‘False-Alarm’ Mammograms Linked to Increased Breast Cancer Risk

Eileen Moleski has received mammogram results suggesting she has breast cancer four times, but further testing showed, each time, that she didn’t have the disease.

Now, she gets anxious each time she’s due for another mammogram, said Moleski, 44, who lives in the Philadelphia area.

A new study suggests that, for women like Moleski who’ve had a false-positive mammogram, continuing to be watchful for signs of breast cancer may be a good idea — such women are 67 percent more likely to eventually develop the disease, compared with women who’ve only had negative mammogram results, the findings showed.

The findings suggest “that either that the false positive mammograms may not be false at all, or that the false positive mammograms may be representative of a biological process which contributes to elevated risk of developing breast cancer in the future,” said Dr. Richard Bleicher, of the Fox Chase Cancer Center, in Philadelphia.

The study is published today (April 5) in the Journal of the National Cancer Institute.

A heightened risk

Researchers at the University of Copenhagen compiled mammography data from more than 58,000 Danish women. The women in the study were between 50 and 69 years old, and were screened between 1991 and 2005.

The findings showed that 339 cases of breast cancer would be expected in one year in a group of 100,000 women who had only negative mammograms, whereas 583 cases would be expected in a year in a group of 100,000 women who’d previously had a false-positive mammogram.

The increased risk of breast cancer remained for six years after a false positive mammogram, compared with women who always had a negative mammogram.

The findings showed an association, not a cause-and-effect link, and further work is needed to confirm the results.

Still, similar findings have been shown in the United States, said Dr. Jeff Tice, of the Helen Diller Family Comprehensive Cancer Center in San Francisco, who was not involved in the study.

The link might be explained by breast density, Tice said. Women with higher-density breast tissue may be more likely to get a false positive mammogram, and studies, including one that Tice worked on, have shown these women also have increased risk of developing breast cancer.

Dr. Dana Whaley, an assistant professor of radiology at the Mayo Clinic in Rochester, Minn., agreed that breast density may be the common link.

“Breast density is an independent risk factor for breast cancer, and it is more significant than family history most of the time,” Whaley said, though he added that why this is the case is not understood.

The study researchers said that the new findings suggest that false positives are a sign of some change occurring in breast tissue. It’s not likely, they said, that there actually was a tumor that was missed in follow-up evaluation: women in the study with a false-positive mammogram tended not to develop cancer within two years of their false-positive tests.

Skepticism of a link

Some experts raised cautions about the new findings.

“We don’t know other critical factors about the risk of the patients in the study — family history, genetic mutations, hormone use,” Bleicher said. The false-positive test might not, in itself, be the risk factor for cancer— it may be related to something else entirely.

The findings would be more convincing if the study researchers had linked the specific location within the breast of the abnormality that caused the false positive with the location of later breast cancer, said Dr. Karla Kerlikowske, also of the Diller Cancer Center.

The underlying biology that might increase the risk of breast cancer in these women needs to be explained with follow-up studies, Kerlikowske said.

Like Moleski, many patients with previous false-positive mammograms have anxiety, Whaley said. But that anxiety is usually about the detection of cancer, not the false-positive result. “When and how this information is presented to women is very important in preventing unnecessary anxiety,” he said.

Pass it on: Women who have a false-positive mammogram should continue to be monitored closely to rule out breast cancer or benign breast disease that may be a risk factor for breast cancer.

This story was provided by MyHealthNewsDaily, a sister site to LiveScience.

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Genentech’s Trastuzumab Emtansine (T-DM1) Showed Positive Phase III Results In HER2-Positive Metastatic Breast Cancer

— EMILIA Study Showed Trastuzumab Emtansine Significantly Extended the Time People with HER2-Positive Metastatic Breast Cancer Lived without Their Disease Getting Worse —

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Mar 30, 2012 – Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced topline results of EMILIA, the first randomized Phase III study of trastuzumab emtansine (T-DM1). The study enrolled people with HER2-positive metastatic breast cancer (mBC) who had previously received treatment with Herceptin® (trastuzumab) and a taxane chemotherapy. The study showed people who received trastuzumab emtansine lived significantly longer without their disease getting worse (progression-free survival, or PFS) compared to those who received lapatinib plus Xeloda® (capecitabine). Final results for overall survival (OS), a co-primary efficacy endpoint of EMILIA, are not yet mature. The safety profile of trastuzumab emtansine was consistent with that seen in previous studies. These data will be submitted for presentation at an upcoming medical meeting.

