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.
” …The study, performed by researchers at Philadelphia’s Fox Chase Cancer Center and Myriad Genetics, Inc., analyzed the prevalence of BRCA1/BRCA2 gene mutations in patients of different ethnicities at risk for hereditary breast and ovarian cancer. The study included test results of 46,276 women during the ten-year period from 1996 to 2006. Study subjects encompassed a broad, diverse ethnic group, including individuals of European, Latin American, African, Asian and Native American ancestries. … Results of the study showed that BRCA disease-causing mutations were identified in 5,780 women tested (12.5%) across all ethnic populations. Importantly, the study demonstrated that individuals of African and Latin American ancestry had as great a risk in having BRCA mutations as women with western European ancestry, when controlled for the level of personal and family history of breast and ovarian cancer. …”
“New Study Published in CANCER Supports Use of BRACAnalysis Testing Across Broad Ethnic Populations
Women of Asian, African and Latin American Ancestry Had Similar Risk of Carrying BRCA Mutations as Those With Western European Ancestry
SALT LAKE CITY, UT, Apr 30, 2009 (MARKET WIRE via COMTEX News Network) — Myriad Genetics, Inc. (NASDAQ: MYGN) announced today that an article entitled ‘BRCA1 and BRCA2 Mutations in Women of Different Ethnicities Undergoing Testing for Hereditary Breast-Ovarian Cancer‘ will appear in the May 15, 2009 issue of the journal CANCER. The study demonstrates that BRACAnalysis(R) testing of at-risk women across diverse ethnicities helps identify individuals who may benefit from improved surveillance, medical and surgical strategies to reduce their hereditary cancer risks.
‘This study, the largest of its kind, shows convincingly that strong family or personal history of breast or ovarian cancer is associated with a high prevalence of BRCA mutations — irrespective of one’s ethnic heritage,’ stated Gregory C. Critchfield, M.D., M.S., President of Myriad Genetic Laboratories.
The association between ethnicity and the risk of BRCA1 or BRCA2 mutations has not been well understood in women of non-European ancestry. This study provides important information for women of Asian, African, Latin American and Native American ancestry that may impact breast cancer [and ovarian cancer] prevention and treatment efforts among women in these populations. The study, performed by researchers at Philadelphia’s Fox Chase Cancer Center and Myriad Genetics, Inc., analyzed the prevalence of BRCA1/BRCA2 gene mutations in patients of different ethnicities at risk for hereditary breast and ovarian cancer. The study included test results of 46,276 women during the ten-year period from 1996 to 2006. Study subjects encompassed a broad, diverse ethnic group, including individuals of European, Latin American, African, Asian and Native American ancestries. To date, this work represents the largest group of patients tested for BRCA mutations reported in the literature. All testing was performed at Myriad Genetics, Inc.
Results of the study showed that BRCA disease-causing mutations were identified in 5,780 women tested (12.5%) across all ethnic populations. Importantly, the study demonstrated that individuals of African and Latin American ancestry had as great a risk in having BRCA mutations as women with western European ancestry, when controlled for the level of personal and family history of breast and ovarian cancer.
Professional medical society guidelines, such as the American Society of Clinical Oncologists (ASCO), the Society of Gynecologic Oncologists (SGO), and the American College of Obstetricians and Gynecologists (ACOG), articulate risk factors for BRCA gene mutations, which include, among others, breast cancer occurring before age 50, personal or family history of ovarian cancer at any age, personal or family history of male breast cancer, Ashkenazi Jewish ancestry with breast cancer at any age, or the presence of a known BRCA mutation in the family.
BRACAnalysis(R) is a comprehensive analysis of the BRCA1 and BRCA2 genes for assessing a woman’s risk for breast and ovarian cancer. A woman who tests positive with the BRACAnalysis(R) test has, on average, an 82% lifetime risk of developing breast cancer during her lifetime and a 44% risk of developing ovarian cancer. BRACAnalysis(R) provides important information that the Company believes will help the patient and her physician make better informed lifestyle, surveillance, preventive medication and treatment decisions. As published in the Journal of the National Cancer Institute, researchers have shown that pre-symptomatic individuals who have a high risk of developing breast cancer can reduce their risk by approximately 50% with appropriate preventive therapies. Additionally, as published in the New England Journal of Medicine, researchers have shown that pre-symptomatic individuals who carry gene mutations can lower their risk of developing ovarian cancer by approximately 60% with appropriate preventive therapies.
For more information about BRACAnalysis(R), please call 1-800-4-MYRIAD, or visit www.myriadtests.com.
