 years of age or older. Unfortunately, however, the number of women in the United States who present with distant disease, only 25% of whom survive for 5 years, appears not to have been affected by screening."

Better therapy may even have altered the impact of screening, they added.

"Ironically, improvements in treatment tend to deteriorate the benefit of screening. As treatment of [disease detected by methods other than screening] improves, the benefit of screening diminishes. For example, since pneumonia can be treated successfully, no one would suggest that we screen for pneumonia."

The findings show that there are not absolutes for women considering whether or not to get a mammogram.

"Proponents of screening should provide women with data from a randomized screening trial that reflects improvements in current therapy and includes strategies to mitigate overdiagnosis in the intervention group. Women should recognize that our study does not answer the question, 'Should I be screened for breast cancer?' However, they can rest assured that the question has more than one right answer."

Dr. Bleyer disclosed that he is a consultant and speaker for Sigma-Tau Pharmaceuticals. Dr. Welch disclosed that he speaks on the topic of overdiagnosis with universities and medical schools, as well as to the Pharmacy Benefit Management Institute; all honoraria were donated to charitable organizations.
__________________
Gregory D. Pawelski
Reply With Quote
  #8  
Old 11-29-2012, 12:21 AM
gdpawel gdpawel is offline
Moderator
 
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,082
Default Commentary - Not a Complete Picture or the Last Word

Dr. J. Leonard Lichtenfeld comments: This paper is going to create discussion and concern, and get people thinking again about mammography. But from my point of view it isn't the final answer.

There's been a substantial amount of research and commentary on the role of mammography - discussion that has split people into two political camps: one saying it's the major reason for the reduced mortality and one saying it has no value whatsoever.

I think the truth lies somewhere in between.

Something has clearly affected breast cancer mortality in the past few decades. Before the 1990s, the rate of breast cancer death in this country was a flat line that had not changed for decades. Then suddenly it began to drop, and it has continued to do so. We are clearly doing something right. The question is: What is it? Probably a combination of mammography, improvements in adjuvant chemotherapy, and a general increase in breast awareness.

In the 1970s, when I was beginning practice - and before that, as a family member - breast cancer was not something anyone spoke about. It was never mentioned publicly. Now we are much more aware. Women are tuned in to the topic and aware of the need to do self-exams. It's a national discussion.

Both our surgeries and our chemotherapy are much improved. But even now, if a woman presents with a palpable breast lesion, the odds are that it's going to be fairly sizable and have lymph node involvement. Can we assume that we are able to effectively treat every woman in this group? I'm not sure we can.

This leads us to mammography. There is no question that it identifies subclinical lesions. But we have to recognize the problem of overdiagnosis and overtreatment.

Mammography and other new imaging modalities are driving the point of detection to much earlier in the history of a woman's breast cancer. We have recognized from autopsy studies that certain cancers can exist in the body for long periods of time without ever causing any problems. We know that most women with breast cancers don't have any readily identifiable risk factors. And we don't have a test that allows us to tell most women whether or not their particular cancer is likely to be aggressive.

The current study doesn't really help us with these questions. There are severe limitations on these data. How often did the women actually have a mammogram? What we consider "regional disease" today is not the same as it was in 1975. Advanced disease today isn't the same as it was in 1975. There are cultural and insurance barriers that affect access to care and, thus, affect mortality. All of these issues must be weighed into the equation.

Right now, we at the American Cancer Society are still confident in our recommendation for women older than 40 to have an annual screening mammogram and clinical breast exam. There are other recommendations from other groups, which may be a better fit for other women. The important thing is for a woman and her physician to pick a program and stay with it.

Everyone wants clear-cut answers in a world that is not clear-cut and is unlikely to become so. So women and doctors are left in the difficult position of weighing what is best for them.

I think we would all be reluctant to completely give this up. A breast cancer diagnosis in the 40s can kill a woman in her 50s. I'm concerned that we will begin missing breast cancers now that will kill in 10-15 years, and that we will lose the gains we've seen in mortality.

