Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers.

BACKGROUND: The relationship between the presence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the risk of subsequent reinfection remains unclear. METHODS: We investigated the incidence of SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) in seropositive and seronegative health care workers attending testing of asymptomatic and symptomatic staff at Oxford University Hospitals in the United Kingdom. Baseline antibody status was determined by anti-spike (primary analysis) and anti-nucleocapsid IgG assays, and staff members were followed for up to 31 weeks. We estimated the relative incidence of PCR-positive test results and new symptomatic infection according to antibody status, adjusting for age, participant-reported gender, and changes in incidence over time. RESULTS: A total of 12,541 health care workers participated and had anti-spike IgG measured; 11,364 were followed up after negative antibody results and 1265 after positive results, including 88 in whom seroconversion occurred during follow-up. A total of 223 anti-spike-seronegative health care workers had a positive PCR test (1.09 per 10,000 days at risk), 100 during screening while they were asymptomatic and 123 while symptomatic, whereas 2 anti-spike-seropositive health care workers had a positive PCR test (0.13 per 10,000 days at risk), and both workers were asymptomatic when tested (adjusted incidence rate ratio, 0.11; 95% confidence interval, 0.03 to 0.44; P = 0.002). There were no symptomatic infections in workers with anti-spike antibodies. Rate ratios were similar when the anti-nucleocapsid IgG assay was used alone or in combination with the anti-spike IgG assay to determine baseline status. CONCLUSIONS: The presence of anti-spike or anti-nucleocapsid IgG antibodies was associated with a substantially reduced risk of SARS-CoV-2 reinfection in the ensuing 6 months. (Funded by the U.K. Government Department of Health and Social Care and others.).

Clinical outcomes after 1 versus 2-3 lines of neoadjuvant therapy in stage III inflammatory breast cancer.

PURPOSE: Many stage III inflammatory breast cancer (IBC) patients experience a sufficient response to first-line (1L) neoadjuvant chemotherapy (NAC) to allow surgery, while some require additional NAC. We evaluated the pathologic complete response (pCR), breast cancer-free survival (BCFS) and overall survival (OS) among patients requiring 1 vs. 2-3 lines (L) of NAC prior to surgery. METHODS: Stage III IBC patients from 2 institutions who received 1L or 2-3L of NAC prior to surgery were identified. Hormone receptor and HER2 status, grade, and pCR were evaluated. BCFS and OS were evaluated by the Kaplan-Meier method. Multivariable Cox models were utilized to estimate the hazard ratio (HR). RESULTS: 808 eligible patients (1997-2020) were identified (median age 51 years, median follow-up 69 months). 733 (91%) had 1L and 75 (9%) had 2-3L of NAC. Grade III, triple-negative and HER2-positive disease were more prevalent in 2-3L patients. 178 (24%) 1L and 14 (19%) 2-3L patients had pCR. 376 1L patients and 41 2-3L patients had recurrences. The 5-year BCFS was worse for the 2-3L group (33 vs. 46%, HR = 1.37; 95% CI 0.99-1.91). However, in 192 patients with a pCR, BCFS was similar (76 vs. 83% in 1L vs. 2-3L, respectively). There were 308 deaths (276 among 1L and 32 among 2-3L patients). The 5-year OS in 1L vs. 2-3L was 60 vs. 53% (HR = 1.32, 95% CI 0.91-1.93). CONCLUSIONS: Among stage III IBC patients, pCR rates were similar, irrespective of the NAC lines number, and BCFS and OS were comparable with pCR after 1L and 2-3L.

Improved Utilization of Serial Testing Without Increased Admissions after Implementation of High-Sensitivity Troponin I: a Controlled Retrospective Cohort Study.