About Myriad Genetics
Myriad Genetics, Inc. is a leading healthcare company focused on the development and marketing of novel molecular diagnostic and therapeutic products. Myriad’s news and other information are available on the Company’s Web site at www.myriad.com.
Myriad, the Myriad logo, BRACAnalysis, Colaris, Colaris AP, Melaris, TheraGuide, Prezeon, OnDose, Azixa and Vivecon are trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and foreign countries. MYGN-G”
- New Study Published in CANCER Supports Use of BRACAnalysis Testing Across Broad Ethnic Populations – Women of Asian, African and Latin American Ancestry Had Similar Risk of Carrying BRCA Mutations as Those With Western European Ancestry, Press Release, Myriad Genetics Inc., April 30, 2009.
- Hall MJ, Reid JE, Burbidge LA et. al. BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast-ovarian cancer. Cancer. 2009; 115(10):2222-2233. doi: 10.1002/cncr.24200
Related Information: CLICK HERE to review all Libby’s H*O*P*E*™ postings relating to BRCA gene mutations.
Evaluating a patient’s risk of hereditary breast and ovarian cancer syndrome is an important first step in cancer prevention and early detection and should be a routine part of ob-gyn practice. Those who are likely to have the syndrome should be referred for further assessment to a clinician with expertise in genetics, according to a new Practice Bulletin jointly released today by The American College of Obstetricians and Gynecologists [ACOG] and the Society of Gynecologic Oncologists [SGO]. The new document also provides information on how to counsel patients with hereditary risk in cancer prevention and how to perform surgical removal of the ovaries and fallopian tubes in this population
“Routine Screening for Hereditary Breast and Ovarian Cancer Recommended
Washington, DC — Evaluating a patient’s risk of hereditary breast and ovarian cancer syndrome is an important first step in cancer prevention and early detection and should be a routine part of ob-gyn practice. Those who are likely to have the syndrome should be referred for further assessment to a clinician with expertise in genetics, according to a new Practice Bulletin jointly released today by The American College of Obstetricians and Gynecologists [ACOG] and the Society of Gynecologic Oncologists [SGO]. The new document also provides information on how to counsel patients with hereditary risk in cancer prevention and how to perform surgical removal of the ovaries and fallopian tubes in this population.
Hereditary breast and ovarian cancer syndrome is an inherited cancer-susceptibility syndrome marked by multiple family members with breast cancer, ovarian cancer or both; the presence of both breast and ovarian cancer in a single individual; and early age of breast cancer onset.
‘The vast majority of families who have hereditary breast and ovarian cancer syndrome carry an inherited mutation of the BRCA1 or BRCA2 tumor suppressor genes. Women in these families may have a higher risk of breast, ovarian, peritoneal, and fallopian tube cancers,’ said Karen Lu, MD, professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center, who helped develop the ACOG Practice Bulletin. ‘Though having a BRCA gene mutation does not mean an individual will undoubtedly develop cancer, it is better to know sooner rather than later who may be at risk.’
Women with either BRCA mutation have a 65%-74% chance of developing breast cancer in their lifetime. Ovarian cancer risk is increased by 39%-46% in women with a BRCA1 mutation and by 12-20% in women with a BRCA2 mutation. Approximately 1 in 300 to 1 in 800 individuals in the US are BRCA carriers. BRCA mutations may occur more frequently in some populations founded by small ancestral groups, such as Ashkenazi (Eastern European) Jews, French Canadians, and Icelanders. An estimated 1 in 40 Ashkenazi Jews has a BRCA1 or BRCA2 mutation.
The new document addresses the ob-gyn’s role in identifying, managing, and counseling patients with an inherited cancer risk. The initial screening evaluation should include specific questions about personal and family history of breast cancer and ovarian cancer. Because BRCA mutations can be passed down from both the father’s and mother’s side of the family, both sides of a woman’s family should be carefully examined. Obtaining a full family history may be impeded in women who were adopted, those from families that have multiple women who had a hysterectomy and oophorectomy at a young age, or those from families with few female relatives. The results of a general evaluation will help determine whether the patient would benefit from a more in-depth hereditary cancer risk assessment, which should be conducted by a health care provider with expertise in cancer genetics.