Dr. Lichtenfeld is the deputy chief medical officer for the national office of the American Cancer Society.
__________________
Gregory D. Pawelski
Reply With Quote
  #9  
Old 01-08-2013, 01:03 AM
gdpawel gdpawel is offline
Moderator
 
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,082
Default The Cost of Breast Cancer Screening in the Medicare Population

(Medscape Medical News) - Medicare costs of screening for breast cancer exceeded $1 billion during 2006 to 2007, according to results from a new study, with those costs substantially linked to regional variations in the use of new, expensive screening technologies.

Still, it remains unclear whether high-tech screening tools improve outcomes, according to the authors of the study.

Writing in an article published online January 7, 2013 in JAMA Internal Medicine (formerly Archives of Internal Medicine), lead author Cary Gross, MD, from Yale University's Cancer Outcomes, Public Policy, and Effectiveness Research Center, New Haven, Connecticut, and colleagues point out that although new screening technologies, such as digital mammography and computer-aided detection, provide more options for screening, they can also drive up Medicare costs in at least 2 ways: first, through Medicare's direct reimbursement for the tests; and second, through the results of the tests possibly triggering the need for more imaging tests, biopsies, and detection of cancers.

"It is critical," the authors write, "to assess the relation between screening expenditures and population outcomes since newer modalities can increase cancer detection rates but may not improve patient outcomes, particularly among older women."

To look into that issue more closely, these investigators used the linked Surveillance, Epidemiology, and End Results–Medicare database to identify 137,274 women between 66 and 100 years of age who had not previously been diagnosed with breast cancer. Then they tallied Medicare's costs during the 2-year period from 2006 to 2007 for fee-for-service breast cancer screening in that cohort of women.

In addition, they assessed Hospital Referral Region (HRR) data to compare regional variations in breast cancer screening costs and assessed the associations among regional screening costs, the incidence of cancer cases, and the costs of treating them.

$1 Billion Annually

The authors report that Medicare's fee-for-service program spent more than a billion dollars annually during the 2 years studied. "This accounted for over 45% of the $2.42 billion total spent by Medicare on screening and the initial treatment phases of breast cancer, suggesting that analyses that focus exclusively on treatment have overlooked a significant contributor to cancer costs," they write.

The authors also found that for women aged 75 years and older, annual costs for screening-related procedures were $410.6 million.

Regional costs of screening varied considerably between geographic areas, in some cases by more than 2-fold ($42 - $107 per beneficiary). The authors say that 2 screening modalities (digital screening mammography and computer-aided detection) accounted for 65% of screening-related costs between HRRs.

The authors further report that women who resided in HRRs with high screening costs were more likely to be diagnosed with early-stage cancers than were their cohorts living in areas where screening costs were lower (incidence rate ratio, 1.78; 95% confidence interval, 1.40 - 2.26).

Even so, the authors write, "There was no significant difference in the cost of initial cancer treatment per beneficiary between the highest and lowest screening cost HRRs ($151 vs $115; P = .20)."

The authors conclude that costs of treating breast cancer in Medicare patients, when screening costs are figured in, are substantially higher than has previously been documented. In addition, they say, those costs may go up more steeply than projected, "owing to Medicare's reimbursement strategy, which supports rapid adoption of newer modalities, frequently without adequate data to support their use."

In an invited commentary, Jeanne Mandelblatt, MD, MPH, from Georgetown University, Washington, DC, and colleagues characterize the findings of the Gross study as "compelling." However, they say the findings do not fully answer the question of whether investing in new, more expensive digital screening technology improves breast cancer outcomes for older women.

They say that definitive randomized clinical trials specific to older populations are needed to help sort out such questions.

The commentators conclude, "For all these conditions, interventions, and decisions about Medicare coverage, the real question raised by the research of Gross et al that must be answered is how we put a value on the life of any person or group."

This study was supported by the National Cancer Institute and the P30 Cancer Center Support Grant at the Yale Comprehensive Cancer Center. One coauthor is supported by the National Institute on Aging and by the American Federation for Aging Research through the Paul B. Beeson Career Development Award Program, by the Centers of Medicare and Medicaid Services, and by the Pew Charitable Trusts. The collection of the California cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's SEER Program, and the Centers for Disease Control and Prevention's National Program of Cancer Registries. Drs. Gross and one coauthor are members of a scientific advisory board for FAIR Health Inc and receive support from Medtronic Inc to develop and implement methods of clinical trial data sharing and patient-level meta-analyses. Another coauthor has received research funding from and has served as a consultant for Abraxis Oncology (currently Celgene), Merck, Novartis, Glaxo-Smith-Kline, and Genentech/Roche. The other authors have disclosed no relevant financial relationships. The editorialists are supported by the National Cancer Institute and the National Institutes of Health.

