Breast Cancer Survivors' Perceptions of Prevention versus Control of Future Cancer Recurrence.

BACKGROUND: The Institute of Medicine has established Survivorship Care Planning as a critical component of cancer care to ensure that cancer survivors receive the appropriate follow-up care in a timely manner and support cancer survivors in dealing with the risk of recurrence, yet little is known about how cancer survivors think about preventing or controlling future cancer recurrence. This study sought to assess breast cancer women's perceived prevention and perceived control of future cancer recurrence. METHODS: Women with a history of breast cancer (n=114) were surveyed, and data were analyzed using concurrent mixed methods. Binary logistic regression models examined predictors of perceived prevention and perceived control of cancer recurrence. RESULTS: Most women perceived that they could control cancer recurrence (89%); few (30%) perceived that they could prevent cancer recurrence. Women reported components of the timeline (e.g., early diagnosis), identity (e.g., cancer in body), causes (e.g., hereditary), consequences (e.g., witness success), and cure/control (e.g., exercise) or lack of cure/control. Women who reported lack of control were less likely to perceive that they could control cancer recurrence. Women who reported causes were less likely to perceive that they could prevent or control cancer recurrence. CONCLUSIONS: Women's perceptions about the prevention and control of cancer recurrence are important and different factors in the minds of women with breast cancer. Most women believed they could control cancer recurrence; however, few believed they could prevent cancer recurrence. Interventions to focus on control of cancer recurrence, focusing on evidence-based clinical and lifestyle interventions, are needed.

The Lack of Consensus of International Contouring Guidelines for the Dorsal Border of the Chest Wall Clinical Target Volume: What is the Impact on Organs at Risk and Relationships to Patterns of Recurrence in the Modern Era?

PURPOSE: Variation exists in cooperative group recommendations for the dorsal border for the chest wall clinical target volume (CTV). We aimed to quantify the impact of this variation on doses to critical organs and examine patterns of chest wall recurrence relative to the pectoralis muscle. METHODS AND MATERIALS: We retrospectively assessed patterns of chest wall recurrence quantified to the recommended CTV borders for women treated between 2005 and 2017. We compared treatment plans for 5 women who were treated with left postmastectomy radiation therapy, with the chest wall contoured using varying dorsal borders for CTV: (1) Anterior pleural surface (Radiation Therapy Oncology Group), (2) anterior surface of pectoralis major (European Society for Radiotherapy and Oncology), and (3) anterior rib surface (institutional practice). Treatment plans were generated for 50 Gy in 25 fractions. Doses to organs-at-risk were compared using paired-sample t tests. RESULTS: Institutional patterns of chest wall recurrence were 64.7% skin and subcutaneous tissue, 23.5% both anterior to and between the pectoralis muscles, and 11.8% isolated to the tissue between the pectoralis major and minor. No chest wall recurrences were noted deep to pectoralis minor. When comparing the plans generated per the Radiation Therapy Oncology Group versus European Society for Radiotherapy and Oncology contouring guidelines, the mean lung V20Gy, heart mean dose, and left anterior descending artery mean dose were 33.5% versus 29.4% (P < .01), 5.2 Gy versus 3.2Gy (P = .02), and 27.3Gy versus 17.8Gy (P = .04), respectively. CONCLUSIONS: The recommended variations in the dorsal chest wall CTV border have significant impact on doses to the heart and lungs. Although our study was limited by small numbers, our institutional patterns of recurrence would support a more anterior dorsal border for the chest wall CTV consistent with older literature.

Healthcare Utilization and Costs During the Initial Phase of Care Among Elderly Women With Breast Cancer.

Background: Understanding the patterns of healthcare utilization and costs during the initial phase of care (12 months after breast cancer [BC] diagnosis) in older women (aged ≥65 years) is crucial in the allocation of Medicare resources. The objective of this study was to determine healthcare utilization and costs during the initial phase of care in older, female, Medicare fee-for-service beneficiaries diagnosed with BC, and to determine the factors associated with higher costs. Methods: A retrospective observational study using the SEER-Medicare linked database was conducted in 69,307 women aged ≥66 years diagnosed with primary incident BC in 2003-2009 to determine healthcare utilization, average costs, and costs for specific services during the initial phase of care. Generalized linear model regression was conducted to identify the factors associated with higher costs in a multivariate framework. Results: A total of 96% of women were treated with surgery during the initial phase of BC care, whereas 21% and 54% underwent chemotherapy and radiotherapy, respectively. Costs during the initial phase of care totalled $28,075 in 2012 USD, comprising $13,344 for physician services and $7,456 for outpatient services. Factors associated with higher costs during the initial phase of care were younger age (66-69 years), African American race, higher household income, advanced stages of BC, initial BC treatment, higher number of primary care physician visits, and presence of comorbidities and/or a mental condition. Conclusions: The economic burden of BC is substantial during the initial phase of care. Physician and outpatient services accounted for the highest proportion of costs. Predisposing factors, need-related factors, healthcare use, and external environmental healthcare factors significantly predicted costs during the initial phase of care.

