BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients.

PURPOSE: BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy. METHODS: Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival. RESULTS: Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as "ypT0; ypN0" was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26-4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status. CONCLUSIONS: BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.

Prediction of pathological complete response and prognosis in patients with neoadjuvant treatment for triple-negative breast cancer.

BACKGROUND: It has been reported that pathological complete response is an important surrogate marker for disease-free survival and overall survival in patients with triple-negative breast cancer. This study investigates predictors of the response to neoadjuvant platinum-based or anthracycline-based treatment, and of the prognosis, in patients with triple-negative breast cancer. METHODS: A total of 121 patients with triple-negative breast cancer received neoadjuvant treatment with either platinum or anthracycline between 2008 and 2013. Pathological complete response was assessed relative to different treatments using logistic regression models with age, clinical tumor stage, grading, and Ki-67 as predictors and interaction terms, to obtain adjusted and subgroup-specific results. The impact of the pathological complete response rate on disease-free survival and overall survival was also analyzed. RESULTS: The pathological complete response rate was higher after platinum/taxane treatment compared with anthracycline/taxane (50.0% vs. 41.8%), but this was not significant in the adjusted analysis (OR 1.44; 95% CI, 0.68 to 3.09). A high histological grade (G3) was a predictor for higher pathological complete response in platinum-based therapy (OR 2.27; 95% CI, 1.00 to 5.30). The effect of neoadjuvant chemotherapy on pathological complete response was significantly different for G1-2 vs. G3 (Pinteraction = 0.013), and additional subgroup-specific differences were noted. Pathological complete response was a predictor for improved disease-free survival and overall survival in both treatment groups, with and without platinum chemotherapy. CONCLUSIONS: This retrospective study of patients with triple-negative breast cancer adds to the evidence that the treatment effect of platinum may be greatest particularly in G3 tumors. In addition, the effect of pathological complete response on the prognosis does not depend on the treatment used.

Comprehensive visualization of paresthesia in breast cancer survivors.

PURPOSE: As breast cancer survivors are benefiting increasingly from advanced forms of therapy, the side effects of locoregional treatment in the adjuvant setting are becoming more and more important. This article presents a new method of assessing the spatial distribution of paresthesia in breast cancer survivors after different locoregional treatments. METHODS: A structured questionnaire assessing paresthesia, with body pictograms for marking paresthesia areas, was completed by 343 breast cancer survivors. The image information was digitized, generating gray-scale summation images with numbers from 0, indicating black (100 % of the patients had paresthesia), to 255, indicating white (none had paresthesia). The resulting map visualization showed the locations of paresthesia on body pictograms. The group included patients who had undergone breast-conserving surgery (BCS) and mastectomy, and also patients who had received percutaneous and interstitial radiation. RESULTS: A total of 56.5 % of the patients stated that they had paresthesia. The paresthesia areas were distributed within the range suggested by clinical experience. Most patients stated that they had paresthesia in the upper outer quadrant and axilla. Patients who had undergone mastectomy or percutaneous radiotherapy appeared to have more paresthesia on some areas of the body surface. Patients who had undergone mastectomy indicated larger areas of paresthesia than those with BCS-4,066 pixels (px) vs. 2,275 px. Radiotherapy did not appear to influence the spatial distribution of paresthesia. CONCLUSIONS: Paresthesia is a common symptom after breast cancer treatment. This paper describes a new method of assessing this side effect to improve and individualize treatment for it in the future.

Prognostic relevance of Ki-67 in the primary tumor for survival after a diagnosis of distant metastasis.

