Breast Cancer: Are Yearly Mammograms Worthwhile?

woman having mammogram

Nov. 21, 2012 — Women over age 40 are often urged to get yearly mammograms with the promise that early detection is their best hope for beating breast cancer.

But a new study published in The New England Journal of Medicine suggests that mammograms may not save as many lives as doctors once thought.

The study also finds that the tests may be responsible for substantial harm, causing an estimated 1.3 million women in the U.S. over the last 30 years to be treated for breast cancers that would not have caused clinical symptoms.

“There’s a definite harm potential. It’s sizeable. It’s greater than we realized,” says researcher Archie Bleyer, MD, clinical research professor of radiation medicine at Oregon Health & Science University in Portland.

Bleyer says the study suggests that while mammograms are good and save lives, they should be used less often.

He supports guidelines from the U.S. Preventive Services Task Force that delay screening for most women until age 50 and only recommend tests every other year until age 75.

Other organizations, including the American Cancer Society and the American College of Obstetricians and Gynecologists, say women should get annual mammograms starting at age 40.

Len Lichtenfeld, MD, deputy chief medical officer at the American Cancer Society, says the study is interesting and will lead to more discussion about mammograms.

“It’s not a study that’s going to close the book, shall we say, on the discussion regarding the value of mammography,” says Lichtenfeld, who was not involved in the research.

Estimating Overdiagnosis of Breast Cancer

The study looked at trends in breast cancer detection in the U.S. from 1976 through 2008.

Researchers compared rates of breast cancer diagnoses before and after mammograms became widely used for screening. They adjusted their results to remove excess cancers thought to be related to the widespread use of hormone replacement therapy (HRT).

Mammograms did help find more early-stage breast cancers. But finding those cancers did not seem to prevent much late-stage disease. The number of late-stage breast cancers, which are most likely to be life-threatening, dropped only slightly, from 102 to 94 cases per 100,000 women.

Researchers think that means that many early breast cancers — perhaps as many as half of all cancers detected by mammograms — are probably harmless and are being “overdiagnosed.”

Overdiagnosis is “the diagnosis of nothing, or something that is nothing,” says Bleyer.

“Whatever is found would never have created a problem during that person’s life. They wouldn’t have known about it otherwise,” he says.

The problem is that doctors can’t tell which early cancers may be harmless and which may become life-threatening. So once the call is made, patients are offered treatment including surgery, chemotherapy, and radiation.

“If we had a way to better distinguish within that diagnosis which cancers were likely to cause a problem, we would save a lot of women from unnecessary treatment,” says Sharon Giordano, MD. Giordano is a breast medical oncologist at MD Anderson Cancer Center in Houston. She was not involved in the research.

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Statistical Image Analysis Method Offers Automatic Mitotic Cell Detection For Breast Cancer Diagnosis

Main Category: Breast Cancer
Also Included In: Medical Devices / Diagnostics;  Cancer / Oncology
Article Date: 14 Nov 2012 – 1:00 PST

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Scientists have developed a statistical image analysis method which can assist in the grading of breast cancer by automatically segmenting tumour regions and detecting dividing cells in tissue samples.

The system, developed at the University of Warwick, promises to bring objectivity and automation to the cancer grading process which is used to determine the aggressiveness of the treatment offered to the patient.

Number of mitotic cells, cells which are dividing to create new cells, is a key indicator used by histopathologists for diagnosing and grading cancer.

At present the dominant system in the UK and much of the world – the Nottingham Grading System – is based on expert analysis of tissue samples to determine the severity of the cancer.

As a subjective system dependent on visual analysis, it can produce substantial variability in diagnostic assessment, resulting in low agreement between pathologists.

A pilot study conducted by researchers at Warwick found there to be an agreement of 19 per cent between three pathologists in identifying the mitotic cells.

In response to the need for more objectivity, a team at the University of Warwick have developed a three-step method which takes an image of tissue samples and applies statistical modelling to detect mitotic cells in that image.

Dr Nasir Rajpoot from the Department of Computer Science at the University of Warwick said: “It has long been recognised that there is a need to increase objectivity in the cancer grading process.

