Hereditary Breast and Ovarian Cancer - Jewish Genetic Disease

Description
Hereditary breast and ovarian cancers are those associated with specific inherited gene mutations. BRCA1 and BRCA2 gene mutations inherited from a parent increase the risk of developing cancers. They tend to cluster in families, and are often seen to occur earlier in life than other non-inherited cancers.

BRCA1 and BRCA2 mutations are inherited in autosomal dominant pattern, which means that only one copy in each cell increases the risk of the individual inheriting this mutation to develop cancer. However, it is only when both copies of the BRCA gene mutate that the cancer develops. Therefore the susceptibility of an individual who inherits a mutated gene is greater, since only one gene has to mutate during their lifetime for cancer to develop.

BRCA1 and BRCA 2 are considered in the class of genes known as “Tumor Suppressor Genes.” In normal cells these genes help stabilize the cell’s DNA and assist in preventing uncontrolled cell growth. Mutations in these genes increase the chance of hereditary cancer. In the Jewish Ashkenazi population, three distinct mutations have been found to be involved with greater frequency. These include two mutations in BRCA1 and one in BRCA2.

The average age of an individual diagnosed with BRCA mutation- cancer is 50 years old.

Symptoms
   • Symptoms of Breast Cancer
   • Symptoms of Ovarian Cancer

Symptoms of Breast Cancer
In the early stages of breast cancer, the growing tumors are not palpable or painful. Masses in the breast are palpable once they reach a certain size but are often still painless. Certain tumors cause visible changes in the breast and nipple.
The following are common symptoms associated with breast cancer:

Cancerous Lumps
   • A distinct, stony, hard lump that feels like a hardened pea or bean in the breast
   • Immobile mass that does not move freely in the breast
   • Lump anchored in surrounding tissues; tissues move when the lump is moved
   • Lumps are non-painful 90 percent of the time
   • Usually occurs as only one lump in one breast. Very rarely will breast cancer appear as several lumps

Nipple Changes
   • A nipple that inverts in a previously normal breast.
   • Scaly nipple
   • Painful nipple

Areola
   • Color of the circle around the nipple changes.

Skin changes
   • A rash on one breast, redness, a bump or sore, skin might look blotchy
   • Skin that looks like an orange peel
   • Skin dimpling - pulling of the skin
   • Bulging of the skin - a swelling of one area of the breast that changes the shape of the breast.

Vein changes
   • An increase in the size or number of veins on one side of the chest

Breast pain
   • All recurring breast pain needs evaluation to determine cause.
   • Most breast pain is not associated with cancer; rather it is caused by monthly female hormones during the menstrual cycle.

Breast discharge
   • Though it may be due to hormonal imbalances, a response to medication, it may also be caused cancer and should be evaluated.

Breast Size
   • Increased in breast size that is not related to menstrual cycle.

Symptoms of Ovarian Cancer
The symptoms presented with Ovarian Cancer are not specific and are often confused with other diseases that have similar symptoms such as gastrointestinal or genitourinary disorders. Symptoms of ovarian cancer tend to be persistent and progressively worsening.
Some of the symptoms include:
   • Abdominal distention
   • Pressure or pain in abdomen, pelvis, legs and back
   • Abnormal menstrual cycle
   • Constant nausea, indigestion and gas
   • Alteration in bowel function – Constipation or Diarrhea
   • Alteration in urinary habits such as frequency
   • Loss of appetite and quick satiation
   • Incessant feeling of fatigue and lack of energy
   • Weight gain or loss

Incidence and Carrierss
Approximately 7-10% of breast and ovarian cancers are hereditary.

Currently it is estimated that the three mutations associated with the Jewish Ashkenazi population may be responsible for approximately one third of the breast cancer occurrences in women under the age of 40 in that population.

The carrier incidence for the three mutations found in the Jewish Ashkenazi population is 1 to 40 or 2.5%, the frequency of carrying the BRCA mutation being five times higher than the general population. The carrier frequency or BRCA1 mutations for the general population is currently estimated to be approximately 1:500 to 1:800 with BRCA2 at a lower frequency.

