Changes in Triple-Negative Breast Cancer Molecular Subtypes in Patients Without Pathologic Complete Response After Neoadjuvant Systemic Chemotherapy.

PURPOSE: Lehmann et al have identified four molecular subtypes of triple-negative breast cancer (TNBC)-basal-like (BL) 1, BL2, mesenchymal (M), and luminal androgen receptor-and an immunomodulatory (IM) gene expression signature modifier. Our group previously showed that the response of TNBC to neoadjuvant systemic chemotherapy (NST) differs by molecular subtype, but whether NST affects the subtype was unknown. Here, we tested the hypothesis that in patients without pathologic complete response, TNBC subtypes can change after NST. Moreover, in cases with the changed subtype, we determined whether epithelial-to-mesenchymal transition (EMT) had occurred. MATERIALS AND METHODS: From the Pan-Pacific TNBC Consortium data set containing TNBC patient samples from four countries, we examined 64 formalin-fixed, paraffin-embedded pairs of matched pre- and post-NST tumor samples. The TNBC subtype was determined using the TNBCtype-IM assay. We analyzed a partial EMT gene expression scoring metric using mRNA data. RESULTS: Of the 64 matched pairs, 36 (56%) showed a change in the TNBC subtype after NST. The most frequent change was from BL1 to M subtypes (38%). No tumors changed from M to BL1. The IM signature was positive in 14 (22%) patients before NST and eight (12.5%) patients after NST. The EMT score increased after NST in 28 (78%) of the 36 patients with the changed subtype (v 39% of the 28 patients without change; P = .002254). CONCLUSION: We report, to our knowledge, for the first time that the TNBC molecular subtype and IM signature frequently change after NST. Our results also suggest that EMT is promoted by NST. Our findings may lead to innovative adjuvant therapy strategies in TNBC cases with residual tumor after NST.

A low intensity dietary intervention for reducing excessive gestational weight gain in an overweight and obese pregnant cohort.

PURPOSE: Excessive gestational weight gain is associated with detrimental outcomes to both the mother and baby. Currently, the best approach to prevent excessive gestational weight gain in overweight and obese women is undetermined. The present study aimed to evaluate the effectiveness of a group-based outpatient dietary intervention in pregnancy to reduce excessive gestational weight gain. METHODS: In this retrospective study, overweight and obese pregnant women who attended a single 90-min group education session were compared to women who received standard care alone. Total gestational weight gain, maternal and neonatal outcomes were compared between the intervention and control groups. Data were analysed using Student t, Mann-Whitney and Chi-squared tests as appropriate. A 24-h dietary recall was analysed and compared to the Australian National Nutrition Survey. RESULTS: A significant reduction in gestational weight gain was observed with this intervention (P = 0.010), as well as in the rate of small for gestational age births (P = 0.043). Those who attended the intervention had saturated fat and sodium intake levels that exceeded recommendations. Intake of pregnancy-specific micronutrients including folate, calcium and iron were poor from diet alone. CONCLUSIONS: A low-intensity antenatal dietary intervention may be effective in reducing excessive gestational weight gain, although multi-disciplinary interventions yield the best success. Further research is required to identify the optimal modality and frequency to limit excessive gestational weight gain. Dietary interventions tailored to ethnicity should also be explored. LEVEL OF EVIDENCE: Level II, controlled trial without randomization.

Poor Response to Neoadjuvant Chemotherapy Correlates with Mast Cell Infiltration in Inflammatory Breast Cancer.

Our understanding is limited concerning the tumor immune microenvironment of inflammatory breast cancer (IBC), an aggressive form of primary cancer with low rates of pathologic complete response to current neoadjuvant chemotherapy (NAC) regimens. We retrospectively identified pretreatment (N = 86) and matched posttreatment tissue (N = 27) from patients with stage III or de novo stage IV IBC who received NAC followed by a mastectomy. Immune profiling was performed including quantification of lymphoid and myeloid infiltrates by IHC and T-cell repertoire analysis. Thirty-four of 86 cases in this cohort (39.5%) achieved a pathologic complete response. Characterization of the tumor microenvironment revealed that having a lower pretreatment mast cell density was significantly associated with achieving a pathologic complete response to NAC (P = 0.004), with responders also having more stromal tumor-infiltrating lymphocytes (P = 0.035), CD8+ T cells (P = 0.047), and CD20+ B cells (P = 0.054). Spatial analysis showed close proximity of mast cells to CD8+ T cells, CD163+ monocytes/macrophages, and tumor cells when pathologic complete response was not achieved. PD-L1 positivity on tumor cells was found in fewer than 2% of cases and on immune cells in 27% of cases, but with no correlation to response. Our results highlight the strong association of mast cell infiltration with poor response to NAC, suggesting a mechanism of treatment resistance and a potential therapeutic target in IBC. Proximity of mast cells to immune and tumor cells may suggest immunosuppressive or tumor-promoting interactions of these mast cells.

