ABC7 Consensus: Assessment by a German Group of Experts.

Background: The "International Consensus Conference for Advanced Breast Cancer" was initiated more than 10 years ago. The rationale was to standardize treatment of advanced breast cancer (ABC) based on available evidence and to ensure that all ABC patients worldwide receive adequate treatment and access to new therapies. Topics of ABC7: The 7th International Consensus Conference for ABC (ABC7) took place from November 9 to 11, 2023 - as in previous years in Lisbon/Portugal. ABC7 focused not only on metastatic disease but also on locally advanced and inflammatory breast cancer. Special topics were the management of oligometastatic disease, leptomeningeal disease, brain metastases, and pregnant women with ABC. Due to the current situation worldwide, there was a special interest to patients living in conflict zones. As in previous years, patient advocates from around the world were integrated into the ABC conference and had a major input to the consensus. Rationale for the Manuscript: A German breast cancer expert panel comments on the voting results of the ABC7 panelists regarding their relevance for routine clinical practice in Germany. As with previous meetings, the ABC7 votes focused on modified or new statements. Regarding the statements not modified for the ABC7 consensus, they are discussed in the published manuscript from 2021 in which the German experts commented on the ABC6 consensus. The German comments are always based on the current recommendations of the "Breast Committee" of the Gynecological Oncology Working Group (Arbeitsgemeinschaft Gynäkologische Onkologie, AGO Mamma).

PRECYCLE: multicenter, randomized phase IV intergroup trial to evaluate the impact of eHealth-based patient-reported outcome (PRO) assessment on quality of life in patients with hormone receptor positive, HER2 negative locally advanced or metastatic breast cancer treated with palbociclib and an aromatase inhibitor or palbociclib and fulvestrant.

BACKGROUND: Efficacy and quality of life (QoL) are key criteria for therapy selection in metastatic breast cancer (MBC). In hormone receptor positive (HR +) human epidermal growth factor receptor 2 negative (HER2 -) MBC, addition of targeted oral agents such as everolimus or a cycline-dependent kinase 4/6 (CDK 4/6) inhibitor (e.g., palbociclib, ribociclib, abemaciclib) to endocrine therapy substantially prolongs progression-free survival and in the case of a CDK 4/6i also overall survival. However, the prerequisite is adherence to therapy over the entire course of treatment. However, particularly with new oral drugs, adherence presents a challenge to disease management. In this context, factors influencing adherence include maintaining patients' satisfaction and early detection/management of side effects. New strategies for continuous support of oncological patients are needed. An eHealth-based platform can help to support therapy management and physician-patient interaction. METHODS: PreCycle is a multicenter, randomized, phase IV trial in HR + HER2 - MBC. All patients (n = 960) receive the CDK 4/6 inhibitor palbociclib either in first (62.5%) or later line (37.5%) together with endocrine therapy (AI, fulvestrant) according to national guidelines. PreCycle evaluates and compares the time to deterioration (TTD) of QoL in patients supported by eHealth systems with substantially different functionality: CANKADO active vs. inform. CANKADO active is the fully functional CANKADO-based eHealth treatment support system. CANKADO inform is a CANKADO-based eHealth service with a personal login, documentation of daily drug intake, but no further functions. To evaluate QoL, the FACT-B questionnaire is completed at every visit. As little is known about relationships between behavior (e.g., adherence), genetic background, and drug efficacy, the trial includes both patient-reported outcome and biomarker screening for discovery of forecast models for adherence, symptoms, QoL, progression free survival (PFS), and overall survival (OS). DISCUSSION: The primary objective of PreCycle is to test the hypothesis of superiority for time to deterioration (TTD) in terms of DQoL = "Deterioration of quality of life" (FACT-G scale) in patients supported by an eHealth therapy management system (CANKADO active) versus in patients merely receiving eHealth-based information (CANKADO inform). EudraCT Number: 2016-004191-22.

ABC6 Consensus: Assessment by a Group of German Experts.

