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FORCE Research Alert

Breast MRI Contrast Agent

By Lisa Rezende, PhD

Breast MRI is an important surveillance tool for finding cancer in high-risk women. This article, prepared in conjunction with our advisory board members, addresses concerns submitted by FORCE members about the use of gadolinium, an MRI contrast agent. These concerns are based on studies that question the safety of gandolinium under certain circumstances.

Gadolinium-containing contrast agent is commonly administered during breast MRI to improve imaging. Because gadolinium is a metal, it is given in a form that is rapidly removed from the body, limiting side effects and making it safe for most patients.1 A 2014 study of 10,595 patients who received a gadolinium-based contrast agent found it to be very safe. None of the patients had severe reactions –43 had mild reactions, and 5 had moderate reactions, including swelling and mild blood pressure changes.2 Precautions are often taken when using gadolinium-containing contrast agents in patients with a history of allergic reactions to imaging agents, women who are pregnant or nursing, and patients with kidney disease, who are risk for a rare kidney disorder known as nephrogenic systemic fibrosis if exposed to gadolinium.

The long-term effects of gadolinium-based contrast agents remain an area of research. A recent small study of 35 patients with existing brain disease showed changes in brain MRI after six or more brain MRI scans with gadolinium3. Dr. Tomonori Kanda, the paper’s lead author, states in the accompanying press release that the study does not prove that gadolinium caused the changes, nor is it clear that these findings affect patient health. Another small study looking at 31 patients undergoing hip replacement surgery found that those who previously had MRI with gadolinium-based contrast agents had a higher concentration of gadolinium in their bones than those who did not4.

Experts on our advisory board feel that these and prior research studies do not raise concern that mutation carriers are more sensitive to the effects of gadolinium, and that the benefits from enhanced contrast on breast MRIs outweigh the theoretical risks. They continue to recommend annual breast MRI with contrast for women at high-risk for breast cancer who have not undergone mastectomy.

1Hao D, Tweedle M, Hu X, et al. “MRI Contrast Agents: Basic Chemistry and Safety,” Journal of Magnetic Resonance Imaging, Volume 36, Number 5, p. 1060-71, November 2012.

2Okigawa T, Utsunomiya D, Yamashita Y, et al., “Incidence and Severity of Acute Adverse Reactions to Four Different Gadolinium-based MR Contrast Agents,” Magnetic Resonance in Medical Science, Volume 13, Number 1, p. 1-6, January 21, 2014.

3Kanda T, Takenaka D, et al., “High Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-weighted MR Images: Relationship with Increasing Cumulative Dose of a Gadolinium-based Contrast Material,” Radiology, Volume 270, Number 3, p. 834-41, March 2014.

4Darrah TH, Hannigan RE, et al., “Incorporation of Excess Gadolinium into Human Bone from Medical Contrast Agents,” Metallomics, Issue 6, p. 445-528, November 1, 2009.

 

Update: Preventative Removal of Ovaries Reduces Risk of Cancer and Increases Survival for Woman with BRCA Mutations

by Lisa Rezende, PhD

Current guidelines recommend that women who carry a mutation in the BRCA1 or BRCA2 genes undergo salpingo-oophorectomy (BSO), the surgical removal of the ovaries and fallopian tubes, to reduce their risk of ovarian and fallopian tube cancers. In the largest study to date, a new report in the Journal of Clinical Oncology from Dr. Steven Narod and colleagues confirms this recommendation by showing that BRCA mutation-carriers who undergo risk-reducing oophorectomy have an 80% reduced risk of ovarian, fallopian tube, and peritoneal cancer and an estimated 77% decreased risk of death from all causes. This confirms the 2010 study from Dr. Susan Domchek, Dr. Timothy Rebbeck, and colleagues that linked BSO in mutation carriers to increased survival (reviewed in the Spring 2011 issue of Joining FORCEs Newsletter).

The new study followed 5,783 women for an average of 5 years. These women were participants in a registry of confirmed BRCA mutation-carriers, enrolled by 43 different clinical centers. Each woman was given a survey of health history— including risk-reducing surgeries and cancer diagnosis—upon entering the registry and at least once during the follow-up period. From this group, 3,513 women had preventative oophorectomy either before entering the registry or during the follow-up period, while 2,270 women did not have the surgery at any point during the study. One advantage of a large study population is that the researchers could separate risk by mutation type and age.

At the end of the follow-up period the researchers found:

  • 108 cases of ovarian, fallopian tube, or peritoneal cancer were diagnosed in women who had not had oophorectomy; 39 of these women died from their cancer during the study period.
  • An additional 46 cancers were detected at the time of oophorectomy; 3 of these women died of their cancer during the study period.
  • 32 women were diagnosed with primary peritoneal cancer after oophorectomy; 13 of these women died of their cancer during the study period. The estimated 20-year risk of primary peritoneal cancer in women who underwent oophorectomy was 3.9% for BRCA1 mutation carriers and 1.9% for BRCA2 mutation carriers.
  • The highest incidence of ovarian cancer for BRCA1 mutation carriers occurred between the ages of 50 and 59
  • The highest incidence of ovarian cancer for BRCA2 mutation carriers was between the ages of 60 and 69.

The researchers used the data to make estimates about the decade-by-decade risks for mutation carriers. They estimated that if a woman with a BRCA1 mutation delays oophorectomy until age 40, she will have about a 4% absolute risk of being diagnosed with ovarian cancer by age 40. The authors estimated that a woman with a BRCA1 mutation who waits until age 50 to undergo oophorectomy will have about a 14.2% absolute risk of being diagnosed with ovarian cancer by age 50. Based on their estimates, the study authors conclude that results of this research support the recommendation that BRCA mutation carriers undergo prophylactic oophorectomy after they have completed childbearing. The authors also conclude that for BRCA1 mutation carriers, the age of oophorectomy should be around 35 years.

Although this is the largest study of this question to date, more research is needed to address some of the study’s limitations, including:

  • The questionnaire did not ask whether or not the fallopian tubes were also removed at the time of oophorectomy, raising the possibility that some of the women in the oophorectomy group still had fallopian tubes in which cancer could occur.
  • The surgeries were performed at medical facilities around the world. There was no way to standardize the type of surgery performed, or the type of pathology done at oophorectomy. Some of the primary peritoneal cancers diagnosed after oophorectomy could have been present but not detected at the time of oophorectomy.
  • A longer follow-up period will allow researchers to better determine the all-cause mortality rate as it may take more time for effects of surgical menopause to become apparent. Longer follow up will allow experts to refine recommendations on the ideal timing of oophorectomy.

If you wish hear more about the study, Dr. Elizabeth Swisher, Professor of Gynecological Oncology at University of Washington School of Medicine and FORCE advisory board member discusses it on a podcast at the Journal of Clinical Oncology website.

Dr. Narod will be speaking at our annual Joining FORCEs Conference, June 12-14, 2014 in Philadelphia.

Finch, A.P.M, Narod, S.A., et al., “Impact of Oophorectomy on Cancer Incidence and Mortality in Women With a BRCA1 or BRCA2 Mutation,” Journal of Clinical Oncology, published online February 24, 2014.

Domchek, S.M., Rebbeck, T.R., et.al “Association of Risk Reducing Surgery in BRCA1 or BRCA2 Mutation Carriers with Cancer Risk and Mortality,” JAMA. 2010;304(9):967-975.

 

Page updated 04/07/14

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