Combination of Eribulin and Aurora A Inhibitor MLN8237 Prevents Metastatic Colonization and Induces Cytotoxic Autophagy in Breast Cancer.

Recent findings suggest that the inhibition of Aurora A (AURKA) kinase may offer a novel treatment strategy against metastatic cancers. In the current study, we determined the effects of AURKA inhibition by the small molecule inhibitor MLN8237 both as a monotherapy and in combination with the microtubule-targeting drug eribulin on different stages of metastasis in triple-negative breast cancer (TNBC) and defined the potential mechanism of its action. MLN8237 as a single agent and in combination with eribulin affected multiple steps in the metastatic process, including migration, attachment, and proliferation in distant organs, resulting in suppression of metastatic colonization and recurrence of cancer. Eribulin application induces accumulation of active AURKA in TNBC cells, providing foundation for the combination therapy. Mechanistically, AURKA inhibition induces cytotoxic autophagy via activation of the LC3B/p62 axis and inhibition of pAKT, leading to eradication of metastases, but has no effect on growth of mammary tumor. Combination of MLN8237 with eribulin leads to a synergistic increase in apoptosis in mammary tumors, as well as cytotoxic autophagy in metastases. These preclinical data provide a new understanding of the mechanisms by which MLN8237 mediates its antimetastatic effects and advocates for its combination with eribulin in future clinical trials for metastatic breast cancer and early-stage solid tumors. Mol Cancer Ther; 15(8); 1809-22. ©2016 AACR.

Pancreatectomy in Patients with Impaired Renal Function: How Risky Is It?

Chronic renal impairment causes profound physiologic and metabolic changes. Its impact on surgical outcome after pancreatectomy is not well established. We sought to quantify complication rates of pancreatectomy in patients with chronic renal impairment. Database from the American College of Surgeons National Surgical Quality Improvement Project (2005-2011) was queried to identify patients with chronic renal impairment who underwent pancreatectomy. The study population consisted of 16,708 patients of whom 16,649 patients were not on dialysis and 59 patients were on dialysis. Overall mortality for those on dialysis was 5.1 per cent, whereas it was 2.3 per cent for those not on dialysis (P = 0.114). Patients on dialysis were more likely to have failure to wean ventilation (P < 0.001), reintubation (P = 0.004), myocardial infarction (P = 0.007), and sepsis (P = 0.046). Patients not on dialysis were then divided into three groups: serum creatinine levels <1.2 mg/dL, between 1.2 mg/dL and 2.0 mg/dL, and >2.0 mg/dL. We found the mortality rates for these three groups were 2.0 per cent, 4.6 per cent, and 7.5 per cent, respectively (P < 0.001). In conclusion, need for dialysis is associated with increased postoperative complications. Increased serum creatinine levels were associated with increased mortality rates. These findings should facilitate informative risk/benefit calculation for patients with renal impairment who are considering pancreatectomy.

Comparison between Ultrasound and Pathologic Status of Axillary Lymph Nodes in Clinically Node-negative Breast Cancer Patients.

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in clinically node-negative breast cancer patients. Ultrasound (US) has shown promise when used to assess axillary lymph nodes preoperatively, thus aiding surgical decision making. We examined the correlation between preoperative US and SLNB results to further clarify the role of US in clinicopathologic staging of breast cancer when the axilla is clinically negative on physical examination. Our institutional cancer registry was used to identify clinically node-negative patients diagnosed with breast cancer from January 1, 2009 to December 31, 2012. Variables including age, body mass index, date of surgery, date of diagnosis, US results, US-directed biopsy results, SLNB results, and final pathology were recorded. Incomplete charts were excluded. In all, 249 patients were included. Sensitivity/specificity of US in the clinically negative axilla were 7.4 per cent and 91.8 per cent, respectively. The false-positive rate was 80 per cent, whereas the negative predictive value was 78 per cent. The effect of time from diagnosis/US to SLNB, interpreting radiologist, year in which US was performed, and body mass index were not statistically significant. US in the clinically node-negative patient, although useful when it leads to a positive needle biopsy result, is unlikely to replace SLNB owing to its low sensitivity and a high false-positive rate. Further prospective study into the role of US in the evaluation of the clinically negative axilla is warranted.