Background: The first International Consensus Conference for Advanced Breast Cancer (ABC1) took place 10 years ago in November 2011. The rationale was - and still is - to standardize treatment of advanced breast cancer (ABC) based on the available evidence and to ensure that worldwide all breast cancer patients receive adequate treatment and access to new therapies. Rationale for the Manuscript: The 6th International Consensus Conference for ABC (ABC6) took place from November 4 to 6, 2021 and was the first in a purely online format, due to the COVID-19 pandemic. In the present manuscript, a working group of German breast cancer experts comments on the voting results of the ABC6 panelists regarding their applicability for routine clinical practice in Germany. Method: The ABC6 votes mainly include modified or new statements. With regard to all statements not modified for the ABC6 consensus, the German experts refer to the published paper of the ABC5 consensus. The German experts base their comments on the current recommendations of the Breast Committee of the Gynecological Oncology Working Group (Arbeitsgemeinschaft Gynäkologische Onkologie, AGO Mamma). Topics: ABC6 focused on new treatment options and their implications for clinical practice. Optimal therapy sequencing for example was one of the issues. To solve the challenge of a more individualized treatment, precision medicine is fundamental. Oligometastatic disease, brain metastases and adequate supportive and palliative care were also addressed. Of special interest was the treatment of inoperable locally advanced breast cancer, which was discussed as a separate topic. As in previous years, patient advocates from around the world were an integral part of the ABC6 conference and had a major input into the consensus.

Economic and Humanistic Burden of Triple-Negative Breast Cancer: A Systematic Literature Review.

BACKGROUND: Triple-negative breast cancer (TNBC) accounts for 10-20% of all breast cancers (BCs). It is more commonly diagnosed in younger women and often has a less favorable prognosis compared with other BC subtypes. OBJECTIVE: The objective of this study was to provide a literature-based extensive overview of the economic and humanistic burden of TNBC to assist medical decisions for healthcare payers, providers, and patients. METHODS: A systematic literature review was performed using multiple databases, including EMBASE, MEDLINE, Econlit, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, from database inception to 16 May 2021. In addition, a targeted search was performed in the Northern Light Life Sciences Conference Abstracts database from 2016 through June 2021. The bibliographies of included articles were reviewed to identify other potentially relevant publications. Quality assessment of the included studies was conducted. RESULTS: The review identified 19 studies assessing the economic burden and 10 studies assessing the humanistic burden of TNBC. Studies varied widely in study design, settings, patient populations, and time horizons. The estimates of mean per-patient annual direct medical costs ranged from around $20,000 to over $100,000 in stage I-III TNBC and from $100,000 to $300,000 in stage IV TNBC. Healthcare costs and resource utilization increased significantly with disease recurrence, progression, and increased cancer stage or line of therapy. Compared with the costs of systemic anticancer therapy, cancer management costs comprised a larger portion of total direct costs. The estimates of indirect costs due to productivity loss ranged from $207 to $1573 per patient per month (all costs presented above were adjusted to 2021 US dollars). Cancer recurrence led to significantly reduced productivity and greater rates of leaving the workforce. A rapid deterioration of health utility associated with disease progression was observed in TNBC patients. Treatment with pembrolizumab or talazoparib showed significantly greater improvements in health-related quality of life (HRQoL) compared with chemotherapy, as measured by EORTC QLQ-C30, QLQ-BR23, and FACT-B. CONCLUSION: TNBC is associated with a substantial economic burden on healthcare systems and societies and considerably reduced productivity and HRQoL for patients. This study synthesized the published literature on the economic and humanistic burden of TNBC and highlighted the need for continued research due to the rapidly changing landscape of TNBC care.

Update Breast Cancer 2021 Part 3 - Current Developments in the Treatment of Early Breast Cancer: Review and Assessment of Specialised Treatment Scenarios by an International Expert Panel.

