Biomedical subjects

S Pyrhönen

Publications and source records attributed to S Pyrhönen.

At least 19 recordsLinked to original sources

PubMed2007

DNA image cytometry is a useful adjunct tool in the prediction of disease outcome in patients with stage II and stage III colorectal cancer.

BACKGROUND: We assessed the prognostic value of the nuclear DNA content measured in the primary tumours of 123 patients with stage II or stage III colorectal cancer (CRC). METHODS: Isolated nuclei from paraffin sections were stained with the Feulgen reaction, and DNA was measured using a computer-assisted image analysis cytometry system. We applied 4 different approaches in the analysis of DNA histograms: the ABCDE approach, histogram range, peak evaluation and DNA cut-off values. RESULTS: Using the histogram range, the narrow range was rare (3.7%) in patients who died of disease (n = 28) as compared with 16.4% among those alive (n = 74; p = 0.017). Modal peak evaluation was a significant predictor of disease-free survival (DFS; Kaplan-Meier log-rank p = 0.0235). In the range evaluation, the 1st set (low-start gates) was a significant predictor of DFS (log-rank p = 0.0121), where disease recurrence was closely associated with the widest range (1.8->10c; c = haploid DNA content) gates. Recurrence-free survival was 3 times better in narrow-gate histograms than wide-range histograms (p < 0.03). The 1st set also proved to be a significant predictor of disease-specific survival (DSS; log-rank p = 0.0045), which was markedly better (77.8-90.0%) among the patients with the narrow-gate histograms. Grading of the histogram range into 2 categories (with 6.0c as cut-off), was a powerful predictor of both DSS (log-rank p = 0.0092) and 5-year DFS (p = 0.0106) in the whole series, and separately in stage III (but not stage II) disease, with p = 0.0131 and p = 0.0201, respectively. CONCLUSION: The DNA image cytometry with careful analysis of the histograms may provide valuable prognostic information in CRC, with potential clinical implications in patient management, particularly in predicting the patients at high risk for recurrence who should be considered as candidates for adjuvant therapy.

Aged↗

PubMed2006

Lymph node status as a guide to selection of available prognostic markers in breast cancer: the clinical practice of the future?

Prognosticators evaluating survival in breast cancer vary in significance in respect to lymph node status. Studies have shown e.g. that HER2/neu immunohistochemistry or HER2/neu gene amplification analysis do perform well as prognosticators in lymph node positive (LN +) patients but are less valuable in lymph node negative (LN -) patients. We collected data from different studies and tried to evaluate the relative significance of different prognosticators in LN+/LN- patient groups. In LN+ patients HER2/neu and E-cadherin immunohistochemistry were the statistically most significant prognosticators followed by proliferation associated features (mitotic counts by SMI (standardised mitotic index) or MAI (mitotic activity index), or S-phase fraction). Bcl-2 immunohistochemistry was also significant but p53 and cystatin A had no significance as prognosticators. In LN- patients proliferation associated prognosticators (SMI, MAI, Ki-67 index, PCNA immunohistochemistry, S-phase fraction) are especially valuable and also Cathepsin D, cystatin A, and p53 are significant, but HER2/neu or bcl-2, or E-cadherin less significant or without significance. We find that in studies evaluating single prognosticators one should distinguish between prognosticators suitable for LN+ and LN- patients. This will allow the choice of best prognosticators in evaluating the prospects of the patient. The distinction between LN+ and LN- patients in this respect may also be of special value in therapeutic decisions.

Journal Article↗

PubMed2006

Prognostic factors in prostate cancer.

Prognostic factors in organ confined prostate cancer will reflect survival after surgical radical prostatectomy. Gleason score, tumour volume, surgical margins and Ki-67 index have the most significant prognosticators. Also the origins from the transitional zone, p53 status in cancer tissue, stage, and aneuploidy have shown prognostic significance. Progression-associated features include Gleason score, stage, and capsular invasion, but PSA is also highly significant. Progression can also be predicted with biological markers (E-cadherin, microvessel density, and aneuploidy) with high level of significance. Other prognostic features of clinical or PSA-associated progression include age, IGF-1, p27, and Ki-67. In patients who were treated with radiotherapy the survival was potentially predictable with age, race and p53, but available research on other markers is limited. The most significant published survival-associated prognosticators of prostate cancer with extension outside prostate are microvessel density and total blood PSA. However, survival can potentially be predicted by other markers like androgen receptor, and Ki-67-positive cell fraction. In advanced prostate cancer nuclear morphometry and Gleason score are the most highly significant progression-associated prognosticators. In conclusion, Gleason score, capsular invasion, blood PSA, stage, and aneuploidy are the best markers of progression in organ confined disease. Other biological markers are less important. In advanced disease Gleason score and nuclear morphometry can be used as predictors of progression. Compound prognostic factors based on combinations of single prognosticators, or on gene expression profiles (tested by DNA arrays) are promising, but clinically relevant data is still lacking.