The lifetime risk for a woman who carries the BRCA mutation for breast cancer is 55-85% and 20-40% for ovarian cancer. Compared to that, overall there is a 12% risk of breast cancer and 1% risk of ovarian cancer in the general population.
Men that that carry the BRCA2 mutation have a 6% risk of developing breast cancer, a relatively rare form of cancer for men.

The probability that breast or ovarian cancer is related to a deleterious BRCA 1/2 mutation is greatest among families with history of several cases of breast cancer, both ovarian and breast cancer, or one or more family members who have two primary cancers. However, not every woman in that family will carry the mutated BRCA gene, not every cancer within that family will be a result of a mutated BRCA gene and not every individual within that family that carries an altered BRCA gene will develop cancer.

Treatment
There are several options for risk reduction and prevention available to those who find out they have a mutation.
- Closer observation which includes:
   • Annual mammogram commencing at an age that is ten years younger than the youngest relative with breast cancer. (or 35 years of age which is ever is younger)
   • Medical breast exam should be done every six months
   • Breast self-exam done every month (after menstrual period)
   • Annual MRI of the breast
   • Yearly pelvic ultrasound
   • Measurement of Ca-125 levels in conjunction with pelvic ultrasound

- Chemoprophylaxis – Administration of medication as a mode of prevention of infection or illness
For prevention of breast cancer
   • Tamoxifen – This drug blocks the effects of estrogen in most of the body including the breasts
Side effects of this drug include: vaginal discharge, vaginal dryness, hot flashes, and urinary issues
Though rare, Tamoxifen can cause endometrial or uterine cancer, blood clots, and stroke
   • Raloxifene – This drug works like Tamoxifen by blocking the effect of estrogen on the breast and the rest of the body. It does not however estrogen effects on the uterus that Tamoxifen does.
Side effects of this drug include: Hot flashes, vaginal dryness, muscle and joint discomfort, increase in weight. Though the risks involved with Raloxifene are similar to Tamoxifen they might be lower.
   • Aromatase Inhibitors – blocks estrogen production by various tissues in the body. However it does not block estrogen production by the ovaries. It is therefore a drug used after menopause.

- Preventative Surgery
   • Mastectomy – Studies have shown that it is highly effective, as it significantly reduces the risk of breast cancer. However, it does not guarantee that breast cancer will not develop. This is because breast tissue is found in other places such as armpits, collarbone or upper abdominal wall. If this breast tissue is not removed, breast cancer can develop, though the likelihood is slim.
Complications can arise with mastectomies such as bleeding, infection and poor wound healing, as well psychological symptoms such as anxiety and depression.
   • Oophorectomy – Though this surgery is regarded as relatively safe, complications can arise, such as; infection and intestinal blockage. In addition those women who are premenopausal may experience complications due to the removal of the ovaries and thereby losing the hormones excreted by the ovaries. This surgery may cause these women to go into early menopause which leads to multiple risks. Those include among others: Osteoporosis, hot flashes, sleep disruption, and sexual problems.

This surgery does not completely protect against cancer as different cancer that has a similar appearance and behaves identically can develop. This cancer is called primary peritoneal cancer but its risk is considered very low.

Testing
   • Annual mammogram commencing at an age that is ten years younger than the youngest relative with breast cancer. (or 35 years of age which is ever is younger)
   • Medical breast exam should be done every six months
   • Breast self-exam done every month (after menstrual period)
   • Annual MRI of the breast
   • Yearly pelvic ultrasound
   • Measurement of Ca-125 levels in conjunction with pelvic ultrasound

The above tests are done as a preventative measure for those who are carriers of the BRCA mutation. However these tests are also use to confirm diagnosis of cancer and as a measure to the efficacy of treatment if cancer does develop.

Genetic testing – Genetic testing for breast and ovarian cancer risk involves looking for BRCA 1 and BRCA2 gene mutations. Genetic testing and counseling will help ascertain family history and genetic inheritance.