The continuous availability of findings from new studies repeatedly results in updated treatment recommendations and guidelines. In the case of breast carcinoma in particular, several studies have been published in the last few years that have transformed how early and advanced breast carcinoma is being treated. However, this by no means means implies that there is agreement among all experts on specific issues. It is precisely the diversity of interpretation of guidelines and study findings that reflects the constantly changing available data and its complexity, as well as the availability of new drugs. In recent years, new substances such as pertuzumab, T-DM1, neratinib and capecitabine have become available to treat patients with early stages of breast carcinoma. Furthermore, the first results on the use of CDK4/6 inhibitors for adjuvant treatment have now been published. Last but not least, the use of multigene tests to avoid the necessity of chemotherapy in certain patients is still under discussion. This review summarises the state of the data and publishes the results of the survey completed by experts at the 2021 St. Gallen Breast Cancer Conference on early-stage breast cancer.

Heregulin (HRG) assessment for clinical trial eligibility testing in a molecular registry (PRAEGNANT) in Germany.

BACKGROUND: Eligibility criteria are a critical part of clinical trials, as they define the patient population under investigation. Besides certain patient characteristics, clinical trials often include biomarker testing for eligibility. However, patient-identification mostly relies on the trial site itself and is often a time-consuming procedure, which could result in missing out on potentially eligible patients. Pre-selection of those patients using a registry could facilitate the process of eligibility testing and increase the number of identified patients. One aim with the PRAEGNANT registry (NCT02338167) is to identify patients for therapies based on clinical and molecular data. Here, we report eligibility testing for the SHERBOC trial using the German PRAEGNANT registry. METHODS: Heregulin (HRG) has been reported to identify patients with better responses to therapy with the anti-HER3 monoclonal antibody seribantumab (MM-121). The SHERBOC trial investigated adding seribantumab (MM-121) to standard therapy in patients with advanced HER2-negative, hormone receptor-positive (HR-positive) breast cancer and HRG overexpression. The PRAEGNANT registry was used for identification and tumor testing, helping to link potential HRG positive patients to the trial. Patients enrolled in PRAEGNANT have invasive and metastatic or locally advanced, inoperable breast cancer. Patients eligible for SHERBOC were identified by using the registry. Study aims were to describe the HRG positivity rate, screening procedures, and patient characteristics associated with inclusion and exclusion criteria. RESULTS: Among 2769 unselected advanced breast cancer patients, 650 were HER2-negative, HR-positive and currently receiving first- or second-line treatment, thus potentially eligible for SHERBOC at the end of current treatment; 125 patients also met further clinical eligibility criteria (e.g. menopausal status, ECOG). In the first/second treatment lines, patients selected for SHERBOC based on further eligibility criteria had a more favorable prognosis than those not selected. HRG status was tested in 38 patients, 14 of whom (36.8%) proved to be HRG-positive. CONCLUSION: Using a real-world breast cancer registry allowed identification of potentially eligible patients for SHERBOC focusing on patients with HER3 overexpressing, HR-positive, HER2-negative metastatic breast cancer. This approach may provide insights into differences between patients eligible or non-eligible for clinical trials. TRIAL REGISTRATION: Clinicaltrials, NCT02338167 , Registered 14 January 2015 - retrospectively registered.

Assessment of the additional clinical potential of X-ray dark-field imaging for breast cancer in a preclinical setup.

