Reliability and Variability of Ki-67 Digital Image Analysis Methods for Clinical Diagnostics in Breast Cancer.

Ki-67 is a nuclear protein associated with proliferation, and a strong potential biomarker in breast cancer, but is not routinely measured in current clinical management owing to a lack of standardization. Digital image analysis (DIA) is a promising technology that could allow high-throughput analysis and standardization. There is a dearth of data on the clinical reliability as well as intra- and interalgorithmic variability of different DIA methods. In this study, we scored and compared a set of breast cancer cases in which manually counted Ki-67 has already been demonstrated to have prognostic value (n = 278) to 5 DIA methods, namely Aperio ePathology (Lieca Biosystems), Definiens Tissue Studio (Definiens AG), Qupath, an unsupervised immunohistochemical color histogram algorithm, and a deep-learning pipeline piNET. The piNET system achieved high agreement (interclass correlation coefficient: 0.850) and correlation (R = 0.85) with the reference score. The Qupath algorithm exhibited a high degree of reproducibility among all rater instances (interclass correlation coefficient: 0.889). Although piNET performed well against absolute manual counts, none of the tested DIA methods classified common Ki-67 cutoffs with high agreement or reached the clinically relevant Cohen's κ of at least 0.8. The highest agreement achieved was a Cohen's κ statistic of 0.73 for cutoffs 20% and 25% by the piNET system. The main contributors to interalgorithmic variation and poor cutoff characterization included heterogeneous tumor biology, varying algorithm implementation, and setting assignments. It appears that image segmentation is the primary explanation for semiautomated intra-algorithmic variation, which involves significant manual intervention to correct. Automated pipelines, such as piNET, may be crucial in developing robust and reproducible unbiased DIA approaches to accurately quantify Ki-67 for clinical diagnosis in the future.

Primary MALT lymphoma of the breast: pathological and radiological characteristics.

PURPOSE: Primary Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare diagnosis in the breast, and clinical diagnosis based on radiological features is often challenging. This study aimed to evaluate the clinicopathological, and radiological characteristics of the patients diagnosed with primary breast MALT lymphoma. METHODS: This study examined 18 cases of primary MALT lymphoma of the breast diagnosed at a single tertiary center between January 2002 to December 2020. Medical charts, radiological imaging and original pathology slides were reviewed for each case. RESULTS: All cases were female (gender assigned at birth) and presented with a palpable mass or an incidental imaging finding. Imaging presentation ranged from mammographic asymmetries, circumscribed masses, and ultrasound masses lacking suspicious features. Seventeen cases were biopsied under ultrasound; one received a diagnostic excision biopsy. Microscopic examination of the breast specimens demonstrated atypical small lymphocyte infiltration with plasmacytoid differentiation and rare lymphoepithelial lesions. Immunohistochemistry was performed in all cases and established the diagnosis. Most patients were treated with radiotherapy, and only three were treated with chemotherapy. The median follow-up period was 4 years and 7.5 months, and all patients were alive at the last follow-up. CONCLUSION: Primary MALT breast lymphomas are usually indolent and non-systemic, and local radiotherapy may effectively alleviate local symptoms. Radiological findings show overlap with benign morphological features, which can delay the diagnosis of this unusual etiology. Although further studies involving a larger cohort could help establish the clinical and radiological characteristics of primary breast MALT lymphomas, pathology remains the primary method of diagnosis. TRIAL REGISTRATION NUMBER: University Health Network Ethics Committee (CAPCR/UHN REB number 19-5844), retrospectively registered.

A proof-of-concept study of iCope: A nurse-led psychoeducational telephone intervention for women attending a rapid diagnostic centre for breast abnormality.