Laboratories and Screening
The following laboratories offer genetic testing for Hereditary Breast and Ovarian Cancer (BRCA1 BRCA2):
   • United States
   • Israel
   • Canada
   • Europe
   • New Zealand
   • South Korea

UNITED STATES
Boston University School of Medicine- Human Genetics
700 Albany Street
Suite 408
Boston, MA 02118-2394
Phone: (617) 638-7083
Fax: (617) 638-7092
***Offers prenatal testing

Division of Molecular Diagnostics
Department of Pathology
University of Pittsburgh Medical Center
Room S780 Scaife Hall
3550 Terrace St.
Pittsburgh, PA 15213
Phone: (412) 648-8519
Fax: (412) 383-9594
Email: mdx@upmc.edu

Fox Chase Cancer Center
Clinical Molecular Genetics Laboratory
Director: Dr Betsy A Bove, PhD, ASCP
West W232
Philadelphia, Pennsylvania
Phone: (215) 728-4785
Fax: (215) 728-4333
***Targeted Mutation Analysis - Mutation panel: Ashkenazi Jewish Founder mutations for BRCA1&2

Myriad Genetic Laboratories, Inc
320 Wakara Way
Salt Lake City, UT 84108
Roa Benjamin, PhD, Director
Phone: (800) 469-7423
Fax: (801) 584-3615
***Target Mutation Analysis –BRCA 1, BRCA2

New Jersey Medical School
Institute of Genomic Medicine
University Hospital
Director: James J Dermody, PhD, FACMG
150 Bergen Street, F Level,
Room F342
Newark, NJ 07103
Phone: (973) 972-3170
Fax: (973) 972-0795
Target Mutation Analysis –BRCA 1

Rush University Medical Center
Inherited Susceptibility to Cancer Center
Risc Center
Phone: (312) 563-2361
Email: contact_rush@rush.edu

UCLA Diagnostic Molecular Pathology Laboratory
11633 San Vicente Blvd.,
Los Angeles, CA 90049
Phone: (310) 794-2781
Fax: (310) 794-2765
***Target Mutation Analysis –BRCA 1, BRCA2

UC – San Francisco
Molecular Diagnostic Laboratory
185 Berry Street, Suite 290 (Central Processing for shipped specimens)
San Francisco CA 94107
Phone: (415) 476-5512
Main Clinical Inquiries
Phone: (415) 353-1667
Director: Farid F Chehab PhD
Phone: (415) 476-0310
Fax: (415) 353-4828
***Offers prenatal testing

UNC Hospitals
McLendon Clinical Laboratories
101 Manning Drive
Chapel Hill, NC 27514
Phone: (919) 966-4408
Fax: (919) 966-6351
***BRCA1, BRCA2 testing only available to those referred by the Cancer Genetics Clinic

University of Chicago
University of Chicago Genetic Services
Director: Soma Das, PhD
5841 South Maryland, Room G701/MC0077
Chicago, IL 60637
Phone: (773) 834-0555
Fax: (312) 729-2808
Toll Free: (888) UC-GENES or (888) 824-3637
***Target Mutation Analysis –BRCA 1, BRCA2

ISRAEL
Assaf Harofeh Medical Center
Molecular Genetics Laboratory
Zerifin, Israel
Phone: (+972) 8-977-9617
Web: http://www.assafh.org/ENG/index.asp

Edith Wolfson Medical Center
Molecular Genetics Laboratory
Holon, Israel
Contact: Esther Leshinsky-Silver, PhD
Phone: (+972) 3-502-8692
Fax: (+972) 3-502- 8543

GGA –Galil Genetic Analysis Ltd
P.O.B. 3664
Kazerin, Hatzafon, Israel 12900
Phone: (+972) 4-900-7100
Fax: (+972) 4-900-7111
Email: gga@gga.org.il