Further genetic risk assessment is recommended for women who have more than a 20%-25% chance of having an inherited predisposition to breast or ovarian cancer. These women include:
- Women with a personal history of both breast cancer and ovarian cancer
- Women with ovarian cancer and a close relative—defined as mother, sister, daughter, grandmother, granddaughter, aunt—with ovarian cancer, premenopausal breast cancer, or both
- Women of Ashkenazi Jewish decent with breast cancer who were diagnosed at age 40 or younger or who have ovarian cancer
- Women with breast cancer at 50 or younger and who have a close relative with ovarian cancer or male breast cancer at any age
- Women with a close relative with a known BRCA mutation
Genetic risk assessment may also be appropriate for women with a 5%-10% chance of having hereditary risk, including:
- Women with breast cancer by age 40
- Women with ovarian cancer, primary peritoneal cancer, or fallopian tube cancer or high grade, serous histology at any age
- Women with cancer in both breasts (particularly if the first cancer was diagnosed by age 50)
- Women with breast cancer by age 50 and a close relative with breast cancer by age 50
- Women with breast cancer at any age and two or more close relatives with breast cancer at any age (particularly if at least one case of breast cancer was diagnosed by age 50)
- Unaffected women with a close relative that meets one of the previous criteria
Before testing, a genetic counselor can discuss the possible outcomes of testing; options for surveillance, chemoprevention, and risk-reducing surgery; cost and legal and insurance matters surrounding genetic tests and test results; and the psychologic and familial implications that may follow. The counselor can also provide written materials that women can share with family members who may also have an inherited risk.
Screening, Prevention, and Surgical Intervention
Those with hereditary breast and ovarian cancer syndrome can begin a screening and prevention plan based on individual risk factors and family history. Ovarian cancer screening approaches are currently limited. For women with a BRCA mutation, ACOG recommends periodic screening with CA 125 and transvaginal ultrasonography beginning between the ages of 30 and 35 years or 5-10 years earlier than the earliest age of first diagnosis of ovarian cancer in the family.
Risk-reducing salpingo-oophorectomy surgery—which removes both of the ovaries and fallopian tubes—can reduce the risk of ovarian and fallopian tube cancer by about 85% to 90% among BRCA carriers. Women who have BRCA1 or BRCA2 mutations should be offered risk-reducing salpingo-oophorectomy by age 40 or when childbearing is complete. The ideal time for this surgery depends on the type of gene mutation.
‘In this population, risk-reducing salpingo-oophorectomy and pathology review must be extremely comprehensive to check for microscopic cancers in the ovaries, fallopian tubes, and abdominal cavity,’ Dr. Lu said. According to the Practice Bulletin, all tissue from the ovaries and fallopian tubes should be removed, and a complete, serial sectioning that includes microscopic examination for occult cancer should be conducted. A thorough visualization of the peritoneal surfaces with pelvic washings should be performed. Any abnormal areas should undergo biopsy.
Strategies recommended to reduce breast cancer risk in women with a BRCA mutation include semiannual clinical breast examination; an annual mammogram and annual breast magnetic resonance imaging screening beginning at age 25 or sooner based on the earliest age onset in the family; chemoprevention therapy with tamoxifen; and bilateral mastectomy to remove both breasts, which reduces the risk of breast cancer by greater than 90%-95%.
Practice Bulletin #103 “Hereditary Breast and Ovarian Cancer Syndrome” is published in the April 2009 edition of Obstetrics & Gynecology.”
About the American College of Obstetricians & Gynecologists
The American College of Obstetricians and Gynecologists is the national medical organization representing over 53,000 members who provide health care for women.
About the Society of Gynecologic Oncologists
The Society of Gynecologic Oncologists is a national medical specialty organization of physician-surgeons who are trained in the comprehensive management of women with malignancies of the reproductive tract. The purpose of the SGO is to improve the care of women with gynecologic cancers by encouraging research and disseminating knowledge to raise the standards of practice in the prevention and treatment of gynecologic malignancies, in cooperation with other organizations interested in women’s health care, oncology and related fields. This is reflected in the Society’s Mission statement to “promote and ensure the highest quality
of comprehensive clinical care through excellence in education and research in gynecologic cancers.”
Primary Source: Routine Screening for Hereditary Breast and Ovarian Cancer Recommended, News Release, American College of Obstetricians & Gynecologists, March 20, 2009.
Christina Applegate – Samantha Who?
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 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.
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:
- family history of male breast cancer; and
- Ashkenazi Jewish ancestry
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%).
- Tough Decisions on Breast Cancer, by Susan Reimer, Baltimore Sun, August 21, 2008.
- What Christina Applegate Faces with Breast Reconstruction, by Deborah Kotz, Health, U.S. News & World Report, August 19, 2008.
- Hereditary Breast Ovarian Cancer Syndrome (BRCA1/BRCA2), Genetics, Information About Cancer, Stanford Cancer Center.
- Genetics of Breast and Ovarian Cancer (PDQ®) (Health Professional Version), National Cancer Institute, June 19, 2008 (last modified)
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.
- Our Community, Toll-Free Help Line (1-866-824-RISK (7475), Facing Our Risk of Cancer Empowered (FORCE).