Health Behaviors Among Breast Cancer Patients and Survivors.

BACKGROUND: With improved treatments, the survival rate for breast cancer patients is increasing. With the improvements in quantity of life, research in the field of cancer survivorship has turned its attention to psychosocial functioning and health behaviors. OBJECTIVES: The purpose of this study was to examine how those currently under treatment and those completing treatment engaged in health behaviors (ie, diet, vitamin use, exercise, and cancer screening) and if psychosocial predictors, guided by the Self-regulation Model, also play a role. METHODS: Using the Self-regulation Model, the current survey and medical record review examined health behaviors (diet, vitamin use, exercise, cancer screening) in individuals in active treatment for breast cancer and in those completing treatment (n = 141). RESULTS: Regression models revealed that those in active treatment had less healthy food consumption, vitamin use, and clinical examinations than did treatment completers. Greater perceived treatment efficacy was associated with diet and vitamin use but not exercise or cancer screening. Greater perceived risk of recurrence was associated with less exercise. Greater distress was associated with greater mammography use. Those from metro areas had greater healthy food consumption. RESULTS: Qualitative data indicated that chemotherapy interfered with health behaviors for those in active treatment; treatment completers wished to have a healthier lifestyle. CONCLUSION: Cancer treatment interferes with health behaviors, and these health behaviors might help individuals manage their cancer treatment more effectively. IMPLICATIONS FOR PRACTICE: Those currently undergoing treatment desire assistance with a healthier lifestyle, and relevant clinical interventions should stress treatment efficacy.

Breast cancer pathology, receptor status, and patterns of metastasis in a rural appalachian population.

Breast cancer patients in rural Appalachia have a high prevalence of obesity and poverty, together with more triple-negative phenotypes. We reviewed clinical records for tumor receptor status and time to distant metastasis. Body mass index, tumor size, grade, nodal status, and receptor status were related to metastatic patterns. For 687 patients, 13.8% developed metastases to bone (n = 42) or visceral sites (n = 53). Metastases to viscera occurred within five years, a latent period which was shorter than that for bone (P = 0.042). More women with visceral metastasis presented with grade 3 tumors compared with the bone and nonmetastatic groups (P = 0.0002). There were 135/574 women (23.5%) with triple-negative breast cancer, who presented with lymph node involvement and visceral metastases (68.2% versus 24.3%; P = 0.033). Triple-negative tumors that metastasized to visceral sites were larger (P = 0.007). Developing a visceral metastasis within 10 years was higher among women with triple-negative tumors. Across all breast cancer receptor subtypes, the probability of remaining distant metastasis-free was greater for brain and liver than for lung. The excess risk of metastatic spread to visceral organs in triple-negative breast cancers, even in the absence of positive nodes, was combined with the burden of larger and more advanced tumors.

Do we glow? Evaluation of trauma team work habits and radiation exposure.

BACKGROUND: Health care workers' potential exposure to ionizing radiation has increased. Annual radiation exposure limit for the general public per US Nuclear Regulatory Commission is 100 mrem (1 mSv). The whole-body annual occupational radiation exposure limit is 5,000 mrem (50 mSv). Studies have been done to evaluate patient radiation exposure. To date, there has been no study to evaluate the radiation exposure of trauma team members or evaluate their behaviors and attitudes. METHODS: Forty primary providers (residents, physician assistants) rotating on the trauma service at an American College of Surgeons Level 1 trauma center participated. Dosimeters were worn by participants, and the radiation doses were measured monthly. A survey detailing the frequency of involvement in radiographic studies, use of protective equipment, and knowledge of education programs was completed monthly. RESULTS: The range of radiation measured was 1 mrem to 56 mrem, with an average effective dose of 10 mrem per month. Thirty-two (80%) of 40 reported daily exposure to x-rays and 28 (70%) of 40 to computed tomographic scans. Thirty-four (85%) of 40 reported that they never or seldom wore lead apron in trauma bay as opposed to 1 (3%) of 40 who failed to wear it during fluoroscopy. Twenty (50%) reported that an apron was not available, while 20 (50%) reported that it was too hot or did not fit. Thirty-nine (97%) of 40 reported that they received training in radiation safety. CONCLUSION: Despite inconsistent use of protective equipment by resident staff, the actual radiation exposure remains low. Hospitals should be sure lead aprons and collars are available. Additional education concerning the availability of programs during pregnancy is needed. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Initial clinical test of a breast-PET scanner.