The period between the initial discovery of a suspicious breast lesion and a confirmed diagnosis is a time of significant psychological distress, heightened anxiety, and uncertainty for many women. This proof of concept (PoC) study explored the clinical outcomes and acceptability of iCope, a nurse-led psycho-educational telephone intervention aimed to assist with uncertainty, anxiety and coping in women going through a Rapid Diagnostic Centre (RDC) offering quick diagnosis of breast cancer (same day to three-day post-investigation). Guided by the Uncertainty Theory, and using a one-arm pretest-posttest design, two brief 15-minute telephone sessions were delivered by a nurse prior to the women's day of testing at the RDC and three days after the receipt of their results. Six women completed measures of anxiety, uncertainty, and coping before the clinic visit, three days and three weeks after receiving their test results. Results show that the implementation of the telephone intervention was challenging, yet may offer potential for positive impact. That is, trends of decreased uncertainty and anxiety in participants over time were noted. Considering the difficulty observed in the recruitment and delivering the two interventions in the timeline planned, feasibility testing is recommended before the conduct of a large-scale study.

Impact of rapid genetic testing for BRCA1 and BRCA2 at time of breast cancer diagnosis on psychosocial functioning.

PURPOSE: Many women are being offered rapid genetic testing (RGT) for cancer predisposition genes, at the time of breast cancer diagnosis prior to surgery. The goal of this study was to determine if psychosocial functioning was affected in women receiving RGT for BRCA1 and BRCA2 at the time of breast cancer diagnosis. METHODS: Participants were women with invasive breast cancer diagnosed between 2013 and 2018, at four centres in Toronto, Canada. Eligible women were referred into the study by their surgeon at the time of diagnosis. Participants received pre-test genetic counselling and were offered RGT for BRCA1 and BRCA2. Standardized questionnaires (Impact of Event Scale and Hospital Anxiety and Depression Scale) were completed before genetic counselling, and follow-up questionnaires at one-week and one-year post-genetic test result disclosure (higher scores indicate higher symptoms). RESULTS: 1007 women had RGT; 60 women (6.0%) were found to have a BRCA1 or BRCA2 mutation, 80 women (7.9%) had a VUS, and 867 (86.1%) had a negative test result. At one-week post-testing, there were no differences in distress (p = 0.32), anxiety (p = 0.14), or depression (p = 0.42) between women with a BRCA1/2 mutation and those with a negative result. At one year, there were no differences in distress (p = 0.75) or anxiety (p = 0.13) between women with a BRCA1 or BRCA/2 mutation and those with a negative result. However, women with a BRCA1 or BRCA2 mutation had significantly lower depression scores compared to women with a negative result (p = 0.03). CONCLUSION: For women who have RGT for BRCA1 and BRCA2 at the time of breast cancer diagnosis, identifying a BRCA1 or BRCA2 mutation does not impair psychosocial functioning in the short or long term.

[SCREENING WOMEN AT HIGH RISK FOR BREAST CANCER - BRCA AND BEYOND].

BACKGROUND: Radiologic screening for breast cancer is performed with the goal of diagnosing the disease at an earlier stage, thus reducing morbidity and mortality. Screening recommendations for women at higher than average risk for breast cancer differ from those of women with an average risk, and include yearly breast MRI and mammography starting at a young age. OBJECTIVES: Review the morbidity and mortality, and check whether the goal of early diagnosis was achieved in the participants of the High-Risk Ontario Breast Screening Program at the Princess Margaret Cancer Centre, Ontario Canada. METHODS: A prospective cohort study was conducted of 2,081 women participating in the Princess Margaret Cancer Centre high risk screening program 2011-2018. Demographic, imaging, and if applicable biopsies, diagnosis and treatment data were captured in a prospectively maintained database starting with each participant's enrolment in the program. RESULTS: A total of 32% of the participants were carriers of pathogenic variants in breast cancer related genes (BRCA, NF, CHEK2, TP53 etc.), 8% had a history of therapeutic chest radiotherapy, and the remaining 60% had a calculated elevated lifetime risk based on family history or personal risk factors, without an identifiable pathogenic mutation or previous radiation. During the follow-up period 89 breast cancer cases were diagnosed at the median age of 49 years. Median tumor size at diagnosis was 0.9 cm, correlating with a T1 disease. Nodal disease was found only in 4 cases. Breast cancer incidence was the same in the mutation carriers and chest radiotherapy groups, but 3-fold lower in the third group. Diagnosis of breast cancer was most commonly conducted by MRI imaging, and only 6% of cases were diagnosed based solely on mammography findings. Furthermore, 38 women died during follow-up, 29 of them (76%) were BRCA carriers who died from ovarian carcinoma. CONCLUSIONS: Diagnosis at an early stage was achieved in this cohort of women followed in the high risk screening program. Most cases were diagnosed by MRI, thus emphasizing the importance of identifying women at high risk for breast cancer and referring them to the appropriate screening program.

