Genetic Testing For Hereditary Breast and Ovarian Cancers Greatly Underutilized By High-Risk Women

A women’s lifetime breast cancer risk is approximately 13 percent, and her ovarian cancer risk is less than 2 percent.  But women with BRCA1 (BReast CAncer 1) or BRCA2 (BReast CAncer 2) gene mutations may be 3 to 7 times more likely to develop breast cancer, and 9 to 30 times more likely to develop ovarian cancer, respectively, than women who do not possess such mutations. A recent report, published online in the Journal of General Internal Medicine on May 20, 2009, states that genetic testing of high-risk women for hereditary breast and ovarian cancers is greatly underutilized.

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Hollywood Celebs Raise Awareness Regarding Hereditary Breast and Ovarian Cancer

Christina Applegate – Samantha Who?


Christina Applegate as Samantha in the ABC sitcom Samantha Who? Photo Credit: American Broadcasting Company

Recently diagnosed in July 2008 with breast cancer, Christina Applegate appeared on ABC’s Good Morning America program in August. The talented, Emmy award winning actress is currently the star of the ABC sitcom “Samantha Who?” Applegate came into the Hollywood limelight when she appeared in popular Fox sitcom “Married With Children,” in the role of “Kelly Bundy.”

With a great deal of courage, Christina revealed in the Good Morning America interview that she had a double mastecomy three weeks earlier to remove a tumor in one breast and prevent future breast cancer in the other. Christina made the decision to have a prophylatic double mastecomy because she tested positive previously for the BRCA 1 (breast cancer 1) gene mutation.

“I just wanted to kind of be rid of it,” explained Christina Applegate. “So this was the choice I made and it was a tough one.” Applegate is 36 years old, but because her mother is a two time survivor of breast cancer, Christina was carefully screened for breast cancer since she was 30 years old. “After looking at all the treatment plans, the one that was going to work for me was to have a bilateral mastectomy,” she said during the interview with ABC’s Robin Roberts, also a breast cancer survivor.

“I didn’t want to go back to the doctors every four months for testing. … I’m clear,” she declared. “Absolutely 100 percent clear and clean. It did not spread. They got everything out, so I’m definitely not going to die from breast cancer.”

To view Christina Applegate’s August 19, 2008 interview on ABC’s Good Morning America, CLICK HERE.

Jessica Queller – Pretty is What Changes

Jessica Queller, author of "Pretty is What Changes"

Jessica Queller, author of "Pretty Is What Changes"

Jessica Queller is a famous Hollywood writer/producer who worked on several hit television programs like Felicity, One Tree Hill, and most recently, the Gilmore Girls, which is an Emmy Award-winning, Golden Globe-nominated, American comedy-drama series. Eleven months after her mother succumbed to cancer, Jessica Queller had herself tested for the breast cancer (BRCA) gene mutation. Queller was 34 years old when she took the BRCA gene mutation blood test, and she tested positive, like Applegate, for the BRCA 1 (breast cancer) gene mutation.

Jessica’s mother had suffered from both diseases and ultimately died of ovarian cancer. In 2005, shortly after testing positive, Jessica wrote an Op-Ed piece for the New York Times entitled Cancer and the Maiden about the burden of knowledge that comes with testing positive for the breast cancer gene. This article was the launching point for her first book, a memoir, called Pretty Is What Changes: Impossible Choices, The Breast Cancer Gene and How I Defied My Destiny. Ultimately, Queller, like Applegate, decided to have both breasts removed to stave off cancer, and she wants to have her ovaries removed before she is 40 in the hope of preventing ovarian cancer in the future.

Jessica Queller is the recipient of the 2008 LIFE Hero award from the Val Skinner Foundation

To view Jessica Queller’s April 2, 2008 interview with Good Morning America’s Robbin Roberts, CLICK HERE.

What is Hereditary Breast and Ovarian Cancer?

