Attitudes and Stereotypes in Lung Cancer versus Breast Cancer.

Societal perceptions may factor into the high rates of nontreatment in patients with lung cancer. To determine whether bias exists toward lung cancer, a study using the Implicit Association Test method of inferring subconscious attitudes and stereotypes from participant reaction times to visual cues was initiated. Participants were primarily recruited from an online survey panel based on US census data. Explicit attitudes regarding lung and breast cancer were derived from participants' ratings (n = 1778) regarding what they thought patients experienced in terms of guilt, shame, and hope (descriptive statements) and from participants' opinions regarding whether patients ought to experience such feelings (normative statements). Participants' responses to descriptive and normative statements about lung cancer were compared with responses to statements about breast cancer. Analyses of responses revealed that the participants were more likely to agree with negative descriptive and normative statements about lung cancer than breast cancer (P<0.001). Furthermore, participants had significantly stronger implicit negative associations with lung cancer compared with breast cancer; mean response times in the lung cancer/negative conditions were significantly shorter than in the lung cancer/positive conditions (P<0.001). Patients, caregivers, healthcare providers, and members of the general public had comparable levels of negative implicit attitudes toward lung cancer. These results show that lung cancer was stigmatized by patients, caregivers, healthcare professionals, and the general public. Further research is needed to investigate whether implicit and explicit attitudes and stereotypes affect patient care.

Review, evaluation, and discussion of the challenges of missing value imputation for mass spectrometry-based label-free global proteomics.

In this review, we apply selected imputation strategies to label-free liquid chromatography-mass spectrometry (LC-MS) proteomics datasets to evaluate the accuracy with respect to metrics of variance and classification. We evaluate several commonly used imputation approaches for individual merits and discuss the caveats of each approach with respect to the example LC-MS proteomics data. In general, local similarity-based approaches, such as the regularized expectation maximization and least-squares adaptive algorithms, yield the best overall performances with respect to metrics of accuracy and robustness. However, no single algorithm consistently outperforms the remaining approaches, and in some cases, performing classification without imputation sometimes yielded the most accurate classification. Thus, because of the complex mechanisms of missing data in proteomics, which also vary from peptide to protein, no individual method is a single solution for imputation. On the basis of the observations in this review, the goal for imputation in the field of computational proteomics should be to develop new approaches that work generically for this data type and new strategies to guide users in the selection of the best imputation for their dataset and analysis objectives.

The impact of lobular and ductal breast cancer histology on the metastatic behavior and long term survival of breast cancer patients.

The aim of the study was to evaluate the long-term survival of patients with invasive lobular carcinomas (ILC) and invasive ductal carcinomas (IDC) and the metastatic behavior of these two disease entities. Originally, all consecutive patients with pure lobular invasive breast cancers diagnosed between 1990 and 1999 in the area served by the Tampere University Hospital and their matched IDC controls were identified and re-evaluated histopathologically in this follow-up study, resulting in a total of 243 ILCs and 243 IDCs. Data on recurrences and survival were collected until the end of year 2009. Statistical analyses including Kaplan-Meier method, log-rank test, Fisher's exact test and Cox regression analysis were performed with the PASW Statistics 18.0 computer program. P-values of <0.05 were considered statistically significant. Within the mean follow-up time of 10.04 years, locoregional recurrences were significantly more common among the ILCs than IDCs (35 vs. 20, p = 0.04), but no differences in the total number of distant recurrences or bilaterality were observed. However, when the first distant recurrence sites were studied, ILC patients had significantly less lung metastases (p = 0.04), but more skin metastases (p = 0.04). During the whole follow-up period IDCs metastasized significantly more frequently to the lungs (p = 0.002), whereas gastrointestinal metastases were more common among ILCs (p = 0.02). Although the known favorable prognostic factors (hormone receptor positivity, low grade, low s-phase) were more common for the ILCs, the disease-free survival, the overall survival and the survival after recurrence did not differ between the groups. However, the Cox-regression model showed significantly worse survival for ILCs after adjusting for age, TNM-status, grade and ER-positivity (p = 0.004). In conclusion, ILC and IDC differ in respect for visceral metastases. Despite the known favorable prognostic factors and originally favorable survival, patients with lobular histology appear to have a worse survival in the multivariate analysis after a prolonged follow-up.