The relationship between the predicted risk of death and psychosocial functioning among women with early-stage breast cancer.

PURPOSE: Many women with early-onset breast cancer experience adverse psychological sequelae which impact on their quality of life. We sought to correlate levels of anxiety and cancer-related distress in women with breast cancer shortly after surgery and one year after treatment with the estimated risk of death. METHODS: We studied 596 women with Stage I to III breast cancer. For each woman we estimated the five-year risk of death based on SEER data from 2010 to 2019. For each woman we measured anxiety and cancer-related distress levels shortly after surgery and one year later. RESULTS: The mean estimated five-year survival was 95%. At one week post-surgery, 59% of women had a clinically significant level of anxiety and 74% had a clinically significant level of cancer-related distress. There was no correlation between the objective risk of death and the level of anxiety or distress, at one week or at one year. CONCLUSIONS: Many women diagnosed with early-stage breast cancers experience significant levels of anxiety and distress. The emotional response to a breast cancer diagnosis is not related to the risk of death per se and other factors should be explored.

Current Issues in Conduct and Reporting of Noninferiority Randomized Controlled Trials in Surgical Management of Cancer Patients.

BACKGROUND: Serious concerns regarding quality of conduct and reporting of noninferiority trials (NITs) have been raised. Systematic analysis of the quality of the surgical NITs is lacking. Assessing the quality of conduct, reporting, and interpretation of surgical NITs in cancer patients is critical given their potential clinical impact. We aim to assess the quality of conduct, reporting, and interpretation of NITs that investigate the effects of surgical management in cancer patients. METHODS: A cross-sectional analysis of papers identified through a comprehensive literature database search was performed. Forty papers employing a phase III noninferiority (NI) randomized trial design to study effects of surgical methodology or sequencing of surgery in patients with solid cancers were included. Papers were assessed for type of analysis, justification of the noninferiority margin (NIM), consistency of type I error with confidence intervals (CIs), ability to achieve the predefined sample size, and interpretations regarding NI. RESULTS: Only half of the papers used both intention-to-treat and per protocol analyses; 62.5% provided no or poor justification for the NIM; 42.5% showed inconsistency of the type I error rate with CIs; 52.5% were deemed poor or fair quality, and 60.0% did not achieve the predefined sample size. One-fifth of the papers provided interpretation of the NI hypothesis that was not in concordance with the CONSORT guidelines. CONCLUSIONS: The quality of conduct, reporting, and interpretation of surgical NITs is suboptimal, requiring further improvements through adherence to guidelines and rigorous assessment at the stages of the study approval, funding, and the peer-review process.

Longitudinal Study of Psychosocial Outcomes Following Surgery in Women with Unilateral Nonhereditary Breast Cancer.

INTRODUCTION: Rates of bilateral mastectomy are rising in women with unilateral, nonhereditary breast cancer. We aim to characterize how psychosocial outcomes evolve after breast cancer surgery. PATIENTS AND METHODS: We performed a prospective cohort study of women with unilateral, sporadic stage 0-III breast cancer at University Health Network in Toronto, Canada between 2014 and 2017. Women completed validated psychosocial questionnaires (BREAST-Q, Impact of Event Scale, Hospital Anxiety & Depression Scale) preoperatively, and at 6 and 12 months following surgery. Change in psychosocial scores was assessed between surgical groups using linear mixed models, controlling for age, stage, and adjuvant treatments. P < .05 were significant. RESULTS: A total of 475 women underwent unilateral lumpectomy (42.5%), unilateral mastectomy (38.3%), and bilateral mastectomy (19.2%). There was a significant interaction (P < .0001) between procedure and time for breast satisfaction, psychosocial and physical well-being. Women having unilateral lumpectomy had higher breast satisfaction and psychosocial well-being scores at 6 and 12 months after surgery compared with either unilateral or bilateral mastectomy, with no difference between the latter two groups. Physical well-being declined in all groups over time; scores were not better in women having bilateral mastectomy. While sexual well-being scores remained stable in the unilateral lumpectomy group, scores declined similarly in both unilateral and bilateral mastectomy groups over time. Cancer-related distress, anxiety, and depression scores declined significantly after surgery, regardless of surgical procedure (P < .001). CONCLUSIONS: Psychosocial outcomes are not improved with contralateral prophylactic mastectomy in women with unilateral breast cancer. Our data may inform women considering contralateral prophylactic mastectomy.

