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Breast Cancer and Fish

December 10th, 2010

Many streams, rivers and lakes already bear warning signs that the fish caught within them may contain dangerously high levels of mercury, which can cause brain damage. But, according to a new study, these fish may also be carrying enough chemicals that mimic the female hormone estrogen to cause breast cancer cells to grow.

“Fish are really a sentinel, just like canaries in the coal mine 100 years ago,” says Conrad Volz, co-director of exposure assessment at the University of Pittsburgh Cancer Institute’s Center for Environmental Ecology. “We need to pay attention to chemicals that are estrogenic in nature, because they find their way back into the water we all use.”

Volz and colleagues, including biochemist Patricia Eagon, took samples from 21 catfish and six white bass donated by local anglers as part of a study presented at the American Association for Cancer Research meeting in Los Angeles this week. The fish were caught in five places: a relatively unpolluted site 36 miles upstream from Pittsburgh on the Allegheny River; an industrial site on the Monongahela River; an Allegheny site downstream from several industries that release toxic chemicals; and the confluence of the Allegheny and Monongahela rivers, where Pittsburgh dumps much of its treated sewage and sewer outflows. “This is the largest concentration of combined sewer outflows in the U.S.,” Volz notes, about the confluence, known as the Point. The researchers also bought several fish at the store as controls.

Using an organic solvent, the researchers created an extract from the skin, flesh and fat of the various fish. They then bathed a breast cancer cell line — known as MCF-7 — in the extract. “We used this cell line because it has estrogen receptors in it, meaning that if estrogens are present it causes this cell line to proliferate,” Volz explains. “If you put something on it and it grows, then it must be stimulating the estrogen receptor.” In addition to responding to pure estrogen applied as a positive control, the extract from two of the white bass and five of the catfish caused the breast cancer cells to thrive.

The highest response came from fish caught in the industrial section of the Monongahela River. “The Monongahela River area is the area in Pittsburgh that was the site of most of the steel production over the last 100 years,” Volz says. “That area is still an industrial beehive.” But the broadest response came from where the sewer outflows and sewage treatment plants flow into the rivers from Pittsburgh; three of the four catfish caught here caused the breast cancer cells to proliferate. “Sewage might be more responsible for putting estrogenic chemicals in the water than the industries alone,” Volz adds. “All of the hormone replacement products that women use go down the drain, along with birth control pills, antibacterial soaps, and many of the plastics we use, like Bisphenol A, have such effects.”

It remains unclear exactly what estrogen-mimicking chemicals were actually present in the fish and what kind of cancer-causing role they might have. But their effects on the fish themselves were clear: the gender of nine of the fish could not be determined. “Increased estrogenic active substances in the water are changing males so that they are indistinguishable from females,” Volz says. “There are eggs in male gonads as well as males are secreting a yolk sac protein. Males aren’t supposed to be making egg stuff.”

And this estrogen burden is widespread. The store-bought white bass caused breast cancer cells to grow like its river-caught counterparts (as well as containing higher levels of mercury, arsenic and other contaminants) after being trucked to Pittsburgh from Lake Erie. “These fish, again, were in waters that were seeing industrial waste as well as possible combined sewer outflows,” Volz notes. “This isn’t just happening in Pittsburgh, this is happening everywhere in the industrialized world.”

Volz says he and his fellow researchers are launching a broader survey this summer that will entail sampling fish all along the Allegheny River. Efforts will be made to determine if it is industrial waste, sewage or agricultural runoff — or all three — that is responsible for the problem. In the meantime, cooking the fat out of fish may be the best defense. “If you broil fish and let the fats drip out that will take most of the contaminants out,” Volz says, though that may not be enough given other exposures to potentially tainted water. “What our study does show us is that there is exposure potential to vast populations that use water from our rivers as their drinking water supply.”

Study Questions Safety of Mammograms for Young Women at High Risk of Cancer

December 1st, 2009

From NYTimes.com:

For young women who have a high risk of breast cancer because of genetic mutations or family history, the radiation from yearly mammograms may make the risk even higher, researchers reported at a radiology conference on Monday.