“This grading process determines the treatment offered to people who have been diagnosed with cancer, so it’s vital to get it right in order to prevent patients undergoing unnecessarily aggressive treatments.

“We believe our method takes a significant step towards this by offering an objective, automatic technique to assist the pathologists in grading of breast cancer.”

The method consists of three key steps. Firstly it segments the tumour margins, a step which is critical to the accuracy of mitotic cell detection.

Secondly it statistically models the intensity distribution of mitotic and non-mitotic cells in tumour areas, ignoring the non-tumorous areas. This step therefore identifies potential mitotic cells in tumour areas.

Finally the method looks at the surrounding architecture of these potential mitotic cell candidates in order to confirm them as mitotic cells, thereby reducing the number of possible false alarms.

Although there are algorithms in existence which provide automation in some parts of the mitotic cell detection process, the method developed at Warwick is the first to offer a comprehensive solution addressing the entire process.

The method is outlined in a study focusing on breast cancer histology images presented at a major conference on the subject.

Although the research to date has centred on breast cancer histology images, the scientists believe the method can be applied to other types of cancer.

In a pilot study, the method has been successfully tested against two expert pathologists’ identification of the mitotic cells. Larger scale trials are currently under way and a patent application has been filed. The researchers are also keen to collaborate with industrial partners.

The study, entitled A Gamma-Gaussian Mixture Model for detection of mitotic cells in breast cancer histopathology images, is authored by PhD student Mr Adnan Khan, his supervisor Dr Nasir Rajpoot, and University Hospitals Coventry and Warwickshire NHS Trustconsultant histopathologist Dr Hesham El-Daly, and is being presented at the International Conference on Pattern Recognition (ICPR 2012) to be held in Tsukuba, Japan between 11-16 November, 2012.

University of Warwick

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African-American Women: Breast Cancer More Deadly?

woman looking at mammogram machine

Oct. 28, 2012 — African-American women may be more likely to die of breast cancer than women of other races, especially in the first few years after the diagnosis, according to new research.

As to why, there are no clear answers yet, but the emphasis on vigilant care is clear for African-American women.

“Black women were almost 50% more likely to die compared to white women within the first three years since breast cancer was diagnosed,” says researcher Erica Warner, ScD, MPH, a postdoctoral research fellow at the Harvard School of Public Health.

That higher risk of death was driven by African-American women who had estrogen receptor-positive tumors, she found. These tumors are usually more treatable than other types.

Asian women, in comparison to whites or African-Americans, had a lower risk of dying from breast cancer, she found.

Warner presented the study today at the American Association for Cancer Research conference on cancer health disparities in San Diego.

About 227,000 new cases of invasive breast cancer will be diagnosed this year, the American Cancer Society predicts, with nearly 40,000 deaths.

Women & Breast Cancer: Ongoing Research

The overall results are not surprising, Warner says. “Other people have shown differences in survival, black compared to white,” she says.

“While black women are less likely to get diagnosed with breast cancer than white women, they are more likely to die if diagnosed,” she says, citing previous research.

In her study, she says, she looked more closely than some other researchers have at tumor subtypes. She found the death risk more striking among African-American women with the ER-positive tumors.

In all, Warner evaluated more than 19,000 women who got care at National Comprehensive Cancer Network centers from January 2000 though December 2007.  These centers are an alliance of 21 leading cancer centers.

More than 16,000 of the women were white. Another 1,500 were African-American, more than 600 were Asian, and about 1,300 were Hispanic. All the women were diagnosed with stage I to III breast cancer.

Warner followed the women for about seven years (half were followed longer, half long).

She took into account such factors as age, tumor features, stage when diagnosed, and treatments.

Asians were 40% less likely than whites to die of breast cancer during the follow-up.

African-Americans were nearly 50% more likely than whites to die of breast cancer during the follow-up.

That first three years after diagnosis, Warner says, were especially risky.

When she took into account age and tumor features, she found no differences between African-American and white women for certain tumors, including estrogen receptor-negative tumors. These are typically more aggressive than others.

Explaining Disparities

Warner can’t fully explain the findings.

“We’ve put everything we can think of in our model,” she says, as a way to explain survival differences. “We still find persistent differences in survival.”