Frequency of Contralateral Prophylactic Mastectomy in Breast Cancer Patients with a Negative BRCA1 and BRCA2 Rapid Genetic Test Result.

BACKGROUND: There is an increasing desire for contralateral prophylactic mastectomy (CPM) among patients with unilateral breast cancer. It is unknown if risk assessment and genetic testing at the time of diagnosis will aid women in their surgical choice. We report on the uptake and predictors of CPM in women receiving a negative genetic test result for BRCA1 and BRCA2 mutations before surgery. METHODS: Women diagnosed with breast cancer between June 2013 and May 2018 were recruited from four academic health sciences centers in Toronto, Canada. Genetic counseling (risk assessment) and genetic testing was performed prior to surgery. Women were asked about their surgical preference before surgery. At 1 year post-surgery we asked what surgery was completed. This study reports on women who received a negative BRCA1/BRCA2 result. RESULTS: A total of 766 women with a mean age of 46 years (range 21-82) were included in the analysis. Before genetic counseling and testing, 37% of the women were undecided or leaning towards CPM; however, after receiving a negative BRCA test, 15% of the women opted for CPM. Thirty percent of women whose mother died of breast cancer elected for CPM, compared with 15% of women whose mother did not die of breast cancer (p = 0.03). CONCLUSIONS: Women receiving a risk assessment and negative BRCA1/BRCA2 genetic test result before surgery use this information to guide their surgical decision. Uptake of CPM for women who were planning on CPM before genetic testing decreases after receiving a negative BRCA1/BRCA2 genetic test result.

Rapid Genetic Testing for BRCA1 and BRCA2 Mutations at the Time of Breast Cancer Diagnosis: An Observational Study.

BACKGROUND: This study aimed to evaluate the impact of rapid genetic testing (RGT) for BRCA1 and BRCA2 at the time of breast cancer diagnosis on treatment choices. Bilateral mastectomy for the treatment of breast cancer in women with a BRCA1 or BRCA2 mutation offers a reduction in the risk of contralateral breast cancer. It is unclear whether offering RGT at the time of breast cancer diagnosis has an impact on women's surgical decision-making. METHODS: Women with breast cancer diagnosed between June 2013 and May 2018 were recruited from four academic health sciences centers in Toronto, Canada. The participants completed a questionnaire before genetic testing, then one week and one year after disclosure of the genetic test result. Before surgery, RGT was performed. Diagnostic, pathologic, and treatment data were compared between those with and those without a BRCA mutation. RESULTS: The study enrolled 1007 women who consented to RGT. The mean age of the participants was 46.3 years, and the median time to result disclosure was 10 days. A BRCA mutation was found in 6% of the women. The women with a BRCA mutation were significantly more likely to elect for bilateral mastectomy than the women without a BRCA mutation (p < 0.0001). Of the BRCA-positive patients, 95.7% reported that they used their genetic test result to make a surgical decision. CONCLUSIONS: The women provided with RGT at the time of breast cancer diagnosis use the genetic information to make treatment decisions, and the majority of those identified with a BRCA mutation elect for a bilateral mastectomy.

TARGIT-R (Retrospective): 5-Year Follow-Up Evaluation of Intraoperative Radiation Therapy (IORT) for Breast Cancer Performed in North America.