Prediction of the prognosis for metastatic breast cancer patients depends on molecular subtypes similar to those found in patients with primary breast cancer. Several studies have shown that estrogen receptor (ER) and progesterone receptor (PR) status determine the course of the disease and the prognosis. As Ki-67 helps to differentiate molecular subtypes in patients with primary breast cancer, the aim of this study was to assess the prognostic relevance of Ki-67 in the primary tumor in relation to its prognostic relevance for patients with metastatic breast cancer. A total of 467 patients with invasive breast cancer were identified in the database of a single breast cancer center, in whom Ki-67 had been assessed in tumor material from the breast at the time of the primary diagnosis and who had developed a metastasis at any time during the subsequent course. For these patients, tumor and patient characteristics were used to determine prognostic factors relative to overall survival after the diagnosis of distant metastases. Ki-67 was added to this model to investigate whether this might improve the prediction of overall survival. In the multivariate Cox model, age at diagnosis, body mass index, nodal status, tumor size, ER and PR status, and time from diagnosis to metastasis were identified as relevant prognostic factors. Adding Ki-67 to the model improved the prediction of overall survival. There was also a significant and relevant interaction with the PR status. In patients with a low-proliferation primary tumor, a high level of PR expression would indicate an extraordinarily good prognosis (HR 0.39; 95 % CI, 0.23-0.66). In patients with higher-proliferation primary tumors, PR status was not capable of differentiating prognostic groups. Ki-67 is useful in addition to known prognostic factors for breast cancer. It is able to indicate a group of women with a poorer prognosis, specifically in the group of patients with PR-positive breast cancer.

Shared decision-making in metastatic breast cancer: discrepancy between the expected prolongation of life and treatment efficacy between patients and physicians, and influencing factors.

Treatment decisions in oncology are based on a balance between the efficacy of therapy and its side effects. Patients with metastases and patients with a limited prognosis are a particular challenge, since communication about the disease situation and the expected therapeutic benefit is difficult not only for patients, but also for physicians. The aim of this study was therefore to compare the benefits expected of therapy by patients and physicians. Questionnaires were sent to 9,000 breast cancer patients and to 6,938 physicians. The questionnaires described 10 cases of breast cancer in the metastatic setting. The patients and physicians were asked to state the treatment benefit they would require to decide for the therapy options chemotherapy, endocrine therapy, antibody therapy, radiotherapy, and bisphosphonates. Additionally, the participants provided data on patient and physician characteristics. Expected treatment benefits were compared between patients and physicians, and influencing factors that modified the expected benefit were identified. Patients expected much greater benefits from the therapies offered than the physicians. For all treatment modalities, about 50 % or more of patients expected more than a 12-month increase in overall survival from all therapies. Among the doctors, this proportion ranged from 7 to 30 %. Among patients, previous experience of side effects and having young children in the family were the strongest influencing factors. Among the doctors, age and level of education had a strong influence on the expected prognostic improvement to indicate a therapy option. As expectations of treatment differ greatly between patients and doctors, a structured approach to solving this conflict is required. There appear to be some indicators that might help address the problem, such as the physicians' level of training and experience and the patients' specific social circumstances.

Financing of certified centers: a willingness-to-pay analysis.

INTRODUCTION: Although care in certified breast centers is now established throughout Germany, numerous services are still not being reimbursed. This also affects other centers involved in the specialty of gynecology such as gynecological cancer centers, perinatal centers, and endometriosis centers. Although a certified center is entitled to charge additional fees, these are in most cases not reimbursed. Calculation of additional costs is limited by the fact that data from the Institute for the Hospital Reimbursement System (Institut für das Entgeltsystem im Krankenhaus, InEK) do not reflect interdisciplinary services and procedures. For decision-makers, society's willingness to pay is an important factor in guiding decisions on the basis of social priorities. A hypothetical maximum willingness to pay can be calculated using a willingness-to-pay analysis, making it possible to identify deficiencies in the arbitrary setting of health budgets at the macro-level. MATERIALS AND METHODS: In a multicenter study conducted between November 2009 and December 2010, 2,469 patients at a university hospital and at a non-university hospital were asked about the extent of their awareness of certified centers, the influence of centers on hospital presentation, and about personal attitudes toward quality-oriented reimbursement. A subjective assessment of possible additional charges was calculated using a willingness-to-pay analysis. RESULTS: In the overall group, 53.4 % of the patients were aware of what a certified center is and 27.4 % had specific information (obstetrics 40.0/32.3 %; mastology 66.8/23.2 %; gynecological oncology 54.7/27.3 %; P < 0.001). For 43.8 %, a certified center was one reason or the major reason for presentation (obstetrics 26.2 %; mastology 66.8 %; gynecological oncology 46.6 %; P < 0.001). A total of 72.6 % were in favor of quality-oriented reimbursement and 69.7 % were in favor of an additional charge for a certified center amounting to €538.56 (mastology €643.65, obstetrics €474.67, gynecological oncology €532.47). In all, 33.9 % would accept an increase in health-insurance fees (averaging 0.3865 %), and 28.3 % were in favor of reduced remuneration for non-certified centers. CONCLUSIONS: The existence of certified centers is being increasingly recognized by patients. Additional charges for certified centers are generally supported. There is therefore a clear demand for them-from patients as well. This may be useful when negotiations are being conducted.