Hadassah Hospital Hadassah Ein Karem
Human Molecular Genetic Laboratory
Dr. Israela (Issy) Lerer (Director)
POB 12000
Jerusalem 91120
Israel
Phone: (+972) 2-677-6016
Fax : (+972) 2-677-7499
Web: http://www.hadassah.org.il

Ha’Emek Medical Center
Molecular Genetics Unit
Afula 18101 , Israel
Phone: (+972) 4-649-5416
Email: morad_kh@clalit.org.il

Kaplan medical center, Molecular Genetics Laboratory
Rehovot, Israel
Phone: (+972) 8-944-1534
Web: http://www.clalit.org.il/kaplan

Pronto Diagnostic Ltd.
19A Habarzel Street
Ramat Hachayal
Tel Aviv, Israel 69710
Phone: (+972) 73-312-6155
Fax: (+972) 73-212-6144
Email: info@prontodiagnostics.com

Rabin Medical Center
Molecular Genetics
Petah Tikva, Israel
Director: Mordechai Shohat, MD
Genetic Counselor: Inbal Kedar, MSc
Phone: (+972) 3-937-7659
Fax: (+972) 3-937-7660
Email: inbalkd@clalit.org.il

Shaare Zedek Medical Center
Medical Genetics Institute
Jerusalem, Israel
Phone: (+972) 2-666-6435
Fax: (+972) 2-666-6935
Director: Prof. Ephrat Levy-Lahad
Email: liorab@szmc.org.il

Sheba Medical Center
The Danek Gertner Institute Human Genetics
Molecular diagnosis Laboratory
Tel Hashomer; Ramat Gan 52621, Israel
Phone: (+972)3-530-3060
Web: http://www.eng.sheba.co.il

CANADA
Alberta Children's Hospital
Molecular Diagnostic Laboratory
Calgary, Alberta, Canada
Phone: (403) 955-7026
Fax: (403) 955-7624

EUROPE
   • Finland
   • Germany
   • Spain
   • United Kingdom

FINLAND
HUSLAB Laboratory of Molecular Genetics
Obstetric Hospital
Haartmaninkatu 2, C-wing, 5th floor
FI-00029 Helsinki, Finland
Sample enquiries: (+358) 9-471 74339
Service enquiries: (+358) 9-471 75905
Fax: (+358) 9-471 74001
Contact persons:
Specialist in Medical genetics
Phone: (+358) 9-471 75905

GERMANY
Bioscientia GmbH
Center for Human Genetics
Ingelheim, Germany
Contact: Dr Nadine Bachmann
Phone: (+49) 6132-781-429
Fax: (+49) 6132-781-194
Email: nadine.bachmann@bioscientia.de

Centogene GmbH
Schillingalee 68
18057 Rostock
Germany
Phone: (+49) 381-203652-0
Fax: (+49) 381-203652-19
Email: office@centogene.com

Diagenom GmbH
Robert-Koch-Str. 10
D-18059 Rostock
Germany
Tel. (+49) 381-7022750
Fax (+49) 381-7022759
Email: mail@diagenom.de

Institute of Medical Diagnostics
Human Genetics
Nicolaistr. 22
Berlin, Germany 12247
Contact: Stephan Niemann, MD, PhD
Phone: (+49) 307-7001 ext 211
Fax: (+49) 307-7001 ext 332
Email: sniemann@imd-berlin.de

MGZ
Medical Genetics Center
Bayerstraße 3-5 (durch die Mathäser-Passage)
Eingang Schlosserstraße 6
80335 München
Phone: (+49) 89-30 90 886-0
Fax: (+49) 89-30 90 886-66
Email: info@mgz-muenchen.de

SPAIN
IMEGEN (Instituto de Medicina Genómica, S.L.)
Science Park. University of Valencia
C/ Catedrático Agustín Escardino, 9
E46980 Paterna (Valencia)
SPAIN
Phone: (+34) 963 212 340
Fax: (+34) 963 212 341
Email: info@imegen.es

UNITED KINGDOM
All Wales Molecular Genetics Laboratory
Institute of Medical Genetics
University Hospital of Wales
Heath Park
Cardiff CF14 4XW
Contact: Sheila Palmer-Smith, DipRCPath
Phone: (+44) 2920 742641
Fax: (+44) 2920 744059

