HPV RNA and DNA testing in Polish women screened for cervical cancer - A single oncological center study.

OBJECTIVES: To evaluate the incidence of HPV infection, and the frequency of the various genotypes, using mRNA and DNA testing; to assess their relationship with the cervical lesions and women's age in the Polish patients. STUDY DESIGN: A group of 1840 women, most of whom had abnormal cytology, from the Franciszek Lukaszczyk Oncology Centre in Bydgoszcz, Poland were screened for presence of at least one of 13 high risk HPV. Following that, 545 HPV DNA positive women were tested for HPV infection using HPV mRNA with the Nucleic Acid Sequence-Based Amplification Assay (NASBA) method. RESULTS: In our study group, 70.1% had DNA HPV positive results. Only 4% of the women had normal cytology. Among 545 HPV DNA positive patients, 36.3% had HPV mRNA positive tests. Moreover, 48% of the HPV mRNA positive patients were infected with HPV 16, followed by 18 (12.6%), 31 (10.1%), 33 (8.6%%), 45 (4.5%), and 16.2% of HPV mRNA positive women were infected with more than one HPV genotype. Furthermore, we found that in women under 30, HPV DNA positivity was higher than HPV mRNA positivity, supporting the hypothesis that younger women's infections are mostly temporary. CONCLUSIONS: The differences in HPV prevalence and genotype distribution observed in our study may have an impact on the efficacy of HPV vaccinations for cervical cancer and the development of screening programs, which should be examined further in future studies.

BRCA1/2 Mutation Detection in the Tumor Tissue from Selected Polish Patients with Breast Cancer Using Next Generation Sequencing.

(1) Background: Although, in the mutated BRCA detected in the Polish population of patients with breast cancer, there is a large percentage of recurrent pathogenic variants, an increasing need for the assessment of rare BRCA1/2 variants using NGS can be observed. (2) Methods: We studied 75 selected patients with breast cancer (negative for the presence of 5 mutations tested in the Polish population in the prophylactic National Cancer Control Program). DNA extracted from the cancer tissue of these patients was used to prepare a library and to sequence all coding regions of the BRCA1/2 genes. (3) Results: We detected nine pathogenic variants in 8 out of 75 selected patients (10.7%). We identified one somatic and eight germline variants. We also used different bioinformatic NGS software programs to analyze NGS FASTQ files and established that tertiary analysis performed with different tools was more likely to give the same outcome if we analyzed files received from secondary analysis using the same method. (4) Conclusions: Our study emphasizes (i) the importance of an NGS validation process with a bioinformatic procedure included; (ii) the importance of screening both somatic and germline pathogenic variants; (iii) the urgent need to identify additional susceptible genes in order to explain the high percentage of non-BRCA-related hereditary cases of breast cancer.

Ten-year survival in patients with BRCA1-negative and BRCA1-positive breast cancer.

PURPOSE: To estimate 10-year overall survival (OS) rates for patients with early-onset breast cancer, with and without a BRCA1 mutation, and to identify prognostic factors among those with BRCA1-positive breast cancer. PATIENTS AND METHODS: A total of 3,345 women with stage I to III breast cancer, age ≤ 50 years, were tested for three founder mutations in BRCA1. Information on tumor characteristics and treatments received was retrieved from medical records. Dates of death were obtained from the vital statistics registry. Survival curves for the mutation-positive and -negative subcohorts were compared. Predictors of OS were determined using the Cox proportional hazards model. RESULTS: Of the 3,345 patients enrolled onto the study, 233 (7.0%) carried a BRCA1 mutation. The 10-year survival rate for mutation carriers was 80.9% (95% CI, 75.4% to 86.4%); for noncarriers, it was 82.2% (95% CI, 80.5% to 83.7%). The adjusted hazard ratio (HR) associated with carrying a BRCA1 mutation was 1.81 (95% CI, 1.26 to 2.61). Among BRCA1 carriers with a small (< 2 cm) node-negative tumor, the 10-year survival rate was 89.9%. Among BRCA1 mutation carriers, positive lymph node status was a strong predictor of mortality (adjusted HR, 4.1; 95% CI, 1.8 to 8.9). Oophorectomy was associated with improved survival in BRCA1 carriers (adjusted HR, 0.30; 95% CI, 0.12 to 0.75). CONCLUSION: The 10-year survival rate among women with breast cancer and a BRCA1 mutation is similar to that of patients without a BRCA1 mutation. Among women with a BRCA1 mutation, survival was much improved after oophorectomy.

Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy.

PURPOSE: To estimate the rate of pathologic complete response (pCR) to neoadjuvant chemotherapy in BRCA1 mutation carriers according to chemotherapy regimen. PATIENTS AND METHODS: From a registry of 6,903 patients, we identified 102 women who carried a BRCA1 founder mutation and who had been treated for breast cancer with neoadjuvant chemotherapy. Pathologic complete response was evaluated using standard criteria. RESULTS: Twenty-four (24%) of the 102 BRCA1 mutation carriers experienced a pCR. The response rate varied widely with treatment: a pCR was observed in one (7%) of 14 women treated with cyclophosphamide, methotrexate, and fluorouracil (CMF); in two (8%) of 25 women treated with doxorubicin and docetaxel (AT); in 11 (22%) of 51 women treated with doxorubicin and cyclophosphamide (AC) or fluorouracil, doxorubicin, and cyclophosphamide (FAC), and in 10 (83%) of 12 women treated with cisplatin. CONCLUSION: A low rate of pCR was observed in women with breast cancer and a BRCA1 mutation who were treated with AT or CMF. A high rate of pCR was seen after treatment with cisplatin. An intermediate rate of PCR was associated with AC or FAC. The relative benefits of AC and platinum therapy need to be confirmed through follow-up of this and other cohorts.

[Problems in diagnosing breast cancer in women younger than 25 years old]. / Trudnosci diagnostyczne w rozpoznawaniu raka piersi u kobiet ponizej 25 roku zycia.

OBJECTIVES: There are several challenges in the diagnosis of breast cancer in young women. Special consideration must be given to the woman's fertility and body image issues, but the difficulty in distinguishing benign from malignant lesions in this group of patients still exists. The aim of our study was to show five cases of breast cancer in young women. MATERIALS AND METHODS: Based on 5 cases of breast cancer in women younger than 25, several methods used in diagnosis in this group of patients were discussed. The role of USG and BAC was analyzed. Moreover, a significant role of RM and PET was emphasized. RESULTS: Diagnosing and treatment of young patients with breast cancer should be performed in specialized oncological centers experienced in dealing with breast cancer in very young women. CONCLUSIONS: 1. Because of the possibility of breast cancer in women under 25 years old, each case of breast tumor should be precisely diagnosed, especially by ultrasonography and biopsy (BAC) 2. Each case suspected of breast cancer in young women should be diagnosed in highly equipped and specialized medical center.

The NOD2 3020insC Mutation in Women with Breast Cancer from the Bydgoszcz Region in Poland. First Results.

The frameshift NOD2 gene mutation 3020insC is predominantly associated with Crohn's disease, but predisposes to many types of common cancers as well. We studied the frequency of this mutant NOD2 allele in 148 breast cancer women from the Bydgoszcz region in Poland. The NOD2 mutation was present in 8.8% of the patients. The mean age at breast cancer diagnosis of the mutation carriers was 43 years. We did not find any mutation in patients diagnosed with breast cancer after the age of 50 years. There was no association of the NOD2 mutation with a strong family history of breast cancer. On the contrary, the mutation frequency (11.4%) was two times higher in women from families with a single case of breast cancer and with aggregation of other common types of cancer, especially digestive tract cancers. Low risk of breast cancer in the mutation carriers seems to be confirmed by finding the 3020insC mutation in three healthy parents of probands aged 73, 74 and 83 years, from three separate families.

[Role of Ca-125 in the differential diagnosis of adnexal mass in breast cancer patients]. / Rola markera Ca-125 w monitorowaniu chorych z rozpoznanym guzem przydatkow po przebytym leczeniu raka piersi.