Shared decision-making in breast cancer: discrepancy between the treatment efficacy required by patients and by physicians.

Several factors can influence individual perceptions of the expected benefit of recommended adjuvant treatment for breast cancer. This study investigated differences between patients and physicians with regard to the required efficacy of treatment and the factors influencing patients' and physicians' willingness to accept different therapeutic options. A total of 9,000 questionnaires were distributed to patients with breast cancer, and 6,938 questionnaires were distributed to physicians treating breast cancer patients. The patients were asked for personal information and about their medical history and experiences during treatment. The physicians were asked about personal information and their specialty and work environment. The treatment efficacy required by the two groups was assessed using six virtual cases of breast cancer and the treatment regimens proposed, with specific benefits and side effects. A total of 2,155 patients and 527 physicians responded to the questionnaire (return rates of 23.9 and 7.6 %). Significantly different ratings between patients and physicians with regard to the expected benefit of certain treatment options were observed. The differences were noted not only for chemotherapy but also for antihormonal and antibody treatments. Whereas physicians had a quite realistic view of the expected treatment benefits, the patients' expectations were varied. Approximately one-fifth of the patients were willing to accept treatment regimens even with marginal anticipated benefits, whereas one-third required unrealistic treatment benefits. Several influencing factors that were significantly associated with the quality rating of treatment regimens in the groups of breast cancer patients and physicians were also identified. In contrast to physicians, many breast cancer patients required treatment benefits beyond what was realistically possible, although a large group of patients were also satisfied with minimal benefits. Individual factors were also identified in both groups that significantly influence thresholds for accepting adjuvant treatment, independently of risk estimates and therapy guidelines.

Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment.

BACKGROUND: The pathological complete response (pCR) after neoadjuvant chemotherapy is a surrogate marker for a favorable prognosis in breast cancer patients. Factors capable of predicting a pCR, such as the proliferation marker Ki67, may therefore help improve our understanding of the drug response and its effect on the prognosis. This study investigated the predictive and prognostic value of Ki67 in patients with invasive breast cancer receiving neoadjuvant treatment for breast cancer. METHODS: Ki67 was stained routinely from core biopsies in 552 patients directly after the fixation and embedding process. HER2/neu, estrogen and progesterone receptors, and grading were also assessed before treatment. These data were used to construct univariate and multivariate models for predicting pCR and prognosis. The tumors were also classified by molecular phenotype to identify subgroups in which predicting pCR and prognosis with Ki67 might be feasible. RESULTS: Using a cut-off value of > 13% positively stained cancer cells, Ki67 was found to be an independent predictor for pCR (OR 3.5; 95% CI, 1.4, 10.1) and for overall survival (HR 8.1; 95% CI, 3.3 to 20.4) and distant disease-free survival (HR 3.2; 95% CI, 1.8 to 5.9). The mean Ki67 value was 50.6 ± 23.4% in patients with pCR. Patients without a pCR had an average of 26.7 ± 22.9% positively stained cancer cells. CONCLUSIONS: Ki67 has predictive and prognostic value and is a feasible marker for clinical practice. It independently improved the prediction of treatment response and prognosis in a group of breast cancer patients receiving neoadjuvant treatment. As mean Ki67 values in patients with a pCR were very high, cut-off values in a high range above which the prognosis may be better than in patients with lower Ki67 values may be hypothesized. Larger studies will be needed in order to investigate these findings further.

Assessment of breast cancer tumour size using six different methods.