Journal Article↗

PubMed2006

Comparison of CD44 expression in primary tumours and metastases of colorectal cancer.

A better understanding on the development of a metastatic phenotype in colorectal cancer (CRC) is essential to help identify patients at high risk for metastasis. Therefore, we have studied the role of the CD44 family of trans-membrane glycoprotein in the process of CRC metastasis, by examining the expression of CD44s and CD44v6 in primary tumours and their metastatic lesions in 46 patients using immunohistochemistry. The expression of both CD44s and CD44v6 was significantly higher (moderate/strong) in primary tumours as compared to their metastases (p=0.008, p=0.0001, respectively). CD44s expression in metastases increased with the degree of the histological grade (p=0.009) and invasiveness of the primary tumour (p=0.002). Disease-free survival (DFS) was shorter in patients who had metastases with a strong/moderate expression of CD44s as compared to those with negative/weak expression (8.3 months vs 16.9 months p=0.221, respectively). Our finding that CD44s expression in metastatic lesions may reflect the aggressiveness of the primary tumour from which it has originated implicates an important link between the two lesions. CD44 expression may also provide valuable biological information as suggested by the observation that up-regulated CD44s expression in metastases is associated with a shorter DFS.

Colorectal Neoplasms↗

PubMed2005

E-cadherin, CD44s and CD44v6 correlate with tumour differentiation in colorectal cancer.

Cell adhesion molecules (CAMs) are cell surface glycoproteins that are important in cell-cell and cell-matrix interactions and play an important role in cell growth and differentiation. We examined immunohistochemically CD44s, CD44v6 and E-cadherin expression in 86 formalin-fixed, paraffin-embedded primary tumours and 5 metastases. Lower levels of CD44s, CD44v6 and membranous E-cadherin expression were significantly associated with higher tumour grade (p=0.022, p=0.016 and p= 0.041, respectively). Moreover, CD44v6 and membranous E-cadherin expression were correlated with the depth of primary tumour invasion (p=0.030 and p=0.020, respectively), and increased expression of CD44v6 and decreased membranous E-cadherin expression were associated with increased primary tumour invasion. The results suggest that these CAMs are associated with tumour differentiation and invasion in locally advanced and metastatic colorectal carcinoma.

Adult↗

PubMed2005

Thymidylate synthase expression levels: a prognostic and predictive role in advanced colorectal cancer.

Thymidylate synthase (TS) is the rate-limiting enzyme in the synthesis of pyrimidine nucleotides, required for DNA synthesis, and is also a critical target for fluoropyrimidines, which are widely used in the treatment of gastrointestinal tumours. We examined TS expression in tumours from 86 patients with advanced colorectal cancer who received one of two chemotherapy regimes (either irinotecan alone or irinotecan and 5-flurouracil with folinic acid). TS expression was determined immunohistochemically in 86 paraffin-embedded primary tumour sections and assessed using image analysis software. TS was significantly associated with survival, with lower levels of TS expression associated with longer patient survival (p=0.02). Patients with an objective response to treatment had a longer median survival than those who did not show an objective response to treatment (p=0.001). A significant association was found between tumour TS expression and response to treatment with 5-FU plus FA with irinotecan (p=0.05). Sixty-four percent of patients with TS expression levels below the median showed an objective (complete or partial) response to treatment while, 38% with TS expression levels above the median responded. Immunohistochemical TS expression levels might be used both as a prognostic marker and to help identify patients who would benefit from 5-FU based regime.

Adult↗

PubMed2004

Interferon update.

Explore the source record for details and available documents.

Antineoplastic Agents, Phytogenic↗

PubMed2004

Response to chemotherapy (irinotecan plus 5-fluorouracil) in colorectal carcinoma can be predicted by tumour DNA content.