JAMA Intern Med. Published online January 7, 2013.

[url]http://archinte.jamanetwork.com/article.aspx?articleid=1555815
__________________
Gregory D. Pawelski
Reply With Quote
  #10  
Old 01-12-2013, 12:32 AM
gdpawel gdpawel is offline
Moderator
 
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,082
Default Can breast cancer simply disappear?

Amy Tuteur, M.D.

A new study in the Archives of Internal Medicine has been getting a lot of attention for its extraordinary claim that breast cancer can spontaneously disappear without any treatment. If it’s true, it raises a host of important questions: Should some women with breast cancer forgo toxic treatments? How does cancer simply disappear? Should we stop aggressive breast cancer screening?

The operative word, of course, is “if.” The case of the disappearing breast cancers described in the scientific paper is powerful but entirely circumstantial. The authors did not see even a single cancer disappear. They hypothesized that some breast cancers disappeared because they did not find as many cancers as they expected.

The paper is The Natural History of Invasive Breast Cancers Detected by Screening Mammography written by Zahl, Maehlan and Welch. The authors recruited over 200,000 Norwegian women ages 50-64 and divided them into two groups. The tested group had mammograms every other year for 6 years (a total of 3 mammograms). The control group had only one mammogram at the end of the 6 year period. The authors were very careful to make sure that the two groups were as similar as possible.

Over the course of the 6 year interval, 1909 cases of breast cancer were diagnosed per 100,000 women who had screening in every other year. In contrast, only 1564 cases of breast cancer were diagnosed per 100,000 women who had only one mammogram at the end of the 6 year interval. The authors concluded that over 300 cases of breast cancer were “missing” from the control group and they believe that those cancers arose and spontaneously disappeared.

Is that what really happened? First, we must consider the fact that the 1564 cases diagnosed in the control group does not include all cancers in the group. Screening mammography is not perfect and some cancers will be missed that might be detected on a subsequent scan.

Second, the use of estrogen replacement therapy in the study group was substantially higher than in the control group. Since hormone therapy has been associated with increases in breast cancer risk, that may account for part of the observed difference.

Third, the incidence of breast cancer in Norway increased over the life of the study. The women in the study group (1996-2002) had a known higher incidence of breast cancer than the women in the control group (1992-1998).

Even taking these factors into account, there is almost certainly a real difference in the cumulative number of breast cancer cases between the study group and the control group. In other words, routine mammography may over diagnose breast cancer by finding cancers that would disappear on their own if not treated.

That’s not a surprising finding. The body has many mechanisms for controlling the growth of runaway cells that could lead to cancer. The appearance of an actual cancer represents a failure of these mechanisms. It is possible, particularly in the case of small cancers detectable only by mammography, that there is still one last fail safe mechanism that could even then attack the tumor and destroy it. This study may be demonstrating that phenomenon.

There are some serious limitations to this study. The study only looks at incidence of cancer. It does not look at outcome and life expectancy. If it turns out that the women in the study group have a much lower incidence of death from breast cancer, because they are treated early and aggressively, it will justify the apparent over diagnosis of breast cancer. That is a very real possibility, because the data show that although the cumulative incidence of breast cancer in the control group was lower, many cases of breast cancer in the control group were not diagnosed until the mammogram at the end of the 6 years.

Finally, and most importantly, there is no way to tell the difference on mammography, or by any other technique, between the cancers that will disappear and the ones that will go on and kill the woman. Without a practical way to separate those who need to be treated from those who do not, the finding is intriguing and worthy of further investigation, but cannot guide us in determining the best way to screen for breast cancer and the best way to treat it.
__________________
Gregory D. Pawelski
Reply With Quote
Sponsored Links
Advertisement
Reply


Thread Tools
Display Modes

Posting Rules
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts

vB code is On
Smilies are On
[IMG] code is On
HTML code is Off
Forum Jump


All times are GMT -5. The time now is 05:27 AM.