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New Clue to Predict Diseases in Women?

mature woman

Oct. 9, 2012 — Evaluating blood levels of a hormone made in the brain and the gut may help predict diseases in women, according to new research.

High levels of the hormone neurotensin appear linked to women’s risk of diabetes, breast cancer, and cardiovascular disease such as heart disease or stroke, according to Swedish researchers.

The researchers looked at levels of a substance called proneurotensin. It turns into neurotensin.

“Proneurotensin is the first blood biomarker ever that can independently identify elevated risk of three major disease threats to women’s health,” says Olle Melander, MD, PhD, professor of internal medicine at Lund University in Malmo, Sweden. He led the study.

The research is published in the Journal of the American Medical Association.

About the Gut Hormone

Neurotensin is released after meals, especially after eating high-fat foods. It’s involved in the digestion of food, the speed at which food moves through the gut, body temperature, and pain sensation, Melander says.

More recently, he says, scientists have found it is involved in regulating appetite and feeling full. Some research suggests that neurotensin release is disturbed in obese people.

Now, Melander and others think that the hormone may also affect the risk of heart attack, other cardiovascular diseases, and breast cancer.

Gut Hormone and Disease Study

Melander and his team focused on men and women enrolled in the Malmo Study. It included nearly 29,000 men and women from Malmo, Sweden.

For this study, the researchers focused on 4,632 men and women who had blood levels of proneurotensin measured between 1991 and 1994.

They were then an average age of 57. The researchers followed these men and women until January 2009.

They looked to see who developed diabetes, cardiovascular diseases including heart disease and stroke, or breast cancer, and who died.

For women, but not men, higher levels of the hormone were linked with getting diabetes, breast cancer, and cardiovascular diseases, as well as dying.

Overall, the increased risk was 50% for death from cardiovascular disease and 33% for getting cardiovascular disease. But those with the highest levels had an even higher risk.

The elevated gut hormone may reflect underlying disease susceptibility, the researchers say.

They found a link or association, not a cause and effect.

In the future, finding high blood levels of the hormone may help identify ”hidden high risk” women who don’t appear to be at risk for heart disease or breast cancer, Melander says.

Why does the link hold only for women? “We do not really know,” he says.

“However, studies of animal models have clearly shown that the female sex hormone estrogen stimulates the growth of cells producing neurotensin, and women obviously have a higher lifetime exposure to estrogen than men,” he says.

In his research, Melander has found women have much higher levels of proneurotensin than men do. However, the process by which the hormone affects disease risk is not fully understood yet, he says.

Melander is an inventor on a patent application for using proneurotensin in disease prediction. A co-researcher is president of the company that holds those patent rights, Sphingo Tec GmbH.

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Improved Treatment Outcomes With Preoperative Needle Breast Biopsies

Main Category: Breast Cancer
Also Included In: Medicare / Medicaid / SCHIP;  Public Health
Article Date: 04 Oct 2012 – 0:00 PDT

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Improved Treatment Outcomes With Preoperative Needle Breast Biopsies

Women suspected of having breast cancer now have more reasons to be diagnosed with a needle biopsy instead of a traditional open surgical biopsy. Besides avoiding the risks and discomfort of an open surgical procedure, needle biopsies can also lead to improved treatment outcomes according to findings from a new study published in the October issue of the Journal of the American College of Surgeons.

Breast cancer is the number one form of cancer diagnosed in women in the United States, according to the U.S. Centers for Disease Control and Prevention. [1] In 2012, more than 226,000 women will be diagnosed, according to estimates from the National Cancer Institute. [2] Findings from an open biopsy or needle biopsy can confirm whether a suspicious breast lesion is actually malignant. During an open biopsy, an operation is performed to remove the concerning breast tissue and then it is examined in the laboratory to determine the presence of any malignant cells. This open procedure typically involves a trip to the operating room, a full surgical incision, and some form of anesthesia. However, a percutaneous needle biopsy procedure, allows physicians to locate the breast lesion without actually opening the breast. Instead, they use imaging techniques and extract a sample of the concerning tissue through a needle. This minimally invasive approach can be performed using a topical anesthetic and takes place in the office setting or radiology suite. There is less discomfort and quicker recovery time compared with open surgical biopsies.