OBJECTIVE: The aim of this study was to identify markers that might predict response to chemotherapy. Postoperative chemotherapy improves the outcome in stage III colon cancer and is widely accepted as a standard therapy, but there are currently no reliable predictors to identify and select patients that will benefit. METHODS: Using DNA image cytometry, the DNA content was determined from the isolated nuclei of 56 primary colorectal carcinomas of patients who received chemotherapy (either irinotecan or irinotecan plus 5-fluorouracil and folinic acid) for advanced disease. Response to chemotherapy could be reliably evaluated in 53 patients. RESULTS: The modal DNA content (ploidy status) of the tumour correlated with the observed response to chemotherapy (p = 0.01). An objective response was observed in 56% of patients whose tumour histograms displayed tetraploid, peri-tetraploid or multiploid patterns of peaks, compared with 19% in patients with diploid, peri-diploid or aneuploid peaks. Notably, 86% (6/7) of patients whose tumours displayed a multiploid peak pattern showed an objective response and 1 patient had stable disease. CONCLUSIONS: This study suggests that modal DNA content can be used to predict a patient's response to chemotherapy in advanced colorectal carcinoma. This may help in identifying patients who will benefit most from therapy for advanced colorectal cancer.

Adult↗

PubMed2004

CD44 variant 6 expression predicts response to treatment in advanced colorectal cancer.

CD44 has diverse functions in cell-cell and cell-matrix interactions and may be a determinant of metastatic and invasive behaviour in carcinomas. CD44 variant 6 (CD44v6) has been postulated to be involved in both carcinogenesis and tumor progression. Therefore, we have examined CD44v6 expression in tumors from 57 patients with advanced colorectal cancer who received one of two chemotherapy regimes (either irinotecan alone or irinotecan and 5-flurouracil with folinic acid). CD44v6 expression was determined immunohistochemically in 57 paraffin-embedded primary tumor sections and assessed using image analysis software. Strong expression levels of CD44v6 were seen in 24/57 (42%) of tumors, moderate levels in 17/57 (30%), weak levels in 9/57 (16%) and no expression was seen in 7/57 (12%). The pattern of staining was predominantly cytoplasmic, 7/57 tumors also exhibited membrane specific expression. A significant association was found between tumor CD44v6 expression and treatment response (Fisher's exact test p=0.01). Only 1/12 patients with no or weak tumor expression of CD44v6 showed a response to treatment whereas 20/41 (49%) patients with moderate or strong CD44v6 expression responded to treatment. Evaluation of CD44v6 expression of locally advanced and metastatic colorectal tumors may enable the clinician to identify and select patients that will show the best response to irinotecan based chemotherapy.

Adult↗

PubMed2003

Bleomycin, vincristine, lomustine and dacarbazine (BOLD) in combination with recombinant interferon alpha-2b for metastatic uveal melanoma.

This EORTC multicentre study analysed the efficacy and tolerability in patients with metastatic uveal melanoma of BOLD chemotherapy in combination with recombinant interferon alpha-2b. The dose of bleomycin was 15 mg on days 2 and 5, of vincristine 1 mg/m(2) on days 1 and 4, of lomustine 80 mg on day 1, and of dacarbazine (DTIC) 200 mg/m(2) on days 1-5, given every 4 weeks for a minimum of two cycles. Subcutaneous (s.c.) interferon alpha-2b at a dose of 3 x 10(6) IU was initiated on day 8 of the first cycle, and continued at a dose of 6 x 10(6) IU three times per week after 6 weeks. A median of two cycles were administered to 24 patients (median age 60.5 years). None achieved an objective response (0%; 95% Confidence Interval (CI): 0-14), 2 (8.3%) remained stable, 20 showed progression, and 2 (8.3%) were invaluable. The median progression-free survival was 1.9 months (95% CI: 1.8-3.4) and overall survival 10.6 months (95% CI: 6.9-16.4). Overall survival improved with increasingly favourable pretreatment characteristics (median, 14.7 versus 6.9 versus 6.0 months for Helsinki University Central Hospital (HUCH) Working Formulation stages IVBa, IVBb and IVBc, respectively; P=0.018). Grade 3 alopecia and neurotoxicity occurred in 13% of the patients. This multicentre study did not confirm earlier reports that BOLD with human leucocyte or recombinant interferon would induce at least 15% objective responses in metastatic uveal melanoma.

Adult↗

PubMed2003

Apoptotic index and bcl-2 expression as prognostic factors in colorectal carcinoma.