BACKGROUND: Mammography can identify calcifications up to 50-100 µm in size as a surrogate parameter for breast cancer or ductal carcinoma in situ (DCIS). Microcalcifications measuring <50 µm are also associated with breast cancer or DCIS and are frequently not detected on mammography, although they can be detected with dark-field imaging. This study examined whether additional breast examination using X-ray dark-field imaging can increase the detection rate of calcifications. Advances in knowledge: (1) evaluation of additional modality of breast imaging; (2) specific evaluation of breast calcifications.Implications for patient care: the addition of X-ray dark-field imaging to conventional mammography could detect additional calcifications. METHODS: Talbot-Lau X-ray phase-contrast imaging and X-ray dark-field imaging were used to acquire images of breast specimens. The radiation dosage with the technique is comparable with conventional mammography. Three X-ray gratings with periods of 5-10 µm between the X-ray tube and the flat-panel detector provide three different images in a single sequence: the conventional attenuation image, differential phase image, and dark-field image. The images were read by radiologists. Radiological findings were marked and examined pathologically. The results were described in a descriptive manner. RESULTS: A total of 81 breast specimens were investigated with the two methods; 199 significant structures were processed pathologically, consisting of 123 benign and 76 malignant lesions (DCIS or invasive breast cancer). X-ray dark-field imaging identified 15 additional histologically confirmed carcinoma lesions that were visible but not declared suspicious on digital mammography alone. Another four malignant lesions that were not visible on mammography were exclusively detected with X-ray dark-field imaging. CONCLUSIONS: Adding X-ray dark-field imaging to digital mammography increases the detection rate for breast cancer and DCIS associated lesions with micrometer-sized calcifications.The use of X-ray dark-field imaging may be able to provide more accurate and detailed radiological classification of suspicious breast lesions.Adding X-ray dark-field imaging to mammography may be able to increase the detection rate and improve preoperative planning in deciding between mastectomy or breast-conserving therapy, particularly in patients with invasive lobular breast cancer.

International Consensus Conference for Advanced Breast Cancer, Lisbon 2019: ABC5 Consensus - Assessment by a German Group of Experts.

The 5th International Consensus Conference for Advanced Breast Cancer (ABC5) took place on November 14-16, 2019, in Lisbon, Portugal. Its aim is to standardize the treatment of advanced breast cancer based on the available evidence and to ensure that all breast cancer patients worldwide receive adequate treatment and access to new therapies. This year, the conference focused on developments and study results in the treatment of patients with hormone receptor-positive/HER2-negative breast cancer as well as precision medicine. As in previous years, patient advocates from around the world were integrated into the ABC conference and had seats on the ABC consensus panel. In the present paper, a working group of German breast cancer experts comments on the results of the on-site ABC5 consensus votes by ABC panelists regarding their applicability for routine treatment in Germany. These comments take the recommendations of the Breast Committee of the Gynecological Oncology Working Group (Arbeitsgemeinschaft Gynäkologische Onkologie; AGO) into account. The report and assessment presented here pertain to the preliminary results of the ABC5 consensus. The final version of the statements will be published in Annals of Oncology and The Breast.

Update Breast Cancer 2019 Part 3 - Current Developments in Early Breast Cancer: Review and Critical Assessment by an International Expert Panel.

The treatment of breast cancer patients in a curative situation is special in many ways. The local therapy with surgery and radiation therapy is a central aspect of the treatment. The complete elimination of tumour cells at the site of the primary disease must be ensured while simultaneously striving to keep the long-term effects as minor as possible. There is still focus on the continued reduction of the invasiveness of local therapy. With regard to systemic therapy, chemotherapies with taxanes, anthracyclines and, in some cases, platinum-based chemotherapies have become established in the past couple of decades. The context for use is being continually further defined. Likewise, there are questions in the case of antihormonal therapy which also still need to be further defined following the introduction of aromatase inhibitors, such as the length of therapy or ovarian suppression in premenopausal patients. Finally, personalisation of the treatment of early breast cancer patients is also being increasingly used. Prognostic tests could potentially support therapeutic decisions. It must also be considered how the possible use of new therapies, such as checkpoint inhibitors and CDK4/6 inhibitors could look in practice once study results in this regard are available. This overview addresses the backgrounds on the current votes taken by the international St. Gallen panel of experts in Vienna in 2019 for current questions in the treatment of breast cancer patients in a curative situation.

An Electronic Patient-Reported Outcome Tool for the FACT-B (Functional Assessment of Cancer Therapy-Breast) Questionnaire for Measuring the Health-Related Quality of Life in Patients With Breast Cancer: Reliability Study.