BACKGROUND: Intraoperative radiation therapy (IORT) has been investigated for patients with low-risk, early-stage breast cancer. The The North American experience was evaluated by TARGIT-R (retrospective) to provide outcomes for patients treated in "real-world" clinical practice with breast IORT. This analysis presents a 5-year follow-up assessment. METHODS: TARGIT-R is a multi-institutional retrospective registry of patients who underwent lumpectomy and IORT between the years 2007 and 2013. The primary outcome of the evaluation was ipsilateral breast tumor recurrence (IBTR). RESULTS: The evaluation included 667 patients with a median follow-up period of 5.1 years. Primary IORT (IORT at the time of lumpectomy) was performed for 72%, delayed IORT (after lumpectomy) for 3%, intended boost for 8%, and unintended boost (primary IORT followed by whole-breast radiation) for 17% of the patients. At 5 years, IBTR was 6.6% for all the patients, with 8% for the primary IORT cohort and 1.7% for the unintended-boost cohort. No recurrences were identified in the delayed IORT or intended-boost cohorts. Noncompliance with endocrine therapy (ET) was associated with higher IBTR risk (hazard ratio [HR], 3.67). Patients treated with primary IORT who were complaint with ET had a 5-year IBTR rate of 3.9%. CONCLUSION: The local recurrence rates in this series differ slightly from recent results of randomized IORT trials and are notably higher than in previous published studies using whole-breast radiotherapy for similar patients with early-stage breast cancer. Understanding differences in this retrospective series and the prospective trials will be critical to optimizing patient selection and outcomes going forward.

Surgical Morbidity of Full-Thickness Chest Wall Resection for Breast Cancer: A Retrospective Study of a National Database.

BACKGROUND: Full-thickness chest wall resection (FTCWR) is an underused modality for treating locally advanced primary or recurrent breast cancer invading the chest wall, for which little data exist regarding morbidity and mortality. We examined the postoperative complication rates in breast cancer patients undergoing FTCWR using a large multinational surgical outcomes database. METHODS: A retrospective cohort analysis was conducted using the American College of Surgeons National Surgical Quality Improvement Program database. All patients undergoing FTCWR for breast cancer between 2007 and 2016 were identified (n = 137). Primary outcome measures included 30-d postoperative morbidity, composite respiratory complications, and hospital length of stay (LOS). The secondary aim was to compare the postoperative morbidity of FTCWR to those of patients undergoing mastectomy. One-to-one coarsened exact matching was conducted between two groups, which were then compared with respect to morbidity, mortality, reoperations, readmissions, and LOS. RESULTS: The overall rate of postoperative morbidity was 11.7%. Two patients (1.5%) had respiratory complications requiring intubation. Median hospital LOS was 2 d. In the coarsened exact matching analysis, 122 patients were included in each of the two groups. Comparison of matched cohorts demonstrated an overall morbidity for the FTCWR group of 11.5% compared with 8.2% for the mastectomy group (8.2%) (P = 0.52). CONCLUSIONS: FTCWR for the local treatment of breast cancer can be performed with relatively low morbidity and respiratory complications. This is the largest study looking at postoperative complications for FTCWR in the treatment of breast cancer. Future studies are needed to determine the long-term outcomes of FTCWR in this patient population.

Improving Arthroplasty Efficiency and Quality Through Concentrating Service Volume by Complexity: Surviving the Medicare Policy Changes.

