Impact of autologous breast reconstruction on bra fit.

PURPOSE: To inform bra design by analyzing 3D surface images of breast cancer patients who underwent autologous breast reconstruction. METHODS: We computed bra design measurements on 3D surface images of patients who underwent unilateral and bilateral autologous breast reconstruction. Breast measurements and right-left symmetry between preoperative baseline and postoperative time points were compared using either paired Student t-test or Wilcoxon signed-rank test, depending on the data's distribution. Regression analysis determined associations between measurements and patient characteristics such as age. Postoperative measurements and symmetry differences were also compared between autologous and implant-based breast reconstruction. RESULTS: Among participants who underwent bilateral autologous breast reconstruction, the reconstructed breasts were smaller and positioned higher on the chest wall than their native breasts. For patients who underwent unilateral reconstruction, similar postoperative changes were observed in the contralateral breast due to symmetry procedures. Overall, for participants whose baseline breast measurements showed substantial asymmetry, unilateral reconstruction decreased right-left asymmetry whereas bilateral reconstruction amplified right-left asymmetry. Preoperative baseline breast measurements, age, and BMI were statistically significantly associated with most postoperative breast measurements for participants who underwent bilateral autologous reconstruction. Compared to implant-based reconstruction, autologous reconstruction resulted in fewer changes in breast shape and symmetry that are pertinent to bra fit. CONCLUSION: Preoperative baseline breast measurements, age, and BMI can impact bra designs for breast cancer survivors who undergo autologous reconstruction due to size, shape, and symmetry changes. Bra needs of people who undergo autologous reconstruction differ from those who undergo implant-based reconstruction.

High-Risk Features of Esophageal Adenocarcinoma Following Neoadjuvant Chemoradiation: Patients for Whom Surgery Should Not Be Delayed.

OBJECTIVE: Clinical predictors of pathological complete response have not reliably identified patients for whom an organ-sparing approach following neoadjuvant chemoradiation be undertaken for esophageal cancer patients. We sought to identify high-risk predictors of residual carcinoma that may preclude patients from a selective surgical approach. BACKGROUND: Patients treated with neoadjuvant chemoradiation followed by esophagectomy for esophageal adenocarcinoma were identified. PATIENTS AND METHODS: Correlation between clinical and pathologic complete responses were examined. Regression models and recursive partitioning were utilized to identify features associated with residual carcinoma. External validation of these high-risk factors was performed on a data set from an independent institution. RESULTS: A total of 326 patients were identified, in whom clinical complete response was noted in 104/326 (32%). Pathologic complete response was noted in only 33/104 (32%) of these clinical complete responders. Multivariable analysis identified that the presence of stricture ( P =0.011), positive biopsy ( P =0.010), and signet ring cell histology ( P =0.019) were associated with residual cancer. Recursive partitioning corroborated a 94% probability of residual disease, or greater, for each of these features. The positive predictive value was >90% for these characteristics. A SUV max >5.4 at the esophageal primary in the absence of esophagitis was also a high-risk factor for residual carcinoma. External validation confirmed these high-risk factors to be implicated in the finding of residual carcinoma. CONCLUSIONS: Clinical parameters of response are poor predictors of complete pathologic response leading to challenges in selecting candidates for active surveillance. However, we characterize several high-risk features for residual carcinoma which indicate that esophagectomy should not be delayed.

Cytoplasmic Cyclin E Expression Predicts for Response to Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND: Pathologic complete response (pCR) has been shown to be associated with favorable outcomes in breast cancer. Predictors of pCR could be useful in guiding treatment decisions regarding neoadjuvant therapy. The objective of this study was to evaluate cyclin E as a predictor of response to neoadjuvant chemotherapy in breast cancer. METHODS: Patients (n = 285) with stage II-III breast cancer were enrolled in a prospective study and received neoadjuvant chemotherapy with anthracyclines, taxanes, or combination of the two. Pretreatment biopsies from 190 patients and surgical specimens following chemotherapy from 192 patients were available for immunohistochemical analysis. Clinical and pathologic responses were recorded and associated with presence of tumor infiltrating lymphocytes, cyclin E, adipophilin, programmed cell death-ligand 1, and elastase staining and other patient, tumor and treatment characteristics. RESULTS: The pCR rate was significantly lower in patients with cytoplasmic cyclin E staining compared with those who had no cyclin E expression (16.1% vs 38.9%, P = 0.0005). In multivariable logistic regression analysis, the odds of pCR for patients who had cytoplasmic negative tumors was 9.35 times (P value < 0.0001) that compared with patients with cytoplasmic positive tumors after adjusting for ER, PR, and HER2 status. Cytoplasmic cyclin E expression also predicts long-term outcome and is associated with reduced disease free, recurrence free, and overall survival rates, independent of increased pretreatment tumor infiltrating lymphocytes. CONCLUSIONS: Cyclin E independently predicted response to neoadjuvant chemotherapy. Hence, its routine immunohistochemical analysis could be used clinically to identify those breast cancer patients expected to have a poor response to anthracycline/taxane-based chemotherapy.