BACKGROUND: Guidelines recommend high-sensitivity cardiac troponin (hs-cTn) for diagnosis of myocardial infarction. Use of hs-cTn is increasing across the U.S., but questions remain regarding clinical and operational impact. Prior studies have had methodologic limitations and yielded conflicting results. OBJECTIVE: To evaluate the impact of transitioning from conventional cardiac troponin (cTn) to hs-cTn on test and resource utilization, operational efficiency, and patient safety. DESIGN: Retrospective cohort study in two New York City hospitals during the months before and after transition from conventional cTn to hs-cTn at Hospital 1. Hospital 2 served as a control. PARTICIPANTS: Consecutive emergency department (ED) patients with at least one cTn test resulted. INTERVENTION: Multifaceted hs-cTn intervention bundle, including a 0/2-h diagnostic algorithm for non-ST-elevation myocardial infarction, an educational bundle, enhancements to the electronic medical record, and nursing interventions to facilitate timed sample collection. MAIN MEASURES: Primary outcomes included serial cTn test utilization, probability of hospital admission, ED length of stay (LOS), and among discharged patients, probability of ED revisit within 72 h resulting in hospital admission. Multivariable regression models adjusted for age, sex, temporal trends, and interhospital differences. KEY RESULTS: The intervention was associated with increased use of serial cTn testing (adjusted risk difference: 48 percentage points, 95% CI: 45-50, P < 0.001) and ED LOS (adjusted geometric mean difference: 50 min, 95% CI: 50-51, P < 0.001). There was no significant association between the intervention and probability of admission (adjusted relative risk [aRR]: 0.99, 95% CI: 0.89-1.1, P = 0.81) or probability of ED revisit within 72 h resulting in admission (aRR: 1.1, 95% CI: 0.44-2.9, P = 0.81). CONCLUSIONS: Implementation of a hs-cTn intervention bundle was associated with an improvement in serial cTn testing, a neutral effect on probability of hospital admission, and a modest increase in ED LOS.

The Placenta in Congenital Langerhans Cell Histiocytosis: A Case Report of Unusual Involvement of Chorionic Plate and Umbilical Vein.

The congenital presentation of Langerhans cell histiocytosis (LCH) is a rare presentation of an uncommon neoplastic process. Concurrent placental parenchymal involvement is even more rare, with just 2 cases of congenital multisystem LCH with placental involvement reported in English medical literature thus far. Here, we present a case of a liveborn male born at 37-weeks, 6-day gestation with congenital LCH focally involving the placenta. Langerhans cells were identified in an area of the placenta showing an unusual mononuclear cell infiltrate in the wall of the umbilical vein. Langerhans cells were also focally identified in areas of chronic villitis, as well as normal-appearing chorionic plate. The examination of the placenta in cases of clinical suspicion of LCH can be of paramount importance since it may provide the early diagnostic evidence of LCH. In this context, placental involvement by LCH should be considered even in the absence of abnormal histology.

An Observational Cohort Study on the Incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and B.1.1.7 Variant Infection in Healthcare Workers by Antibody and Vaccination Status.

BACKGROUND: Natural and vaccine-induced immunity will play a key role in controlling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity. METHODS: In a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, United Kingdom, we investigated the protection from symptomatic and asymptomatic polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role. We estimated protection conferred after 1 versus 2 vaccinations and from infections with the B.1.1.7 variant identified using whole genome sequencing. RESULTS: In total, 13 109 HCWs participated; 8285 received the Pfizer-BioNTech vaccine (1407 two doses), and 2738 the Oxford-AstraZeneca vaccine (49 two doses). Compared to unvaccinated seronegative HCWs, natural immunity and 2 vaccination doses provided similar protection against symptomatic infection: no HCW vaccinated twice had symptomatic infection, and incidence was 98% lower in seropositive HCWs (adjusted incidence rate ratio 0.02 [95% confidence interval {CI} < .01-.18]). Two vaccine doses or seropositivity reduced the incidence of any PCR-positive result with or without symptoms by 90% (0.10 [95% CI .02-.38]) and 85% (0.15 [95% CI .08-.26]), respectively. Single-dose vaccination reduced the incidence of symptomatic infection by 67% (0.33 [95% CI .21-.52]) and any PCR-positive result by 64% (0.36 [95% CI .26-.50]). There was no evidence of differences in immunity induced by natural infection and vaccination for infections with S-gene target failure and B.1.1.7. CONCLUSIONS: Natural infection resulting in detectable anti-spike antibodies and 2 vaccine doses both provide robust protection against SARS-CoV-2 infection, including against the B.1.1.7 variant.