The report is particularly troubling because it suggests that the very women who are told they need mammograms most may also be the most vulnerable to harm from them. Doctors routinely urge high-risk women to have mammograms earlier in life and more often than women judged to be at average risk.

Researchers caution that the new report is not conclusive, and that the issue needs more study.

High doses of radiation can increase the risk of breast cancer, especially in young women, but mammography uses a low dose. The American Cancer Society and many breast cancer experts say the benefits of screening far outweigh any theoretical risk from the radiation.

But the new findings will probably fuel the debate that was ignited by a recent article in The Journal of the American Medical Association questioning the value of breast cancer screening and a report by a government task force suggesting that most women could start having mammograms later in life and repeat them less often than had generally been recommended.

The latest findings come not from new research, but from an analysis that pooled the data from six earlier studies involving about 5,000 high-risk women in the United States and Europe, some who had breast cancer and some who did not. Their median age was 45.

Looking back at their medical histories, researchers found that those women who had had mammograms or chest X-rays (which use a lower radiation dose than mammography) were more likely to have breast cancer.

Specifically, women exposed to radiation before age 20 or women with five or more exposures were 2.5 times more likely to develop breast cancer than were women who had not been exposed. The difference was statistically significant after all the data was pooled, but only some of the individual studies had significant findings; in those that did not reach statistical significance, the results could have been due to chance.

The analysis applies only to women who, like those in the study, have a high risk of breast cancer — about 0.5 percent to 1 percent of the population.

Marijke C. Jansen-van der Weide, the first author of the study and an epidemiologist at University Medical Center Groningen in the Netherlands, presented the analysis in Chicago at a meeting of the Radiological Society of North America.

In a telephone interview, Dr. Jansen-van der Weide said it was of concern to find a doubling of risk in women whose baseline risk was already high, and she suggested that young women at high risk should avoid repeated exposure to even low-dose radiation. She said the same mutation that increased the risk of breast cancer might make the breast more susceptible to cancer caused by radiation.

“For high-risk women, it’s important to weigh the benefits and risks of mammography with their doctor and come together on a screening strategy, and to keep in mind that at a young age you can use an alternative screening technique like M.R.I.,” Dr. Jansen-van der Weide said.

Robert Smith, director of cancer screening for the American Cancer Society, questioned the analysis’ methodology and disagreed with the idea that M.R.I. could replace mammography in high-risk women. Dr. Smith said M.R.I. missed some tumors that mammography could find, and vice versa, so the best approach for high-risk women was to use the two tests together.

“It’s not as if clinicians are unaware and unconcerned about radiation risks in young women,” he said. “If mammography offered no advantage, they wouldn’t do it.”

Scientists Develop ‘Natural’ Breast Implants

November 30th, 2009

From FoxNews.com:

British women may be offered a “natural” form of breast enlargement that uses stem cells and fat from a woman’s own body, under plans being considered by doctors.

The technique, pioneered in Japan, results in breasts that look and feel smoother than conventional cosmetic surgery using implants. This is because the stem cells enable the fat to grow its own blood supply, thus becoming an integral part of the breast rather than a foreign lump.

Stem cells have the potential to change into any cells in the body. They are found in most tissues, especially fat.

Dozens of women in Japan have received the breast enlargements during trials. Last week German medical authorities gave approval to the process. Under Brussels rules, this means that the procedure is now legal throughout the European Union, including Britain.

Doctors here said last week they found the technique “appealing”. The technique’s long-term effectiveness without side — effects still needs further tests, but doctors are already enthusiastic.

“I’m newly convinced,” said Venkat Ramakrishnan, a specialist in plastic and reconstructive surgery at Mid Essex Hospital Services NHS Trust. “A lot more people have to use it and prove it, but it does seem to have something to it.”

In addition to cosmetic breast enlargements, which 26,000 women in Britain underwent last year, the procedure can be used for rebuilding breasts after cancer surgery and to repair facial disfigurements.

In a further variation of the technique, a Spanish hospital last week treated a patient with fat-derived stem cells to repair a severely damaged heart.