Hereditary breast and ovarian cancer (HBOC) is identified generally by one or more of the following characteristics found in a family:

  • early age onset of breast cancer (often before age 50);
  • family history of both breast and ovarian cancer;
  • bilateral cancers (cancer that develop in both breasts, or both ovaries, independently) or an individual with both breast and ovarian cancer;
  • an autosomal dominant pattern of inheritance (vertical transmission through either the mother or father’s side of the family); and
  • an increased incidence of tumors of other specific organs, such as the prostate.

Other factors that increase the chance that hereditary breast and ovarian cancer exists within a family include:

What Are BRCA 1 & BRCA 2 Genes?

In 1990, DNA linkage analysis studies on large families with the characteristics described above, identified the first gene associated with breast cancer. Scientists named this gene “breast cancer 1″ or “BRCA1.” BRCA1 mutations are transmitted in an autosomal dominant pattern within a family. Since it was clear that not all breast cancer families were linked to BRCA1, studies continued and in 1994, scientists discovered another gene similar to BRCA1, and named it “breast cancer 2″ or “BRCA2.” BRCA2 gene mutations are also transmitted in an autosomal dominant pattern within a family. If a disease is autosomal dominant, it means that an individual only needs to get the abnormal gene from one parent to inherit the disease. One of the parents may often have the disease.

BRCA1 and BRCA2 are tumor suppressor genes, which means that they are responsible for controlling cell growth and cell death. Each individual possesses two BRCA1and two BRCA2 genes. When an individual possesses one altered or mutated copy of the BRCA1 or BRCA2 gene, the risk for various types of cancer increases:

  • BRCA1 Mutation Risks

— 36 percent to 85 percent lifetime risk for breast cancer

— 40 percent to 60 percent lifetime risk for second breast cancer (not reappearance of first tumor)

— 20 percent to 60 percent lifetime risk for ovarian cancer

— increased risk for other cancer types, such as prostate cancer

  • BRCA2 Mutation Risks

— 36 percent to 85 percent lifetime risk for breast cancer in females

— 6 percent lifetime risk for breast cancer in males

— up to 27 percent lifetime risk for ovarian cancer

— increased risk for other cancer types, such as pancreatic, prostate, laryngeal, stomach cancer, and melanoma

It is important to note that both copies of a tumor suppressor gene must be altered or mutated before a person will develop cancer. In HBOC, the first mutation is inherited from the mother or father and is therefore present in all cells of the body. This is called a “germline mutation.” Whether an individual with a germline mutation will develop cancer and where the cancer(s) will develop depends upon where (which cell type) the second mutation occurs. For example, assuming the second mutation is in the ovary, then ovarian cancer could develop. Assuming the second mutation is in the breast, breast cancer could develop. The development of a tumor ultimately requires mutations in multiple growth control genes. Loss of both copies of BRCA1 or BRCA2 is just the first step in the process. What causes these additional mutations to be acquired is unknown. Possible causes include chemical, physical, or biological environmental exposures, or cell replication errors.

An individual who possesses an inherited germline BRCA1 or BRCA2 mutation may not develop cancer in the future due to the non-occurrence of a second gene mutation which is necessary to knock out the function of the gene and start the process of tumor formation. The lack of a second gene mutation can make the cancer appear to skip generations in a family, when, in reality, one gene mutation is present. Regardless of whether cancer ultimately develops, an individual with a mutation possesses a 50/50 chance of passing the mutation on to the next generation, which could include male and/or female children. It is also important to note that the BRCA1 and BRCA2 genes are not located on the sex chromosomes, and therefore, BRCA gene mutations can be inherited from the mother’s or father’s side of the family.

What is a founder’s effect?

The majority of BRCA1 or BRCA2 gene mutations within a single family are unique. There are, however, a few exceptions. For example, specific recurring mutations have been found in individuals of Ashkenazi (Eastern Europe) Jewish descent, and persons from the Netherlands, Iceland, and Sweden. Mutations recur in these groups because of a so-called “founder’s effect.” “Founders” consist of a small group of people that interbred due to geographic or religious isolation. The “founder’s effect” occurs when that small group of people interbreeds over generations, thereby causing specific rare gene mutations to recur and become more common in the population.