OBJECTIVES: Tumour size estimates using mammography (MG), conventional ultrasound (US), compound imaging (CI) and real-time elastography (RTE) were compared with histopathological specimen sizes. METHODS: The largest diameters of 97 malignant breast lesions were measured. Two US and CI measurements were made: US1/CI1 (hypoechoic nucleus only) and US2/CI2 (hypoechoic nucleus plus hyperechoic halo). Measurements were compared with histopathological tumour sizes using linear regression and Bland-Altman plots. RESULTS: Size prediction was best with ultrasound (US/CI/RTE: R (2) 0.31-0.36); mammography was poorer (R(2) = 0.19). The most accurate method was US2, while US1 and CI1 were poorest. Bland-Altman plots showed better size estimation with US2, CI2 and RTE, with low variation, while mammography showed greatest variability. Smaller tumours were better assessed than larger ones. CI2 and US2 performed best for ductal tumours and RTE for lobular cancers. Tumour size prediction accuracy did not correlate significantly with breast density, but on MG tumours were more difficult to detect in high-density tissue. CONCLUSIONS: The size of ductal tumours is best predicted with US2 and CI2, while for lobular cancers RTE is best. Hyperechoic tumour surroundings should be included in US and CI measurements and RTE used as an additional technique in the clinical staging process.

Quality assured health care in certified breast centers and improvement of the prognosis of breast cancer patients.

BACKGROUND: Increasing effort has been put in the implementation and certification of breast centers in order to establish standardized, quality assured health care for breast cancer patients. The aim of this analysis was to investigate whether patients treated in certified breast centers (CBC) have a favorable prognosis as compared to patients treated outside of certified breast treatment units. PATIENTS AND METHODS: The data of 3,940 patients with invasive nonmetastatic breast cancer were analyzed with regard to differences in patient and tumor characteristics and crude overall survival according to diagnosis in or outside CBC in Middle Franconia, Germany. Patient, tumor, and follow-up data were obtained from the clinical cancer registry. RESULTS: Patients in CBC were younger, and had lower disease stages and lower grading. Independent of the effects of these variables on overall survival, being treated at a CBC added to the prediction of overall survival. Patients treated at a CBC had a hazard ratio of 0.70 (95% confidence interval 0.52-0.93) in the adjusted Cox model. CONCLUSIONS: Independent from common prognostic factors, diagnosis and treatment of breast cancer at a CBC improves the prognosis of patients. It can be hypothesized that this effect is mediated through quality assured health care provided by the certification process.

Breast volumetry using a three-dimensional surface assessment technique.

BACKGROUND: Breast volume is a relevant measure for the prevention and prediction of diseases and for aesthetic surgery. This study evaluated a new technique to determine breast volume and compared measures using a three-dimensional (3D) body surface scanner and magnetic resonance imaging (MRI) scans, with the latter used as the standard method. METHODS: Both MRI scans and body surface 3D scans were obtained from 22 women. For each method, breast volumes were assessed. The MRI calculations of the breast volumes were performed by a specially trained radiologist using analysis software. A textured 3D image was generated by a calibrated digital texture camera after breast surface data acquisition. The volume assessment of the 3D photography was calculated using a software package after manual outlining of the breast and automated projection of a dorsal limit. Linear regression was used to predict the MRI volume assessment with the 3D image volume assessment. RESULTS: The mean breast volume according to MRI volumetry was 442.8 ml on the left side and 471.8 ml on the right side. The mean breast volume using a 3D body surface volume assessment method was 273.8 ml (observer A) and 226.2 ml (observer B) on the left side and 284.4 ml (observer A) and 234.9 ml (observer B) on the right side. The use of linear regression models showed R (2) values of 0.59-0.77. The mean time for MRI recording and volume assessment was 68.0 ± 14.1 min for both sides and 11.6 ± 1.5 min for 3D recording and volume assessment. CONCLUSIONS: The 3D surface-based volume measurements are feasible in terms of time and can predict the MRI breast volume with sufficient accuracy. This might facilitate the broad use of such an assessment technique in a large-scale epidemiologic study using breast volume as a study aim. Additionally, further development of volume assessments could help to implement this technique in breast surgery procedures.

Pain perception and detailed visual pain mapping in breast cancer survivors.