BACKGROUND: The most frequent malignant disease in women is breast cancer. In the metastatic setting, quality of life is the primary therapeutic goal, and systematic treatment has only a limited effect on survival rates; therefore, the concept of the health-related quality of life (HRQoL) and measurement of patient-reported outcomes (PROs) are gaining more and more importance in the therapy setting of diseases such as breast cancer. One of the frequently used questionnaires for measuring the HRQoL in patients with breast cancer is the Functional Assessment of Cancer Therapy-Breast (FACT-B). Currently, paper-based surveys still predominate, as only a few reliable and validated electronic-based questionnaires are available. ePRO tools for the FACT-B questionnaire with proven reliability are missing so far. OBJECTIVE: The aim of this study was to analyze the reliability of tablet-based measurement of FACT-B in the German language in adjuvant (curative) and metastatic breast cancer patients. METHODS: Paper- and tablet-based questionnaires were completed by a total of 106 female adjuvant and metastatic breast cancer patients. All patients were required to complete the electronically based (ePRO) and paper-based version of the FACT-B. A frequency analysis was performed to determine descriptive sociodemographic characteristics. Both dimensions of reliability (parallel forms reliability using Wilcoxon test and test of internal consistency using Spearman ρ) and agreement rates for single items, Kendall tau for each subscale, and total score were analyzed. RESULTS: High correlations were shown for both dimensions of reliability (parallel forms reliability and internal consistency) in the patients' response behavior between paper-based and electronically based questionnaires. Regarding the reliability test of parallel forms, no significant differences were found in 35 of 37 single items, while significant correlations in the test for consistency were found in all 37 single items, in all 5 sum individual item subscale scores, as well as in total FACT-B score. CONCLUSIONS: The ePRO version of the FACT-B questionnaire is reliable for patients with breast cancer in both adjuvant and metastatic settings, showing highly significant correlations with the paper-based version in almost all questions all subscales and the total score.

Filtration based assessment of CTCs and CellSearch® based assessment are both powerful predictors of prognosis for metastatic breast cancer patients.

BACKGROUND: The assessment of circulating tumor cells (CTCs) has been shown to enable monitoring of treatment response and early detection of metastatic breast cancer (MBC) recurrence. The aim of this study was to compare a well-established CTC detection method based on immunomagnetic isolation with a new, filtration-based platform. METHODS: In this prospective study, two 7.5 ml blood draws were obtained from 60 MBC patients and CTC enumeration was assessed using both the CellSearch® and the newly developed filtration-based platform. We analyzed the correlation of CTC-positivity between both methods and their ability to predict prognosis. Overall survival (OS) was calculated and Kaplan-Meier curves were estimated with thresholds of ≥1 and ≥5 detected CTCs. RESULTS: The CTC positivity rate of the CellSearch® system was 56.7% and of the filtration-based platform 66.7%. There was a high correlation of CTC enumeration obtained with both methods. The OS for patients without detected CTCs, regardless of the method used, was significantly higher compared to patients with one or more CTCs (p < 0.001). The median OS of patients with no CTCs vs. ≥ 1 CTC assessed by CellSearch® was 1.83 years (95% CI: 1.63-2.02) vs. 0.74 years (95% CI: 0.51-1.52). If CTCs were detected by the filtration-based method the median OS times were 1.88 years (95% CI: 1.74-2.03) vs. 0.59 years (95% CI: 0.38-0.80). CONCLUSIONS: The newly established EpCAM independently filtration-based system is a suitable method to determine CTC counts for MBC patients. Our study confirms CTCs as being strong predictors of prognosis in our population of MBC patients.

Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer.

Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6607 EC cases and 37 925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P=1.86×10(-5)), which was stronger for cancers of endometrioid subtype (P=3.76×10(-6)). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types.

Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with prognosis of estrogen receptor-negative breast cancer after chemotherapy.