OBJECTIVES: Serum CA-125 is of value in differential diagnosis of benign and malignant adnexal masses, especially in postmenopausal women. In ovarian cancer preoperative CA-125 levels are related to tumor stage, histologic grade, but are not an independent prognostic factor. DESIGN: The aim of our study was to determine CA-125 serum level in women with ovarian tumor treated previously because of breast cancer. MATERIALS AND METHODS: Due to our research, we examined 51 women operated on for adnexal masses in the Department of Oncological Gynaecology in Bydgoszcz, 1996 - 2002. All those patients were treated because of breast cancer previously. RESULTS: In 19 women (37,3%) benign ovarian tumors were found, in 4 cases (7,8) - primary ovarian cancer whereas in 28 patients (54,9%) breast cancer metastases were detected. Based on CA-125 levels before surgery, correlation between CA-125 concentration and malignant histologic type was observed. CONCLUSIONS: 1. Higher CA-125 serum levels were found in a group of patients with metastatic adnexal masses compared to primary ovarian cancer. 2. In a group of women with breast cancer and ovarian tumor, metastatic adnexal masses were observed in more than 50% of cases.

[Breast conserving treatment in patients with early detection of breast cancer]. / Leczenie oszczedzajace chorych z wczesnymi postaciami raka piersi z uwzglednieniem zmian wykrytych w badaniach profilaktycznych.

OBJECTIVES: Kujawsko-pomorskie province is a region with high morbidity and death-rate from breast cancer. One method of detected less advanced forms of breast cancer and increased number of patients with BCT having prophylactic medical examination. DESIGN: The aim of the study was the treatment evaluation of patients with noninvasive and invasive cancer treated with BCT, screening-detected and non-screening detected. MATERIALS AND METHODS: Prophylactic mammography for breast cancer was taken in three medical centers. First one so called "mobile" was localized in the health service center, second one in the bus with the mammography reaching distant areas and third one was performing examinations locally. There were 63401 people examined for breast cancer (age 35 -79), detected 288 breast cancers (0.54% of examined population). 260 of them were operated on. 1149 breast cancers were detected in non-screening group. The number of detected noninvasive cancers, their sizes and methods of treatment were analysed. RESULTS: Twelve of 260 (4,62%) cancers detected in screening patients were carcinoma noninvasive and 34 invasive cancers treated with BCT. In non-screening patients 20 carcinoma noninvasive and 104 invasive cancers were found and treated with BCT The number of patients with noninvasive and invasive cancers treated with BCT in prophylactic group is statistically higher. Sizes and clinical stages of malignant tumours detected in both groups were not different CONCLUSIONS: 1. Prophylactic breast cancer examinations increase the number of noninvasive cancers. 2. Breast cancer prophylactic examinations increase the number of patients treated with BCT.

[Prophylactic medical examinations for breast cancer at the Oncology Center of Bydgoszcz in the years 2001-2003]. / Ocena wyników badan profilaktycznych w kierunku raka piersi w Centrum Onkologii w Bydgoszczy w latach 2001-2003.

OBJECTIVES: Kujawsko-pomorskie province is a region with high morbidity and mortality from breast cancer. One of the method of improving this situation is to perform prophylactic medical examinations aiming to find out the most advanced forms possible. DESIGN: The aim of the study was to estimate the results of prophylactic medical examinations for breast cancer that took place in Center of Oncology in Bydgoszcz between 2001-2003. MATERIALS AND METHODS: Prophylactic examinations (mammography) for breast cancer were taken in 3 medical centers. First one so called "mobile" was localized in chosen health service centre, second one in the bus with the mammography reaching distant areas and third one was performing examinations locally. Mammographic examinations were rated with BI-RADS system. There were 63,401 women examined for breast cancer (age 35-79). 19,221 medical examinations were performed by "mobile" device, 16,488 in mammobus and 27,692 locally. Population of women from kujawsko-pomorskie province was 39,0936 persons. Number of detected breast cancers, their sizes and methods of treatment were analysed. RESULTS: Mammography was performed by 16.22% population of women from kujawsko-pomorskie province. The biggest group of patients were women at the age of 50-54 years, and of 45-49 years. 288 cases of breast cancer were discovered (0.45% of examined population). Twelve out of them (4.16%) were non-invasive carcinoma and 153 (53.4%) was smaller than 2 cm. 46 (16.6%) out of 276 detected invasive cancers were treatment by breast conserving treatment, 210 (76.1%) by mastectomy, 11 (14%) by chemo-, radio- and hormonotherapy. CONCLUSIONS: (1) Prophylactic medical examinations let detect cancer in early state of development. (2) Detection of carcinomas smaller than 2 cm allowed to increase the number of breast conserving treatment (BCT).