The present day Ashkenazi Jewish population arose from a small group of founders. One or more of those founders probably carried specific gene mutations in BRCA1 or BRCA2. Notably, there are three mutations (two in BRCA1 and one in BRCA2) that account for the majority of the BRCA gene mutations possessed by Ashkenazi Jews. Accordingly, the existence of the founder’s effect is important to Ashkenazi Jewish individuals because it results in an increased occurrence of BRCA gene mutations in this population. This information hold practical importance within the context of gene testing, because some testing laboratories offer “ethnic-specific” gene mutation panels. Thus, laboratories can first investigate for specific gene mutations based upon the ethnic background of the indivdual, rather than search through the entire gene each time that person is tested.

In the general population, it is estimated that 1 in 500 individuals has a mutation in BRCA1 or BRCA2. In contrast, 1 in 40 Ashkenazi Jews possess recurring BRCA mutations. This increased occurrence places added emphasis on the assessment of family history for breast and ovarian cancer in Ashkenazi versus non-Ashkenazi persons.

NCI Population Estimates — Likelihood of a BRCA1 or BRCA2 Gene Mutation

The National Cancer Institute (NCI) statistics regarding the percentage of women found to possess BRCA gene mutations, as compared to samples of women and men with a variety of personal cancer histories regardless of family history, are provided below. The estimates are general in nature and cannot replace a personalized risk assessment by a certified genetic counselor, which may indicate a higher or lower mutation likelihood based upon specific family history characteristics.

Among non-Ashkenazi Jewish individuals (likelihood of having any BRCA mutation):

  • General non-Ashkenazi Jewish population: 1 in 500 (.2%).
  • Women with breast cancer (all ages): 1 in 50 (2%).
  • Women with breast cancer (younger than 40 years): 1 in 11 (9%).
  • Men with breast cancer (regardless of age): 1 in 20 (5%).
  • Women with ovarian cancer (all ages): 1 in 10 (10%).

Among Ashkenazi Jewish individuals (likelihood of having one of three founder mutations):

  • General Ashkenazi Jewish population: 1 in 40 (2.5%).
  • Women with breast cancer (all ages): 1 in 10 (10%).
  • Women with breast cancer (younger than 40 years): 1 in 3 (30%-35%).
  • Men with breast cancer (regardless of age): 1 in 5 (19%).
  • Women with ovarian cancer or primary peritoneal cancer (all ages): 1 in 3 (36%-41%).


Comment: The vast majority of cancers are not due to inherited mutations. The decision to obtain genetic testing, and the action to take if you test positive for a gene mutation(s), are intensely personal decisions. It is generally recommended that you speak with a certified genetic counselor or similarly trained healthcare professional prior to engaging in genetic testing.

Additional Resources:

P.O.V. Documentary “In the Family”: One Woman’s Journey Through the Unpredictable World of Predictive Genetic Testing

“At the age of 27, filmmaker Joanna Rudnick tested positive for the BRCA mutation. Joanna now faces an impossible decision: remove her healthy breasts and ovaries or risk incredible odds of developing cancer. Armed with a positive test result that leaves her essentially “a ticking time bomb,” she balances dreams of having her own children with the unnerving reality that she is risking her life by holding on to her fertility. IN THE FAMILY follows Joanna as she takes us on a journey through the unpredictable world of predictive genetic testing.

Turning the camera on herself, Joanna bares her conflicting emotions about preventative surgery and the potential consequences. Turning the camera on her new relationship, she and her partner capture a young couple falling in love in the shadow of the mutation. Turning the camera on the company that owns the patents to the BRCA genes, she questions their control over access to the test. Along the way, she looks to other women and families dealing with the same unbelievable information.