Incidence, characteristics, and management of central nervous system metastases in patients with inflammatory breast cancer.

BACKGROUND: Patients with inflammatory breast cancer (IBC) have a high risk of central nervous system metastasis (mCNS). The purpose of this study was to quantify the incidence of and identify risk factors for mCNS in patients with IBC. METHODS: The authors retrospectively reviewed patients diagnosed with IBC between 1997 and 2019. mCNS-free survival time was defined as the date from the diagnosis of IBC to the date of diagnosis of mCNS or the date of death, whichever occurred first. A competing risks hazard model was used to evaluate risk factors for mCNS. RESULTS: A total of 531 patients were identified; 372 patients with stage III and 159 patients with de novo stage IV disease. During the study, there were a total of 124 patients who had mCNS. The 1-, 2-, and 5-year incidence of mCNS was 5%, 9%, and 18% in stage III patients (median follow-up: 5.6 years) and 17%, 30%, and 42% in stage IV patients (1.8 years). Multivariate analysis identified triple-negative tumor subtype as a significant risk factor for mCNS for stage III patients. For patients diagnosed with metastatic disease, visceral metastasis as first metastatic site, triple-negative subtype, and younger age at diagnosis of metastases were risk factors for mCNS. CONCLUSIONS: Patients with IBC, particularly those with triple-negative IBC, visceral metastasis, and those at a younger age at diagnosis of metastatic disease, are at significant risk of developing mCNS. Further investigation into prevention of mCNS and whether early detection of mCNS is associated with improved IBC patient outcomes is warranted.

Mental health among transgender women living with HIV in Canada: findings from a national community-based research study.

Antiretroviral therapy adherence among transgender (trans) women living with HIV (WLWH) is negatively impacted by depression and post-traumatic stress disorder (PTSD). Yet, little is known about factors associated with depression or PTSD among trans WLWH. Using cross-sectional data from a national community-based study of 1422 WLWH (n = 53 trans women), we characterized the prevalence of depressive and PTSD symptoms among trans WLWH and examined associations between factors (e.g., Trans stigma) and depressive and PTSD symptoms. Nearly half of participants reported clinically significant PTSD (45.3%) and depressive symptoms (45.3%) [mean Post-traumatic Stress Disorder Civilian Checklist Version-C score 13.8 (SD = 5.8); mean Center for Epidemiological Studies - Depression score 9.4 (SD = 8.0)]. Univariate linear regression analyses showed that <95% adherence, higher internalized HIV-related stigma, frequency of past-month hazardous alcohol use, and current injection drug use were significantly associated with both higher PTSD and depressive symptom scores, and higher resilience and social support with lower scores. A history of violence in adulthood was associated with higher depressive symptoms scores, whereas sexual relationship power and less difficulty meeting housing costs were associated with lower scores. Findings suggest a need for multi-level interventions to reduce barriers to mental wellbeing while fostering resilience and social support.

Discrepancy between FDG-PET/CT and contrast-enhanced CT in the staging of patients with inflammatory breast cancer: implications for treatment planning.