Trastuzumab emtansine is an investigational medicine known as an antibody-drug conjugate (ADC). It is comprised of the antibody trastuzumab and the chemotherapy DM1 attached together using a stable linker. It is designed to target and inhibit HER2 signaling and deliver the chemotherapy directly inside HER2-positive cancer cells. Trastuzumab emtansine reinforces Roche’s personalized healthcare approach of developing targeted medicines to fight cancer.

“Trastuzumab emtansine represents a new approach for the treatment of people with HER2-positive breast cancer that comes from our decades of research on the HER pathway,” said Hal Barron, M.D., chief medical officer and head, Global Product Development. “We are excited about the EMILIA results because trastuzumab emtansine is our first antibody-drug conjugate and it may help people who still need more treatment options for this aggressive disease. We will work to submit these data to regulatory authorities as quickly as possible.”

Based on these findings, Genentech plans to submit a Biologics License Application for trastuzumab emtansine to the U.S. Food and Drug Administration (FDA) this year for HER2-positive mBC. In addition, Roche plans to submit a Marketing Authorization Application to the European Medicines Agency (EMA) this year for the same indication.

About the EMILIA Study

EMILIA (TDM4370g/BO21977) is an international, Phase III, randomized, open-label study comparing trastuzumab emtansine alone to lapatinib in combination with Xeloda in 991 people with HER2-positive mBC whose disease progressed after initial treatment with Herceptin and a taxane chemotherapy.

Participants in the trastuzumab emtansine arm received:

Trastuzumab emtansine 3.6 mg/kg every three weeks

Participants in the lapatinib and Xeloda arm received:

Lapatinib 1250 mg dailyXeloda 2000 mg/m2, days 1 – 14, every three weeks

The co-primary efficacy endpoints of the study are PFS (as assessed by an independent review committee) and OS. Other study endpoints include safety profile, one-year and two-year survival rates, PFS as assessed by investigator, overall response rate, duration of response and quality of life.

About Trastuzumab Emtansine

Trastuzumab emtansine is an ADC being studied in HER2-positive cancers. Trastuzumab emtansine is designed to inhibit HER2 signaling and deliver the chemotherapy agent DM1 directly inside HER2-positive cancer cells. Trastuzumab emtansine binds to the HER2-positive cancer cells, and is thought to block out-of-control signals that make the cancer grow while also calling on the body’s immune system to attack the cancer cells. Once trastuzumab emtansine is absorbed into those cancer cells, it is designed to destroy them by releasing the DM1.

In addition to EMILIA, there are two ongoing Phase III studies of trastuzumab emtansine:

MARIANNE is comparing three different regimens (trastuzumab emtansine alone, trastuzumab emtansine plus pertuzumab, and Herceptin plus a taxane chemotherapy) in people with HER2-positive mBC who have not been previously treated for their metastatic disease.TH3RESA is comparing trastuzumab emtansine to physician’s choice of treatment in people with HER2-positive mBC who have already received both Herceptin and lapatinib.

Genentech, a member of the Roche Group, licenses technology for trastuzumab emtansine under an agreement with ImmunoGen, Inc.

Building on the results of trastuzumab emtansine studies to date, Roche/Genentech have approximately 30 ADCs in the pipeline.

About Breast Cancer

Breast cancer is the most common cancer among women worldwide. According to the American Cancer Society, approximately 229,000 people will be diagnosed with breast cancer, and 40,000 will die from the disease in 2012. In HER2-positive breast cancer, increased quantities of the Human Epidermal growth factor Receptor 2 (HER2) are present on the surface of the tumor cells. This is known as “HER2 positivity” and affects approximately 25 percent of people with breast cancer. HER2-positive cancer is a particularly aggressive form of breast cancer.