Despite the less invasive nature of needle biopsy, “some physicians are still doing open biopsy, perhaps because of limited resources or lack of awareness. Needle biopsies require special instruments, techniques, and skills that may not be available at all treatment sites,” explained Ted A. James, MD, FACS, associate professor of surgery at the University of Vermont College of Medicine and lead author of the study. The advantage of the needle biopsy approach is that women may avoid an operation if the results are benign, and can get the benefit of appropriate preoperative planning if cancer is detected. “There are certainly some legitimate reasons to do an open biopsy, such as when the lesion is in a difficult position for the needle to reach. But the open approach should only be used for about 10 percent of cases, Dr. James estimates. “A needle biopsy is a more efficient, less invasive way to get the same diagnosis,” he said.

Dr. James and colleagues investigated whether better patient outcomes could be added to the list of needle biopsy advantages. They analyzed data on 1,135 patients who had been diagnosed with breast cancer and treated at hospitals in Vermont between 1998 and 2006. Patient data came from the Vermont Breast Cancer Surveillance System (VBCSS), the Vermont Cancer Registry (VCR), and the Centers for Medicare and Medicaid Services (CMS) enrollment and claims data.

None of the patients had a previous history of breast cancer, and 62.8 percent were diagnosed after needle biopsies. Patient data included the tumor’s size, stage, and estrogen receptor status. The surgeons also looked at education level and whether the patients were rural or urban residents, just in case there were correlations between socioeconomic status and biopsy procedure.

Data analysis revealed that needle biopsy became more common over time. Between 1998 and 2000 about 48.7 percent of patients underwent needle biopsies. That figure jumped to 73.6 percent between 2004 and 2006. Results showed that patients who had an open biopsy were more likely to have positive margins than those who had a needle biopsy. This finding indicates that after surgeons removed the breast lesion, cancerous cells were still present along the edges of the specimen – in 37.4 percent of open surgical patients – requiring another operation. This scenario was only true for 20.1 percent of patients diagnosed with needle biopsy.

Because the primary goal of open biopsy is to diagnose breast cancer rather than treat it, patients with open biopsy were less likely to have adequate amounts of the tumor excised. They were also less likely to have their lymph nodes assessed. Therefore, the open biopsy approach also led to more re-excisions – additional operations to remove more malignant tissue, as well as additional operations to assess lymph nodes when indicated. A single operation was needed 76.4 percent of the time for needle biopsy patients, but only 44 percent of the time for open biopsy patients.

Age and education status had no bearing on which type of biopsy was performed, but the researchers did discover residential differences. Urban patients were more likely to have a needle biopsy than rural patients – 70.6 percent compared with 57.5 percent, respect-tively. “Again that finding could have a lot to do with resources at some smaller hospitals,” Dr. James said. His team noticed that this gap was actually much narrower at the end of the study period. “That’s a very encouraging sign that things are moving in the right direction; however, there is still much room for improvement.”

Dr. James said the findings have implications for national health care policy, which has shifted toward declining reimbursement if patients are readmitted 30-days later for the same condition: “It’s really about quality, and trying to find ways to deliver better outcomes to our patients. It’s also only a matter of time before Medicare and Medicaid start looking at why patients at hospital A are going back for more reexcisions than patients at hospital B.”

The study is also a call to action for women to be more proactive in weighing their health care options. “Patients have to be active partners in their care,” he added. “I would recommend a woman with a suspicious breast lesion – who was told she needed to have an open biopsy – to ask, ‘why not a needle biopsy?’ If a needle biopsy is appropriate but just not available, it could simply mean being referred to a neighboring hospital or a colleague. But it starts with knowing there’s a better option,” he concluded.

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Genetic Researchers Find New, Low-Cost Approach For Ovarian And Breast Cancer Testing

Main Category: Ovarian Cancer
Also Included In: Breast Cancer;  Medical Devices / Diagnostics;  Genetics
Article Date: 29 Sep 2012 – 0:00 PDT

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Genetic Researchers Find New, Low-Cost Approach For Ovarian And Breast Cancer Testing

In a new genetic study, researchers said they may have found a way to cut the cost of genetic screening for breast and ovarian cancers from $3000 to $400.