Both types of treatment rely on a process developed by Cytori, a Californian firm, for extracting adipose tissue and concentrating its stem cells. It has mechanised the process so that procedures which used to take weeks can be done in hours.

Much stem cell research has been directed at finding therapies for diseases such as Parkinson’s, Alzheimer’s, motor neurone and muscular wasting.

The use of the cells for cosmetic breast surgery was begun in 2004 by Kotaro Yoshimura, a surgeon at Tokyo University medical school. He said last week: “I believe that within five years my procedure will be available as plastic surgery and that it will prove very popular.”

“Scientists and doctors are starting to believe that the best clues to curing and improving our bodies are inside our bodies in the form of stem cells,” said Cynthia Fox, author of Cell of Cells, a new book about the worldwide race to master stem cell technology.

“Breast augmentation is cosmetic but these cells have the potential to treat diseases ranging from cancer to Alzheimer’s.”

Yoshimura said last week he had had “no major problems” with the 39 women to whom he had so far administered the treatment. He has also used it to grow new tissue on the faces of three people with disfigurements.

He claims his technique has advantages over, for example, silicon and water implants which can leak. In addition, some 50% of implants that use plain fat — without the stem cells “boost” — die. This is usually caused by the fat losing blood supply when it is transplanted from the patient’s buttocks or thighs.

The process used by Yoshimura, Cytori and others involves extracting twice as much fat as is required for the implant. Half is treated to separate out the stem cells. These are then added back into the remaining fat to be injected into the breast in a series of treatments.

Some stem cells form more fat and others develop into a living blood supply for the new tissue which can grow into the surrounding breast.

The main drawback is that the stem cell implant gives only half the extra volume of new breast compared with conventional enhancements — 150 cubic cm per side compared with 300 cubic cm for implants. Another limitation is that thin patients may not have enough spare fat.

Eva Weiler-Mithoff, a consultant at Canniesburn hospital in Glasgow, said the technique offered particular benefits for patients needing reconstructive surgery after having mastectomies.

“The most distressing effect of radiotherapy is that the blood vessels shrivel up,” she said. “Stem cells can differentiate into new blood vessels, which could mean that more fat cells will survive.”

MRI Beats Mammograms at Spotting Early Breast Cancer

November 17th, 2009

From USNews.com:

MRI appears to be better than mammograms at finding breast cancer before it spreads, German researchers report.

However, despite the technology’s advantages, its cost and a lack of people skilled at reading breast MRIs means it won’t replace mammograms any time soon, experts say.

“MRI is more powerful and accurate for diagnosing pre-invasive breast cancer called ductal carcinoma in situ (DCIS),” concluded lead research Dr. Christiane Kuhl, from the Department of Radiology at the University of Bonn.

Her team published its findings in the Aug. 11 issue of The Lancet.

Most breast cancers arise from cells that build up in the inner lining of the milk duct, Kuhl explained. As long as this cancer is confined to the duct, it is considered benign and does not spread.

“If you identify breast cancer at this stage and remove it, the patient is healed — always,” she said. “Avoiding invasive breast cancer is even better than early diagnosis.”

In the study, Kuhl and colleagues collected data on more than 7,300 women over five years. In addition to mammograms, the women were also given MRIs. The researchers wanted to see if MRIs could detect DCIS.

They found that among the 167 women who had a DCIS, 92 percent were found by MRI compared with 56 percent found by mammography.

Moreover, of the 89 women diagnosed with “high grade” DCIS — the ones most likely to develop into cancer — 98 percent were found by MRI, compared with 52 percent found by mammography. In addition, 48 percent were missed by mammography but found by MRI alone.

High-grade DCIS almost always becomes invasive and does so after a short time, Kuhl explained. “When it becomes invasive, it is biologically aggressive — that means it kills,” she said.

In contrast, low-grade DCIS usually remains within the duct and poses no threat. In fact, women can have low-grade DCIS for a lifetime with no ill effects, Kuhl said.