Intensely personal and timely, IN THE FAMILY is a groundbreaking investigation that attempts to answer the question: How much do you sacrifice to survive?”


Producer/Director: Joanna Rudnick

Co-production: Kartemquin Films and the Independent Television Service (ITVS).

Date of Completion: February 2008

Running Time: 90 Minutes

US Broadcast: PBS/P.O.V. will air the film on Wednesday, October 1, 2008 at 10:00 P.M. (to have a reminder sent to you by email, click here, then click on the “Send Me A Reminder” link)

Filmmaker’s Website:


Quoted Source: IN THE FAMILY – How much do you sacrifice to survive? (Synopsis), Press Kit, IN THE FAMILY website, accessed July 16, 2008 (Adobe Reader PDF document).

Comment: Visit the filmmaker’s website for more information about the film and upcoming screenings, by clicking on the link above. A brief video excerpt of IN THE FAMILY is provide below.

POV Website Note: “Want to hold a screening of In the Family in your community? If you are an organizer, a teacher, a young person using media to reach your peers or a PBS station employee interested in planning free local screenings of P.O.V. films, apply through P.O.V.’s Community Network and we’ll loan you a copy of the film (for free!) along with a toolkit including a discussion guide.”

Additional Resources:

P.O.V. – In the Family by Joanna Rudnick | PBS 2008

Canadian Women of Ashkenazi Jewish Ancestry Offered Free Testing For Cancer Gene Mutation

“One-thousand Canadian Jewish women are being offered a chance to take a free test to find out if they are at a high risk of developing breast and ovarian cancers. Scientists with Women’s College Research Institute will screen for three inherited breast cancer gene mutations common to people of Ashkenazi Jewish ancestry with the aim of preventing the disease. …”

“One-thousand Canadian Jewish women are being offered a chance to take a free test to find out if they are at a high risk of developing breast and ovarian cancers. Scientists with Women’s College Research Institute will screen for three inherited breast cancer gene mutations common to people of Ashkenazi Jewish ancestry with the aim of preventing the disease.

Adult Jewish women in Ontario, who have no known family history of breast or ovarian cancer, are being offered a blood test to screen for three specific mutations of the BRCA1 and BRCA2 genes, beginning this Thursday in Toronto. Jewish women with a family history of breast or ovarian cancer who have never been tested are also eligible. If expanding genetic testing to this group proves worthwhile, it could change the way the testing is offered across Canada by recognizing cancer risk due to ancestry.

The goal of the test is ‘to prevent cancer,’ said Steven Narod, director of the familial breast cancer research unit at Women’s College Research Institute. He said one in 44 Ashkenazi Jewish people carry the mutation compared to the general population in which an estimated one in 400 individuals carries a mutation in BRCA1 or BRCA2. According to UIA Federations Canada, most of Canada’s Jewish population is Ashkenazi — 327,360 out of a total of 370,055 — and about half of the Ashkenazi Jewish population, 165,175 — live in Toronto.

About 70 per cent of women who are BRCA1 mutation carriers will develop breast cancer by age 70 while 40 per cent will develop ovarian cancer by the same age. Those who carry the BRCA2 genetic mutation face the same breast cancer risk as those BRCA1 mutation carriers, but their risk of developing ovarian cancer is between 15 and 20 per cent by age 70, according to Narod’s group.”

[Quoted Source: Women of Ashkenazi Jewish Ancestry To Be Tested For Cancer Gene Mutation, Times & Transcript, May 28, 2008.]

Federal Enactment of the 2008 Genetic Information Nondiscrimination Act (GINA) As Law Appears Imminent

“Although nearly 40 states have had individual forms of the legislation in place, with the federal passage of GINA, the message would be unambiguous: the misuse of genetic information resulting in discrimination in employment or health insurance is against the law in all U.S. states.”