INTRODUCTION: The goal of this initial clinical study was to test a new positron emission/tomography imager and biopsy system (PEM/PET) in a small group of selected subjects to assess its clinical imaging capabilities. Specifically, the main task of this study is to determine whether the new system can successfully be used to produce images of known breast cancer and compare them to those acquired by standard techniques. METHODS: The PEM/PET system consists of two pairs of rotating radiation detectors located beneath a patient table. The scanner has a spatial resolution of ∼2 mm in all three dimensions. The subjects consisted of five patients diagnosed with locally advanced breast cancer ranging in age from 40 to 55 years old scheduled for pre-treatment, conventional whole body PET imaging with F-18 Fluorodeoxyglucose (FDG). The primary lesions were at least 2 cm in diameter. RESULTS: The images from the PEM/PET system demonstrated that this system is capable of identifying some lesions not visible in standard mammograms. Furthermore, while the relatively large lesions imaged in this study where all visualised by a standard whole body PET/CT scanner, some of the morphology of the tumours (ductal infiltration, for example) was better defined with the PEM/PET system. Significantly, these images were obtained immediately following a standard whole body PET scan. CONCLUSIONS: The initial testing of the new PEM/PET system demonstrated that the new system is capable of producing good quality breast-PET images compared standard methods.

Role of obesity and exercise in breast cancer survivors.

Over 60% of the American population meets the criteria for obesity, and obesity is very common in patients with breast cancer. Many studies have shown that obese patients with breast cancer have a worse prognosis compared to normal weight individuals. Tumor characteristics and other factors contribute to this. Exercise could reverse some of the pathophysiologic factors that contribute to this increased risk, and has been shown in some studies to improve survival in patients with breast cancer. In addition to administering anticancer therapy, cancer clinicians should make concerted attempts to get patients to enroll in weight management and exercise programs, which could improve survival in patients with breast cancer.

Triple-negative breast cancer in West Virginia.

In 2007, the American Cancer Society ranked West Virginia 43rd in breast cancer incidence rates for individual states. Despite our improvements in medical care, the advanced pathological characteristics of breast cancer at diagnosis receive little attention. Consequently, we compared the changing pattern of early breast cancer in several cohort studies conducted at regional medical centers in West Virginia. The data used in this analysis was derived from 320 women presenting at West Virginia University Hospital (WVUH) in Morgantown between 1999 and 2004, with a diagnosis of invasive breast cancer. Details of age, tumor size and axillary lymph node status were compared with tumor registry information published from a cohort study of 191 patients from the Charleston Area Medical Center (CAMC) between 1990 and 1991. Only histologically documented adenocarcinomas of the breast were included. Tumor size was characterized using the TNM system and staged according to AJCC criteria. For comparative purposes, details from the two regional centers were compared with tumor characteristics from a large longitudinal cohort of 2,484 breast cancers from the Women's Health Initiative (WHI) study. Baseline median age at diagnosis of women screened at WVUH was younger than patients at CAMC (52 vs. 60). Women diagnosed with triple-negative breast cancer at WVUH and CAMC had similar age distributions. Within the triple-negative patients at WVUH, 44% of patients were less than 50 years of age and 20% were less than 40 years of age. At CAMC, 35% were less than 50 years of age and 7% were less than 40 years of age. For women at WVUH, 61.5% presented with T1 tumors compared to 65.5% at CAMC. These figures were lower than the WHI average of 80.3%. In contrast, more women presented with larger T2 tumors at our medical centers compared with the national study, 32.6% versus 17.4% respectively. At WVUH, 2.3% of women had T3 tumors (> or =5 cm) compared with 1% at CAMC. Similar to the WHI study, 35-42% of women at WVUH and CAMC were diagnosed at the T1c stage. Approximately, 30% were diagnosed with positive lymph nodes, compared to 23% in the national study. Combined breast cancer data from our medical centers show an increase in more advanced tumors and positive regional lymph node involvement at the time of diagnosis compared to national reports. Other factors such as obesity, diabetes, poverty and access to mammography screening could be influencing the poorer outcomes for women with breast cancer in West Virginia.