Is Sentinel Lymph Node Dissection Warranted for Patients with a Diagnosis of Ductal Carcinoma In Situ?

BACKGROUND: Positive sentinel lymph node (SLN) findings in ductal carcinoma in situ (DCIS) range from 1 to 22 % but have unknown biologic significance. This study sought to identify predictors of positive SLNs and to assess their clinical significance for patients with an initial diagnosis of DCIS. METHODS: The study identified 1234 patients with an initial diagnosis of DCIS who underwent SLN dissection (SLND) at our institution from 1997 through 2011. Positive SLN findings were categorized as isolated tumor cells (ITCs) (≤0.2 mm), micrometastases (>0.2-2 mm), or macrometastases (>2 mm). Predictors of positive SLNs were analyzed, and survival outcomes were examined. RESULTS: Positive SLN findings were identified in 132 patients (10.7 %): 66 patients with ITCs (5.4 %), 36 patients with micrometastases (2.9 %), and 30 patients with macrometastases (2.4 %). Upstaging to microinvasive (n = 68, 5.5 %) or invasive (n = 259, 21.0 %) cancer occurred for 327 patients (26.5 %). Factors predicting positive SLNs included diagnosis by excisional biopsy (odds ratio [OR] 1.90; P = 0.007), papillary histology (OR 1.77; P = 0.006), DCIS larger than 2 cm (OR 1.55; P = 0.030), more than three interventions before SLND (4 interventions: OR 2.04; P = 0.022; ≥5 interventions: OR 3.87; P < 0.001), and occult invasion (microinvasive: OR 3.44; P = 0.001; invasive: OR 6.21; P < 0.001). The median follow-up period was 61.7 months. Patients who had pure DCIS with and without positive SLNs had equivalent survival rates (100.0 vs 99.7 %; P = 0.679). Patients with occult invasion and positive SLNs had the worst survival rate (91.7 %; P < 0.001). CONCLUSIONS: Occult invasion and more than three total interventions were the strongest predictors of positive SLN findings in patients with an initial diagnosis of DCIS. This supports the theory of benign mechanical transport of breast epithelial cells. Except for patients at high risk for invasive disease, routine use of SLND in DCIS is not warranted.

Undergarment Needs and Challenges for Breast Cancer Survivors: A Qualitative Study.

Purpose: Breast cancer surgery, even with reconstruction, can make it difficult for patients to find a bra that fits properly, is comfortable, and meets their aesthetic standards. We explored breast cancer survivors' experiences with bras over time to identify preferences, needs, and challenges throughout their journeys. Methods: Fifteen women who had undergone mastectomy and either delayed or immediate breast reconstruction participated in the study. Focus groups were conducted to explore the participants' current experiences with bras. They were also prompted to recall their experiences before mastectomy and immediately after reconstruction. The discussion included bra materials, styles, construction techniques, color, quality, and price. Results: Thematic analysis generated five major themes: "Sense of normalcy and personal well-being," "Struggles immediately following surgery," "Transitions in bra experiences and preference," "Practicality with outfit," and "Association between quality and price". Conclusion: Breast cancer survivors' well-being is linked to their experiences with bras and the associated purchasing process, and bra needs change throughout the cancer care journey. Survivors' experiences with bras impact their sense of normalcy and sense of control over significant bodily changes arising from cancer and its treatment. The study underscores the importance of future research on examining the relationship between survivors' quality of life and garment experiences, including factors such as color choices, closure options, and adjustability for individual needs.

The influence of histopathologic tumor viability on long-term survival and recurrence rates following neoadjuvant therapy for esophageal adenocarcinoma.