About Genentech

Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

Contact: Genentech
Media:
Krysta Pellegrino, 650-467-6800
or
Advocacy:
Sonali Padhi, 650-467-0842
or
Investor:
Thomas Kudsk Larsen, 650-467-2016
Karl Mahler, 011 41 61 687 8503

Posted: March 2012

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Mammograms Cited in Breast Cancer Overdiagnosis

Up to a fourth of breast cancers found through mammograms are harmless and would not cause noticeable disease during the women’s lifetimes, a new study from Norway suggests.

Such women are said to be overdiagnosed, because their cancers would not have caused symptoms or death. Overdiagnosis is a problem because women may receive tests and treatment they did not actually need.

However, researchers currently have no way of knowing which women have these cases; the study showed that it’s statistically probable that such cases are occurring.

“These women are treated with all the harms of treatment, and without the benefit of it,” said study researcher Mette Kalager, at the Telemark Hospital in Norway.

In the study, for every 2,500 women who underwent mammogram screening over a 10-year period, 20 cases of breast cancer were identified that would have caused significant disease if they went undetected, and one death was prevented. However, 6 to 10 cases of overdiagnosis occurred.

Women should be informed about the benefits and risks of breast cancer screening, including the risk of overdiagnosis, so they can decide if they want a mammogram.

“You have to weigh the benefits and the harms, and you have to make up your mind [about] what is most important for you,” Kalager said.

Most guidelines recommend mammograms for older women, but there are differences about what age mammograms should start, and how frequently they should be done. The U.S. Preventive Services Task Force recommends women ages 50 to 74 receive a mammogram every two years, while the American Cancer Society recommends yearly mammograms beginning at age 40.

Breast cancer overdiagnosis

Any screening test that attempts to identify a disease early on will come with a risk of overdiagnosis. Previous studies have found that rates of overdiagnosis from mammograms vary, from 0 percent to 54 percent, Kalager said.

In the new study, Kalager and colleagues analyzed cases of invasive breast cancer that occurred in Norway between 1996 and 2005, a time period over which the country began a breast cancer screening program for women ages 50 to 69. Different regions of the country began the screening program at different times, and the researchers compared cases among women who had been offered screening with those not offered screening.

About 7,800 women were diagnosed with breast cancer during the 10-year study period. Of these, the researchers estimated between15 percent and 25 percent were overdiagnosed — in other words, between 1,169 and 1,948 women would never have faced illness due to their cancers.

Because screening is started earlier in the United States than in Norway, overdiagnosis probably occurs more often here, according to Dr. Joann Elmore, of the University of Washington School of Medicine in Seattle, and Dr. Suzanne Fletcher, of Harvard Medical School in Boston, who wrote an editorial accompanying the study.

Patients want control

But while a doctor might consider the diagnosis of a cancer that never causes symptoms or death to be overdiagnosis, from a patient’s perspective, it might be exactly what they want “because they want control of their lives,” said Dr. Leo Twiggs, a professor of obstetrics and gynecology at the University of Miami School of Medicine, who was not involved in the study.

A person who is diagnosed with pre-cancer might want to change their behavior, such as increasing the frequency of their mammograms, Twiggs said.

Overdiagnosis and overtreatment could be reduced if researchers had tools to distinguish between cancers that are likely to progress and those that are unlikely to cause any problems within a patient’s lifetime, Kalager said. But currently, we don’t have those tools, she said.

A “watch and wait” approach may also be a tough sell for anxious patients, or for radiologists who don’t want to be sued if they miss signs of disease, Elmore and Fletcher said in the editorial.

“Nevertheless, unless serious efforts are made to reduce the frequency of overdiagnosis, the problem will probably increase,” as new imaging techniques are introduced, they wrote.

The study and editorial are published in the April 3 issue of the Annals of Internal Medicine.

Pass it on:  Between 15 and 25 percent of breast cancer cases diagnosed through mammography may be cases of overdiagnosis.

This story was provided by MyHealthNewsDaily, a sister site to LiveScience. Follow MyHealthNewsDaily staff writer Rachael Rettner on Twitter @RachaelRettner. Find  us on Facebook.

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