Distinct prevalence of the CYP19 Delta3(TTTA)(7) allele in premenopausal versus postmenopausal breast cancer patients, but not in control individuals.

The CYP19 gene encodes the enzyme aromatase, which plays a key role in the conversion of androgens to oestrogens. A polymorphism in CYP19 in intron 4 (TTTA)n has been reported to be associated with breast cancer (BC) risk, although conflicting evidence has also been published. Here, we employ a non-traditional, highly demonstrative design of a molecular epidemiological study, where the comparison of BC cases and healthy middle-aged female donors was supplemented by an analysis of groups with extreme characteristics of either BC risk (bilateral breast cancer (biBC) patients) or cancer tolerance (tumour-free elderly women aged >or=75 years). None of the (TTTA)n polymorphic variants was significantly overrepresented among the affected women compared with any of the control groups. However, a 3-bp deletion/insertion CYP19 polymorphism, which is located in the same intron approximately 50 bp upstream to the (TTTA)n repeat, was evidently associated with the menopausal status in both the BC and biBC cohorts. In particular, the Delta3(TTTA)(7) allele occurred significantly more frequently in premenopausal than in postmenopausal BC patients (65/172 (38%) versus 67/310 (22%); P=0.0001; Odds Ratio (OR)=2.20 (95% Confidence Interval (CI) 1.46-3.32)), while the perimenopausal cases demonstrated an intermediate value (9/34 (26%)). In the biBC cohort, women who developed both tumours during their premenopausal period had a significantly higher prevalence of the Delta3(TTTA)(7) allele than patients with a postmenopausal onset of bilateral disease (16/46 (35%) versus 8/50 (16%); P=0.035; OR=2.80 (1.08-7.23)); those biBC patients, whose tumours were diagnosed before and after the cessation of menses, displayed an intermediate occurrence of the Delta3(TTTA)(7) allele (7/32 (22%)). Similar tendencies in the Delta3(TTTA)(7) allele distribution in BC and biBC patients suggest that its association with the menopausal status of the patients is truly non-random and thus this observation deserves further detailed investigation.

CYP17 polymorphism in the groups of distinct breast cancer susceptibility: comparison of patients with the bilateral disease vs. monolateral breast cancer patients vs. middle-aged female controls vs. elderly tumor-free women.

The CYP17 gene encodes an enzyme involved in several critical steps of steroidogenesis. The promoter region of the CYP17 displays a single-nucleotide polymorphism, which is suspected to modulate the expression of the gene and thus may contribute in the interindividual variations of hormonal background. In agreement with this functional hypothesis, the MspA1+ allele (designated as A2) of the CYP17 was shown to render an increased risk of breast cancer (BC). However, the latter observation was disputed by a series of negative reports. Here, we re-evaluated the role of CYP17 MspA1 polymorphism in the BC susceptibility, using a non-traditional design of a case-control study. In addition to randomly selected 183 BC patients and 107 female middle-aged donors, we examined the groups with apparently extreme characteristics of either BC risk or BC resistance, namely the 57 bilateral breast cancer (biBC) patients and 75 elderly (>/=75 years old) tumor-free women. Neither BC nor biBC patients showed increased prevalence of 'unfavorable' A2 allele as compared with the non-affected cohorts. Moreover, the A2 variant was not significantly associated with the tumor size, nodal involvement and menopausal status in the patients either with the monolateral or bilateral disease. Thus, our data argue against the earlier reported role of the CYP17 in BC predisposition and progression. In addition, usual distribution of the CYP17 alleles in the elderly group indicates a neutral effect of this polymorphism on the longevity in females.

[The effectiveness of adjuvant systemic therapy in organ-preserving therapy of breast cancer]. / Otsenka effektivnosti ad''juvantnoi sistemnoi terapii pri vypolnenii organosokhraniaiushchego lecheniia raka molochnoi zhelezy.

The role of adjuvant therapy in breast-conserving treatment was studied in 360 cancer patients (reproductive, aged < or = 55 yrs, and postmenopausal, aged > 55 yrs) with T1-2N0M0 tumors under 2.5 cm (1985-1996). Mortality rates fell by 17% in postmenopausal patients who received adjuvant therapy (tamoxifen) and by 34%--in the reproductive group after polychemotherapy (CMF) and 36%--after hormonal therapy (tamoxifen).

[Breast-preserving (conservative) therapy of breast cancer]. / Organosokhraniaiushchee (konservativnoe) lechenie raka molochnoi zhelezy.

Conservative surgery (sectoral or segmental + axillary dissection) was performed in 278 patients with breast cancer (T1-2N0M0) at the Institute Clinic in 1990-1995. Following thorough morphological examination. 148 patients (53.2%) were selected to form a clinical study group for an investigation of the role of postoperative radiotherapy in the conservative treatment of breast cancer. Two groups-irradiation of the remaining breast tissue and controls-were formed on the basis of randomized data. Follow-up continued 3-60 months (average duration-37.7 months). Local recurrence was detected in 3 out of 73 (4.2%) patients of group I. A similar relapse was detected in 6 out of 75 (8.0%) patients of group II. No significant difference in total survival rates in the two groups was observed (97.3 and 96.0%; p > 0.05).

[Preliminary results of the Russia (St.Petersburg)/WHO program for the evaluation of the effectiveness of breast self-examination]. / Promezhutochnye rezul'taty programmy Rocciia (Sankt-Peterburg)/VOZ po otsenke éffektivnosti samoobsledovaniia molochnykh zhelez.

Although an absolute difference of 10% (65,4 vs. 54,9%) in 5- and 9-year survival in breast cancer patients was recorded between the self-examination and control groups a large-scale randomized population-controlled study of 122,471 females has failed to provide significant differences (Log-rank - 0,774, p > 0.05). No significant decrease in mortality was observed in the self-examination group as compared with the untrained controls. As a result of providing more information to the population on risk factors. twice as many of the trained females consulted oncologists. Also, the number of early detection of breast tumor (T1-2NOMO) in both groups was 1,5-2,5 times that recorded elsewhere. Since 3,55 per 1,000 patients with breast tumors per year, aged 50-59, died of cardio-vascular disease, i.e. 3,1 times the expected 1,16 per 1,000, more attention should be focused on timely diagnosis and treatment of concomitant cardio-vascular pathology.

[Sparing and organ-saving operations in breast cancer]. / Sberegatel'nye i organosokhraniaiushchie operatsii pri rake molochnoi zhelezy.

The paper discusses the interim results of the use of organ-saving surgery for T1-2N0M0 breast cancer ("superficial" tumors not larger than 2.5 cm in diameter). Since 1985, two-hundred and twelve patients have been included into the study, of whom 105 underwent en bloc segmental resection with axillary lymph node dissection, whereas 107--modified mastectomy after Patey-Diasson. In the first group, local recurrence was observed in 4 (3.8%) patients and distant metastases--in two, whereas in the latter group, no recurrence was registered within four years of follow-up and distant metastases occurred in 4 (3.7%) cases. Three-year survival rates in the two groups were similar: 96.8 and 98.2%, respectively.