PURPOSE: Optimizing treatment strategies for patients with inflammatory breast cancer (IBC) relies on accurate initial staging. This study compared contrast-enhanced computed tomography (ce-CT) and FDG-PET/CT for initial staging of IBC to determine the frequency of discordance between the two imaging modalities and potential impact on management. METHODS: 81 patients with IBC underwent FDG-PET/CT and ce-CT prior to starting treatment. FDG-PET/CT and ce-CT scans were independently reviewed for locoregional and distant metastases and findings recorded by anatomic site as negative, equivocal, or positive for breast cancer involvement. Each paired ce-CT and FDG-PET/CT case was classified as concordant or discordant for findings. Discordant findings were subclassified as (a) related to the presence or absence of distant metastases; (b) affecting the locoregional radiation therapy plan; or (c) due to incidental findings not related to IBC. RESULTS: There were 47 discordant findings between ce-CT and FDG-PET/CT in 41 of 81 patients (50.6%). Thirty (63.8%) were related to the presence or absence of distant metastases; most commonly disease detection on FDG-PET/CT but not ce-CT (n = 12). FDG-PET/CT suggested alterations of the locoregional radiation therapy plan designed by CT alone in 15 patients. FDG-PET/CT correctly characterized 5 of 7 findings equivocal for metastatic IBC on ce-CT. CONCLUSIONS: This study demonstrates differences between ce-CT and FDG-PET/CT for initial staging of IBC and how these differences potentially affect patient management. Preliminary data suggest that FDG-PET/CT may be the imaging modality of choice for initial staging of IBC. Prospective trials testing initial staging with FDG-PET/CT versus important clinical end-points in IBC are warranted.

Characteristics associated with inflammatory breast cancer (IBC): An epidemiologic study from a dedicated IBC program.

There are scant data identifying epidemiologic characteristics among individuals diagnosed with inflammatory breast cancer (IBC), which is considered the most aggressive subtype of breast cancer. The purpose of this study was to evaluate the epidemiologic features among patients seen at a dedicated IBC program, to elucidate the potential causes of this disease and guide prevention strategies. We reviewed retrospective data from 447 patients enrolled in an IRB-approved IBC registry through Dana-Farber Cancer Institute from 1997 to 2016. The data examined included the following: demographics, medical, reproductive and family history, duration of symptoms prior to the diagnosis of IBC, pathologic characteristics, and clinical outcome. JMP statistical software was used to compile the data. Descriptive statistics were used to evaluate the data. The majority of patients (66.0%) were overweight or obese (body mass index [BMI] ≥25) at the time of diagnosis. Fifty patients (11.1%) had "secondary" IBC, defined as developing IBC after a previous history of non-IBC breast cancer in an ipsilateral breast. Of those patients with secondary IBC, 60% were also overweight or obese at the time of IBC diagnosis. Approximately 58% of IBC patients had a family history of breast or ovarian cancer, including first- and second-degree relatives. This analysis suggested a high frequency of familial breast/ovarian cancer among IBC patients which supports further evaluating genetic risks. This may have implications for screening and prevention strategies as well as insight into additional contributing risk factors. The prevalence of a high BMI among both pre- and postmenopausal women with IBC, including those diagnosed with secondary IBC, warrants focusing on strategies targeting the obesity crisis as a potential means of reducing the risk of developing this disease.

Patterns of care and predictors of adjuvant radiation therapy in phyllodes tumor of the breast.

Patterns of care, utilization, and predictors of adjuvant radiation therapy (RT) for phyllodes tumors of the breast were retrospectively analyzed using the National Cancer Database. We identified 3080 patients; 53.4% received lumpectomy and 35.9% mastectomy. 25.9% of patients had lymph node sampling or dissection. 23.2% received adjuvant RT, which doubled in utilization over a decade. Predictors of RT were younger age, fewer comorbidities, less favorable pathologic features, and treatment at academic centers. There was no association between RT and overall survival (AHR 1.21, 95% CI 0.97-1.53, P = .097). Despite national guidelines recommending against nodal sampling or RT, it remains prevalent. Further research on indications for adjuvant radiation for phyllodes is needed.

Patterns of breast reconstruction in patients diagnosed with inflammatory breast cancer: The Dana-Farber Cancer Institute's Inflammatory Breast Cancer Program experience.