Chronic pain and neural irritation after breast surgery and radiation are still relevant sequelae of the treatment. Pain quantification and localization in patient groups are difficult to standardize. In order to quantify and localize pain in a group of breast cancer patients, a Java-based program was developed to visualize the frequency of pain in "pain maps." A questionnaire with structured questions on the perception of pain included pictograms of a body to mark possible pain areas. A group of 343 breast cancer survivors completed the questionnaires. The image information was digitalized and processed using a Java applet. Gray-scale summation pictures with numbers from "0," indicating black (100% pain), to "255," indicating white (0% pain), were generated. The visualization of pain by creating pain maps revealed the location of pain in breast cancer survivors on pictograms of the body. Analyzing the total number of pixels, in which pain was stated, made it possible to compare pain areas in several subgroups, showing that patients after mastectomy versus breast-conserving therapy (3,011 vs. 2,224 pixels), and patients with lymphedema versus patients without lymphedema (3,010 vs. 2,239 pixels), have larger pain areas. This study presents a method of visualizing pain areas and assigning them to a pictogram of the body in a sample of breast cancer patients. The method is easy to use and could help generate pain maps in several types of disease.

Neurokinin 1 receptor gene polymorphism might be correlated with recurrence rates in endometriosis.

INTRODUCTION: Dysmenorrhoea is the major symptom in women with endometriosis. Recently, pain modulation through Neurokinin-1-receptor (NK1R) pathways have been investigated in neuropathic pain patients. Aim of this study was, therefore, to examine the effect of a single nucleotide polymorphism (SNP) of the NK1R gene on the susceptibility for endometriosis and the disease free survival (DFS) after surgery for endometriosis. MATERIAL AND METHODS: A case-control study was conducted and germline DNA was isolated. Patients were followed up for a recurrence of the disease up to 4 years. Case-control analyses were performed for parameters of the medical history and the genotype of the NK1R-SNP rs881. Furthermore, DFS probabilities were calculated. RESULTS: Concerning the DFS preoperative pain levels and the NK1R genotype were independent predictors for a recurrence with hazard ratios of 2.55 (95% CI: 1.32-4.95) for patients with a high preoperative pain level and 0.44 for patients with a heterozygous or homozygous variant genotype in rs881 (95% CI: 0.21-0.88). CONCLUSION: The polymorphism rs811 seems to be associated with a lower recurrence risk in endometriosis patients. Thus, there might be a clinical relevant role of the NK1 pathway in the pain perception of endometriosis patients.

Diagnostic Accuracy of Breast Medical Tactile Examiners (MTEs): A Prospective Pilot Study.

BACKGROUND: The usefulness of clinical breast examination (CBE) in general and in breast cancer screening programs has been a matter of debate. This study investigated whether adding vision-impaired medical tactile examiners (MTEs) improves the predictiveness of CBE for suspicious lesions and analyzed the feasibility and acceptability of this approach. METHODS: The prospective study included 104 patients. Physicians and MTEs performed CBEs, and mammography and ultrasound results were used as the gold standard. Sensitivity and specificity were calculated and logistic regression models were used to compare the predictive value of CBE by physicians alone, MTEs alone, and physicians and MTEs combined. RESULTS: For CBEs by physicians alone, MTEs alone, and both combined, sensitivity was 71, 82, and 89% and specificity was 55, 45, and 35%, respectively. Using adjusted logistic regression models, the validated areas under the curve were 0.685, 0.692, and 0.710 (median bootstrapped p value (DeLong) = 0.381). CONCLUSION: The predictive value for a suspicious breast lesion in CBEs performed by MTEs in patients without prior surgery was similar to that of physician-conducted CBEs. Including MTEs in the CBE procedure in breast units thus appears feasible and could be a way of utilizing their skills.

Evaluation of mathematical models for breast cancer risk assessment in routine clinical use.