[Estimated results of prophylactic physical examinations detecting cervical cancer in Center of Oncology in Bydgoszcz in years 2001-2003]. / Ocena wyników badan profilaktycznych w kierunku raka szyjki macicy w Centrum Onkologii w Bydgoszczy w latach 2001-2003.

OBJECTIVES: Kujawsko-pomorskie province is a region with high morbidity and death-rate from uterine cervix cancer. One of the methods of improve this situation is to perform prophylactic physical examinations to find the least advanced stages as possible. DESIGN: The aim of the study was to estimate the results of prophylactic physical examinations for cervical cancer that took place in Center of Oncology in Bydgoszcz between 2001-2003. MATERIALS AND METHODS: Pap Smear with prophylactic examination for breast cancer were taken in 3 medical centers. First on, according to called "mobile", was localized in the health service center, second one in the bus with the mammography, reaching distant areas and third one was performing examinations locally. Cytologic examinations were rated Bethesda system and according to Papanicolau. There were 28372 women examined (age 30-60). 8996 medical examinations were performed by "mobile" device, 6726 in the second center and 12650 locally. 8237 examinations were performed in 2001 year, 9444 in 2002, and 10691 in 2003. RESULTS: Among all the Pap Smears the results were as following: I group--14267, II group--14017, III group--73, IV group--13, V group--2.43 (0.15%)intraepithelial dysplasia was found in them CIN I--23 (0.08%), CIN II--10 (0.035%), CIN III--10 (0.35%).21 (0.1%) cervical cancers were detected, 12 of them were praeinvasive cancers. 0.31% of the all Pap Smears were abnormal. CONCLUSIONS: (1) The number of abnormal Pap Smears and severe dysplastic lesions proves the usefulness of the prophylactic physical examinations. (2) The above programme shows the that the access to oncological care for women living in rural areas, has a social aspect and should have affect the health awareness of the potential patients.

[Prophylactic medical investigations for breast cancer and uterine cervix cancer in Regional Oncology Centre of Bydgoszcz in 2003]. / Ocena wyników badan profilaktycznych w kierunku raka piersi i raka szyjki macicy w Centrum Onkologii w Bydgoszczy w 2003 roku.

UNLABELLED: Kujawsko-pomorskie province is a region with high morbidity and death rate of breast cancer and uterine cervix cancer. Prophylactic medical investigations are methods to find less advanced forms as possible. The aim of the study was to estimate the results of prophylactic medical investigations of Regional Oncology Centre in Bydgoszcz in 2003. Mammography investigations were undertaken in 3 forms. The first one--so called "mobile"--was localized in chosen health service centres, the second one in "mammo-bus" reaching distant communes and the third one local outpatient clinics. Cytological investigations were rated by Bethesda and Papanicolau system. 23 923 people were investigated for breast cancer (age 35-79) and 7946 ones for uterine cervix cancer (age 30-74). 9183 medical investigations were taken by "mobile" device, 4592 in "mammo-bus" and 10 148 locally. 11 986 people had breast examinations, 6118 had gynaecologic examinations. There were cytological investigations results: I group--3902, II group--4019, III group--21, IV group--3, V group--1. Ten uterine cervix cancers were diagnosed (0.13% of investigated population). Five of them were histologically recognised as: carcinoma planoepitheliale praeinvasivum. 91 cases of breast cancers were diagnosed (0.38% of investigated population). Five of them were histologically recognised as: carcinoma intraductale typus comedo (there were: 3 simplex mastectomy, 2 tumorectomy with radiotherapy). The treatment of invasive cancers included 9 breast-conserving treatments. CONCLUSIONS: Prophylactic medical investigations let us find the cancer in early development stage and a number of cancer detections is a justification of this project continuation. The possibility to examine women from villages should have the influence on the detection of early breast and uterine cervix cancer.

[Skin cancer screening program in the population of Bydgoszcz]. / Badania profilaktyczne w kierunku nowotworów skóry w populacji mieszkanców Bydgoszczy.

The results of prophylactic medical skin examinations in inhabitants of Bydgoszcz were estimated. A prophylactic skin examination in asymptomatic patients was performed, and the most suspicion lesions were selected to excision. 750 persons were examined (age 15-93 years). 133 persons were operated. 173 skin lesions were removed. 32 skin cancers (18.53%), 3 melanomas (1.73%) and 34 skin lesions (which are base for melanoma) were confirmed. Detected carcinomas and melanomas were in early state of development. Prophylactic medical skin examination enable the detection of skin neoplasms in early state of development. Percent of detected carcinomas and melanomas of skin justify continuation this kinds of screening.