“After installing compromises and ‘minor’ changes, including a ‘firewall’ separating the potential liabilities insurers and employers could face, the US Senate last week unanimously passed the Genetic Information Nondiscrimination Act [‘GINA’].

The bill, which seeks to protect individuals’ genetic information from being misused by insurers and employers, now moves to the House, where it is also expected to pass, and then to the White House, where President Bush is expected to sign it into law.

According to American Society of Human Genetics Executive VP Joann Boughman, the Senate version of the bill adopts language appearing in the House bill (HR 493) designed to ‘limit, but not completely prevent,’ employees from suing their employer for being denied insurance based on genetic information obtained by a payor.

The bill exempts employers from liabilities if the employer ‘inadvertently’ garners genetic information through a company-sponsored wellness program, or must request such information in order to monitor biological effects of toxic substances in the workplace. The bill’s language also specifies that ‘an employer, employment agency, labor organization, or joint labor-management committee shall not be considered to be in violation … [for the] use, acquisition, or disclosure of medical information that is not genetic information about a manifested disease, disorder, or pathological condition of an employee or member, including a manifested disease, disorder, or pathological condition that has or may have a genetic basis.’

Industry observers have long said that the lack of legal protections for people’s genetic information deters them from participating in clinical trials for gene-based therapies and tests, which in turn hampers advances in the genetics field.

In an NIH-funded study of families newly -diagnosed with a hereditary cancer syndrome named hereditary non-polyposis colorectal cancer, researchers found that participants consistently asked how their involvement in the study would impact their and their families’ insurance. During the study, ‘it was clear that there was an overwhelming concern, and in some cases, a palpable anxiety about the impact of genetic testing on health insurance,’ Donald Hadley, an associate investigator and a genetic counselor with the National Human Genome Research Institute, said in a 2004 testimony to the HHS Secretary’s Advisory Committee on Genetics, Health, and Society.

‘These concerns dominate our informed consent process and recur session after session with an intensity that opened our eyes to the level of concern that the public feels about genetic discrimination,’ Hadley said in his testimony.

With the expected passage of GINA, academic genetic researchers, diagnostics firms, and pharmacogenomics companies can better assure clinical trial participants that their genetic data will not be used to make insurance or employment decisions, and that they have recourse under the law if their genetic information is abused in such a manner.

GINA is expected to go back to the House of Representatives where it will be aligned with the Senate version of the bill and voted on again. Because GINA has already passed in the House twice with ‘considerable support,’ it is not expected to encounter any problems when the lower chamber votes on it, which can happen as early as this week.

Once it clears the House, GINA is expected to be signed into law ‘in short order,’ Kurt Bardella, press secretary for GINA sponsor Sen. Snowe, told Pharmacogenomics Reporter sister publication GenomeWeb Daily News last week.

In a recent address to the National Institutes of Health, President George Bush said he is willing to sign the bill into law if it passes Congress.

GINA’s Long Haul

Since last summer, after GINA cleared the House the first time by a vote of 420 to 3, the bill has had many detractors. The bill’s main opponent was Senator Coburn, who placed a hold on GINA, citing concern that the bill could potentially increase lawsuits against employers.

Mainly, Coburn wanted the bill to include a ‘firewall’ that would prohibit employees from being able to sue their employers if an insurer denied coverage based on genetic information.

Then in March, in a surprising move, the House passed GINA by a vote of 264 – 148 as part of the Paul Wellstone Mental Health and Addiction Equity Act of 2007 (H.R. 1424), which would require health insurers to cover mental health and substance abuse-related disorders under group health plans.

Attaching GINA to that bill appeared to invite more detractors to the expanded legislation. When the Wellstone bill passed in the House, 11 senators, including Coburn, sent a letter to Democratic leaders in Congress raising concerns about GINA’s ability to ‘maintain current law distinctions between employee benefit disputes … and disputes about civil rights in the employment context.’