Rising incidence of small size papillary thyroid cancers with no change in disease-specific survival in Finnish thyroid cancer patients.

BACKGROUND: The aim of this study was to investigate trends in the incidence, diagnostics, treatment and survival of thyroid cancer in Tampere University Hospital (TAUH) region in recent decades. MATERIAL AND METHODS: New thyroid cancer cases from 1981 to 2002 were ascertained from the Finnish Cancer Registry. Follow-up data was collected from medical records of TAUH. Differentiated thyroid cancer (DTC; consisting of papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC)) patients' data was analyzed and divided into two equal time periods (1981-1991 and 1992-2002). RESULTS: The total amount of thyroid cancer cases was 553, of which 427 (77%) were papillary and 72 (13%) follicular. Thyroid cancer was four times more common in females than in males and the median age at the time of diagnosis was 52 years. The incidence of DTC was 4.5/100,000 in the earlier group and 6.0/100,000 in the later group (IRR 1.33, CI 1.11-1.60). The proportion of papillary thyroid cancer rose from 81% to 89% (p=0.02) in two study periods. Median tumour size became smaller, from 25 mm to 15 mm (p<0.001). Surgery became more radical as total thyroidectomies were performed almost exclusively on the later group (p<0.001). Median cumulative dose of radioiodine (I131) therapy was higher in the later group (p=0.04). There was no difference in number of cancer recurrences (p=0.54). The prognosis of DTC was good; 10-year disease-specific survival was 92% in the earlier group and 94% in the later group (p=0.43). CONCLUSIONS: The incidence of thyroid cancer has risen and proportion of papillary cancer has increased, however, median size of tumour has decreased. No difference was seen in either all-cause or disease-specific survival.

The effect of hospital volume on the outcome of breast cancer surgery.

BACKGROUND: This study was conducted to investigate whether annual surgical unit caseload affects extent of breast cancer surgery, breast cancer recurrence or breast cancer-specific survival. METHODS: In a population-based cohort study, 12,604 women diagnosed with breast cancer in Finland during the years 1998-2001 were followed up until the end of year 2008. Surgical units were divided into subgroups: >200, 100-200, 50-99 or <50 breast cancer operations per year. Information on patients, treatment, and follow-up was obtained from two national registries. The analyses were adjusted for age and disease stage. The reliability of the registry information was validated by comparison with information from one hospital area. Cox proportional hazard and logistic regression models were employed in the analyses. RESULTS: Validation of the registry data showed that date of diagnosis, age, stage, extent of surgery, and date and cause of death were reliably recorded in the registers. Information on radiotherapy was obtained by combining different registry data. Data on local and distant recurrences were not reliable enough to allow analyses. Patients in hospitals with smaller caseloads underwent mastectomy more often than those operated in hospitals with higher caseloads (P < 0.001). Higher caseloads were also related to improved survival (P = 0.031). CONCLUSIONS: National registries should include information on both local and distant recurrences in order to provide reliable population-based data for evaluation of treatment results. Centralization of surgery to high-volume centers is supported by a higher incidence of conservative surgery and better survival.

ONCOPOOL - a European database for 16,944 cases of breast cancer.

ONCOPOOL is a retrospectively compiled database of primary operable invasive breast cancers treated in the 1990s in 10 European breast cancer Units. Sixteen thousand and nine hundred and forty four cases were entered, with tumours less than 5 cm diameter in women aged 70 or less (mean age 55). DATA: Data were date of birth, mode of diagnosis, pathology (size, lymph node status, grade, type, lympho-vascular invasion and hormone receptor) and therapies and outcome measures: first local, regional or distant recurrences, contralateral primary, date and cause of death. TUMOUR CHARACTERISTICS: Mean diameter 1.8 cm, 66% lymph node negative, 24% 1-3 lymph nodes involved and 10% had 4 or more involved. Grade 1, 29%; Grade 2, 41%; and Grade 3, 30%. Polynomial relationships were established between grade, stage and size. Seventy-five percent were oestrogen receptor (ER) positive. ER closely related to grade. OUTCOMES: Overall Survival was 89% at 5 years from diagnosis, 80% 10 years and 73% 15 years; Breast Cancer-Specific survivals were 91%, 84% and 79%. Survival strongly related to the Nottingham Prognostic Index (NPI). Cases detected at screening had 84% 10-year survival, those presenting symptomatically 76%. ER positive cases treated with adjuvant hormone therapy had a reduction in risk of death of 13% over those not receiving adjuvant therapy (p=0.000). ER negative cases treated with chemotherapy showed a risk reduction of 23% over those not receiving chemotherapy (p=0.000).

