| Japanese Journal of Clinical Oncology | Pages |
Letter
Introduction of a German Genetic Counseling Program for Hereditary Breast and Ovarian Cancer
To the Editor:
Recently I had an opportunity to visit Tokyo as a fellow of the Foundation for Promotion of Cancer Research for 12 weeks. Although my task was to learn some research techniques at the Growth Factor Division in the National Cancer Center Research Institute, I encountered two interesting papers on cancer genetic counseling in Japan (1,2). I was lucky to be able to meet the authors and discuss the issue. Since I am involved in the genetic counseling program in Germany, I would like to introduce our concept and planing.
The etiology of breast cancer involves various factors, and it has been recognized for many years that family history is an important risk factor for the development of carcinoma of the breast. Approximately 20% of breast cancer patients have a family history, and in about 5% of these cases, breast and ovarian cancer appears to be inherited by several identified genes (3,4). The recently identified and cloned BRCA-I and BRCA-II genes appear to account for the majority of hereditary breast cancer (5,6). However, other known genes contribute to breast cancer susceptibility, notably the TP53 gene in Li-Fraumeni syndrome (7), the ATM gene in ataxia teleangiectasia (8) and the genes causing rare syndromes like Cowdens disease (9), Peutz-Jeghers (10) and Muir-Torre syndromes (11).
In 1994, we began at 10 university hospitals a Genetic Counseling Program for hereditary breast and ovarian cancer, in Germany. This program is supported by the German Cancer Foundation (Deutsche Krebshilfe), and was initiated to establish genetic counseling guidelines for patients with a family history of breast and ovarian cancer. Beside the establishment of genetic counseling centers for individual risk assessment for high-risk patients, the collection of information about the distribution of BRCA-mutations in the German population and improvements of the various techniques for genetic testing has been conducted as part of this program.
Because of the high scientific interest and clinical relevance of the BRCA-I gene, we have focused our analysis strategy on a search for mutations within that gene. Because of the extremely large size of this gene (> 100 000 bp of genomic DNA with 24 exons), the detection of mutations in the BRCA-I gene remains a technical challenge. In addition to the standard mutation screening methods of SSCP, DGGE, PTT and ASO, we use DNA-sequencing. Although the direct sequencing method has the highest sensitivity and specificity for the detection of BRCA mutations, it remains a time-consuming and expensive procedure that can still miss promoter regions or significant intronic mutations. However, the identification and uniform establishment of a BRCA-I gene test for the clinical setting is part of the German research program.
Cancer genetic counseling is a wide field that cannot be covered by a single medical discipline alone. A multidisciplinary approach involving geneticists, genetic counselors, surgical and medical oncologists and psychologists is required. In Germany, unlike the Japanese, American and British systems, a gynecological oncologist takes care of breast cancer patients (including surgical procedures and medical treatment). He/she is in general the first contact physisian for the consultand with a family history of breast cancer (see Figure 1).
Figure 1. The consultand is not necessarily a patient; he/she can be a healthy family
member with a no greater than average risk. Baseline risk perception and the
patient's own risk estimation are part of the first visit. Data from our own
hospital showed that 75% of the patients overestimated their individual risk
(Kiechle M, unpublished observations). The first counseling session with the
gynecological oncologist also includes the collection of a precise family and
medical history of the client and her/his relatives, basic information about
the limitations and benefits of genetic testing, and explanations about available
options for the prevention, detection and therapy of breast and ovarian cancer. In a separate session, the genetic counselor analyzes the individual risk of
the client for breast/ovarian cancer, using available pedigree information
and empirical data, and discusses the possible consequences of a positive or
negative BRCA-mutation test result. This discussion again includes the information
about the limitation of the different gene tests (including false-positive
and false-negative results) and the currently available diagnostic and therapeutic
options. On request of the patient, a psychologist can be involved in this
session.
After a period of 4 weeks, the client decides for or against genetic testing
with the genetic counseling group of members of all three disciplines (gynecological
oncologist, genetic counselor and psychologist). In the cases in which no genetic
testing is chosen a final consultation including individual information for
prevention and follow-up is held. For clients who choose a genetic analysis,
the next appointment is scheduled as soon as the results are available (about
2 weeks). This session involves staff from all three disciplines and provides
an extensive discussion of the individual prevention, diagnostic and therapeutic
options for the client and offers further consultations with the staff of the
separate disciplines. The client and the family doctor receive a detailed report
of the final counseling session. The German nation-wide recommendations for the prevention of patients with
BRCA mutations includes: semiannually (beginning at age 25): clinician breast examination; gynecological pelvic examination (including ultrasonography (US) and Doppler); breast-US
and CA-125 evaluation; annually: breast MRI (> 25 years); mammography (> 30 years); hematocult test (> 35 years). These are flexible guidelines that represent only the present recommendations,
with possible changes in the near future. At the present time, we neither do
prophylactive mastectomy or oophorectomy nor administer preventive medical
therapies, such as tamoxifen. Not every client is suitable for the BRCA gene test. Our present criteria for
the genetic testing are: – breast or ovarian cancer in at least 2 patients of one family (diagnosis of cancer <50 years in one case); – breast or ovarian cancer in at least 3 patients of one family independent of age of diagnosis; – breast or ovarian cancer before the age of 30 years; – bilateral breast cancer; – more than one primary tumor in the same patient. At the present time genetic testing is only available for clients fulfilling
the above criteria and being enrolled in the study of one of the 10 counseling
centers. The costs for the counseling and the genetic testing are covered (within
the present 5-year program) by the German Cancer Foundation. After this program
is completed, the costs will be covered by health insurance companies. The genetic counceling system discussed above is focusing on hereditary breast
and ovarian cancer. The multidisciplinary work between genetic counselors,
gynecological (medical/surgical) oncologists and psycho-oncologists is very
similar to the American system (12). The cancer genetic counseling and psycho-oncology has also become very popular
in Japan (1,2). As recently published by H. Okamura in the editorial of the
Japanese Journal of Clinical Oncology, there are several projects to establish
a corresponding system in Japan. In close relation to the American system,
the genetic counseling and psycho-oncology research in Japan should mainly
include the development of a cancer genetic counseling model, distinction between
genetic counseling and psychological counseling, methological subjects and
education of cancer genetic councelors including health-care providers and
nurses (1). There are already three protocol studies on cancer genetic testing approved
by the National Cancer Centers IRB; including APC mutations for familial adenomatous
polyposis, hMSH2 or hMLH1 mutations for nonpolyposis colon cancer and Rb mutations
for retinoblastoma (1). Although inherited cancer affects only a minority of all cancer patients, nationwide
genetic counseling systems are needed and furthermore international cooperation
is aspired. References
Nicolai Maass
Department of Gynecology and Obstetrics
Christian-Albrechts-University of Kiel
Kiel, Germany
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Comments and feedback: jnl.info{at}oup.co.uk
Last modification: 13 Apr 1999
Copyright© 1999 Foundation for Promotion of Cancer Research.
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