[Evaluation of breast conserving therapy (BCT) standards for invasive and preinvasive breast cancer adapted in RCO in Bydgoszcz]. / Ocena standardów postepowania wdrozonych w Regionalnym Centrum Onkologii w Bydgoszczy dla oszczedzajacego leczenia inwazyjnego raka piersi oraz dla przedinwazyjnych raków piersi.

INTRODUCTION: Prophylactic campaign against breast cancer wide spread by Regional Center of Oncology made significant influx of patients coming to our place and presenting less advanced stages of the mentioned disease. AIM: The aim of this work was estimate of BCT treatment standard for invasivum cancer and preinvasivunm breast cancer treatment standard which was adapted in RCO. MATERIALS AND METHOD: Patients presenting unifocal invasive cancer smaller than 2 cm, stage No, where the minimal margin of more than 1 cm was possible to perform, were qualified to BCT. Minimal surgical border during tumorectomy was 1 cm. We were excluded patients with carcinoma lobulare and carcinoma mucinosum. During qualification to DCIS treatment standard first we must exclusion multifocalis cases based on Anderson classification and Falun consens. In the other cases we based on Van Nuys Prognostic Index (VNPI) considering the patient's age. We have 3 forms of treatment: simplex mastectomy, tumorectomy and tumorectomy with RTG-therapy. To BCT standard were qualified 52 patients. Schematically was attended 45 peoples. We had 5 patients which was attended based on preinvasivum breast cancer treatment standard. RESULTS: The size of breast cancer tumor at the patients which was attended based on BCT standard was 0,5-2 cm. 3 patients was disqualified from BCT because we found second breast cancer focus in histopathological material. We must widen surgical border post tumorectomy in 5 cases. Among 5 patients with preinvasivum cancer was 3 simplex mastectomy and 2 cases tumorectomy with RTG-therapy. CONCLUSIONS: In our opinion BCT treatment standard and breast preinvasivum cancer treatment standard should be using only in high specialty oncological center. It is a guaranty of right qualification and treatment for breast cancer patients.

[Prophylactic medical examinations for breast cancer and uterine cervix cancer in Regional Oncological Center of Bydgoszcz in year 2002]. / Badania profilaktyczne w kierunku raka piersi i szyjki macicy w Regionalnym Centrum Onkologii w Bydgoszczy w 2002 roku.

OBJECTIVES: Kujawsko-pomorskie province is a region with high morbidity and death-rate from breast cancer and uterine cervix cancer. One method of improving this situation is prophylactic medical examinations aiming to find out the less advanced forms. DESIGN: The aim of work was to estimate the results of prophylactic medical examinations that were taken in Regional Oncological Center of Bydgoszcz during a 2002 year. MATERIALS AND METHODS: Mammography were taken using 3 devices. First one so called "mobile" localized in chosen health service centres, second in mammobus reaching distant communes and third taking examinations locally, where gynaecologic examination and breast examination took place. Cytologic examination were rated with Bethesda's system and according to Papanicolau. There was 23923 people examined for breast cancer (age 35-79) and 7946 for uterine cervix cancer (age 30-74). 9183 medical examinations were taken by "mobile" device, 4592 in mammobus and 10148 locally. 11986 people had breast examination, 6118 had gynaecologic examination. RESULTS: Among cytologic examinations results were: I group--3902, II group--4019, III group--21, IV group--3, V group--1. Ten uterine cervix cancers were found, that makes 0.13% of examined population. Five of them were carcinoma planoepitheliale praeinvasivum. Among prophylactic of breast cancer 91 cases were discovered (0.38% of examined population). Five of them were carcinoma intraductale typus comedo (3 were mastectomy simplex, 2 tumorectomy with radiotherapy). The treatment of invasive carcinomas was breast conserving. CONCLUSIONS: Prophylactic medical examinations let to find cancer in early state of development, and number of detection of carcinomas is a justification of continuation of this project. Possibility to do examinations for women from villages should have influence on detection early breast cancer and uterine cervix cancer.