Bone morphogenetic protein 7 expression associates with bone metastasis in breast carcinomas.

BACKGROUND: We recently showed that bone morphogenetic protein 7 (BMP7) is overexpressed in primary breast tumors. Here we explored the clinical significance of BMP7 expression in breast cancer. MATERIALS AND METHODS: This study included 483 breast cancer patients with complete clinicopathological information and up to 15 years of follow-up. Samples contained 241 lobular carcinomas, 242 ductal carcinomas, and 40 local recurrences. BMP7 protein expression was determined using immunohistochemistry. RESULTS: BMP7 was expressed in 47% of the primary tumor samples and 13% of the local recurrences. The primary tumors expressed BMP7 more often than the corresponding local recurrences (P = 0.004). BMP7 expression was dependent on the tumor subtype; 57% of the lobular carcinomas but only 37% of the ductal carcinomas were BMP7 positive (P = 0.0001). BMP7 expression was associated with accelerated bone metastasis formation (P = 0.040), especially in ductal carcinomas (P = 0.033), and multivariate analysis confirmed that BMP7 is an independent prognostic indicator for early bone metastasis development (P = 0.032). CONCLUSION: BMP7 is clearly associated with bone metastasis formation and thus might have clinical utility in identification of patients with increased risk of bone metastasis. This is the first time that bone inducing factor BMP7 has been linked to the bone metastasis process in breast cancer.

Intensity of diagnostic and treatment activities during the end of life of patients with advanced breast cancer.

The aim of this study was to assess the intensity of diagnostic testing and cancer treatment of 335 women with advanced breast cancer during their last 6 months before death between 1995 and 1998 in the Pirkanmaa and Satakunta health care districts and to compare it to the practice in earlier decades, the 1970s and 1980s. Data for 1990s material were collected from medical records in 30-day periods starting from the patient's death backwards. In this material 46.9% of all laboratory tests and 40% of radiological tests during the last 6 months of life were made during the last 2 months prior to death. In the last month 63.9% of patients continued on endocrine therapy and 19.7% on chemotherapy. Patient symptoms and deterioration in general condition showed the appropriate point to discontinue cancer-related treatment and concentrate on palliation of symptoms to be about 2 months prior to death. Resources devoted to diagnostic investigations and treatment of cancer in terminally ill patients could be better used for their care. This would be more likely to improve patients' quality of life and save resources.

Clinical validation of the LKB model and parameter sets for predicting radiation-induced pneumonitis from breast cancer radiotherapy.

The choice of the appropriate model and parameter set in determining the relation between the incidence of radiation pneumonitis and dose distribution in the lung is of great importance, especially in the case of breast radiotherapy where the observed incidence is fairly low. From our previous study based on 150 breast cancer patients, where the fits of dose-volume models to clinical data were estimated (Tsougos et al 2005 Evaluation of dose-response models and parameters predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy Phys. Med. Biol. 50 3535-54), one could get the impression that the relative seriality is significantly better than the LKB NTCP model. However, the estimation of the different NTCP models was based on their goodness-of-fit on clinical data, using various sets of published parameters from other groups, and this fact may provisionally justify the results. Hence, we sought to investigate further the LKB model, by applying different published parameter sets for the very same group of patients, in order to be able to compare the results. It was shown that, depending on the parameter set applied, the LKB model is able to predict the incidence of radiation pneumonitis with acceptable accuracy, especially when implemented on a sub-group of patients (120) receiving [see text]|EUD higher than 8 Gy. In conclusion, the goodness-of-fit of a certain radiobiological model on a given clinical case is closely related to the selection of the proper scoring criteria and parameter set as well as to the compatibility of the clinical case from which the data were derived.