Inflammatory breast cancer (IBC) exhibits dermal lymphatic involvement at presentation, and thus, the standard surgical approach is a nonskin-sparing modified radical mastectomy (MRM) without breast reconstruction (BR). In this study, we evaluated immediate and delayed BR receipt and its outcomes in IBC. Using an IRB-approved database, we retrospectively evaluated stage III IBC patients who received trimodality therapy (preoperative systemic therapy, followed by MRM and postmastectomy chest wall/regional nodal radiation). Patients with an insufficient response to preoperative systemic therapy and/or who required preoperative radiotherapy were excluded. BR receipt, timing, and morbidity were evaluated. Among 240 stage III IBC patients diagnosed between 1997 and 2016, 40 (17%) underwent BR. Thirteen (33%) had immediate, and 27 (67%) had delayed BR. Four patients had complications (1 [8%] immediate BR and 3 [11%] delayed BR); only 1 BR (delayed) was unsuccessful. From the MRM date, the median time to recurrence was 35 months (<1-212) and median overall survival was 87 months (<1-212). In this cohort of stage III IBC patients, only 11% pursued delayed BR following trimodality therapy, possibly attributable to the observed high recurrence rates hindering BR. Further studies addressing BR outcomes in IBC are needed for better counseling patients regarding their reconstructive options.

Long-term outcomes of breast-conserving therapy for women with ductal carcinoma in situ.

PURPOSE: Improved imaging, surgical techniques, and pathologic evaluation likely have decreased local recurrence rates for patients with ductal carcinoma in situ (DCIS). We present long-term outcomes of a large single-institution series after breast-conserving surgery (BCS) and adjuvant radiation therapy (RT). METHODS: We retrospectively reviewed the records of 245 women treated for DCIS with BCS and RT between 2001 and 2007. Competing risk analysis was used to calculate local recurrence (LR) as a first event with the development of a second non-breast malignancy, contralateral breast cancer, and death as competing first events. RESULTS: At a median follow-up of 10.6 years, 4 patients had a LR (2 DCIS, 2 invasive) as a first event with a cumulative LR incidence of 0.0% and 1.5% at 5 and 10 years, respectively. Most patients had > 2 mm margins (90%), specimen radiographs (93%), and received a tumor bed boost (99%). The majority (60%) of patients with hormone receptor-positive disease received adjuvant endocrine therapy. Ten-year cumulative incidence of contralateral breast cancer (CBC) was 7.9%, second non-breast malignancy was 4.5%, and death unrelated to breast cancer was 3.5%. Family history, age at diagnosis, and receipt of endocrine therapy were not significantly associated with the development of CBC (all P > 0.05). CONCLUSIONS: With mature follow-up, our rates of local recurrence following breast-conserving therapy for DCIS remain very low (1.5% at 10 years). The incidence of CBC was higher than the LR incidence. Predisposing factors for the development of CBC are worthy of investigation.

The Current and Evolving Role of Radiation Therapy for Central Nervous System Metastases from Breast Cancer.

PURPOSE OF REVIEW: For patients with breast cancer who develop brain metastases, radiation therapy (RT) provides local control. Here, we review the current role for central nervous system RT, particularly focusing on the evolving role for stereotactic radiosurgery (SRS). RECENT FINDINGS: SRS treats only known CNS disease as opposed to whole-brain radiation therapy (WBRT), which treats the entire brain parenchyma. SRS has been found to cause less neurocognitive decline than WBRT. SRS is currently utilized in patients with four or fewer brain metastases, but several ongoing trials are examining the use of SRS for greater than four metastases. For patients requiring WBRT, hippocampal avoidance WBRT and memantine concurrent with and adjuvant to WBRT have been found to reduce the risk of neurocognitive decline. Both SRS and WBRT are used as a local therapy for brain metastases. SRS is increasingly preferred given fewer long-term neurocognitive side effects.

Myotubes derived from human-induced pluripotent stem cells mirror in vivo insulin resistance.

