© Borgis - Postępy Nauk Medycznych 8/2008, s. 534
Komentarz do prac
According to our experience the progress in clinical genetics of cancer is so quick that it is raising severe educational problem for doctors and other counselors to get updated information in concise, ordered and reasonably complete form. This is why we decided to publish in Postepy Nauk Medycznych the critical parts of monograph "Clinical genetics of cancer 2008” which has been prepared by our centre and updated annually.
We present several aspects of clinical genetics of cancer which address particularly important questions related to risk assessment and management of the patients we see in our clinics.
Since the early 90s it has become possible to support clinical cancer genetics by adding DNA testing for mutations within high-risk genes, such as BRCA1, BRCA2, MSH2, MLH1, APC and VHL. These opportunities have revolutionized the clinical situation of patients, but many doctors have been very pessimistic about some aspects of the large-scale and worldwide introduction of DNA testing into clinical practice, which is fuelled mainly by the high cost of screening for mutations within genes of large size such as BRCA1, where the actual cost of BRCA1/BRCA2 testing by DNA sequencing is around 3000 EUR/US dollars. Except for a small number of rich countries, this cost is prohibitively high. Fortunately, several of these cancer predisposition genes show a strong founder effect. Thus, for many populations, including those from the poorest countries, it is possible to offer inexpensive and rapid DNA testing. In this way doctors and scientists from regions like Eastern Europe can significantly contribute to worldwide progress in understanding inherited cancer syndromes.
Particularly important are chapters on BRCA1 and HNPCC (Lynch) syndromes. I´d like to underline several special topics.
Prophylactic adnexectomy is critical for women with BRCA1/BRCA2 constitutional mutations. Undoubtedly, this option has to be presented to high-risk women. However, all of us undertaking routine practice in outpatient clinics are exposed to different reactions of women to the notion of prophylactic adnexectomy offered. Experience of our centre indicates that 15% of women do not accept it. And an even higher proportion of women delay the timing of the procedure. One of the critical questions asked by our patients is whether it is safe to use oestrogens after adnexectomy. In my opinion based on the analysis of existing data, there is no contraindication to offer hormone replacement therapy (HRT) after prophylactic adnexectomy to BRCA1/BRCA2 carriers. At present, there is no definite answer available based on prospective study.
We question the rationale behind offering tamoxifen as chemoprevention to young BRCA1/BRCA2 carriers following surgical menopause. Narod SA summarizes published data concerning this aspect and suggests that tamoxifen should be considered, even for carriers after oophorectomy.
The most significant one is a description of the response to neo-adjuvant chemotherapy in women with BRCA1 mutation positive breast cancer, which is based on a papers by Byrski et al. (Breast Cancer Res Treat 2007, 2008). These reports presents a clinical observations that taxanes show reduced and cis-platinum extremely high efficacy for this subgroup of patients. Despite the limitations of the reported study the role of taxane hemotherapy vs. non-taxane therapies should be examined within the context of research trials and offered to breast cancer patients with confirmed causative BRCA1 mutations. In countries where there is a strong founder effect of mutations, it is reasonable to offer BRCA1 testing to all consecutive breast cancer patients.
Finally, we are convinced that the described "suspected HNPCC” clinical criteria elaborated by our centre are of particular value in solving the problem of families with Lynch syndrome.
Personally, I deeply believe that a new era is coming in the field of clinical genetic of cancer - application in clinical practice of moderate/low cancer genetic risk markers. Even at present we can consider like on option some changes in surveillance, treatment and prognosis, depending on results of DNA testing for above markers. In our centre we are offering it since a few years – e.g. CHEK2, NOD2, CDKN2 or CYP1B1 testing, and we believe it is not ethical to do not present such options for patients from so well studied population like Polish one.