Study question Can the plasticizer diisopentyl phthalate (DiPeP) disrupt testosterone biosynthesis and alter fetal rat testis histology similarly to other common toxic phthalates? Summary answer DiPeP can dose-dependently suppress mRNA levels of steroidogenic genes and induce multinucleated gonocytes in the fetal rat testis, resembling the effects of other toxic phthalates. What is known already DiPeP is an uncommon phthalate, whose metabolites have been ubiquitously detected in urinary samples from Brazilian pregnant women and children. These results, which contrast with the undetected levels of DiPeP metabolites in other human biomonitoring studies worldwide, led us to investigate DiPeP reproductive and developmental toxicity in rats. Our preliminary data indicate that DiPeP is a potent antiandrogenic phthalate, but no studies have been conducted to assess the impact of DiPeP exposures on the incidence of multinucleated gonocytes in the rat fetal testis, a common feature of the rat phthalate syndrome. Study design, size, duration Pregnant Wistar rats (n = 7-9 dams/group) were treated orally (gavage) with DiPeP 0 (control), 11, 33, and 100 mg/kg/day between gestation days 14-20. Dose levels were based on prior rat phthalate toxicity studies and canola oil was used as a vehicle. On gestation day 20, dams were euthanized and up to three male fetuses from each litter were removed for the collection of fetal testes and the assessment of the study endpoints. Participants/materials, setting, methods Fetal rat testes were used for enzyme immunoassay quantification of testosterone production following ex vivo incubation of testes in culture media, analysis of mRNA levels of steroidogenic genes and insulin-like factor 3 (Insl3) by quantitative polymerase chain reaction (qPCR), and histological assessment of multinucleated gonocytes by optical microscopy. Main results and the role of chance No signs of systemic toxicity were observed as indicated by the lack of alterations in maternal body weights and the unchanged number, viability, and weight of fetuses. There were no significant changes in the ex vivo testosterone production at any DiPeP dose. On the other hand, DiPeP induced significant reductions in the mRNA expression of key steroidogenic genes, including suppressed mRNA levels of the steroidogenic acute regulatory protein (Star) and cytochrome P450 family 11 subfamily A member 1 (Cyp11a1) at 100 mg/kg/day and of cytochrome P450 family 17 subfamily A member 1 (Cyp17a1) at 33 and 100 mg/kg/day. Gene expression of Insl3, which is essential for the process of testis descent, was reduced at the highest dose by 58% in relation to control, but this change was not significant (p = 0.07). The number of multinucleated gonocytes, corrected for the number of testicular cord sections or the total area of analyzed testicular cords was significantly increased in the groups exposed to 33 and 100 mg/kg/day. Chance is an unlikely explanation for our results considering the observed dose-dependent responses and the consistency of our findings with prior phthalate reproductive toxicity data. Limitations, reasons for caution The tested doses are higher than the expected human exposure levels and animal-to-human extrapolation should be done with caution. Wider implications of the findings DiPeP suppresses the expression of steroidogenic genes and induces multinucleated gonocytes in the fetal rat testis. These endpoints seem more sensitive than inhibition of ex vivo testosterone production. Although human exposure levels are lower than the doses tested here, DiPeP can potentially act cumulatively with chemicals that share similar mechanisms. Trial registration number not applicable

Introduction: Gestational gigantomastia (GG) is a rare condition known for the massive growth of one or both breasts during pregnancy. Objectives: to describe three cases of GG in patients assisted Hospital de Clínicas do Paraná. Case Reports: Case 1 ‒ Twenty-four year old pregnant woman, of 9 weeks, presented with mastalgia and increasing breast volume associated with phlogistic signs and orange peel-like skin. Breast ultrasound showed diffuse inflammatory process. A biopsy was performed and showed ductal ectasia and stromal fibroadenomatoid changes. On the 20th week, she was hospitalized with fever, voluminous breasts and drainage of purulent secretion and long ulcers in the inframammary fold. She was administered antibiotics and local care. The choice was to interrupt the pregnancy of 33 weeks. She presented with relative reduction of the breasts and breastfed, but had severe psychological problems caused by the aesthetic dissatisfaction. Case 2 ‒ Eighteen-year old patient presented with infiltrating ductal breast carcinoma in the right breast, treated with sectorectomy, with sentinel lymph node and conventional radiotherapy. After one year of follow-up, ductal carcinoma in situ (DCIS) was diagnosed in the left breast, being submitted to sectorectomy and intraoperative radiotherapy. Two years after DCIS, she became pregnant and presented with GG only in the left breast, with remarkable asymmetry and skin edema. After the Cesarean section, breastfeeding was normal on the GG side, but not on the right side, due to a sequel from total radiotherapy. Case 3 ‒ Twenty-two year old pregnant women, of 12 weeks, presented with mastalgia and exaggerated growth of the breasts, with and orange peel-like skin. Breast ultrasound showed bilateral inflammatory process. On the 15th week, she presented with bleeding ulcers, right breast with latero-lateral diameter of 48 cm, and craniocaudal diameter of 56 cm, and left breast with 49 cm and 58 cm, respectively. Due to the fast and progressive growth of the breasts, with difficulties to breath, major venous and lymph stasis and extensive skin ulceration/maceration, with risk of infection, the patient and relatives agreed on conducting a therapeutic abortion, followed by a reduction mammoplasty. Discussion: It is a rare disease, and its etiology remains unknown. Medicinal therapy seems to be first option, but it is often necessary to complement it with a surgical procedure. Conclusions: GG is a pathology of great morbidity, with tendency to recede in the puerperium. In case it is not possible to wait, the recommendation is to intervene in the pregnancy.

e18818 Background: The concept of financial toxicity (FT) has been used to describe the unanticipated economic damage potentially caused by cancer treatment. Currently, it has been associated with decreased health-related quality of life (QoL), treatment nonadherence and increased risk of mortality. Even in publicly funded environments as Brazilian Unified National Health System, factor such as income loss or out-of-pocket costs could become an issue for cancer care. The aim of this study was to examine the FT related to the breast cancer diagnosis and treatments in a public Brazilian tertiary hospital through Comprehensive Score for Financial Toxicity (COST) instrument. The COST is a 12-item survey scored from 0 to 44, with lower scores reflecting worse financial well-being. Methods: This cross-sectional study was conducted among breast cancer patients in active treatment for at least 6 months attending medical oncology out-patient department. Socio-demographic, clinical characteristics and a simplified assessment of QoL were collected as well as responses to COST questionnaire. Descriptive statistic and analysis of correlations between quantitative variables and scores of QoL and COST were performed. Results: A total of 100 female patients were included with median age of 53 years old. The mean time from initial diagnosis was of 49.6 months and clinical stage IV represented 46% of all cases. Prior to the cancer treatment, 48 (48%) of the patients had their own job as a main source of income. However, after the cancer diagnosis, only 9 (9%) patients keep working, 36 (36%) needed to use savings and 29 (29%) applied for a bank loan. To adjust their finances, 66 (66%) patients reduced spending on leisure. The median COST score was 18.5 (ranged from 4 to 41). According to the age, patients with ≤ 45 years old were at higher risk of suffering FT (p = 0.01). There was also an association between the COST score and QoL since the higher the FT, the lower the QoL (p < 0.001). Conclusions: Patients with breast cancer are at risk of losing their work capacity, become financially dependent of other, and suffering a reduction in QoL as a result of FT. Mostly younger patients are at greater risk of FT. Despite a universal health-model, this study highlights a substantial proportion of patients who experienced FT. Therefore, further studies confirming these findings in larger groups are warranted to develop better strategies and policies to mitigate this form of toxicity.