BRCA mutations in women with inflammatory breast cancer.

BACKGROUND: Inflammatory breast cancer (IBC) often affects women at a relatively young age. To the authors' knowledge, the rate of BRCA variants among patients with IBC is not known. To determine the association between BRCA status and IBC, the authors evaluated its rate and compared the clinicopathologic characteristics of patients with IBC with those of patients with other breast cancers (non-IBC). METHODS: Patients who presented at the study institution's cancer genetics program and who underwent BRCA genetic testing were included in the current study. The authors compared clinicopathologic data between patients with IBC and those with non-IBC using propensity score matching to identify predictors. RESULTS: A total of 1789 patients who underwent BRCA genetic testing (1684 with non-IBC and 105 with IBC) were included. BRCA pathogenic variants were found in 27.3% of patients with non-IBC and 18.1% of patients with IBC (P = .0384). After propensity score matching, there were no significant differences noted between patients with IBC and those with non-IBC, including the rate of BRCA pathogenic variants (P = .5485). However, a subgroup analysis of the 479 patients with BRCA pathogenic variants demonstrated that patients with IBC (19 patients) were diagnosed at significantly younger ages compared with patients with non-IBC (P = .0244). CONCLUSIONS: There was no clear association observed between BRCA pathogenic variants and IBC. However, among patients who tested positive for BRCA pathogenic variants, those with IBC were younger at the time of diagnosis compared with those with non-IBC breast cancers. These results confirm that genetic testing is important for patients with IBC who meet the current clinical criteria for genetic testing in breast cancer. Cancer 2018;124:466-74. © 2017 American Cancer Society.

Impact and management of dual relationships in metropolitan, regional and rural mental health practice.

OBJECTIVE: To explore the extent and impact of professional boundary crossings in metropolitan, regional and rural mental health practice in Victoria and identify strategies mental health clinicians use to manage dual relationships. METHOD: Nine geographically located focus groups consisting of mental health clinicians: four focus groups in rural settings; three in a regional city and two in a metropolitan mental health service. A total of 52 participants were interviewed. RESULTS: Data revealed that professional boundaries were frequently breached in regional and rural settings and on occasions these breaches had a significantly negative impact. Factors influencing the impact were: longevity of the clinician's relationship with the community, expectations of the community, exposure to community 'gossip' and size of the community. Participants reported greater stress when the boundary crossing affected their partner and/or children. Clinicians used a range of proactive and reactive strategies, such as private telephone number, avoidance of social community activities, when faced with a potential boundary crossing. The feasibility of reactive strategies depended on the service configuration: availability of an alternative case manager, requirement for either patient or clinician to travel. The greater challenges faced by rural and regional clinicians were validated by metropolitan participants with rural experience and rural participants with metropolitan experience. CONCLUSIONS: No single strategy is used or appropriate for managing dual relationships in rural settings. Employers and professional bodies should provide clearer guidance for clinicians both in the management of dual relationships and the distinction between boundary crossings and boundary violation. Clinicians are clearly seeking to represent and protect the patients' interests; consideration should be given by consumer groups to steps that can be taken by patients to reciprocate.

Dual relationships in mental health practice: issues for clinicians in rural settings.

OBJECTIVE: This paper aims to provide an overview of the literature on non-sexual dual relationships, and to discuss these in the context of rural mental health practice in Australia. METHOD: An internet-driven literature search was undertaken using OVID databases, which include MEDLINE, PsycINFO, CINAHL, and EMBASE: Psychiatry. Ethical codes of practice for the mental health professions of psychiatry, psychology, occupational therapy, social work and nursing were referred to. Searches were not limited by year of publication. Other unpublished material or information was included where relevant. RESULTS: Dual relationships are common in rural mental health practice. However, research on non-sexual dual relationship boundary issues in rural mental health is limited. Ethical codes of practice of mental health professional bodies provide little guidance regarding non-sexual dual relationships. Decision-making models addressing the ethics of dual relationships are restricted to considerations of whether to enter a dual relationship rather than how to manage such a relationship. CONCLUSIONS: Everyday' dual relationships are a predictable part of rural mental health practice. Further research is required to identify the benefits and/or problems in clinical practice resulting from non-sexual dual relationships. Responsibility for identifying and implementing ways of appropriately managing such relationships should be shared by the patient, the clinician, mental health services and professional organizations.