OBJECTIVES: To examine programmed cell death in 57 colorectal carcinomas (49 primary tumours and 8 metastases) and determine the prognostic significance of apoptosis in colorectal cancer. METHODS: Apoptotic index (AI) was ascertained by counting apoptotic bodies, using terminal deoxynucleotidyl transferase mediated digoxigenin nick end labelling (Tunel assay) and the expression of bcl-2 was examined immunohistochemically. Statistical analysis was used to test the value of clinical variables, histopathological data, AI and bcl-2 expression in predicting the clinical outcome of these patients and the survival function was calculated using the Kaplan-Meier method. RESULTS: AI was found to have a significant independent effect on survival (p = 0.0006), with lower values of AI conveying better survival. CONCLUSION: In summary, these findings reveal that AI is a useful prognostic factor in colorectal carcinoma.

Adult↗

PubMed2003

Low collagenase-1 (MMP-1) and MT1-MMP expression levels are favourable survival markers in advanced colorectal carcinoma.

OBJECTIVE: Extracellular matrix degradation is required for invasive growth and metastasis formation in colorectal carcinoma; therefore, we examined matrix metalloproteinases expression (MMP-1, MMP-13 and MT1-MMP) and apoptosis in tumours from 49 patients with advanced colorectal disease. METHODS: MMP expression was determined immunohistochemically and apoptotic index (AI) was ascertained using the TUNEL assay. RESULTS: Low levels of MT1-MMP, MMP-1 and AI were found to be favourable markers significantly associated with longer survival. MT1-MMP expression levels below the median (</=14.0% of tumour cells) were associated with better overall survival (median 26.2 vs. 15.6 months, p = 0.02) and MMP-1 expression levels below the median (</=28.7% of tumour cells) correlated with longer survival following metastasis (median 21.5 vs. 13.3 months, p = 0.05). MT1-MMP, MMP-1 and AI were all found to have significant independent effects on survival. Interestingly, MMP-1 expression levels above the median were associated with distal disease of the colon (p = 0.02). CONCLUSIONS: These findings reveal that MT1-MMP and MMP-1 expression levels and AI are useful prognostic indicators in advanced colorectal carcinoma and suggest that markers of MMP expression might be used in identifying patients who would benefit from new treatment modalities involving MMP inhibitors.

Adult↗

PubMed2002

Irinotecan combined with bolus 5-fluorouracil and folinic acid Nordic schedule as first-line therapy in advanced colorectal cancer.

BACKGROUND: This multicentre phase II study evaluated the efficacy and safety of irinotecan combined with the Nordic schedule of 5-fluorouracil (5-FU) and folinic acid (FA) as first-line therapy in patients with advanced colorectal cancer. PATIENTS AND METHODS: Seventy-four patients with measurable disease and a WHO performance status of 2 or less were treated with irinotecan 210 mg/m(2) as a 30-90 min intravenous infusion on day 1, followed by 5-FU 500 mg/m(2) and FA 60 mg/m(2) bolus on days 1 and 2, every 2 weeks, until disease progression or unacceptable toxicity. The primary end point was the objective response rate. RESULTS: Twenty-nine out of 68 evaluable patients achieved a complete (n = 7) or partial (n = 22) response, leading to an overall response rate of 43% [95% confidence interval (CI) 31% to 55%]. The median duration of response was 10 months. The estimated median time to progression and survival were 6.4 months (95% CI 5.4-9.0) and 15.6 months (95% CI 13.3-19.0), respectively, in the intention-to-treat population. A total of 860 cycles were administered to 74 patients. Neutropenia was the main adverse event with grade 3-4 toxicity in 66% of patients and 17.5% of cycles. Grade 3-4 non-haematological toxicities were infrequent and included diarrhoea in 16% of patients and 2% of cycles and nausea/vomiting in 10% of patients and 1% of cycles. CONCLUSIONS: Irinotecan combined with the bolus Nordic schedule of 5-FU/FA is active in advanced colorectal cancer with an easily managed safety profile which ensures good schedule compliance. The low incidence of grade 3-4 non-haematological toxicity justifies the further evaluation of this combination in the context of randomised clinical trials.

Adenocarcinoma↗

PubMed2002

Epirubicin/docetaxel regimen in progressive breast cancer-a phase II study.