OBJECTIVE: Our aim was to validate the effect of histopathologic tumor viability (HTV) on extended survival outcomes and assess the prognostic ability of the current staging system in patients receiving preoperative chemoradiotherapy (CRT). BACKGROUND: The American Joint Committee on Cancer, 7th Edition, esophageal carcinoma staging system is derived from patients treated with surgery alone and does not account for the treatment effect of CRT. The extent of HTV after CRT is based on response to neoadjuvant therapy and has been shown to correlate with patient outcome. METHODS: Medical records of 1278 patients who underwent esophagectomy (1990-2011) were reviewed; 784 patients underwent preoperative CRT. Histologic tumor viability was assessed in 602 patients and classified as 0% to 10%, 11% to 50%, and more than 50%. Survival was estimated using the Kaplan-Meier method at potential median follow-up of 67 months. Univariate and multivariate analyses identified variables associated with survival. RESULTS: Multivariate analysis identified HTV of greater than 50% (P < 0.001, HR 2.5), positive pathologic nodal status (P < 0.001, HR 1.6), and positive clinical nodal status (P = 0.002, HR 1.5) but not pathologic T status (P = 0.816, HR 1.2) to be independently associated with survival. Actuarial 5- and 10-year survival was 52% and 43% (HTV of 0%-10%), 45% and 33% (HTV of 11%-50%), and 16% for both (HTV of >50%). The best 5-year survival 56% was achieved in N0 patients with HTV of 0% to 10% (P = 0.056, HR 1.0), contrary to 6% observed in node-positive patients with HTV of greater than 50% (P < 0.001, HR 3.1). Patients with HTV of greater than 50% demonstrated distant recurrence more frequently than those with HTV of less than 50% (51% vs 33%, P = 0.010, OR: 2.2) CONCLUSIONS:: After preoperative chemoradiation, long-term outcomes of esophageal carcinoma are best predicted utilizing histologic tumor viability; HTV may be a practical early endpoint predicting efficacy of therapy.

Impact of Autologous Breast Reconstruction on Bra Fit.

Purpose: To inform bra design by analyzing 3D surface images of breast cancer patients who underwent autologous breast reconstruction. Methods: We computed bra design measurements on 3D surface images of patients who underwent unilateral and bilateral autologous breast reconstruction. Breast measurements and right-left symmetry between preoperative baseline and postoperative time points were compared using either paired Student t test or Wilcoxon signed rank test, depending on the data's distribution. Regression analysis determined associations between measurements and patient characteristics such as age. Postoperative measurements and symmetry differences were also compared between autologous and implant-based breast reconstruction. Results: Among participants who underwent bilateral autologous breast reconstruction, the reconstructed breasts were smaller and positioned higher on the chest wall than their native breasts. For patients who underwent unilateral reconstruction, similar postoperative changes were observed in the contralateral breast due to symmetry procedures. Overall, for participants whose baseline breast measurements showed substantial asymmetry, unilateral reconstruction decreased right-left asymmetry whereas bilateral reconstruction amplified right-left asymmetry. Preoperative baseline breast measurements, age, and BMI were statistically significantly associated with most postoperative breast measurements for participants who underwent bilateral autologous reconstruction. Compared to implant-based reconstruction, autologous reconstruction resulted in fewer changes in breast shape and symmetry that are pertinent to bra fit. Conclusion: Preoperative baseline breast measurements, age, and BMI can impact bra designs for breast cancer survivors who undergo autologous reconstruction due to size, shape, and symmetry changes. Bra needs of people who undergo autologous reconstruction differ from those who undergo implant-based reconstruction.

Followup of patients with papillary thyroid cancer: in search of the optimal algorithm.

BACKGROUND: Cervical recurrence occurs in up to 30% of patients after surgical treatment for papillary thyroid cancer. This study sought to determine an appropriate algorithm for followup evaluation. STUDY DESIGN: Patients undergoing total thyroidectomy for papillary thyroid cancer were identified. Clinicopathologic data were recorded, as were the results of all followup evaluations including radioiodine scan, cervical ultrasonography, and serum thyroglobulin levels. The disease recurrence-free survival probability was estimated, and risk factors for recurrence were determined. RESULTS: Thyroidectomy with or without neck dissection was performed in 162 patients. We excluded 36 patients (followup less than 6 months in 26, extracervical disease at diagnosis in 4, unknown tumor size in 6) from the analysis. Of the remaining 126 patients, 109 (86.5%) had no evidence of disease, with serum thyroglobulin < 1 ng/mL at last followup; 4 (3.2%) had no evidence of disease (negative imaging), with serum thyroglobulin > 1 ng/mL, and 13 (10.3%) had recurrent disease. Cervical recurrence occurred in nine patients, all detected by routine ultrasonography. Pulmonary metastases occurred in four patients; three were diagnosed by chest CT and one by radioiodine scan. Thyroid stimulating hormone-suppressed thyroglobulin levels were available in 11 of the 13 patients and were elevated in 9. Patients with high T stage (extrathyroidal extension), or high N stage had an increased risk of recurrence. CONCLUSIONS: A followup strategy emphasizing routine cervical ultrasonography and unstimulated thyroglobulin is effective in identifying patients with recurrent papillary thyroid cancer, and may minimize the indiscriminate use of therapeutic radioiodine for radiographically occult disease. Surgery remains the optimal treatment of cervical recurrence, which is the dominant pattern of treatment failure.

CDK4/6 Inhibitors Sensitize Rb-positive Sarcoma Cells to Wee1 Kinase Inhibition through Reversible Cell-Cycle Arrest.