- Hereditary Cancer & Cancer Genetics, Facing Our Risk of Cancer Empowered (FORCE).
- Cancer Genetics Overview (PDQ®)(Health Professional Version), National Cancer Institute, February 28, 2008 (last modified)(includes online genetic resources list)
- Genetics of Breast and Ovarian Cancer (PDQ®) (Health Professional Version), National Cancer Institute, June 19, 2008 (last modified).
- Elements of Cancer Genetics Risk Assessment and Counseling (PDQ®)(Health Professional Version), National Cancer Institute, June 19, 2008 (last modified).
- P.O.V. Documentary “In the Family”: One Woman’s Journey Through the Unpredictable World of Predictive Genetic Testing, by Paul Cacciatore, Libby’s H*O*P*E*™ posting, July 16, 2008.
- Making Informed Decisions: Testing & Management for Hereditary Breast and Ovarian Cancer, Myriad Genetic Laboratories, Inc. (May 8, 2008 posting, Libby’s H*O*P*E*™ Ovarian Cancer Video Archive).
- Search: Cancer Genetics Services Directory, National Cancer Institute.
- Infomed Medical Decisions (Genetic Couseling via telephone by board-certified genetic counselors).
“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.]
The title quote above was spoken by Elana Waldman, who is the inspirational ovarian cancer survivor highlighted and honored by H*O*P*E* this week. Simply put, Elana Waldman is an outstanding advocate for cancer research. She educated and inspired luncheon guests at the 2007 Israel Cancer Research Fund (ICRF) Women of Action Luncheon held in Toronto, Canada on April 19, 2007. During her talk, Elana provided an account of her illness and discussed her decision to be the first person in Canada to try an unconventional chemotherapy protocol. “I’m young,” Elana says, “my daughter is young, and the numbers are stacked against me. You do whatever you have to do to get the most time possible.” “Cancer,” Elana says, “has given me a clearer understanding of what life is about.”
As you will see from the excerpt of her April 2007 speech and the video below, “Elana’s courageous battle with ovarian cancer will touch your heart. Elana’s appreciation for everyday miracles will open your eyes. Elana’s determination to help others will inspire you …”
“…I was diagnosed 20 months ago on August 19, 2005. Time is running.
On September 23, 2005, after extensive surgery, I was told the cancer was stage 3c despite my doctor’s earlier belief that it was not that advanced. The diagnosis meant that I needed chemotherapy and only had a 30% chance of surviving 5 years from that point. At 32 years old, while trying to build my family and with a 2 year old daughter, this news was devastating.
When I was told the statistics though, I guess I couldn’t wrap my head around them because I never thought I would die. No one I knew had ever died from cancer. My own mother had fought and beat the disease twice. I knew I had a tough road ahead of me but I always focused on the light at the end of the tunnel and just did what I had to do to get better. It was hard but many others had done it before me and I knew I could and had to do it for my family…..
My cancer has returned. When I was told this time, the news hit me like a Mack truck. The numbers for a recurrence are even worse than for an original diagnosis and my chances for survival are small. I understood the numbers this time and the implications for me and my family. The diagnosis shook me to my core and I had a huge reality check. I have cancer, a potentially fatal disease. This is not something that regular medication can treat and I am now literally fighting for my life, everyday. I have given up my career to focus on my health and my family. I want to enjoy as much time as I can while I feel strong and healthy. I want to be a spokesperson for ovarian cancer for a long time but more importantly I want to see my daughter grow up and I want to grow old with my husband.
These simple goals in life that I now set for myself are in jeopardy so I have truly learned to enjoy all the everyday miracles that I do have – my daughter’s smile, my husband’s kiss, my mother’s laugh. I am more than this disease and I do not want to let it take away everything else that makes me the person that I am. I am asking you to help me continue to enjoy these miracles. Your donations and your generosity allow our scientists to do cutting edge research which will hopefully lead to a cure for cancer. Your support for ICRF directly benefits people who are battling cancer and on all their behalves, I say thank you.”
[Quoted Sources: Israel Cancer Research Fund Newsletter – Issue #5, Summer 2007; “Like Getting Hit By a Mack Truck: One Woman’s Fight With Cancer,” Chaim Steinmetz – Happiness Warrior Blog, April 25, 2007.
“One in 40 Ashkenazi Jews – compared to one in 500 in the general population – carries a mutation that gives women a 50 percent to 85 percent chance of getting breast cancer by the time they are 80. The genetic mutation, discovered in 1994, also increases the likelihood of melanoma and ovarian, prostate or pancreatic cancer. While within the general population about 5 percent of cancers can be attributed to a hereditary syndrome, in the Jewish community, that number is closer to 30 percent. ”
“Erika Taylor didn’t want to know whether she had the breast cancer gene.