Also, MRI was not associated with many false positive findings. The positive predictive value of both methods was similar — 55 percent for mammography and 59 percent for MRI, the researchers reported.

There’s one big downside, however: MRI is very expensive compared with mammography. “Also, MRI is more difficult to read, and you have to use different criteria to diagnose DCIS than for invasive breast cancer,” Kuhl said.

Since MRI is used less often than mammography “the number of radiologists who are experienced in interpreting breast MRIs is far smaller than the number of radiologists who are able to accurately interpret a mammogram,” further limiting its use, the German researcher said.

And more studies that compare MRI with mammography are needed before MRI can be recommended as the best way to diagnose DCIS, she added. “This is the beginning of the death of mammography, but that is going to be a long death,” Kuhl predicted.

One expert wasn’t surprised by the findings.

“This study shows that MRI is definitely better than mammography for detecting DCIS,” said Dr. Kristin Byrne, chief of breast imaging at Lenox Hill Hospital in New York City. “We have known that MRI is better for detecting cancer, but there has been a debate whether MRI was best for detecting DCIS,” she said.

The enhanced ability to find DCIS using MRI is due to better quality images and improved ability in reading the MRI, Byrne said. “We are now detecting much more DCIS than what is seen on the mammogram,” she said.

The American Cancer Society does recommend that women who are at high risk for breast cancer get an MRI in addition to their yearly mammogram, Byrne noted.

Still, it will take a long time before breast MRI replaces mammograms, she said, for the reasons Kuhl laid out.

Another expert agreed that a larger study is needed before MRI can become the preferred breast cancer screening method.

“We don’t know yet how much MRI screening will add and at what price this comes, economically and psychologically, [because of the] emotional burden due to increased absolute amount of unnecessary recalls,” said Dutch radiologist Ritse M. Mann, of Radboud University Nijmegen Medical Centre in Nijmegen.

But Mann, the co-author of an accompanying journal editorial, said that “MRI can no longer be regarded as [just] an adjunct to mammography, even though this needs considerable funding.”

“MRI screening will detect malignancies more often and earlier and will increase breast cancer survival. Therefore, it is time to start a large multicenter trial on MRI screening for breast cancer in the general population,” Mann said.

Study Shows Women With a Gene Variant Respond Better to Tamoxifen Treatment

November 15th, 2009

Comment by Dr. Perlmutter:
This particular detoxification genetic marker is easily tested and widely available.
From WebMD.com:

A single gene variant predicts breast cancer survival after tamoxifen treatment, a new study finds.

In the 46% of women with the “good” gene, tamoxifen works as well as newer drugs. For women with the gene variant linked to poor response to tamoxifen treatment, other treatment strategies would be a better choice.

In the past 25 years, tamoxifen has prevented more than half a million deaths from breast cancer. The drug helps prevent breast cancer recurrence after surgery. Tamoxifen is still a useful drug, although newer drugs called aromatase inhibitors seem to work better in clinical trials.

Now it appears that some women will do at least as well if they’re treated with tamoxifen. Such women carry a version of a gene called CYP2D6 that makes tamoxifen work better.

The gene encodes an enzyme crucial to tamoxifen activity. About 46% of women have a version of the gene that contributes to high enzyme activity. Others have genes that contribute to low or intermediate activity of the enzyme.

Werner Schroth, PhD, of Germany’s Fischer-Bosch Institute of Clinical Pharmacology, and colleagues analyzed CYP2D6 genes in 1,325 postmenopausal women treated with tamoxifen for early-stage breast cancer in Germany and in the U.S.

They found that women with the highly active version of the gene were significantly less likely to have their breast cancer come back after five years of tamoxifen treatment. These women had outcomes similar to those seen in women treated with aromatase inhibitors.

“[This] should provide new impetus to the medical and scientific community to revisit the issue of the relative efficacy of these two approaches in women with early breast cancer,” Schroth and colleagues conclude.

The researchers suggest that genetic testing could identify women who should not be treated with tamoxifen.

Schroth and colleagues report the findings in the Oct. 7 issue of TheJournal of the American Medical Association.