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Background The phase III MONALEESA-3 trial included first- (1L) and second-line (2L) patients and demonstrated a significant overall survival (OS) benefit for ribociclib + fulvestrant in patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2−) advanced breast cancer (ABC) in the final protocol-specified and exploratory (longer follow-up) OS analyses. At the time of these analyses, the full OS benefit of 1L ribociclib was not completely characterized because the median OS (mOS) was not reached. As CDK4/6 inhibitor (CDK4/6i) + endocrine therapy (ET) is now a preferred option for 1L HR+/HER2− ABC, we report an exploratory analysis (median follow-up, 70.8 months; 14.5 months longer than the prior analysis) to fully elucidate the OS benefit in the MONALEESA-3 1L population. Methods Postmenopausal patients with HR+/HER2− ABC were randomized 2:1 to 1L/2L fulvestrant + ribociclib or placebo. OS in 1L patients (de novo disease or relapse > 12 months from completion of [neo]adjuvant ET) was assessed by Cox proportional hazards model and Kaplan–Meier methods. Progression-free survival 2 (PFS2) and chemotherapy-free survival (CFS) were analyzed. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615). Results At data cutoff (January 12, 2022; median follow-up time, 70.8 months), mOS was 67.6 versus 51.8 months with 1L ribociclib versus placebo (hazard ratio (HR) 0.67; 95% CI 0.50–0.90); 16.5% and 8.6% of ribociclib and placebo patients, respectively, were still receiving treatment. PFS2 (HR 0.64) and CFS (HR 0.62) favored ribociclib versus placebo. Among those who discontinued treatment, 16.7% and 35.0% on ribociclib or placebo, respectively, received a subsequent CDK4/6i. No new safety signals were observed. Conclusions This analysis of MONALEESA-3 reports the longest mOS thus far (67.6 months) for 1L patients in a phase III ABC trial. These results in a 1L population show that the OS benefit of ribociclib was maintained through extended follow-up, further supporting its use in HR+/HER2− ABC.

Background: Predict ( www.predict.nhs.uk ) is an online, breast cancer prognostication and treatment benefit tool. The aim of this study was to incorporate the prognostic effect of HER2 status in a new version (Predict+), and to compare its performance with the original Predict and Adjuvant!. Methods: The prognostic effect of HER2 status was based on an analysis of data from 10 179 breast cancer patients from 14 studies in the Breast Cancer Association Consortium. The hazard ratio estimates were incorporated into Predict. The validation study was based on 1653 patients with early-stage invasive breast cancer identified from the British Columbia Breast Cancer Outcomes Unit. Predicted overall survival (OS) and breast cancer-specific survival (BCSS) for Predict+, Predict and Adjuvant! were compared with observed outcomes. Results: All three models performed well for both OS and BCSS. Both Predict models provided better BCSS estimates than Adjuvant!. In the subset of patients with HER2-positive tumours, Predict+ performed substantially better than the other two models for both OS and BCSS. Conclusion: Predict+ is the first clinical breast cancer prognostication tool that includes tumour HER2 status. Use of the model might lead to more accurate absolute treatment benefit predictions for individual patients.

Purpose This Phase I, multicenter, randomized study (ClinicalTrials.gov NCT01220128) evaluated the safety and immunogenicity of recombinant Wilms’ tumor 1 (WT1) protein combined with the immunostimulant AS15 (WT1-immunotherapeutic) as neoadjuvant therapy administered concurrently with standard treatments in WT1-positive breast cancer patients. Methods Patients were treated in 4 cohorts according to neoadjuvant treatment (A: post-menopausal, hormone receptor [HR]-positive patients receiving aromatase inhibitors; B: patients receiving chemotherapy; C: HER2-overexpressing patients on trastuzumab–chemotherapy combination; D: HR-positive/HER2-negative patients on chemotherapy). Patients (cohorts A–C) were randomized (2:1) to receive 6 or 8 doses of WT1-immunotherapeutic or placebo together with standard neoadjuvant treatment in a double-blind manner; cohort D patients received WT1-immunotherapeutic in an open manner. Safety was assessed throughout the study. WT1-specific antibodies were assessed pre- and post-vaccination. Results Sixty-two patients were randomized; 60 received ≥ one dose of WT1-immunotherapeutic. Two severe toxicities were reported: diarrhea (cohort C; also reported as a grade 3 serious adverse event) and decreased left ventricular ejection fraction (cohort B; also reported as a grade 2 adverse event). Post-dose 4 of WT1-immunotherapeutic, 10/10 patients from cohort A, 0/8 patients from cohort B, 6/11 patients from cohort C, and 2/3 patients from cohort D were humoral responders. The sponsor elected to close the trial prematurely. Conclusions Concurrent administration of WT1-immunotherapeutic and standard neoadjuvant therapy was well tolerated and induced WT1-specific antibodies in patients receiving neoadjuvant aromatase inhibitors. In patients on neoadjuvant chemotherapy or trastuzumab–chemotherapy combination, the humoral response was impaired or blunted, likely due to either co-administration of corticosteroids and/or the chemotherapies themselves.