Induced pluripotent stem cells (iPS cells) represent a unique tool for the study of the pathophysiology of human disease, because these cells can be differentiated into multiple cell types in vitro and used to generate patient- and tissue-specific disease models. Given the critical role for skeletal muscle insulin resistance in whole-body glucose metabolism and type 2 diabetes, we have created a novel cellular model of human muscle insulin resistance by differentiating iPS cells from individuals with mutations in the insulin receptor (IR-Mut) into functional myotubes and characterizing their response to insulin in comparison with controls. Morphologically, IR-Mut cells differentiated normally, but had delayed expression of some muscle differentiation-related genes. Most importantly, whereas control iPS-derived myotubes exhibited in vitro responses similar to primary differentiated human myoblasts, IR-Mut myotubes demonstrated severe impairment in insulin signaling and insulin-stimulated 2-deoxyglucose uptake and glycogen synthesis. Transcriptional regulation was also perturbed in IR-Mut myotubes with reduced insulin-stimulated expression of metabolic and early growth response genes. Thus, iPS-derived myotubes from individuals with genetically determined insulin resistance demonstrate many of the defects observed in vivo in insulin-resistant skeletal muscle and provide a new model to analyze the molecular impact of muscle insulin resistance.

Development of a Group-Based, Peer-Mentor Intervention to Promote Disease Self-Management Skills Among Youth With Chronic Medical Conditions.

STUDY PURPOSE: The purpose of this paper is to describe the development of a group-based peer-mentor intervention to enhance knowledge/skills of transition-age youth (TAY) from three clinical services (gastroenterology, renal or rheumatology) at a large children's hospital in order to facilitate transition from pediatric to adult healthcare. DESIGN AND METHODS: Using a multi-modal, iterative approach, the structure/content of the intervention was based on peer-reviewed literature; surveys/interviews conducted with TAY, families, and adult and pediatric providers; principles of Self-Determination Theory and motivational interviewing; and guided by a logic model. A TAY community advisory board helped interpret the information and develop the intervention. RESULTS: The resulting intervention has eight sessions led by peer mentors (young adults who have successfully transitioned to adult healthcare, who are trained to use a motivational interviewing approach) covering topics such as goal setting; understanding my diagnosis; organizing personal, health & insurance information; characteristics of a good provider; filling/refilling prescriptions; and mental well-being. The TAY community advisory board recommended holding two sessions on each of four Saturdays, using interactive group activities to make it fun, and creating a written complimentary manual for caregivers. CONCLUSIONS: A TAY community advisory board was instrumental in developing an innovative peer-mentor intervention to promote the development of specific skills TAY require to manage their disease within adult healthcare. PRACTICE IMPLICATIONS: Although the intervention was developed with extensive stakeholder input, a next step is to evaluate the intervention with respect to how well it fits the broader membership in the target population.

Analysis of menstrual effluent: diagnostic potential for endometriosis.