The purpose of this investigation was to evaluate the efficacy and toxicity of 6 months' treatment with the combination of epirubicin and docetaxel in metastatic breast cancer. Thirty-eight women (mean age 51 years, range 35-72) with metastatic breast cancer were treated with a regimen of epirubicin 75 mg/m and docetaxel 75 mg/m every 3 weeks, given 4 times if progression was seen upon evaluation after 4 courses or 8 times in responding/stable patients. The patients received 285 cycles of combination treatment and two treatments with docetaxel or epirubicin alone. When neutropenia with fever was observed, further cycles were given with dose reduction. The median cumulative docetaxel dose was 462 mg/m (range 199-600) and that of epirubicin 476 mg/m (range 199-740). The overall response rate was 54% (95% CI 37-71), with a median duration of response of 14.8 months (95% CI 8.8-27.8). Median time to progression was 12 months, median survival 26 months. Neutropenia below 0.5 x 10 /l occurred following 113 (39%) of the total of 285 cycles given; 21 patients (55%) were hospitalized for febrile neutropenia. We conclude that dose tailoring is required in treatment with an epirubicin and docetaxel regimen to avoid grade 3/4 adverse effects in a significant number of patients treated for metastatic breast cancer.

Adult↗

PubMed2002

Prognosis of primary melanoma.

MATERIALS AND METHODS: To investigate the prognosis of primary melanoma, we studied a Finnish population of 298 primary melanoma patients, the majority with stage I or II tumours. The median clinical follow-up (4.8 years) was acquired from the patients' records, and the overall survival thereafter was collected from patient registries. The median follow-up for overall survival was 9.5 years. RESULTS: The overall survival rate was 66.8%. 24.5% developed metastasis, 17.8% died of melanoma, and 15.4% died of some other cause. Surgical margins had no effect on survival. In univariate analysis the most significant prognostic factors for disease-free and overall survival were stage of tumour (p < 0.0001), thickness of tumour (p < 0.0001), depth of tumour invasion (p < 0.0001) and tumour ulceration (p = 0.0005, p < 0.0002). Ulceration was an unfavorable prognostic marker. Younger patients had better survival outcomes than older ones (p = 0.04). Accordingly, in the multivariate Cox model the independent prognostic factors for both disease-free and overall survival were stage of tumour and thickness of tumour. Tumour location on trunk was an independent adverse prognosticator for overall survival. CONCLUSION: We conclude that the prognosis of primary melanoma has improved in Finland in the last decades being in line with a global tendency.

Adolescent↗

PubMed2001

A prospective study on women with a history of breast cancer and with or without estrogen replacement therapy.

OBJECTIVE: Because a categorical refusal of estrogen replacement therapy (ERT) from postmenopausal patients with a history of breast cancer is not based on any research evidence and may be more harmful than beneficial, we evaluated the safety and efficacy of ERT in these women. METHODS: We recruited 131 patients who had been treated for breast cancer for a mean of 4.2 years (range 1 month to 20 years) before. Eighty-eight decided to use ERT, whereas 43 refused or had no need for ERT. At recruitment, the patients were carefully examined for breast and gynaecologic findings. Non-hysterectomized patients wishing to receive ERT (n=54) then started using estradiol as oral tablets (2 mg/day) (n=44) or as transdermal gel (1.5 mg/day) (n=10) in combination with 10-day courses of oral medroxyprogesterone acetate at 4-week intervals, whereas hysterectomized patients (n=34) used only estradiol, orally (2 mg/day) (n=31) or transdermally (1.5 mg/day) (n=3). The patients using ERT were carefully examined 6 and 12 months later, and then annually at a specific outpatient department, and the mean follow-up time is now 2.5 years (range from 1 month to 5.2 years, 216 woman-years). The 43 patients not wishing to receive ERT were followed annually at the oncologic department for a mean of 2.6 years (range from 1 month to 4.7 years), and served as a control group. RESULTS: ERT significantly reduced climacteric symptoms, and the Kupperman score fell by 63%, from 26.9+/-8.6 to 9.9+/-6.7 (mean+/-SD). In non-hysterectomized women, medroxyprogesterone acetate triggered withdrawal bleeding in all except seven women. Seven patients (13%) experienced spotting during ERT. In 27 women, endometrial thickness exceeded 10 mm, and two of the total of 54 patients (3.7%) had simple hyperplasia. This vanished spontaneously in 3-6 months. Ten patients terminated the use of ERT within the first 12 to 39 months due to the lack of severe vasomotor symptoms (n=4) or due to the recurrence of breast cancer or to cancer of the contralateral breast (n=6). Eighty-one of the 88 patients (92%) using ERT showed no evidence of recurrence, whereas five patients (5.7%) had recurrence in 12-36 months and two patients (2.3%) developed a cancer of the contralateral breast in 14-24 months; another one of those wanted to continue with ERT. Thus the combined risk of recurrence or a new cancer of the contralateral breast in ERT users was 7/216 woman-years (3% per year). In the control group, 38 of 43 patients (88.4%) showed no evidence of recurrence or contralateral cancer, whereas four patients had recurrence and one developed a contralateral breast cancer (5/112 woman-years, 4% per year). CONCLUSIONS: Symptomatic climacteric patients with a history of breast cancer benefited from ERT without increasing their risk of recurrence, but the short follow-up and the small number of patients limit any definitive recommendations.