Background Breast cancer screening programs seem to be an insufficient tool for women at high genetic risk for breast cancer. These women are not adequately monitored yet. Genetic testing may improve clearly the quality of breast cancer prevention programs. At present, blood samples are favored for obtaining high-quality DNA; however, DNA can also be obtained by collecting saliva. The aim of this study was, on the one hand, to determine whether saliva sampling is a practicable means to obtain sufficient quantity and quality of DNA and, on the other hand, whether it is accepted by patients throughout mammographic diagnostics. Methods 67 consecutive women with diagnostic need for mammography with or without a family history for breast cancer were asked for their basic willingness to undergo a genetic testing by saliva sample in addition to standard diagnostics. Saliva samples were analyzed in terms of DNA quantity and quality. Results 64 (95.6%) women agreed to provide a saliva sample; 3 of them denied participation. And even 63 out of 64 (98.4%) were interested in their specific results. 45 out of 64 samples contained a DNA concentration above 50 ng/µl, 12 samples were between 25 and 50 ng/µl and only 7 of them were under 25 ng/µl with the standard extraction procedure. Conclusion A high number of patients seem to accept salvia samples as a risk assessment tool in breast diagnostics and are interested in their specific risk situation. At the same time, it could be demonstrated that it is an effective way to provide high-quality DNA for breast cancer gene analysis. However, it remains to be shown whether it would be possible to integrate it with the same acceptance in a nationwide breast cancer screening program.

Background: We were able to demonstrate a predictive value of serum HER2 (sHER2) in patients receiving trastuzumab in the neoadjuvant GeparQuattro trial. However, the role of sHER2 in patients receiving neoadjuvant therapy (NT) with lapatinib is still unclear. Methods: The neoadjuvant GeparQuinto trial compared trastuzumab vs lapatinib in addition to chemotherapy in HER2-positive primary breast cancer patients. The sHER2 levels were measured by enzyme-linked immunosorbant assay in 210 patients, of whom 109 (52%) patients received trastuzumab and 101 (48%) lapatinib at three different time points. Results: Twenty-two percent of patients had elevated baseline sHER2 levels (>15 ng ml −1 ). A decrease of sHER2 levels (>20%) in the trastuzumab and lapatinib-treated group during NT was seen in 44% and 24% of the patients, an increase of sHER2 levels (>20%) was seen in 6% and 41% of patients, respectively. Higher pre-chemotherapy sHER2 levels were associated with higher pathological complete remission (pCR) rates in the entire study cohort (OR 1.8, 95% CI 1.02–3.2, P =0.043). A decline of sHER2 levels (>20%) during NT was a predictor for pCR in the lapatinib-treated patient group (OR: 11.7, 95% CI 1.3–110, P =0.031). Conclusion: Results of this study demonstrate that sHER2 levels change differently during NT depending on the anti-HER2 treatment strategy. Elevated baseline sHER2 levels (>15 ng ml −1 ) and a decrease of sHER2 levels (>20%) early after therapy initiation are both relevant criteria to predict response to lapatinib-based treatment.

The aim of this study was to correlate chemotherapy-induced nausea and vomiting (CINV) with commonly occurring single nucleotide polymorphisms (SNP) in the 5-hydroxytryptamine receptor 3 genes ( HTR3 ). Women with breast cancer without previous chemotherapy were eligible for this prospective study. All patients received epirubicin, with or without cyclophosphamide, and preventive medication with ondansetron and dexamethasone. The patients documented every vomiting event on an hourly basis. Real-time polymerase chain reaction (PCR) analysis was performed for the following nonsynonymous SNPs: p.Y129S ( HTR3B), p.K163N ( HTR3C ) and p.A405G (HTR3C). The overall proportion of patients (total n  = 110) who reported vomiting in the first 24 h after chemotherapy was 31.8%. The variant genotype of K163N ( HTR3C ) was associated with vomiting, which occurred in 50.0% ( P  = 0.009). Polymorphisms in the HTR3C gene could serve as a predictive factor for CINV in patients undergoing moderately emetogenic chemotherapy.

