Preexisting musculoskeletal burden and its development under letrozole treatment in early breast cancer patients.

One of the most common adverse events (AEs) occurring during treatment with aromatase inhibitors (AIs) is musculoskeletal pain. The aim of our study was to analyze the influence of preexisting muscle/limb pain and joint pain on the development of AI-induced musculoskeletal AEs. Women eligible for upfront adjuvant endocrine therapy with letrozole were included in the PreFace study, a multicenter phase IV trial. During the first treatment year, they were asked to record musculoskeletal AEs monthly by answering questions regarding pain symptoms and rating the pain intensity on a numeric rating scale from 0 (no pain) to 10 (very strong pain). Pain values were compared using nonparametric statistical tests. Overall, 1,416 patients were evaluable. The average pain value over all time points in women with preexisting muscle/limb pain was 4.3 (median 4.3); in those without preexisting pain, it was 2.0 (median 1.7). In patients without preexisting muscle/limb pain, pain levels increased relatively strongly within the first 6 months (mean increase +0.9, p < 0.00001) in comparison with those with preexisting pain (mean increase +0.3, p < 0.001), resulting in a statistically significant difference (p < 0.00001) between the two groups. The development of joint pain was similar in the two groups. Women without preexisting muscle/limb pain or joint pain have the greatest increase in pain after the start of adjuvant AI therapy. Women with preexisting pain have significantly higher pain values. The main increase in pain values takes place during the first 6 months of treatment.

Association between breast cancer risk factors and molecular type in postmenopausal patients with hormone receptor-positive early breast cancer.

PURPOSE: Evidence shows that genetic and non-genetic risk factors for breast cancer (BC) differ relative to the molecular subtype. This analysis aimed to investigate associations between epidemiological risk factors and immunohistochemical subtypes in a cohort of postmenopausal, hormone receptor-positive BC patients. METHODS: The prospective, single-arm, multicenter phase IV PreFace study (Evaluation of Predictive Factors Regarding the Effectivity of Aromatase Inhibitor Therapy) included 3529 postmenopausal patients with hormone receptor-positive early BC. Data on their epidemiological risk factors were obtained from patients' diaries and their medical histories. Data on estrogen receptor, progesterone receptor, and HER2 receptor status were obtained from pathology reports. Patients with incomplete information were excluded. Data were analyzed using conditional inference regression analysis, analysis of variance, and the chi-squared test. RESULTS: In a cohort of 3392 patients, the strongest association with the molecular subtypes of BC was found for hormone replacement therapy (HRT) before diagnosis of early BC. The analysis showed that patients who took HRT at diagnosis had luminal A-like BC more often (83.7%) than those who had never taken HRT or had stopped taking it (75.5%). Luminal B-like BC and HER2-positive BC were diagnosed more often in women who had never taken HRT or had stopped taking it (13.3% and 11.2%, respectively) than in women who were taking HRT at diagnosis of BC (8.3% and 8.0%, respectively). CONCLUSIONS: This analysis shows an association between HRT and the distribution of molecular subtypes of BC. However, no associations between other factors (e.g., age at diagnosis, body mass index, smoking status, age at menopause, number of deliveries, age at first delivery, breastfeeding history, or family history) were noted.

Benchmarking of a checklist for the identification of familial risk for breast and ovarian cancers in a prospective cohort.

The detection of deleterious germline mutations in BRCA1 and BRCA2 considerably influences the clinical management of healthy and diseased carriers. Therefore, the identification of persons at risk who could uptake genetic counseling and testing is pivotal. We developed a checklist with validated criteria to improve the identification, and prospectively evaluate the incidence, of familial cancer history in 5091 breast cancer patients. The rate of 30.4% of patients at high genetic risk underpins the demand for care in risk identification and counseling. The easy-to-use instrument promotes the implementation and dissemination of risk counseling by physicians.

Emergency cerclage following a standardized protocol offers an effective and safe therapeutic option for women with high risk for prematurity - a retrospective monocentric cohort study on 130 pregnancies and 155 neonates.

OBJECTIVE: To present emergency cerclage (EC) as a safe and effective therapeutic option for prevention of prematurity in women with advanced cervical dilation in second-trimester pregnancy. It is focused on seemingly futile situations like cervical dilation >5 cm, bulging membranes and multifetal pregnancies. The outcomes of interest are the prolongation of pregnancy, gestational age at delivery and neonatal morbidity and mortality related to distinct risk factors. STUDY DESIGN: Retrospective monocentric cohort study involving 130 pregnancies (105 single and 25 twin pregnancies) and 155 neonates by using a standardized protocol. Women between 18 and 28 gestational weeks with cervical shortening of <10 mm + cervical dilation >2 cm and/or bulging membranes were included. Analyses of maternal and neonatal parameters were done by chart review. RESULTS: The medium gestational age at delivery was 35 5/7 week with a medium interval from cerclage placement to delivery of 83 days. Overall, 46.5% (72/155) neonates were born beyond 37 weeks, extreme prematurity of less than 28 gestational weeks was observed in 14.8% (23/155), no miscarriage before 22 weeks was documented. The neonatal mortality was 1.9% (3/155). Neonatal deaths and morbidity was related to severe prematurity exclusively. The association of amnion-infection syndromes and failing therapy was significantly with respect to bulging membranes and advanced cervical dilation >5 cm. CONCLUSIONS: Even in futile cases EC can be an option to save the pregnancy and prevent severe prematurity. However, a standardized protocol is imminent for successful therapy and every indication has to be a case by case decision.

Immunostaining of ∆Np63 (using the p40 antibody) is equal to that of p63 and CK5/6 in high-grade ductal carcinoma in situ of the breast.

As a result of breast cancer screening programs, high-grade ductal carcinoma in situ (DCIS) of the breast is diagnosed more often. Frequently, a DCIS diagnosis can only be made using immunohistochemical stains to visualize the myoepithelial layer in order to assess microinvasion. Standard markers for myoepithelial cells are CK5/6 and p63. An isoform of the latter, ∆Np63, is recognized by a recently developed antibody, p40. Here, we compare the standard myoepithelial markers CK5/6 and p63 with p40. We immunostained full sections of tissue samples of 35 high-grade DCIS and compared the staining pattern of CK5/6, p63 and p40 in tumour tissue and in normal glands. Staining patterns of myoepithelial cells for p63 and p40 were similar in terms of the percentage of stained nuclei. In all cases, p63 was strongly expressed, while this was the case for p40 in 31 (89%) and moderately in 4 (11%) cases. All but one case (97%) showed a similar percentage of stained myoepithelial cells in comparing CK5/6 and p40 staining. CK5/6 expression was heterogeneous and strong/moderate/weak in 60, 34 and 6 % respectively. Compared to surrounding normal glands, staining of myoepithelial cells for all three markers in the neoplastic lesion was attenuated. In high-grade DCIS, p40 staining is highly specific for myoepithelial cells. Its staining pattern and intensity are equal to p63, which opens up its use for daily practice. Staining with p40 is less heterogeneous than that for CK5/6.