We have an academic medical center (AMC), an associated community-based hospital (CBH) and several ambulatory care centers which are being prepared to provide same day discharge (SDD) total joint arthroplasty (TJA) and unicompartmental knee arthroplasty (UKA). The near-capacity AMC cared for medically and technically complicated TJA patients. The CBH wanted to increase volume, improve margins, and become a center of excellence with an efficient hospital outpatient department and SDD TJA experience. METHODS: We transitioned primary, uncomplicated TJA, UKA, and minimally invasive TJA to the CBH. Revision surgeries, patients with extensive comorbidities, and complex primaries were performed at the AMC. Protocols were developed to facilitate SDD UKA and total hip arthroplasty (THA) as well as rapid recovery protocols for total knee arthroplasty (TKA) at both hospitals. A protocol-based system was put in place to make both hospitals ready for the removal of TKA from the Inpatient-Only list to avoid Quality Improvement Organization and possible resultant Recovery Audit Contractor audits if referred after implementation. RESULTS: The CBH volume increased 36.7% (+239). AMC volume slightly decreased (-0.46%, -5) resulting in an increase in margin contribution for the system. CBH quality metrics (surgical site infections, length of stay, readmissions, and mortality) were improved. Surgeon satisfaction improved as their volume, efficiency, quality metrics, and finances were enhanced. Although CBH per case revenue was 80.3% and 74.4% of the AMC for THA and TKA, net margins were 3.6% and 18.8% higher for THA and TKA, respectively. Increased efficiency, lower hospital cost, and higher volume at the CBH allowed for an increase in revenue despite lower reimbursement per case. CONCLUSION: This strategy will help hospital systems improve net margins while improving patient care despite lower net revenue per TJA episode. These strategies will become increasingly important going forward with the transition of higher numbers of TJA patients to outpatient which will be subjected to further decreases in net revenue per patient.

Does oncoplastic surgery increase immediate (30-day) postoperative complications? An analysis of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database.

PURPOSE: Although there has been a significant increase in the use of oncoplastic surgery (OPS), data on the postoperative safety of this approach are limited compared to traditional lumpectomy. This study aimed to compare the immediate (30-day) postoperative complications associated with OPS and traditional lumpectomy. METHODS: An analysis of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was performed on women with breast cancer who underwent OPS or traditional lumpectomy. Logistic regression was used to explore the effect of type of surgery on the outcome of interest. RESULTS: A total of 109,487 women were analyzed of whom 8.3% underwent OPS. OPS had a longer median operative time than traditional lumpectomy. The unadjusted immediate (30-day) overall complication rate was significantly higher with OPS than traditional lumpectomy (3.8% versus 2.6%, p < 0.001). After adjusting for baseline differences, overall 30-day postoperative complications were significantly higher amongst women undergoing OPS compared with traditional lumpectomy (OR 1.41, 95%CI 1.24-1.59). Factors that were independent predictors of overall 30-day complications included higher age, higher BMI, race, smoking status, lymph node surgery, neoadjuvant chemotherapy, ASA class ≥ 3, in situ disease, and year of operation. The interaction term between type of surgery and operative time was not statistically significant, indicating that operative time did not modify the effect of type of surgery on immediate postoperative complications. CONCLUSIONS: Although there were slightly higher overall complication rates with OPS, the absolute rates remained quite low for both groups. Therefore, OPS may be performed in women with breast cancer who are suitable candidates.

Screening women at high risk for breast cancer: one program fits all? : Subgroup analysis of a large population high risk breast screening program.

INTRODUCTION: The Ontario High Risk Breast Screening program follows women aged 30-69 at an increased risk of breast cancer, using a yearly mammography and breast MRI. The aim of this study is to determine the clinical outcomes for the enrolled women. METHODS: Observational cohort study following 2081 participants in the high-risk screening program 2011-2017. The participants were divided into three subgroup according to their risk criteria: (a) known carriers of pathogenic variants (PV) in hereditary breast cancer genes. (b) Previous chest radiotherapy. (c) Estimated life time risk (ELR) ≥ 25%, calculated using the International Breast Cancer Intervention Study (IBIS) tool, with no known mutation or previous radiation. All Breast Cancer (BC) diagnosed during the follow-up time were recorded. RESULTS: 673 women carried PVs in hereditary breast cancer genes, 159 had a history of chest radiotherapy, and 1249 had an ELR ≥ 25%. The total cohort of screening years was 8126. Median age at BC diagnosis was 41 for the first group, 47 for the second group and 51 for the third. BC incidence rate was 18.2 for PV mutation carriers, 17.9 for the chest radiotherapy group and 6.2 for ELR ≥ 25%. Hazard ratio was similar for the first two groups, but significantly lower for the ELR ≥ 25% group. When stratifying by age, the incidence rate in the ELR ≥ 25% increased over time, until it became similar to that of the other subgroups after age 50. CONCLUSION: Our findings question the need to screen women with an elevated lifetime risk using the same screening practices used for women who are PV mutation carriers, or with a history of chest radiation, prior to the age of 50.