BACKGROUND: Endometriosis is a chronic and underdiagnosed disease which affects 5-10% of women of childbearing age and is characterized by growth of endometrial tissue outside of the uterus, most often in the peritoneal cavity. Delay in diagnosis is a major problem for management of this disorder, and treatment is often not initiated until the disease has progressed for many years. Although the exact etiology of endometriosis remains unknown, retrograde menstruation is recognized as a common underlying factor leading to the deposit of menstrual effluent (ME) into the peritoneal cavity. Differences in the cellular biology and genetics of the cells within ME are therefore likely to explain why endometriosis develops in only a subset of women. METHODS: Patients with and without endometriosis were consented to provide ME. ME was analyzed by flow cytometry for CD45- and CD45+ cell populations or used to isolate stromal fibroblast cells. ME-derived stromal fibroblast cells were assessed using decidualization assays following the addition of cAMP and IGFBP-1 concentrations in the culture supernatants were measured by ELISA. In addition, RNA was collected and analyzed by RNA-Seq and qPCR for markers of decidualization and to identify differentially expressed genes in ME-derived stromal fibroblast cells obtained from controls and subjects with endometriosis (±cAMP). RESULTS: Flow cytometry analysis of cell subsets within the CD45+ fraction of ME revealed a significant decrease in the number of uterine NK cells in endometriosis patients compared with controls (p < 0.01). No other significant differences within either the CD45+ or CD45- cell populations were observed. Most strikingly, ME-derived stromal fibroblast cells cultured from endometriosis subjects showed impaired decidualization potential compared with controls. Highly significant differences in decidualization response were detected by measuring IGFBP-1 production at multiple time points after cAMP stimulation (p = 0.0025 at 6 h; p = 0.0045 at 24 h; p = 0.0125 at 48 h). RNA-Seq and qPCR analyses were used to identify genes differentially expressed by ME-derived stromal fibroblast cells obtained from endometriosis and control subjects. CONCLUSIONS: Menstrual effluent can be useful for investigating the pathobiology of endometriosis and for developing a non-invasive diagnostic for endometriosis which may lead to earlier and more effective treatments for this common disorder.

The Impact of Residual Disease After Preoperative Systemic Therapy on Clinical Outcomes in Patients with Inflammatory Breast Cancer.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and aggressive disease treated with multimodality therapy: preoperative systemic therapy (PST) followed by modified radical mastectomy (MRM), chest wall and regional nodal radiotherapy, and adjuvant biologic therapy and/or endocrine therapy when appropriate. In non-IBC, the degree of pathologic response to PST has been shown to correlate with time to recurrence (TTR) and overall survival (OS). We sought to determine if pathologic response correlates with oncologic outcomes of IBC patients. METHODS: Following review of IBC patients' records (1997-2014), we identified 258 stage III IBC patients; 181 received PST followed by MRM and radiotherapy and were subsequently analyzed. Pathologic complete response (pCR) to PST, hormone receptor and human epidermal growth factor receptor 2 (HER2) status, grade, and histology were evaluated as predictors of TTR and OS by Cox model. RESULTS: Overall, 95/181 (52%) patients experienced recurrence; 93/95 (98%) were distant metastases (median TTR 3.2 years). Seventy-three patients (40%) died (median OS 6.9 years). pCR was associated with improved TTR (hazard ratio [HR] 0.20, 95% confidence interval [CI] 0.09-0.46, p < 0.01, univariate; HR 0.17, 95% CI 0.07-0.41, p < 0.0001, multivariate) and improved OS (HR 0.26, 95% CI 0.11-0.65, p < 0.01, univariate). In patients with pCR, grade III (HR 1.91, 95% CI 1.16-3.13, p = 0.01), and triple-negative phenotype (HR 3.54, 95% CI 1.79-6.98, p = 0.0003) were associated with shorter TTR, while residual ductal carcinoma in situ was not (HR 0.85, 95% CI 0.53-1.35, p = 0.48, multivariate). CONCLUSIONS: In stage III IBC, pCR was associated with prognosis, further influenced by grade, hormone receptor, and HER2 status. Investigating mechanisms that contribute to better response to PST could help improve oncologic outcomes in IBC.

Body Mass Index and Locoregional Recurrence in Women with Early-Stage Breast Cancer.