GSTS Pathology
DNA Laboratory
London, United Kingdom
Director: Stephen Abbs, PhD, FRCPath
Phone: (+44) 20-71882582
Fax: (+44) 20-71887273
Email: stephen.abbs@gsts.com

Northwick Park and St. Mark's Hospitals
Kennedy-Galton Centre - NW Thames Regional Genetics Service
Harrow, United Kingdom
Director: Stewart Payne, DipRCPath
Phone: (+44) 20-88693180
Fax: (+44) 20-88693106
Email: stewart.payne@nwlh.nhs.uk

NEW ZEALAND
LabPLUS - Auckland City Hospital
Molecular Genetics Laboratory - Diagnostics Genetics
Auckland, New Zealand
Contact: Alice George, BSc (Hons)
Phone: (+64) 9-3074949 ext 6396
Fax: (+64) 9-3072826
Email: aliceg@adhb.govt.nz

SOUTH KOREA
Samsung Laboratory of Medicine
50, Irwon - Dong, Gangnam - Gu,
Seoul, Korea 135 - 230
Phone: (+82) 2-3410 -6469
Fax: (+82) 2-3410 - 0022
Email: samsunglab.smc@samsung.com
Web: http://www.samsunglab.org

Resources and More
The Metropolitan New York Registry of Breast Cancer Families

The Metropolitan New York Registry of Breast Cancer Families, which enrolls families that have several members stricken with breast and/or ovarian cancer, is a resource for future studies. Qualified researchers will be able to use the resources of the Registry for research on genetic and environmental factors in cancer.

The Registry will include members of families with a history of breast and ovarian cancer.

Families with the following health histories will be encouraged to participate:
   • Two or more relatives with breast or ovarian cancer
   • One or more relatives with early age at diagnosis
   • A relative with both breast and ovarian cancer, or bilateral breast cancer
   • A male relative with breast cancer

Contact the Metropolitan New York Registry
Phone: (212) 263-5964
or
Fax: (212) 263-8570
Web: http://www.med.nyu.edu/Biostat-Epi/mnyr.htm

Collaborating National & International Institutions:
   • New York University Medical Center
      Department of Environmental Medicine
      341 East 25th Street, Room 209; New York, NY 10010
   • Memorial Sloan Kettering Cancer Center
      Cancer Information Service - call 1-800-4CANCER
   • Beth Israel Medical Center
   • Columbia-Presbyterian Medical Center
      Women at Risk Program – Call 212-586-9525
   • Mt. Sinai Medical Center
   • SUNY-Stonybrook Medical Center
   • Fox Chase Cancer Center, Philadelphia
   • Northern California Cancer Center, San Francisco
   • Huntsman Cancer Institutes, Salt Lake City, Utah
   • Ontario Cancer Treatment & Research Foundation,Toronto, Canada
   • University of Melbourne, Australia

Support Groups

Breast Cancer
Sharsheret
1086 Teaneck Road, Suite 3A
Teaneck, NJ 07666
Toll Free: (866) 474-2774
Phone: (201) 833-2341
Fax: (201) 837-5025
Email: info@sharsheret.org

FORCE: Facing Our Risk of Cancer Empowered
16057 Tampa Palms Blvd. W, PMB #373
Tampa, FL 33647
Toll-free: (866) 288-RISK (7475)
Fax: (954) 827-2200
Email: info@facingourrisk.org
Toll-free Helpline: (866) 824-RISK (7475)

Bright Pink
400 N. State Street Suite: 230
Chicago, IL 60554
Web: http://www.bebrightpink.org

Ovarian Cancer
Ovations for the Cure of Ovarian Cancer
251 West Central Street, Suite 32
Natick, MA 01760
Phone: (508) 655-5412
Fax: (508) 655-5414
Toll Free: (866) 920-OFTC (6382)
Email: info@ovationsforthecure.org