Cellular fibroepithelial lesions diagnosed on core needle biopsy: Is there any role of clinical-sonography features helping to differentiate fibroadenomas and phyllodes tumor?

OBJECTIVE: The purpose of this study is to determine the role of clinico-sonographic features of breast cellular fibroepithelial lesions (CFELs) diagnosed on core needle biopsy (CNB) in the differentiation between fibroadenoma (FA) and phyllodes. MATERIALS AND METHODS: Results of consecutive women with a CNB showing CFEL from 2005 to 2010 were retrospectively reviewed. Clinical and sonographic findings were compared with surgical outcomes. Chi-square and Fisher's exact tests were used followed by a regression model for statistical analysis. RESULTS: A total of 131 women with 134 CFEL were included in the study; 89 (66%) were FAs and 45 (34%) were phyllodes (32 benign; 13 malignant). Significant predictors of increased risk of phyllodes tumor were patient age equal to or greater than 50 years (P = .021) and lesion size less than 2 cm at sonography (P = .043). No other imaging or clinical features were able to differentiate FA from phyllodes tumors. CONCLUSION: CFEL with a larger size in older women is associated with the surgical pathological result of phyllodes tumor and management should be tailored accordingly. Younger patients with small size nodules might be approached less aggressively, depending on a personalized discussion with the surgeons, taking into account the results obtained in this study.

Derivation of cancer no significant risk levels and screening safety assessment for 2-nitropropane in spray products.

Two proposition 65 no-significant-risk level (NSRL)-type values were derived for 2-nitropropane (2-NP), in the absence of a Californian published NSRL. In addition, a safety assessment was performed based on estimated typical consumer inhalation and dermal exposure to 2-NP during indoor application of paint from a spray can containing the solvent 1-nitropropane. For the NSRL derivation, benchmark dose (BMD) modeling was performed using hepatocellular carcinoma incidence data from 2-NP single exposure inhalation studies in Sprague-Dawley rats. Several BMD models provided an acceptable fit for the male rat hepatocellular carcinoma incidence data (gamma, log-probit, log-logistic and multistage); therefore, the mean of the BMD lower limits from each model were used as the point of departure to derive the inhalation cancer potency. The oral human cancer potency was derived from the inhalation human cancer potency based on the ratio of the uptake factors for inhalation vs. oral routes. The derived inhalation and oral NSRLs are 67 µg/day and 32 µg/day, respectively. For the inhalation and dermal exposure assessment, three key factors were analyzed: the 2-NP residual concentration in the spray paint product, the mass of spray paint used and the frequency of use. Based on the screening exposure assessment, potential consumer inhalation and dermal exposure to 2-NP from indoor application of paint from a spray can does not exceed our proposed NSRLs, and a warning label is therefore not required for spray can products containing the solvent 1-nitropropane where 2-NP is a minor contaminant.

Predictors of uptake of contralateral prophylactic mastectomy in women with nonhereditary breast cancer.