Chemoprevention, prophylactic surgery, and intensified screening can be offered to patients with an increased lifetime risk, p(life), for breast cancer. Estimation of p(life) includes BRCA analysis and risk estimation based on individual risk factors and family history. MENDEL and BRCAPRO are models that estimate the probability of BRCA1/2-mutations, p(mut), and p(life). In this study, the models are compared with Ford and Claus penetrance/frequency functions. The results were compared with the Tyrer-Cuzick model. Genetic analysis of 111 breast cancer-affected patients from 103 kindreds with a family history of breast and/or ovarian cancer (German Consortium for Hereditary Breast and Ovarian Cancer) was carried out by sequencing BRCA1 and BRCA2. p(life) and p(mut) were calculated with MENDEL, BRCAPRO(Claus), BRCAPRO(Ford), as well as the Tyrer-Cuzick model. The accuracy of p(mut) was analyzed by receiver operating characteristics, and p(life) of each model was compared. The strongest correlation of p(life) was shown by BRCAPRO(Ford)/MENDEL, at r=0.69; no correlation was shown by BRCAPRO(Claus)/MENDEL, at r=0.018. The Tyrer-Cuzick model had the strongest correlations with MENDEL and BRCAPRO(Ford). For MENDEL and BRCAPRO, low correlation or p(mut)-prediction was improved by excluding kindreds with ovarian cancer. p(mut) showed the best accuracy for BRCAPRO(Ford) and MENDEL. BRCAPRO and MENDEL are useful tools for calculating p(mut). They can provide support in decision-making for or against genetic analysis. Estimations of p(life) and p(mut) based on a mathematical model should use algorithms and penetrance/frequency data appropriate to the population counseled. Reproductive/hormonal data, should be incorporated as Tyrer-Cuzick does.

Lymphedema in breast cancer survivors: assessment and information provision in a specialized breast unit.

OBJECTIVE: Assessment and adequate treatment of lymphedema is required by the European Society of Mastology. The purpose of our study was the evaluation of self-reported incidences of lymphedema in breast cancer survivors and the effect of providing the patients with information about lymphedema on the extent to which lymph-drainage massage services and compression garments were used. METHODS: A total of 742 breast cancer survivors were analysed in this questionnaire-based survey. The associations between lymphedema and the patients' medical history; morbidity located in the breast, axilla, and arm; the amount of information the patients had received concerning lymphedema; and the extent to which lymph-drainage massage services and compression garments were analyzed. RESULTS: 31.67% of the patients stated to have lymphedema. Radiotherapy was identified as a significant risk factor. Pain, paresthesia, and functional limitations were associated with the occurrence of lymphedema. The only independent positive predictive factor found to be associated with the use of lymph-drainage massage services (OR 5.74) was the provision of information about the condition. CONCLUSIONS: Self-reported assessment of lymphedema is feasible. The observed lymphedema incidence of approximately 30% may be able to serve as a basis for benchmarking in quality-assurance procedures at breast centers. PRACTICE IMPLICATIONS: Control mechanisms are required to assess if the indication for lymphdrainage is adequate and the compliance to this subject is sufficient.

Influence of mammographic density on the diagnostic accuracy of tumor size assessment and association with breast cancer tumor characteristics.

PURPOSE: The accuracy of breast cancer staging involves the estimation of the tumor size for the initial decision-making in the treatment. We investigated the accuracy of tumor size estimation and the association between tumor characteristics and breast density (BD). MATERIALS AND METHODS: A total of 434 women with a primary diagnosis of breast cancer were included in this prospective study at a specialist breast unit. Estimated tumor characteristics included tumor size, nodal status, estrogen/progesterone receptor status, Ki-67, HER2/neu, vascular invasion. Radiomorphological data included tumor size as assessed by mammography, breast ultrasonography, and clinical examination, and American College of Radiology (ACR) categories for BD. RESULTS: BD did not have a significant impact on the assessment of tumor size using breast ultrasound (deviation from ACR categories 1-4: 0.55-0.68 cm; P=0.331). The deviation in mammography was significantly different dependent on BD (0.42-0.9 cm; P<0.001). The clinical examination was not affected by BD. Age and tumor size were the only parameters associated with a denser breast in the multivariate analysis. Older women were less likely to have dense breasts (odds ratio 0.157 for women aged >or=70 years), and patients with larger tumors were less likely to have dense breasts (adjusted OR 0.36 for tumors>2 cm). CONCLUSION: Breast ultrasonography is more accurate than mammography for assessing tumor size in breasts with a higher BD. The difference in tumor size assessment needs to be taken into consideration in the design of clinical trials and treatment decisions.