Follow-up cost of breast cancer patients with localized disease after primary treatment: a randomized trial.

We studied the cost of follow-up of 472 breast cancer patients without distant metastasis after primary treatment in four different schedules in a randomized trial. The mean follow-up was 4.2 years. The four schedules differed in frequency of follow-up visits (every third or sixth month) and in intensity of diagnostic examinations (routine or on clinical grounds). Neither the frequency of visits nor the intensity of diagnostic examinations had any effect on disease-free or overall survival of patients. The total costs of follow-up, however, were different in the four follow-up schedules and varied between arms per patient from 1050 to 2269 euros and per detected recurrence from 4166 to 9149 euros. Outpatient visits every third month compared to every sixth month and routine examinations in the follow-up of asymptomatic primary breast cancer patients do not improve patient disease-free or overall survival, but increase the costs of follow-up 2.2 times.

A comparison of the biological and clinical features of invasive lobular and ductal carcinomas of the breast.

Altogether 295 consecutive pure lobular invasive breast cancers diagnosed between 1990 and 1999 in the area of Tampere University Hospital were compared to 295 ductal invasive breast cancers. Biological factors, DFS, OS, recurrence types, survival after recurrence and other primary cancers were analyzed. ILC tumors were more often hormone receptor-positive, slowly proliferative and Erbb-2-negative. During the mean follow-up time of 5.1 years 76 recurrences in both groups were discovered. During the whole follow-up time there was more metastation to gynecological organs and GI tract in the ILC group. Bilateral breast cancers did not differ between the groups. DFS and OS were the same between the groups despite the fact that ILC patients received statistically significantly less adjuvant treatment. In conclusion, since ILC cancers are more often hormone receptor-positive, there is a good option to adjuvant endocrine therapy with present and future preparations, this possibly leading to improvement in OS.

Role of chest X-ray in diagnosis of the first breast cancer relapse: a randomized trial.

Between May 1991 and December 1995, follow-up after primary therapy for 472 consecutive patients with localized breast cancer was randomly assigned to assess the efficacy of routine chest X-ray in detecting intrathoracic relapse as the first metastatic event. One group had regular chest X-rays while the other group had chest radiographs only when clinically needed (spontaneous). Patients were followed up until December 1999 or death. In the routine group, 243 patients had 1429 chest X-rays (mean 5.9 chest X-rays per patient). In the spontaneous group, 229 patients had 411 chest X-rays (mean 1.8 chest X-rays per patient). Both sensitivity and specificity were somewhat higher in the spontaneous arm compared to the routine arm. Patient sensitivity was 30% in the regular arm and 36% in the spontaneous arm. Film sensitivity was 11% in the regular arm and 20% in the spontaneous arm. Patient specificity was 85% in the regular arm and 86% in the spontaneous arm. The predictive values were practically the same in both arms. Patient positive predictive values were 22% in both arms and film positive predictive values were 21% in the regular and 22% in the spontaneous arm. Patient negative predictive values were 90% in the regular and 92% in the spontaneous arm. Film negative predictive values were 93% in the regular and 89% in the spontaneous arm. The differences in accuracy were not statistically significant between the arms. There were no significant differences in disease free survival or overall survival. The 5-year disease free survival was 86% in the regular and 89% in the spontaneous arm and the overall survival was 88 and 85% in the regular versus spontaneous arm, respectively. Routine chest X-ray in the follow-up of breast cancer patient is evidently of little use and is not likely to be of benefit to the patient in terms of disease free survival or overall survival as compared to the spontaneous schedule.

Ocular side-effects in breast cancer patients treated with tamoxifen and toremifene: a randomized follow-up study.