‘My thinking was I would never get a prophylactic mastectomy,’ Taylor, 44, said of the idea of removing her breasts as a preventive measure. ‘I just thought it was horrible thing to do to myself, and if I was unwilling to do that, why bother finding out?’
Her grandmother died of breast cancer at 56, and her mother battled and beat the disease in her 30s. Taylor, who is single and the mother of a 14-year-old boy, always suspected cancer was in her future, but taking steps to confirm that was not something she wanted to do. Until she got her own diagnosis.
All of a sudden, the idea of ‘I would never do such a thing’ goes out the window,’ she said. ‘It’s astonishing how quickly you go, ‘OK, OK, what do I need to do? I’ll do it.” Taylor’s mother tested first, and when she was identified as a carrier of the BRCA 2 genetic mutation common in Ashkenazi Jews, Taylor tested next. In January, she found out she, too, carries the gene that makes it likely that even if she were to rid herself of her diagnosed cancer, it would probably recur.
Like a growing number of women, Taylor faced both the gift and the terror of knowledge.
One in 40 Ashkenazi Jews – compared to one in 500 in the general population – carries a mutation that gives women a 50 percent to 85 percent chance of getting breast cancer by the time they are 80. The genetic mutation, discovered in 1994, also increases the likelihood of melanoma and ovarian, prostate or pancreatic cancer. While within the general population about 5 percent of cancers can be attributed to a hereditary syndrome, in the Jewish community, that number is closer to 30 percent.
The good news is that knowledge about how the mutation causes cancer is opening scientific doors to more effective, targeted treatment for those already diagnosed. And people who have the genetic mutation can take preventative measures to drastically reduce their breast and ovarian cancer risk.
Surgery – removal of the breasts and ovaries – reduces the risk of breast cancer by 90 percent, to well below the 13 percent odds of getting breast cancer in the general population. But less-drastic measures, such as drug therapy, removal of just the ovaries and careful screening to catch and cure the cancer at an early stage, can also save lives. Genetic information also helps women feel empowered to take control of other factors that raise risk, such as smoking, alcohol consumption and obesity.
‘The use of genetic information to understand a person’s risk for diseases like cancer is clearly reaping huge benefits,’ said Dr. William Audeh, a medical oncologist with an emphasis on hereditary risk at Cedars-Sinai Medical Center‘s Samuel Oschin Comprehensive Cancer Institute. ‘It’s gone from being a somewhat frightening piece of information that gave people concerns to a hugely important piece of information that empowers people to either take preventative steps that can save their lives or to accurately target therapy if one develops cancer. There is a general understanding that genetic information for cancer is going to be critical for taking the best care of people.’
Knowing she had the genetic mutation sent Taylor, editor of the trade publication, Pool and Spa magazine, into a tailspin of research and soul-searching. Treatment for DCIS (ductal carcinoma in situ) usually consists of removal of the tumor and perhaps radiation. But Taylor’s genetic status put her in a different risk category, and after hearing from four different doctors that her cancer, even if cured, would return, she opted for a double mastectomy and reconstruction. Her surgery is scheduled for May.
Taking the test
While Taylor confirmed her genetic status after a cancer diagnosis, experts encourage people to test before cancer strikes. For Ashkenazi Jews, having just one relative who has had premenopausal breast cancer warrants getting tested, according to geneticists. (For non-Jews, testing is indicated if there are two relatives.) Any history of male breast cancer or any ovarian cancer in the family also raises a red flag, as do multiple cases of melanoma or pancreatic cancer. And women who themselves have early onset breast cancer should be tested, so they can tailor their treatment and inform other family members.
In the last five years, the number of people testing for the BRCA mutation has increased by 50 percent every year, according to Myriad Genetics, which patented the blood test for BRCA about 12 years ago. About 70,000 people tested last year. Myriad recently launched an East Coast direct-marketing campaign for the test.
Of the estimated 600,000 people who carry the gene in the United States, only about 20,000 have been identified. Of those 600,000 carriers, about 150,000 are Jewish, mostly Ashkenazi. Other ethnic groups, such as French Canadians and Filipinas, also have a genetic predisposition, as do some Latina subpopulations – some of which have been traced back to having Jewish genes.
Only about 15 percent of people who test come out with positive results, though the percentage is somewhat higher among Jews. But even a negative result is not entirely reassuring, since it indicates only that the specific mutations were not found. Other as-yet-undiscovered mutations, or other genes, could also cause a heavy incidence of cancer in a family, according to Dr. Ora Gordon, director of the GenRISK adult genetics program at Cedars.