Research into the biology of soft tissue sarcomas has uncovered very few effective treatment strategies that improve upon the current standard of care which usually involves surgery, radiation, and chemotherapy. Many patients with large (>5 cm), high-grade sarcomas develop recurrence, and at that point have limited treatment options available. One challenge is the heterogeneity of genetic drivers of sarcomas, and many of these are not validated targets. Even when such genes are tractable targets, the rarity of each subtype of sarcoma makes advances in research slow. Here we describe the development of a synergistic combination treatment strategy that may be applicable in both soft tissue sarcomas as well as sarcomas of bone that takes advantage of targeting the cell cycle. We show that Rb-positive cell lines treated with the CDK4/6 inhibitor palbociclib reversibly arrest in the G1 phase of the cell cycle, and upon drug removal cells progress through the cell cycle as expected within 6-24 hours. Using a long-term high-throughput assay that allows us to examine drugs in different sequences or concurrently, we found that palbociclib-induced cell-cycle arrest poises Rb-positive sarcoma cells (SK-LMS1 and HT-1080) to be more sensitive to agents that work preferentially in S-G2 phase such as doxorubicin and Wee1 kinase inhibitors (AZD1775). The synergy between palbociclib and AZD1775 was also validated in vivo using SK-LMS1 xenografts as well as Rb-positive patient-derived xenografts (PDX) developed from leiomyosarcoma patients. This work provides the necessary preclinical data in support of a clinical trial utilizing this treatment strategy. Mol Cancer Ther; 16(9); 1751-64. ©2017 AACR.

Global Adverse Event Reports of Breast Implant-Associated ALCL: An International Review of 40 Government Authority Databases.

BACKGROUND: Tracking world cases of breast implant-associated anaplastic large cell lymphoma (ALCL) is currently limited to patient registries at a few academic centers, dependent upon patient referral and case reports in the literature. The purpose of this study was to review and compare federal database adverse event reports of breast implant-associated ALCL encompassing the major breast implant markets worldwide. METHODS: Federal implantable device regulatory bodies were contacted and database queries were performed for 40 countries. Demographics, device characteristics, pathology, treatment modalities, and outcomes were assessed when available. RESULTS: For the countries queried, 363 unique cases were reported for breast implant-associated ALCL. Search terms "anaplastic" and "ALCL" were queried of the U.S. Manufacturer and User Facility Device Experience (MAUDE) database and yielded 258 unique cases as of September 2015, of which only 130 had pathologic markers performed. Implant surface was textured significantly more than smooth (50 percent versus 4.2 percent; p = 0.0001). Treatment, when reported (n = 136), included explantation [n = 125 (91.9 percent)], chemotherapy [n = 42 (30.8 percent)], radiation therapy [n = 25 (18.4 percent)], and/or stem cell transplant [n = 9 (6.6 percent)], and five deaths were reported. CONCLUSIONS: Federal reporting of breast implant-associated ALCL has limitations in providing clinical history, treatment, and oncologic follow-up. Worldwide and country-specific total and textured implant sales data are needed to determine critical incidence and prevalence analysis. International multi-institutional collaborations and centralized tissue consortiums working in concert with federal authorities are necessary to acquire accurate complete data on breast implant-associated ALCL.

Impact of tumor length on long-term survival of pT1 esophageal adenocarcinoma.

INTRODUCTION: The impact of esophageal tumor length on pT1 esophageal adenocarcinoma has not been well evaluated. METHODS: Case histories of all patients (n = 133) undergoing esophageal resection from 1979 to 2007 with pT1 adenocarcinoma of the esophagus were reviewed. Univariate and multivariate analyses of esophageal tumor length and other standard prognostic factors were performed. RESULTS: Patients with early-stage pT1 esophageal adenocarcinoma with tumors less than 3 cm demonstrate decreased long-term survival (3 years: >3 cm = 46% vs 93%; P < .001) and higher risk of lymph node involvement (lymph node positive: >3 cm = 47% vs 10%; P < .001). Multivariable analysis shows that esophageal tumor length (>3 cm) is an independent risk factor for survival in patients with pT1 early-stage esophageal cancer (hazard ratio: 4.8, 95% confidence intervals: 1.4-16.5; P < .001) even when controlled for submucosal involvement, lymph node involvement, and lymphatic/vascular invasion status. In combination with submucosal involvement, esophageal tumor length (>3 cm) identifies a high-risk population of pT1 esophageal adenocarcinoma (3 years: group 1 [0 risk factors] = 100%, group 2 [1 risk factor] = 87%, and group 3 [2 risk factors] = 33%; P < .001). CONCLUSIONS: This study demonstrates that esophageal tumor length (>3 cm) is a risk factor for long-term survival and lymph node involvement in early-stage pT1 esophageal adenocarcinoma. Esophageal tumor length (>3 cm) in combination with submucosal involvement may help to identify a high-risk group of patients with pT1 esophageal adenocarcinoma.