PURPOSE: 3Tamoxifen and toremifene are non-steroidal anti-oestrogens widely used in the treatment of advanced breast cancer and as adjuvant therapy following surgery in early stage disease. Tamoxifene has also been approved for use in reducing the incidence of breast cancer amongst high risk women. However, certain well documented adverse effects, mainly involving the reproductive organs, have been reported amongst users of both drugs. The aim of this study was to monitor the ocular side-effects of both of these commonly used anti-oestrogens. METHODS: Sixty postmenopausal (age range 50-79 years) breast cancer patients were randomized into adjuvant tamoxifen or toremifene therapy groups for 3 years. Prior to commencement of medication, a thorough ocular examination was undertaken. The first follow-up visit took place after 6 months and the remaining three at 12-month intervals thereafter. RESULTS: Sixteen patients had cataract at the first visit (seven in the tamoxifen group and nine in the toremifene group). Ten patients developed cataract during the study period (five in each group), giving annual cataract rates of 6.8% and 6.2% in the tamoxifen and toremifene groups, respectively. Three patients had macular crystals at the first visit (one in the tamoxifen group and two in the toremifene group). The crystals remained stable throughout the follow-up. Macular drusen were diagnosed in five patients at the first ophthalmological check-up (two in the tamoxifen and three in the toremifene group). Two patients in the toremifene group developed drusen maculopathy during follow-up visits. Yellowish spots in the macular area were found in one tamoxifen-treated patient at the second visit. At the final visit after 3.5 years' follow-up the spots had disappeared. No abnormal corneal findings or keratopathy were documented during the follow-up. CONCLUSION: We observed no serious ocular side-effects among the 60 breast cancer patients treated with tamoxifen or toremifene over a 3.5-year period.

Ca 15-3 in the follow-up of localised breast cancer: a prospective study.

Altogether, 243 female breast cancer patients with localised disease diagnosed between 1991 and 1995 in the Tampere University Hospital area were followed prospectively after primary treatment until the first relapse. In the follow-up period, the serum tumour marker Ca 15-3 was analysed every 6 months to ascertain the validity of this marker in detecting the first relapse. The sensitivity and specificity of the test were analysed in different metastatic situations. During the 5 years of follow-up, 59 (24%) relapses were discovered. Ca 15-3 was elevated in 21/59 (36%) of the relapsed cases at least once. The 59 patients were subjected to 199 tests, of which 25 (13%) were positive. Among the 184 patients without recurrence, there were 6 (3%) with a positive Ca 15-3 level. The test failed to detect locoregional relapse or contralateral breast cancer. It was elevated in approximately half of bone-only metastases and in all of the liver-only metastases. In the pulmonary-only recurrences, the marker value was not elevated. We conclude that the Ca 15-3 tumour marker test is specific, but not sensitive enough to indicate the first relapse earlier than other methods. The positive predictive value especially remained poor in patients with a relatively good prognosis. Our results confirm that the test is not suitable alone for breast cancer follow-up.

Postoperative PINP in serum reflects metastatic potential and poor survival in node-positive breast cancer.

The aim of this work was to evaluate the postoperative serum markers of type I collagen synthesis (PINP,PICP) and degradation (ICTP) and their possible potential for predicting the spread of disease and survival. 373 node-positive breast cancer patients were enrolled. 120 patients (32%) developed recurrent disease in the follow-up. The mean time to recurrence was 17 months and the mean follow-up time was 45 months. The mean level of PINP was significantly elevated in the patients who developed metastatic disease in the follow-up as compared with those without metastases. PINP was statistically significantly higher in all the patients who developed bone metastases than in those without metastases. When patients with only bone metastases or patients with bone and soft tissue and/or visceral metastases and patients with only visceral or soft tissue metastases were compared with those not exhibiting metastases, PINP was significantly higher in the group with recurrence in the bone, but there were no significant differences in serum PINP, PICP or ICTP values between the patients with only bone metastases and those who developed soft or visceral metastases during the follow-up. Postoperative high PINP was also a factor for poorer survivaL Tumor size, malignancy grade and progesterone receptors were shown in multivariate analysis to be predictors of recurrence and tumor size and PINP and progesterone receptors to be predictors of survivaL

Quality assurance in radiotherapy of breast cancer--variability in planning target volume delineation.