Some of GINA’s other detractors, including the US Chamber of Commerce, the National Association of Manufacturers, and the National Retail Federation, shared the Senators’ concerns. These groups, which formed the Genetic Information Non-Discrimination in Employment Coalition, remained optimistic that the group may be appeased with ‘minor technical fixes’ to GINA, according to Michael Eastman, executive director of labor policy at the US Chamber of Commerce.

With GINA’s passage in the Senate, it seems those ‘minor fixes’ are now in place.

Senator Coburn’s office did not return requests for comment on GINA’s passage prior to deadline.

Employer Exemptions

Although the bill would make it unlawful for an employer to obtain genetic information from an employee or a family member in order to make employment decisions, the employer is not held liable for a number of scenarios.

For example, an employer would not be breaking the law if he “inadvertently requests or requires family medical history of the employee or family member of the employee” through a employee-provided wellness program; if the employee provides prior, knowing, voluntary, and written authorization; if the employee and the doctor receive individually identifiable information concerning the results of such services; and if the employer receives genetic information regarding these services in ‘aggregate terms that do not disclose the identity of specific employees.’

The employer is also exempt if genetic information is requested to comply with medical leave laws; if an employer purchases documents that are commercially and publicly available that include family medical history; or where the information involved is to be used for genetic monitoring of the biological effects of toxic substances in the workplace. In the last instance, the employer is required to provide written notice of the genetic monitoring on an employee.

Genetic Alliance President Sharon Terry described the compromise as a product of a “great conversation” between all parties involved and the engagement of the genetics community. She also suggested that the sudden advancement in consumer genetic testing businesses over the past year, and greater discussion in the media about the uses and ethics of such tests, could have helped push the bipartisan effort to pass GINA.

Grassroots Instruction

Expecting GINA to be signed into law, its supporters are now focused on educating physicians and patients regarding their rights.

‘Our challenge now is to make sure that doctors and patients are aware of these new protections so that fear of discrimination never again stands in the way of a decision to take a genetic test that could save a life,’ Kathy Hudson, director of the Genetics and Public Policy Center at Johns Hopkins University.

The pending passage of the bill also was lauded by the Personalized Medicine Coalition, a collection of industry, academic, payor, and other partners. The PMC lauded two of its members, IBM and Eli Lilly, for adding genetic nondiscrimination to their employment policies in advance of GINA’s passage.

‘GINA closes important gaps in the current patchwork of federal and state protections against the misuse of genetic information,’ the PMC said in a statement. ‘Current federal statutes for protecting medical information, including the Health Insurance Portability and Accountability Act, do not prohibit insurers from requiring genetic testing or from denying coverage based on genetic information; and while the Americans with Disabilities Act protects individuals with symptomatic genetic disabilities, it is not clear if it explicitly covers discrimination based on unexpressed genetic susceptibility to disease.’

In the ASHG‘s view, the promulgation of a national genetic anti-discrimination law will help clear up the confusing patchwork of state laws that have emerged.

‘Although nearly 40 states have had individual forms of the legislation in place, with the federal passage of GINA the message would be unambiguous: the misuse of genetic information resulting in discrimination in employment or health insurance is against the law in all US states,’ the ASHG said in a statement.”

[Quoted Source: “Senate Unanimously Passes GINA, Though With‘Compromises’; Now Faces Sympathetic House,” by Turna Ray, Pharmacogenomics Reporter, April 30, 2008.]

Comment: For additional GINA and genetic discrimination information, please refer to the following: (i) “Genetic Information Nondiscrimination Act: 2007-2008,” National Human Genome Research Institute, National Institutes of Health, April 24, 2008; (ii) “Senate Gives GINA Critical Boost Toward Becoming Law,” National Human Genome Research Institute, National Institutes of Health, April 24, 2008; (iii) “Genetic Discrimination” Overview, National Human Genome Research Institute, National Institutes of Health, April 28, 2008; and (iv) “State Genetic Privacy Laws,” National Conference of State Legislatures, January 2008.