BACKGROUND: Higher body mass index (BMI) has been associated with increased distant recurrence and decreased survival for women with breast cancer. However, the relationship between BMI and locoregional recurrence (LRR) has been less well studied and was therefore the subject of this investigation. METHODS: The study identified 878 women with early-stage invasive breast cancer who underwent breast-conservation therapy (BCT) between June 1997 and October 2007. Time from diagnosis to LRR was calculated using a competing risk analysis with contralateral breast cancer (CBC), distant metastases (DM), and death as the competing risks. Gray's competing risks analysis, which included an interaction term between menopausal status and BMI, was used to identify significant risk factors for the development of LRR. RESULTS: After a median follow-up period of 10.8 years, LRR was diagnosed as a first event for 45 women. In a multivariable analysis, BMI was positively associated with LRR but only in premenopausal women. Specifically, when these women were compared with normal- and underweight women, both the overweight women (hazard ratio (HR), 2.97; 95 % confidence interval (CI) 1.04-8.46; p = 0.04) and the obese women (HR, 3.36; 95 % CI 1.07-10.63; p = 0.04) showed a higher risk of LRR. A similar association between BMI and disease-free survival was noted for premenopausal but not postmenopausal women. CONCLUSION: For premenopausal women with invasive breast cancer who undergo BCT, BMI is an independent prognostic factor for LRR. If confirmed, these findings suggest that more aggressive treatment strategies may be warranted for these women.

Inflammatory breast cancer and development of brain metastases: risk factors and outcomes.

Brain metastases are associated with significant morbidity. Minimal research has been conducted on the risk factors for and incidence of brain metastases in women with inflammatory breast cancer (IBC). 210 women with Stage III or IV IBC diagnosed from 1997-2011 were identified. Competing risk analysis and competing risks regression were used to calculate the incidence of brain metastases and identify significant risk factors. After a median follow-up in surviving patients of 2.8 years (range 0.6-7.6) and 3.3 years (range 0.2-14.5) in the 47 and 163 patients with (MET) and without (non-MET) metastatic disease at diagnosis, 17 (36 %) and 30 (18 %) developed brain metastases, respectively. The cumulative incidence at 1, 2, and 3 years was 17 % [95 % confidence interval (CI), 8-30], 34 % (95 % CI, 20-48), and 37 % (95 % CI, 22-51) for the MET cohort. The corresponding non-MET values were 4 % (95 % CI, 2-8), 8 % (95 % CI 5-13), and 15 % (95 % CI, 10-22). Once non-MET patients developed extracranial distant metastases, the subsequent 1, 2, and 3 years cumulative incidence of brain metastases was 18 % (95 % CI, 10-28), 25 % (95 % CI, 15-36), and 31 % (95 % CI, 20-43). On multivariate analysis, brain metastases were associated with younger age [hazard ratio (HR), 0.73; 95 % CI, 0.53-1.00; P = 0.05] and distant metastases at diagnosis (HR, 2.33; 95 % CI, 1.11-4.89; P = 0.03). The incidence of brain metastases is high in women with IBC. Particularly for patients with extracranial distant metastases, routine screening with magnetic resonance imaging should be considered.

Long-term outcomes among breast cancer patients with extensive regional lymph node involvement: implications for locoregional management.

Extensive lymph node (LN) involvement portends significant risk for distant metastasis (DM) among breast cancer patients. As a result, local management may be of secondary import to systemic control in this population. We analyzed patients with ≥10 involved LNs (N3) to evaluate the feasibility of breast conserving therapy (BCT) vs modified radical mastectomy (MRM) in this high-risk cohort. Among 98 women with N3 disease 46 (46.9%) underwent BCT and 52 (53.1%) received MRM. Nearly all patients (92%) received comprehensive radiotherapy (RT) including axillary and supraclavicular fields. The Kaplan-Meier method and Cox regression analyses were used to analyze time-to-event outcomes. Median follow-up was 76 months, with a 5-year DFS of 64.9% and OS of 71.9% among the cohort. Poorly differentiated (p = 0.007), ER-negative tumors (p = 0.015) had adverse DFS outcomes. Treatment groups did not differ with regard to 10-year DFS (45.4% for MRM vs. 57.6% for BCT; p = 0.31), or OS (61.4 vs. 63.7%; p = 0.79). DM-free survival was 48.9% following MRM and 60.6% following BCT (p = 0.19). Patients with ≥10 involved LNs have similar outcomes following BCT or MRM, suggesting that RT may obviate the need for more-extensive surgery. While local control is comparably favorable regardless of surgical approach, systemic control remains a challenge in this population.