Age of uptake of early cancer detection facilities by low-risk and high-risk patients with familial breast and ovarian cancer.

INTRODUCTION: Some 5-10% of all cases of breast cancer and ovarian cancer have a hereditary genesis. In the setting of an interdisciplinary cancer genetics clinic, a study of the age at which patients first take advantage of early cancer detection (ECD) facilities was conducted in order to assess the influence of familial risk on health issues. METHODS: The study included 556 women who fulfilled the inclusion criteria (IC) for genetic analysis of the BRCA1 and BRCA2 genes, as well as 205 who did not meet these criteria but attended the primary consultation. RESULTS: Consulters who met the inclusion criteria took advantage of nearly all methods of ECD at an earlier time than women who did not. A comparison of consulters with or without breast cancer showed that those without breast cancer participated in all methods of ECD at an earlier time. CONCLUSION: Methods of improving and increasing participation in ECD facilities, and of encouraging women who are at risk to start on such programs at a younger age, need to be discussed. In this study, familial risk already resulted in a younger age of uptake of ECD facilities.

Health utilities in gynecological oncology and mastology in Germany.

BACKGROUND AND AIMS: Cost increases in the healthcare system are leading to a need to distribute financial resources in accordance with the value of each service performed. Health-economic decision-making models can support these decisions. Due to the previous unavailability of health utilities in Germany (scored states of health as a basis for calculating quality-adjusted life-years, QALYs) for women undergoing treatment, international data are often used for such models. However, these may widely deviate from the values for a woman actually living in Germany. It is, therefore, necessary to collect and analyze health utilities in Germany. MATERIALS AND METHODS: In a questionnaire survey, health utilities were collected, along with data for a healthy control group, for 580 female patients receiving treatment in the fields of mastology and gynecological oncology using a German version of the EuroQol questionnaire (EQ-5D) and a visual analogue scale (VAS). Data were also collected for the patients' medical history, tumor disease, and treatment. RESULTS: Significant differences with regard to quality of life were measured in relation to the individual tumor entities and in comparison to the controls. Apart from the healthy control group, patients with breast or cervical carcinoma had the best quality of life. In patients with recurrent and metastatic disease, those with breast carcinoma experienced the greatest impairment of their quality of life. According to current treatment, the most important impairment of life quality occurred in patients under radiotherapy and after surgical treatment. There are significant differences from the health utilities recorded for other countries - for example, the state of health declines much more markedly in patients with metastatic disease among American women with breast carcinoma than among German women, in whom recurrent disease and a first diagnosis of metastasis were comparable. Overall, the VAS was able to distinguish more adequately than the EQ-5D questionnaire between the different situations and impairments resulting from diagnosis and therapy. CONCLUSION: Health utilities are now, for the first time, available for further health-economics analyses in the field of gynecological oncology and mastology for women living in Germany. Important differences in these utilities from those of other countries are evident.

Assessment of breast volume changes during human pregnancy using a three-dimensional surface assessment technique in the prospective CGATE study.

Pregnancies and breastfeeding are two important protective factors concerning breast cancer risk. Breast volume and breast volume changes might be a breast phenotype that could be monitored during pregnancy and breastfeeding without ionizing radiation or expensive equipment. The aim of the present study was to document changes in breast volume during pregnancy prospectively. In the prospective Clinical Gravidity Association Trial and Evaluation programme, pregnant women were followed up prospectively from gestational week 12 to birth. Three-dimensional breast surface imaging and subsequent volume assessments were performed. Factors influencing breast volume at the end of the pregnancy were assessed using linear regression models. Breast volumes averaged 420 ml at the start of pregnancy and 516 ml at the end of pregnancy. The first, second and third quartiles of the volume increase were 41, 95 and 135 ml, respectively. Breast size increased on average by 96 ml, regardless of the initial breast volume. Breast volume increases during pregnancy, but not all womens' breasts respond to pregnancy in the same way. Breast volume changes during pregnancy are an interesting phenotype that can be easily assessed in further studies to examine breast cancer risk.