BACKGROUND: The rates of contralateral prophylactic mastectomy (CPM) are increasing in women with breast cancer. Previous retrospective research has examined clinical and demographic predictors of the uptake of CPM. However, to the authors' knowledge, there has been very little prospective research to date that has examined psychosocial functioning prior to breast cancer surgery to determine whether psychosocial functioning predicts uptake of CPM. The current study was conducted to evaluate demographic, clinical, and psychosocial predictors of the uptake of CPM in women with unilateral breast cancer without a BRCA1 or BRCA2 mutation. METHODS: Women with unilateral non-BRCA-associated breast cancer completed questionnaires prior to undergoing breast cancer surgery. Participants completed demographic and psychosocial questionnaires assessing anxiety, depression, cancer-related distress, optimism/pessimism, breast satisfaction, and quality of life. Pathological and surgical data were collected from medical charts. RESULTS: A total of 506 women consented to participate, 112 of whom (22.1%) elected to undergo CPM. Age was found to be a significant predictor of CPM, with younger women found to be significantly more likely to undergo CPM compared with older women (P < .0001). The rate of CPM was significantly higher in women with noninvasive breast cancer compared with those with invasive breast cancer (P < .0001). Women who elected to undergo CPM had lower levels of presurgical breast satisfaction (P = .01) and optimism (P = .05) compared with women who did not undergo CPM. CONCLUSIONS: Psychosocial functioning at the time of breast cancer surgery decision making impacts decisions related to CPM. Women who have lower levels of breast satisfaction (body image) and optimism are more likely to elect to undergo CPM. It is important for health care providers to take psychosocial functioning into consideration when discussing surgical options.

Phase II clinical trial of adoptive cell therapy for patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and low-dose interleukin-2.

Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) has shown significant clinical benefit, but is limited by toxicities due to a requirement for post-infusion interleukin-2 (IL-2), for which high dose is standard. To assess a modified TIL protocol using lower dose IL-2, we performed a single institution phase II protocol in unresectable, metastatic melanoma. The primary endpoint was response rate. Secondary endpoints were safety and assessment of immune correlates following TIL infusion. Twelve metastatic melanoma patients were treated with non-myeloablative lymphodepleting chemotherapy, TIL, and low-dose subcutaneous IL-2 (125,000 IU/kg/day, maximum 9-10 doses over 2 weeks). All but one patient had previously progressed after treatment with immune checkpoint inhibitors. No unexpected adverse events were observed, and patients received an average of 6.8 doses of IL-2. By RECIST v1.1, two patients experienced a partial response, one patient had an unconfirmed partial response, and six had stable disease. Biomarker assessment confirmed an increase in IL-15 levels following lymphodepleting chemotherapy as expected and a lack of peripheral regulatory T-cell expansion following protocol treatment. Interrogation of the TIL infusion product and monitoring of the peripheral blood following infusion suggested engraftment of TIL. In one responding patient, a population of T cells expressing a T-cell receptor Vß chain that was dominant in the infusion product was present at a high percentage in peripheral blood more than 2 years after TIL infusion. This study shows that this protocol of low-dose IL-2 following adoptive cell transfer of TIL is feasible and clinically active. (ClinicalTrials.gov identifier NCT01883323.).

Is immediate breast reconstruction safe in women over 70? An analysis of the National Surgical Quality Improvement Program (NSQIP) database.

PURPOSE: The safety of immediate breast reconstruction (IBR) in older women is largely unknown. This study aimed to determine the 30-day postoperative complication rates following IBR (implant-based or autologous) in older women (≥ 70 years) with breast cancer and to compare them to younger women (18-69 years). METHODS: The National Surgical Quality Improvement Program (NSQIP) database was used to identify women with in situ or invasive breast cancer who underwent IBR (2005-2016). Outcomes included 30-day postoperative morbidity and mortality, which were compared across age groups stratified by type of reconstruction. RESULTS: Of 28,850 women who underwent implant-based and 9123 who underwent autologous reconstruction, older women comprised 6.5% and 5.7% of the sample, respectively. Compared to younger women, older women had more comorbidities, shorter operative times, and longer length of hospital stay. In the implant-based reconstruction group, the 30-day morbidity rate was significantly higher in older women (7.5% vs 5.3%, p < 0.0001) due to higher rates of infectious, pulmonary, and venous thromboembolic events. Wound morbidity and prosthesis failure occurred equally among age groups. In the autologous reconstruction group, there was no statistically significant difference in the 30-day morbidity rates (older 9.5% vs younger 11.6%, p = 0.15). Both wound morbidity and flap failure rates were similar between the two age groups. For both reconstruction techniques, mortality within 30 days of breast surgery was rare. CONCLUSION: Immediate breast reconstruction is safe in older women. These data support the notion that surgeons should discuss IBR as a safe and integral part of cancer treatment in well-selected older women.