The inter-physician and inter-patient variability in planning target volume delineation for the radiotherapy of breast cancer after conservative surgery is presented. Eleven experienced radiation oncologists determined the planning target volume (PTV) for four breast cancer patients. Delineation was based on CT slices taken at intervals of 15 mm. The variability in target volume delineation was determined by measuring the volumes in units of cc and the position of the drawn PTVs. Statistical analysis was based on X/R-charts and on Pareto chart and analysis. The maximum range in PTV for one patient was from 670 to 1,200 cc. The observations of three physicians were in excess of the warning limit altogether 18 times. The methods used in this study clearly reveal inter-physician variability in PTV delineation and widest variations found are not acceptable. Training targeted to some physicians and more detailed and unambiguous protocols for PTV delineation are needed.

c-erbB-2 positivity is a factor for poor prognosis in breast cancer and poor response to hormonal or chemotherapy treatment in advanced disease.

The aim of this work was to evaluate the prognostic and predictive values of c-erbB-2 in breast cancer. 650 patients were enrolled. The amplification/overexpression of c-erbB-2 from fresh frozen or paraffin-embedded breast tumour tissue samples was analysed by polymerase chain reaction (PCR) technique (75%), immunohistochemically (17%) or by Southern blot analysis (8%). 126 patients (19%) were positive for c-erbB-2. 148 patients developed metastatic disease, but only 35 were positive for c-erbB-2. Positivity for c-erbB-2 was significantly associated with node positivity, large tumour size, high grade of malignancy, low receptor status, postmenopausal status, and with a shorter overall survival. In multivariate regression analysis, only tumour size and nodal involvement were risk factors for poor survival when analysed separately together with c-erbB-2 and receptor status. Metastatic patients with c-erbB-2 positivity had a significantly shorter survival and disease-free survival (DFS) than the c-erbB-2-negative patients. 29 advanced patients with c-erbB-2 positivity showed a poor response rate to hormonal, non-anthracycline-based and anthracycline-based therapies. Positivity for the c-erbB-2 is a poor prognostic factor in breast cancer, but it also emerges as predictive of the response to hormonal or chemotherapy treatment once the disease has recurred.

Involvement of BRCA1 and BRCA2 in breast cancer in a western Finnish sub-population.

To date, two major familial breast cancer predisposition genes, BRCA1 and BRCA2, have been identified with hundreds of germ-line mutations, accounting for 5--10% of all breast cancer and 40--60% of all inherited breast cancer. Unexpectedly elevated incidence of breast cancer, especially in the older age classes, was observed in a Western Finnish region representing a relatively homogeneous population. This study was designed to test the hypothesis that there are inherited BRCA1 or BRCA2 mutations, which confer variable and/or age-dependent penetrance on carriers. Expecting a founder effect, we searched for geographical clustering of breast cancer cases and searched for associations between the affected phenotype and shared genomic segments in the BRCA1 and BRCA2 genomic regions. Our haplotype association study did not reveal any founder effects for either BRCA1 or BRCA2. However, there were two mutations prevalent in this geographical area with minor founder effects, BRCA2 T8555G and 999del5. This is one of the few geographically ascertained, population-based studies that indicate an overall frequency of BRCA1 and BRCA2 mutations at about 2--3% in all breast cancer cases. The geographical clustering of breast cancer cases was not explained by BRCA1 or BRCA2 genes.

Lumpectomy with or without postoperative radiotherapy for breast cancer with favourable prognostic features: results of a randomized study.

The aim of this trial was to study the value of adding post-operative radiotherapy to lumpectomy in a subgroup of breast cancer patients with favourable patient-, tumour-, and treatment-related prognostic features. 152 women aged over 40 with unifocal breast cancer seen in preoperative mammography were randomly assigned to lumpectomy alone (no-XRT group) or to lumpectomy followed by radiotherapy to the ipsilateral breast (50 Gy given within 5 weeks, XRT group). All cancers were required to be invasive node-negative, smaller than 2 cm in diameter and well or moderately differentiated, to contain no extensive intraductal component, to be progesterone receptor-positive, DNA diploid, have S-phase fraction