Gordon encourages anyone being tested to see a genetic counselor to get the results properly interpreted and to understand their options if they find out they are carriers.
‘When learning about this for the first time, very frequently people say to themselves, If I’m not going to have surgery, I shouldn’t get this test.” Gordon said. ‘But that would be a tremendous loss in terms of potential reassurance for people who are not carriers and for identifying people who might have a whole variety of other options that might provide very substantial risk reduction.’
Prophylactic bilateral mastectomy – or having both breasts removed before any sign of cancer – seems to be growing in popularity as an option in the United States, though hard statistics are just now being compiled.
One recent study of women with the BRCA mutation and a cancer diagnosis put the rate of mastectomy at 50 percent in the United States, the highest by far of anywhere in the world. In Israel, that number is 2 percent, Gordon said.
In Los Angeles in particular, the numbers seem to be especially high.
Gordon estimates that 65 percent to 70 percent of BRCA-positive women in Cedars’ cancer programs opt for the surgery, some immediately, some after a few years of surveillance. ‘The quantity and quality of medical options makes the surgery more attractive in big cities, and Los Angeles has a high tolerance for breast surgery,’ Gordon said. She is spearheading a study about decision-making among BRCA-positive women at Cedars’ Gilda Radner early detection program, which screens genetically high-risk women for ovarian cancer.
Gordon understands that a woman’s decision about treatment is intertwined with her relationship status, her self-image and how many family members she saw battle or succumb to cancer.
Surgery or surveillance?
‘The decision to take off your breasts is really hard. It’s a part of your body that is associated with your outward appearance, and it’s a part of who you are. It’s a part of your sex life,’ said Joi Morris, who was 41 when she learned she carried the same genetic mutation that gave her mother and grandmother breast cancer at a young age.
Morris remembers a day, not long after she found out, when she really confronted the issue as her sons, then 7 and 10, played at the beach.
‘My kids were in the water and jumping and playing and having a fabulous time, and I looked down at my breasts in my swimming suit and thought, “Oh my God, what would it be like to not have these?'” ‘It’s a seesaw of emotions,’ she said, because at the same time, ‘you wake up every morning, and you know you are at risk, and you wonder if there is something in there you can’t find.’
Morris initially opted for close surveillance – a regimen of regular mammograms, manual exams, ultrasounds and breast MRIs – the most sensitive, noninvasive screening available, used only for high-risk patients. Her first MRI revealed a lump close to her chest wall.
‘I panicked. There is no other way to put it. That lump turned out to be benign, but the whole process was so stressful for me and hard on my family. I just decided if this lump is not cancer, the next one could be,’ Morris said.
She had a prophylactic bilateral mastectomy, with immediate reconstruction. As it turned out, her surgery wasn’t prophylactic at all – pathology revealed pre-cancerous cells scattered throughout both breasts.
Early in the process, Morris turned for support and information to FORCE: Facing Our Risk for Cancer Empowered, an organization that advocates for people at high genetic risk for breast and ovarian cancer.
Today, she is an outreach coordinator for FORCE, helping link women through face-to-face groups and one-on-one pairings as they face life-altering decisions.
‘It was very hard getting those results,’ said Lisa Stein, a 43-year-old mother of two, who found out she has the gene last year. ‘I was trying to prepare for being positive, but I don’t think you ever can. After I got the results, I really struggled. I was feeling raw for a while, crying easily knowing that it was going to be life-changing.’
Stein’s mother died of breast cancer at 57, and her grandmother died of ovarian cancer, but she didn’t test until her older sister, Lauren Rothman, tested positive.
Rothman opted for a mastectomy, but Stein chose to keep her breasts.
‘I think I knew instinctively that I was not going to have a double mastectomy. That felt too radical to me,’ Stein said. ‘I didn’t feel psychologically prepared or that it was necessary. I don’t feel like cancer is imminent; I feel like I have a few years to take it in and think about it and prepare, so I’ve put that decision on hold.’
She goes in for screening every few months, and she said the anxiety of waiting for those results has been manageable.
Both Rothman and Stein had their ovaries removed, however, which doctors are now recommending for women who test positive and who are finished having children or who are over age 35. Removing ovaries not only reduces the risk of ovarian cancer – which is notoriously hard to catch early and thus has a high mortality rate – but it reduces the risk of breast cancer by 50 percent. Stein also went on Tamoxifen, a drug taken by breast cancer survivors to reduce the risk of recurrence and which reduces risk by 50 percent in BRCA-positive women. The birth control pill, which stops the ovaries from cycling, can also reduce the risk of ovarian cancer but requires more vigilant screening for breast cancer.