Administration, Cutaneous↗

PubMed2001

Feasibility of prolonged use of interferon-alpha in metastatic kidney carcinoma: a phase II study.

BACKGROUND: Interferon-alpha has proven effective in the treatment of metastatic renal cell carcinoma. However, the optimal schedule has not yet been determined. The authors have studied the efficacy and toxicity of prolonged use interferon-alpha2a (IFN-alpha) in metastatic renal cell carcinoma (RCC). Interferon-alpha was administered intermittently for outpatients. METHODS: Seventy-five patients with metastatic RCC without prior biochemotherapy were treated. During the first month, the IFN-alpha dose was increased from 4.5 to 18 million units (MU) 3 times a week to define the individual maximal tolerated dose for each patient. The treatment was continued at the maximal tolerated dose with a 1-week pause each month until either progression or intolerable toxicity was observed or up to 2 years. RESULTS: The overall response rate (5 complete response [CRs] and 8 partial responses [PRs]) was 17% (95% confidence interval, 10-28%). Stable disease was observed in 32 patients (43%). Three late objective responses (4%) occurred after 12 months treatment. The median progression free time of all patients was 12.3 months, and median survival time was 19.3 months. The median duration of response in CR/PR patients was 16 months. In multivariate analysis independent prognostic factors were poor performance status (P = 0.004), presence of bone metastases (P = 0.001), and time to metastases less than 24 months (P = 0.003), which predicted poor survival. Six patients (8%) discontinued the treatment because of fatigue, elevation of liver enzymes, or cardiac arrhythmias. No life-threatening side effects were observed. CONCLUSIONS: Prolonged and intermittently administered IFN-alpha2a three times per week in 3 weekly cycles in metastatic RCC is a feasible and effective therapy. A prolonged treatment duration of more than 12 months for stable and responding patients is beneficial and may improve the outcome of patients with RCC.

Adult↗

PubMed2001

Survival of breast cancer patients in BRCA1, BRCA2, and non-BRCA1/2 breast cancer families: a relative survival analysis from Finland.

Reports on the prognosis of familial breast cancer patients have been contradictory. True differences in survival, if they exist, would have important implications for genetic counselling and in treatment of hereditary breast cancer. We assessed the survival rates of 359 familial breast cancer patients (32 patients from BRCA1-positive families, 43 patients from BRCA2-positive families and 284 patients from BRCA1/2-negative breast cancer families) and compared them with those of all other breast cancer patients diagnosed in Finland from 1953 to 1995 (n = 59,517). Cumulative relative survival rates (RSR) were calculated by dividing the observed survival rates by the expected ones. The expected survival rates were derived from the sex, age and calendar year specific life-tables of the general population in Finland. Regression model was used to calculate relative excess risk of death (RR) and to adjust for confounding factors. The overall 5-year RSR of the patients in the BRCA1 families, BRCA2 families, non-BRCA1/2 families and among sporadic cases was 67%, 77%, 86% and 78%, respectively. However, we found no significant differences in the RR adjusted for age, stage and year of diagnosis between the different familial patient groups or the general breast cancer population. In the BRCA1 families the RR tended to be higher [RR 1.30, 95% confidence interval (CI) 0.63--2.70] and in the BRCA2 families lower (RR 0.78, 95% CI 0.39--1.57) than among the general breast cancer patient population. The RR among patients in the non-BRCA1/2 families did not differ from that of the general patient population.

Adolescent↗