Three teams of infertility scientists in New York and Austria collaborated to study gene mutations that increase a woman’s likelihood of breast and ovarian cancers. In the process, they made a discovery that could reduce to the cost of breast and ovarian cancer screening, making diagnosis more widely available to women in need.

The study, which was recently published in the PLoS ONE1 medical journal, examined the genetic variables in woman who were known carriers of the mutated breast and ovarian cancer susceptibility gene BRCA1/2. Women without BRCA 1/2 mutations have a lifetime risk f 12 percent for breast and 1.4 percent for ovarian cancers. However, with a BRCA 1/2 mutation, the risk for breast cancer increases to 60 percent and for ovarian cancer to between 15 and 40 percent.

Researchers from the Center for Human Reproduction (CHR) in New York, the Medical University Vienna in Vienna, Austria, and the Medical University Graz in Graz, Austria worked on the study.

Together they found nearly all of the 99 subjects who were carriers of the BRCA1/2 mutations also had a very specific genotype known as “low” FMR1. In contrast, over 300 control subjects, who were not carriers of the mutated BRCA1/2 gene, showed normal distribution of the FMR1 genotypes with only about 25% of the subjects having the “low” FMR1.

The authors concluded that because BRCA1/2 mutations are almost exclusively found in women with low FMR1, women without the low FMR1 genotype would not be at risk for BRCA1/2 mutations and, therefore, associated breast and ovarian cancer risks.

Researchers found the link between the genotype and these specific cancer risks suggests that less expensive FMR1 gene testing could be used in place of the current method of the costly BRCA1/2 screening for these cancer risks.

“We were very surprised by these results,” said David H. Barad, MD, MS, Director of Clinical ART and Senior Scientist at CHR, a senior author of the study. “This observation, if confirmed, can greatly impact current cancer screening methods for BRCA1/2-associated cancers in women, and greatly reduce costs.”

At the moment, the only available genetic screening for breast and ovarian cancers is through the testing of the BRCA1/2 gene, but since the procedure requires extremely high costs – about $3,000 – testing is only recommended for women with a strong family history of these cancers. FMR1 testing, on the other hand, is available for as little as $400.

The finding is especially important, as recent research has shown females with a BRCA gene mutation today are being diagnosed with breast and ovarian cancer about eight years earlier than their mothers or aunts were.

University of Texas researchers at the MD Anderson Cancer Center identified 132 women with the BRCA 1/2 genes who also had breast cancer. Of the 132, they 106 had a mother or aunt who was also diagnosed with BRCA-related breast or ovarian cancer, and the researchers recorded the female’s age at the time of diagnosis. In the end, they saw a 7.9 year age difference between the generations – finding that may change the screening and genetic counseling for women with BRCA genes in the future.

CHR and Austrian researchers hope their findings will help explain the mystery of the “BRCA-paradox,” which has puzzled scientists for years. This paradox refers to the fact that BRCA1/2 mutation prevents cell growth and replication in embryonic tissue – making it lethal to a growing human embryo. However, in cancerous tissues, these mutations have exactly the opposite effect, allowing cancer cells to proliferate.

“Confirmed, these findings could mean that ‘low’ FMR1 alleles de-suppress the anti-proliferative activity of BRCA1/2 in both tissues, in embryonic tissues allowing the embryo to survive, while in cancers having the negative effect of allowing cancer to proliferate,” said Norbert Gleicher, MD, Medical Director and Chief Scientist of CHR, and another senior author of the study. “This, of course, could open major therapeutic options for improving embryo growth and inhibiting cancer growth.”

Written by Diego Cupelo

Reviewed by Robyn Nazar, RN.

Center for Human Reproduction. “Genetic study reveals potential low-cost testing and treatment alternatives for ovarian and breast cancers”. 12, Sept. 2012

Funding

Funding for this article has been provided by New Wave Enterprises LLC. The sources of the research cited in article, Center for Human Reproduction, is a client of NWE.

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