Both ovary removal and Tamoxifen push women into menopause, with all its emotional, sexual and physiological ramifications.
‘I think of myself as a healthy person but not like I used to – it’s kind of tainted,’ Stein said. ‘It’s an identity issue. I still think of myself as youthful, but suddenly, I’m dealing with instant menopause, and that doesn’t sit well with me. But I’m dealing with it.’
Stein and Rothman provide support for each other, despite the different routes they’ve taken.
‘I came to reality very quickly – and the reality was I wanted to see my children grow up, and I didn’t want cancer, and I didn’t want chemotherapy. I wanted the rest of my life,’ Rothman said. Her daughters were 3 and 5 years old when she had surgery.
Rothman, a program director for Hadassah of Southern California, traveled to New Orleans for her breast procedure – two surgeries and tatoooing – at a small clinic that specializes in natural-tissue reconstruction, where a solid flap of fat is removed from the belly and inserted into the shell of the breast after tissue has been removed. The surgery offers a more natural result than silicone implants, though it is longer and more involved.
‘This procedure has provided me with a new outlook on life. It has taken a huge weight off my shoulder,’ Rothman said. ‘I no longer go into mammograms thinking, “Is this the year I’m going to get cancer like mom?'”
And she loves her new body – she got not only a breast lift but a bonus tummy tuck, too.
Advances in reconstructive techniques mean that women have several options for maintaining a body they can feel proud of.
Decades ago, radical mastectomies removed all the tissue and muscle of the chest wall. Today, the muscle is not removed, and reconstructive surgery, usually at the time of mastectomy, can leave intact the women’s natural skin, but in most cases the nipples and areola are removed. A silicone implant, or, as in Rothman’s case, fat from the abdomen, fills the pocket from which breast tissue was removed. Nipples and areola are tattooed on, or some surgeons use a new technique that leaves a woman’s own nipple and areola intact. Doctors try to bury scars in the fold beneath the breast, though that is not always possible.
But even the most beautifully done reconstructions leave a woman with scars and no sensation in her breasts.
‘When women come to see me, my approach is to listen to them and find out where they are in life and how they relate to their own breasts,’ said Dr. Kristi Funk, a breast surgeon and director of patient education at Cedars’ Brandman Breast Center. ‘Women have different feelings about sexuality and what roles breasts play, and that makes a big difference.’
Funk also finds out about the woman’s relationship status, and how she has been affected by a family history of cancer.
More information, better treatment
Family histories can be deceptive, however. Some families don’t know their medical histories, because they were lost due to the Holocaust or immigration.
The gene also can hide out in male members of a family.
A BRCA 1 gene mutation raises the risk of male breast cancer to 6 percent, and there is no increased risk for other cancers. BRCA 2 mutation also increases the risk for melanoma, prostate and pancreatic cancer. Still, men who carry the gene are likely never to get any cancer, although they have a 50 percent chance of passing the gene to children. Families with few females may never discern any cancer history.
Dora Cohen (not her real name) suspects it was her father who passed the BRCA 1 gene mutation to her. Last year, she was diagnosed with DCIS, a noninvasive cancer, which was treated with a lumpectomy and radiation. Of the many oncologists she saw, only one recommended that as an Ashkenazi woman in her 40s, she probably should have genetic testing.
In the last six months, Dora has had her ovaries, uterus and breasts removed.
Her daughter, Diane (not her real name), who is 27 and has been married for two years, doesn’t want to get tested yet.
‘I see what my mom is going through,’ Diane said. ‘I want to have kids, and I’m not in a place where I would take those measures [mastectomy and removal of the ovaries]. Knowing I’m positive and having that pressure on me would be something very difficult to live with.’
She and her husband of two years have pushed up their plans for children, and she worries that a positive test could jeopardize her medical insurance, especially because she is self-employed.
Federal and California law provide fairly good protection against genetic discrimination from insurers, stipulating that a genetic predisposition cannot be considered a pre-existing condition. But individual policies are not as well protected as group policies.
Still, genetics experts say much of the fear is overblown. They point out that there has been little litigation involving genetic discrimination, and that the insurance industry is open to the reality that genetic testing can lead to better and more cost-effective treatment. Most insurers cover genetic testing, and some genetic counseling – a rapidly growing field.
‘The genetics community has been struggling to help people understand the importance of talking to someone who knows the nuances of genetic testing,’ said Heather Shappell, a genetic counselor and founder of Informed Medical Decisions, which offers over-the-phone genetic counseling.
‘Genetic tests do not always yield a yes-or-no answer,’ Shappell said, ‘and often doctors aren’t sure how to read the results and guide patients through their decisions.’
