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Jewish Genetics and Breast/Ovarian Cancer
Bernard A. Lublin, M.D.

Critical new information on Jewish genetics and breast / ovarian cancer is not well known, either by most physicians or by the Ashkenazi Jewish community. The BRCA (BReast CAncer) mutations (three possible chromosomal mutations) occur in the population-at-large at an incidence of 1:800. Among Ashkenazi Jews (men and women), the incidence is 1:40.

The normal healthy genes are considered tumor-suppressant genes. Everyone has a pair of these genes, one set inherited from each parent. In most individuals, each set is healthy. When an individual inherits one set with a mutation, it is comparable to having a car or bicycle with two brakes, one of which is not working. If the individual then loses function of the other, normal gene (for example, through damage from pesticides or industrial chemicals) then all “braking” control has been lost, and cancerous cell reproduction proceeds.

THE RISKS are considerable. Whereas the female population-at-large has a lifetime breast cancer risk of 8-12 %, women with one of these three BRCA mutations have a lifetime breast cancer risk of 60-87 %. And women born after 1940 with one of these BRCA mutations have a 67 % risk of breast cancer before age 50. Whereas the female population-at-large has a lifetime ovarian cancer risk of 1 %, women born with one of these mutations have a lifetime ovarian cancer risk of 27-44 %.

RISK REDUCTION is now available via several measures. These may prove life-saving to those women with a BRCA mutation:

  • Annual Mammograms beginning at age 25 yrs., instead of age 40 yrs.
  • Annual MRI exams. (This is a recommendation of the American Cancer Society as of March 2007). The MRI should be at a facility with a dedicated “breast coil”, experienced in timing sequence of contrast agent, and able to perform MRI-guided needle sampling and /or wire localization.
  • Prophylactic Tamoxifen or Raloxifen (Evista) provides a 50 % risk reduction of breast cancer. Benefit/risk profiles for these two medicines are more favorable for women below age 50 yrs.
  • Prophylactic removal of ovaries (post-child-bearing) reduces the risk of breast cancer 50 % and reduces risk of ovarian cancer 96 %. This procedure, called an Oophorectomy, is now often done via a laparoscope as an outpatient. The side effects of Oophorectomy may be alleviated by medicines other that hormonal replacement. Non-hormonal biphosphonates (such as Fosamax and Actonel) increase bone strength and are available as once-a-week pills. Low-dose Selective Serotonin Reuptake Inhibitors (e.g. Paxil, Prozac) alleviate vasomotor menopausal symptoms (e.g. “hot flashes”).
  • Prophylactic mastectomy (and reconstruction) provides a 97 % risk reduction. (Options for breast reconstruction include not only implants, but also muscle transposition – with results which are usually well-accepted.)

THE RISKS OF A SECOND, LATER CANCER are magnified with a BRCA mutation. A woman with an initial breast cancer and a BRCA mutation has a 22-30 % risk of a second cancer in the same breast within 10 years (versus 7-16 % for women who do not carry a BRCA mutation). This is not a result of residual cancer cells “left behind” by the surgery. Rather it is a result of the remaining cells all being mutated, and therefore themselves susceptible to development of cancer. A woman with a breast cancer and a BRCA mutation has a 27-42 % risk of a second cancer in the opposite breast in 10-12 years (versus 10 % risk for women who do not have the BRCA genetic mutation). This is a result of the cells in the opposite breast also being genetically compromised, and therefore also susceptible to turning cancerous.

REDUCTION of RISK of SECOND BREAST CANCER. As a result of these findings, The National Comprehensive Cancer Network (http://www.nccn.org/about/default.asp), as of 2007, now recommends that women with a BRCA mutation and an initial breast cancer consider bilateral mastectomy as their initial treatment.

GENETIC TESTING can determine if a woman (or man) has one of these BRCA mutations. The results will provide guidelines for surveillance as well as for treatment. The earlier paragraph “Risk Reduction” provides answers to the question: What Would I Do If I Knew?” Genetic testing is indicated for:

  • Having a blood relative with breast cancer before age 50 yrs.
  • Having a blood relative with ovarian cancer at any age.
  • An initial diagnosis of breast cancer in a woman below 50 yrs.
  • An initial diagnosis of ovarian cancer at any age.

The blood can be taken at a lab, hospital, or doctor’s office. It is put in a special tube and sent to Myriad Genetic Laboratories, 320 Wakara Way, Salt Lake City, Utah 84108-9930. Myriad Genetic Laboratories may be reached at 1-800-469-7423 or at www.bracanalysis.com (email: BRCA@myriad.com). Results are available in three to four weeks.

The costs as of 1-1-07:

  • For the three founder mutations in people of Ashkenazi Jewish descent: $460.
  • For rapid testing for the three Ashkenazi mutations: $690. A woman with a newly discovered breast cancer may suspect a BRCA mutation (especially if she is under 50 yrs. age, of Ashkenazi descent, or has a family history of breast or ovarian cancer). If a rapid (two week) test showed a BRCA mutation—indicating a high risk of recurrence in the same and opposite breasts—the woman might then choose complete mastectomy (rather than lumpectomy/radiation) for the involved breast, and prophylactic mastectomy of the opposite breast. These considerations for mastectomy (and reconstruction) are based upon diagnoses of both breast cancer and BRCA mutation.
  • Complete genetic testing: $3,120.

PREIMPLANTATION GENETIC DIAGNOSIS (PGD) offers the opportunity to have offspring free of the parental BRCA mutation. (A parent - either father or mother - with the mutant gene has a 50 % risk of passing that mutation to each offspring.) An in-vitro fertilization clinic harvests eggs from the mother-to-be and sperm from the father-to-be, and brings about the fertilization on an agar plate. On the third day (when cell division has led to perhaps 6-15 cells), one of the cells is removed, placed in a test tube, and sent via FedEx to a lab in the U.S. Within 24 hours, it is known whether the cell is free of the mutation. If so, on day 5, the multiplying embryonic cells are implanted in the mother-to-be with the (98-100 %) expectation of offspring who will be free of the cancer-causing mutation (instead of only a 50 % chance).

Preimplantation Genetic Diagnosis can be secured at an in-vitro fertilization clinic near the couple’s home, and within their own health network. Couples may discuss PGD advantages and disadvantages with their obstetrician and with physicians at the in-vitro fertilization clinic. National / International Laboratories performing BRCA PGD for IVF clinics are:

Bernard A. Lublin, M.D. has had a successful second career in the field of Jewish Genetics & Breast / Ovarian Cancer. After graduation from Yale University and New York University School of Medicine, his first career was as a busy orthopedic surgeon. Forty years ago, as a young surgeon, he diagnosed ovarian cancer in his mother-in-law after her own internist missed the diagnosis. Seven years ago, when his 33-year-old niece developed breast cancer, it was he who identified the genetic basis of this cancer (the niece being the granddaughter of his mother-in-law).. Since then, Dr. Lublin has educated physicians and the Jewish community about genetic risks and new risk-reduction measures. Dr. Lublin has enjoyed the cooperation of the National Institutes of Health, Duke Medical Center, Mayo Medical Center, Moffitt Cancer Center, and the National Comprehensive Cancer Network. He has sponsored seminars for the Jewish community and written articles in Federation newspapers in Florida, Virginia, and Michigan.