INTRODUCTION: Tumor lymphocyte infiltration is associated with clinical response to chemotherapy in estrogen receptor (ER) negative breast cancer. To identify variants in immunosuppressive pathway genes associated with prognosis after adjuvant chemotherapy for ER-negative patients, we studied stage I-III invasive breast cancer patients of European ancestry, including 9,334 ER-positive (3,151 treated with chemotherapy) and 2,334 ER-negative patients (1,499 treated with chemotherapy). METHODS: We pooled data from sixteen studies from the Breast Cancer Association Consortium (BCAC), and employed two independent studies for replications. Overall 3,610 single nucleotide polymorphisms (SNPs) in 133 genes were genotyped as part of the Collaborative Oncological Gene-environment Study, in which phenotype and clinical data were collected and harmonized. Multivariable Cox proportional hazard regression was used to assess genetic associations with overall survival (OS) and breast cancer-specific survival (BCSS). Heterogeneity according to chemotherapy or ER status was evaluated with the log-likelihood ratio test. RESULTS: Three independent SNPs in TGFBR2 and IL12B were associated with OS (P <10⁻³) solely in ER-negative patients after chemotherapy (267 events). Poorer OS associated with TGFBR2 rs1367610 (G > C) (per allele hazard ratio (HR) 1.54 (95% confidence interval (CI) 1.22 to 1.95), P = 3.08 × 10⁻4) was not found in ER-negative patients without chemotherapy or ER-positive patients with chemotherapy (P for interaction <10-3). Two SNPs in IL12B (r² = 0.20) showed different associations with ER-negative disease after chemotherapy: rs2546892 (G > A) with poorer OS (HR 1.50 (95% CI 1.21 to 1.86), P = 1.81 × 10⁻4), and rs2853694 (A > C) with improved OS (HR 0.73 (95% CI 0.61 to 0.87), P = 3.67 × 10⁻4). Similar associations were observed with BCSS. Association with TGFBR2 rs1367610 but not IL12B variants replicated using BCAC Asian samples and the independent Prospective Study of Outcomes in Sporadic versus Hereditary Breast Cancer Study and yielded a combined HR of 1.57 ((95% CI 1.28 to 1.94), P = 2.05 × 10⁻5) without study heterogeneity. CONCLUSIONS: TGFBR2 variants may have prognostic and predictive value in ER-negative breast cancer patients treated with adjuvant chemotherapy. Our findings provide further insights into the development of immunotherapeutic targets for ER-negative breast cancer.

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.

Financial viability of perinatal centers in the longer term, taking legislative requirements into account. An examination of the cost-revenue structure of a Level I perinatal center.

BACKGROUND: Debate is currently taking place over minimum case numbers for the care of premature infants and neonates in Germany. As a result of the Federal Joint Committee (Gemeinsamer Bundesauschuss, G-BA) guidelines for the quality of structures, processes, and results, requiring high levels of staffing resources, Level I perinatal centers are increasingly becoming the focus for health-economics questions, specifically, debating whether Level I structures are financially viable. MATERIALS AND METHODS: Using a multistep contribution margin analysis, the operating results for the Obstetrics Section at the University Perinatal Center of Franconia (Universitäts-Perinatalzentrum Franken) were calculated for the year 2009. Costs arising per diagnosis-related group (DRG) (separated into variable costs and fixed costs) and the corresponding revenue generated were compared for 4,194 in-patients and neonates, as well as for 3,126 patients in the outpatient ultrasound and pregnancy clinics. RESULTS: With a positive operating result of € 374,874.81, a Level I perinatal center on the whole initially appears to be financially viable, from the obstetrics point of view (excluding neonatology), with a high bed occupancy rate and a profitable case mix. By contrast, the costs of prenatal diagnostics, with a negative contribution margin II of € 50,313, cannot be covered. A total of 79.4% of DRG case numbers were distributed to five DRGs, all of which were associated with pregnancies and neonates with the lowest risk profiles. CONCLUSION: A Level I perinatal center is currently capable of covering its costs. However, the cost-revenue ratio is fragile due to the high requirements for staffing resources and numerous economic, social, and regional influencing factors.