Mammography (MG), breast (BU) and axillary ultrasound (AU), and clinical examination (CE) are commonly used for clinical staging. These different methods were compared in order to assess the accuracy of clinical tumor staging (cT). About 503 breast cancer (BC) patients were prospectively measured by MG, ultrasound and clinical examination. Pearson's correlation to pathological tumor size (pT) was tested and the deviation of MG, BU and CE to pT was analyzed in subgroups defined by pT, grading (G), estrogen receptor (ER), progesteron receptor (PR), proliferation (MIB-1) and HER2/neu. Association of AU to pN was examined by chi(2)-test. Receiver operating characteristics (ROC) were used to test the prediction of a pT > 2 cm. Mammography correlated best with pT (r = 0.752). Mammography (mean (MG) = 2.17 cm) overestimated tumors in size (mean (pT) = 2.04 cm) rather than ultrasound (mean (BU) = 1.86 cm) and clinical examination (mean (cT) = 1.70 cm). pT of invasive ductal BC could be estimated significantly better than pT of invasive lobular BC. Smaller tumors were better to assess than larger ones. Tumors with a grading G1 were easier to estimate than tumors with G2/3. Best predictor of a pT > 2 cm was the mammography with an area under the curve of 0.876. The combination of all three modalities by linear regression performed even better with an AUC of 0.906. The dimension of invasive ductal carcinomas, small and low grading tumors is significantly better to estimate. Concerning treatment decisions, we propose a combination of all three modalities, as the best predictive value was seen for the complementary use of mammography, ultrasound and clinical examination.

Background: Patients with metastatic breast cancer (MBC) are increasingly exposed to anthracyclines and taxanes either during treatment of primary breast cancer or during initial therapy of metastatic disease. The combination of gemcitabine and carboplatin was therefore investigated as an anthracycline- and taxane-free treatment option. Patients and Methods: MBC patients previously treated with chemotherapy were enrolled in a multicenter phase II study. Treatment consisted of gemcitabine (1,000 mg/m 2 i.v. on days 1 and 8) and carboplatin (AUC 4 i.v. on day 1) applied every 3 weeks. Results: Thirty-nine patients were recruited, and a total of 207 treatment cycles were applied with a median of 5 cycles per patient. One complete response and 11 partial responses were observed for an overall response rate of 31% (95% CI: 17–48%). Twelve patients (31%) had stable disease. Median time to progression was 5.3 months (95% CI: 2.6–6.7 months) and median overall survival from start of treatment was 13.2 months (95% CI: 8.7–16.7 months). Grade 3/4 hematological toxicity included leukopenia (59%/5%), thrombocytopenia (26%/23%) and anemia (10%/0%). Nonhematological toxicity was rarely severe. Conclusion: Combination chemotherapy with gemcitabine and carboplatin is an effective and generally well-tolerated treatment option for intensively pretreated patients with MBC. Due to a considerable incidence of severe thrombocytopenia it would be reasonable to consider starting gemcitabine at the lower dose level of 800 mg/m 2 .

In gynecological oncology, there is growing interest in the use of complementary and alternative medicine (CAM) methods. The lack of data regarding side effects, the lack of any survival advantages, and the costs of these methods appear to have no influence on patients' decisions on whether to use CAM. Our interest was to evaluate the association between CAM use and the patients' quality of life/life satisfaction (QoL/LS). One thousand thirty women with breast cancer of gynecologic malignancies were asked to participate in this study, which included a questionnaire and a personal interview on CAM. User status was compared with the patient's own description of her QoL/LS and with the cancer type. CAM was used by 48.7% of all women (n = 502). Breast cancer patients stated that they used CAM in 50.1% and women with gynecological cancer in 44.0%. The use of mistletoe was widespread (77.3%) and was more often seen in breast cancer patients than in gynecological cancer patients (74.4% vs 67.0%). CAM users less frequently stated an overall deterioration of their health status (35.1%) compared to nonusers (50.1%). CAM use resulted in a stated improvement in family conditions (6%) in comparison with the nonusers (2%). With regard to patients' perception of health status, CAM use is associated with a better coping with their disease. Most other categories of LS are not affected by CAM use. Patient-oriented information comparing standard therapies with CAM methods should be made widely available, and patients' expectations of CAM use should be discussed between the physician and the patient.

Purpose It is considered that establishing accredited specialized centers can serve as a marketing tool. This study investigated whether accredited specialized centers influence patients’ choice of hospital. Methods A total of 2,389 patients was included in a questionnaire survey: 468 at the Department of Gynecology, 745 at the certified University Breast Center of Franconia, 1,000 at the University Perinatal Center of Franconia and 176 for whom classification details were lacking. Results Among the oncological patients, physicians in private practice played an important role in the choice of hospital (58.4 vs. 25.7%; P  < 0.001; OR 4.058). Among obstetric patients, the primary factors were recommendations from family [odds ratio (OR) 0.495], friends (OR 0.218), and previous personal experience of the hospital (OR 0.695). For oncological patients, treatment quality (OR 2.693), availability of a center (OR 1.785), and certification (OR 3.939) were comparatively more important. For obstetric patients, friendliness (OR 0.409) and attractive accommodation (OR 0.153) were more important. Conclusions Physicians are the most important source of recommendations for oncological patients. From the marketing point of view, intensive involvement of local private-practice physicians is necessary. The availability of certified perinatal centers does not currently play any part in patients’ choice of hospital.