In August, Aetna extended full coverage for Shappell’s phone-counseling services to its 14 million policyholders.
What geneticists are looking for is an error in the sequencing of the BRCA gene.
All people carry two genes, BRCA 1 and BRCA 2, which prevent cancer by repairing damaged cells. A mutation damages the genes’ repair function, which leads to uncontrolled growth and causes cells to become cancerous.
About 95 percent of Ashkenazi Jews who have the mutation have one of three errors, which means the mutation is easier to find and the test costs much less – about $400, as compared to $3,000 for a test that analyzes the entire gene.
As researchers learn more about how BRCA mutations cause cancer, they are developing targeted treatments.
A clinical trial with sites at Cedars and City of Hope uses a drug called a PARP-inhibitor to shut down the cell’s backup repair function. Normal cells are not affected, because the primary repair pathway is still functioning. But cancerous cells are left with no functioning repair system, so those cells die. Because normal cells are not affected, there are few major side effects.
‘We have a promising situation where you have a treatment which is completely targeted to cancer and leaves the normal cells alone. And that is very different from treatments like chemotherapy, where there is toxicity to every cell,’ said Audeh of Cedars.
Another study in Israel has found that women with ovarian cancer who are BRCA positive respond better to chemotherapy and have a higher survival rate than women who are not carriers, according to Jeff Weitzel at City of Hope. Weitzel, an investigator in the PARP-inhibitor trial, is also working on a study that manipulates hormones to reduce breast density, which makes surveillance through mammography and ultrasound more effective.
In February, the Jerusalem Post reported that doctors for an Orthodox woman undergoing in-vitro fertilization at Hadassah Hospital were able to identify and screen out embryos that had inherited her BRCA mutation. [Jerusalem Post Feb. 2008 article abstract]
A gift of life?
But while such progressive procedures have been generally well received in Israel, there is still social reluctance to test for the gene, especially in traditional circles, where families fear a genetic flaw could hurt the marriageability of their kids.
Debra Nussbaum Stepen, a Los Angeles therapist who now lives in Israel, is trying to break those perceptions. She works as a therapist at a clinic for hereditary breast and ovarian cancer, and she volunteers for Bracha, a Hebrew-language Web site for BRCA carriers.
The name of the site – bracha means blessing and is a play on BRCA – connotes that knowing one’s genetic makeup is a blessing that can save one’s life.
It is a lesson Stepen learned personally.
Her father had several kinds of cancer, including breast cancer, and before he died at 77, Debra urged him to get genetic testing. She was 51 and had never had cancer when she found out she carried the gene.
‘My doctor told me my breasts were ticking time bombs, and I couldn’t go to bed at night knowing that and thinking today am I going to get cancer?’ said Stepen, who has three stepchildren and a new stepgranddaughter.
She observed her father’s first yahrzeit in New Orleans, where she was undergoing the third and last part of a double mastectomy and reconstruction.
‘I said to my husband, in my father’s death he gave me the gift of life,’ Stepen said.
It takes time to reach this comfort level. As Erika Taylor prepares for her surgery in a few weeks, she worries about the ‘gift’ she may give to her son. She and her mom have talked about how irrational that guilt is.
‘I can say to my mom, “You didn’t know. It’s OK. It’s not your fault,’” she said. ‘But when it comes to me and my son, I think how could I have done this to my son. I am in abject horror that I might have passed this on to him. I know it’s irrational, but the whole idea fills me with grief.’
At the same time, she has hope.
‘My grandmother died from breast cancer at 56. My mother almost died of this disease. And I’m not going to even come close to dying,’ Taylor said. ‘My hope for my son, if he has this, is that he may not have to have any medical intervention at all. Maybe they can repair this mutation. The idea that there is trajectory moving in the right direction gives me some comfort and hope.’”
[Quoted Source: “Jewish women change their destinies by testing for genetic mutation,” by Julie Gruenbaum Fax (Jewish Journal of Greater Los Angeles), Texas Jewish Post, April 24, 2008 (emphasis added)]
Comment: For additional information relating to hereditary breast and ovarian cancer with respect to all women (Jewish and Non-Jewish), refer to the following: (i) FORCE: Facing Our Risk of Cancer Empowered; (ii) National Breast and Ovarian Cancer Coalition; (iii) “Clinical Considerations,” Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility Recommendation Statement, U.S. Preventive Services Task Force (USPSTF), Agency for Healthcare Research & Quality (AHRQ), U.S. Department of Health & Human Services, September 2005; (iv) “Genetics” hyperlinked materials, H*O*P*E* Blog homepage.