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.

Assessment of hepatocyte growth factor in ovarian cancer mortality.

BACKGROUND: Invasive ovarian cancer is a significant cause of gynecologic cancer mortality. METHODS: We examined whether this mortality was associated with inherited variation in approximately 170 candidate genes/regions [993 single-nucleotide polymorphisms (SNPs)] in a multistage analysis based initially on 312 Mayo Clinic cases (172 deaths). Additional analyses used The Cancer Genome Atlas (TCGA; 127 cases, 62 deaths). For the most compelling gene, we immunostained Mayo Clinic tissue microarrays (TMA, 326 cases) and conducted consortium-based SNP replication analysis (2,560 cases, 1,046 deaths). RESULTS: The strongest initial mortality association was in HGF (hepatocyte growth factor) at rs1800793 (HR = 1.7, 95% CI = 1.3-2.2, P = 2.0 × 10(-5)) and with overall variation in HGF (gene-level test, P = 3.7 × 10(-4)). Analysis of TCGA data revealed consistent associations [e.g., rs5745709 (r(2) = 0.96 with rs1800793): TCGA HR = 2.4, CI = 1.4-4.1, P = 2.2 × 10(-3); Mayo Clinic + TCGA HR = 1.6, CI = 1.3-1.9, P = 7.0 × 10(-5)] and suggested genotype correlation with reduced HGF mRNA levels (P = 0.01). In Mayo Clinic TMAs, protein levels of HGF, its receptor MET (C-MET), and phospho-MET were not associated with genotype and did not serve as an intermediate phenotype; however, phospho-MET was associated with reduced mortality (P = 0.01) likely due to higher expression in early-stage disease. In eight additional ovarian cancer case series, HGF rs5745709 was not associated with mortality (HR = 1.0, CI = 0.9-1.1, P = 0.87). CONCLUSIONS: We conclude that although HGF signaling is critical to migration, invasion, and apoptosis, it is unlikely that HGF genetic variation plays a major role in ovarian cancer mortality. Furthermore, any minor role is not related to genetically-determined expression. IMPACT: Our study shows the utility of multiple data types and multiple data sets in observational studies.

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.

Cost-Benefit Analysis of Endocrine Therapy in the Adjuvant Setting for Postmenopausal Patients with Hormone Receptor-Positive Breast Cancer, Based on Survival Data and Future Prices for Generic Drugs in the Context of the German Health Care System.

BACKGROUND: Cost-effectiveness analyses have focused on aromatase inhibitors (AIs), but the results are inconsistent and disease-free survival has often been extrapolated to overall survival. The present study calculates the cost-effectiveness of 5 years of letrozole versus tamoxifen versus anastrozole in the context of the German health care system, using survival data from the Breast International Group (BIG) 1-98 study and the Arimidex, Tamoxifen, Alone or in Combination (ATAC) study and generic prices. MATERIALS AND METHODS: A hybrid model was developed that incorporates recurrence rates, overall survival, treatment costs and treatment-associated adverse events and the resulting costs. The basic assumption was that generic anastrozole would lead to a price reduction to 75% of the original price. Further analyses were carried out with 50% and 25% of the original prices for anastrozole and letrozole. RESULTS: The cost-benefit model showed a gain of 0.3124 or 0.0659 quality-adjusted life years (QALYs) for letrozole or anastrozole. Incremental costs of € 29,375.15/QALY for letrozole (100% of original price) were calculated and € 94,648.03/QALY for anastrozole (75% of original price). Marked increases in cost-effectiveness are observed with further decreases in price (anastrozole: 50% price € 54,715.17/QALY, 25% price € 14,779.57/QALY; letrozole 75% price € 20,988.59/QALY, 50% price € 12,602.03/QALY, 25% price € 4,215.46/QALY). CONCLUSION: The present model including the inverse probability of censoring weighted analysis (IPCW) for letrozole and generic prices for both AIs shows that letrozole is cost effective.