Triple-negative breast cancer and obesity in a rural Appalachian population.

BACKGROUND: Our objective was to determine the clinicopathologic features of triple-negative (estrogen receptor, progesterone receptor, and human epidermal growth factor-2 receptor negative) breast cancer and their relationship to obesity in women drawn from a population with one of the highest obesity rates in the United States. METHODS: This retrospective study involved 620 White patients with invasive breast cancer in West Virginia. Hospital tumor registry, charts, and pathology records provided age at diagnosis, tumor histologic type, size, nodal status, and receptor status. Body mass index was calculated and a value of > or = 30 was considered indicative of obesity. RESULTS: Triple-negative tumors occurred in 117 (18.9%) of the 620 patients, most often in association with invasive ductal carcinomas. Patients with triple-negative tumors were younger than those with other receptor types, 44.5% and 26.7%, respectively, being diagnosed at age <50 years (P = 0.0004). The triple-negative tumors were larger (P = 0.0003), most notably in the younger women, but small tumors (<2.0 cm) were more often accompanied by lymph node metastases. Obesity was present in 49.6% of those with triple-negative tumors but in only 35.8% of those with non-triple-negative tumors (P = 0.0098). Lymph node metastases were more frequently associated with T(2) tumors in obese patients (P = 0.032) regardless of their receptor status. CONCLUSIONS: Triple-negative breast cancers within a White, socioeconomically deprived, population occurred in younger women, with later stage at diagnosis, and in association with obesity, which itself has been associated with a poor prognosis in breast cancer.

Surgical resection of the primary tumor, chest wall control, and survival in women with metastatic breast cancer.

BACKGROUND: Among women presenting with de novo stage IV breast cancer, 35% to 60% undergo local therapy, presumably to avoid uncontrolled chest wall disease. Several studies suggest that resection of the primary tumor may prolong survival, but chest wall outcome data are notably lacking. The authors reviewed chest wall status, time to first progression (TTFP), and overall survival (OS) in this group of women. METHODS: Women presenting at the Lynn Sage Breast Center (1995-2005) with an intact primary tumor and stage IV breast cancer or postoperative diagnosis of distant metastases were identified. Logistic regression and Cox proportional hazards models, adjusted for relevant covariates, were used to examine associations between surgical treatment and chest wall status, TTFP, and OS. RESULTS: Of 111 eligible women, 47 (42%) underwent early resection of the primary tumor. Chest wall status was available for 103 women. Local control was maintained in 36 of 44 (82%) patients in the surgical group versus 20 of 59 (34%) patients without surgery (P = .001). TTFP was prolonged in the surgical group (adjusted hazards ratio [HR], 0.493; P = .015). The adjusted HR for OS in the surgical group was 0.798 (P = .520). Chest wall control was associated with improved OS regardless of whether surgical resection of the tumor was performed (HR, 0.415; P < .0002). CONCLUSIONS: These data support the notion that improved local control may play a role in improving outcomes in women with stage IV breast cancer, and resection of in-breast tumors can help to achieve this. A randomized trial is needed to rule out selection bias as an explanation for these findings.

Image-guided procedures for breast masses.

Breast cancer is a disease affecting millions of women worldwide. In the United States, the institution of screening mammography protocols has increased the number of suspicious breast abnormalities requiring diagnostic intervention. Up to 80% of these lesions are benign, forcing the medical community to devise minimally invasive techniques for tissue sampling. A reduction in the number of needle-localized open breast biopsies reduces the morbidity and cost associated with image-detected breast masses. Ultrasound, stereotaxis, and MRI are excellent modalities for detection of breast cancers. Image-guided, large-core biopsy systems have been developed for each of these imaging modalities, enabling successful and accurate tissue sampling and, ultimately, diagnosis of a suspicious lesion. Care must be taken to ensure correlation between imaging findings and pathologic diagnosis; if the two are discordant, further investigation is mandatory. There remains a role for needle-localized open breast biopsy, although is has been reduced significantly. Some patients prefer this method of diagnosis, and in others further investigation in required because of discordant findings. When the documented pathology of the breast abnormality is ADH, ALH, or LCIS, the patient should undergo surgical excision because of the possibility of DCIS or invasive disease in the same area. Some lesions are inaccessible with the current imaging modalities and biopsy systems available. Minimally invasive, image-guided biopsy for breast masses promises to continue to evolve, enabling physicians to diagnose breast cancer with a high degree of accuracy without significant morbidity.