Palliative Chemotherapy and Radiotherapy for Pancreatic Cancer: Is It Worthwhile?

The role of palliative chemotherapy or radiotherapy (or both) in pancreatic cancer is discussed. In patients with disseminated pancreatic cancer chemoradiotherapy has so far not been effective in prolonging survival. Recent trials with gemcitabine has shown a modest improvement in clinical benefit and survival. Patients with locally advanced disease should be offered 5-fluorouracil and radiation therapy, as valid data have repeatedly shown better median survival compared to no therapy. The option of a second-look laparotomy to evaluate resectability after palliative chemoradiotherapy in patients with locally advanced disease should be applied liberally because currently available imaging techniques sometimes do not accurately reflect tumor size and tumor progression. New treatment strategies, such as regional perfusion, are being investigated.     

Surgical Management of Multifocal and Multicentric Breast Cancers: Can We Achieve the Same,with Less?

Annals of Surgical Oncology -     

Treatment of Advanced and Metastatic Renal Cancer: A Revolution?

ContextA significant proportion of patients with renal cell carcinoma (RCC) will experience recurrence or tumour progression after surgical treatment. Nowadays, several treatment options, including immunotherapy and targeted therapies, are available for management of advanced and metastatic RCC.ObjectiveThis paper aims to give an overview of the current treatment options for patients with advanced and metastatic RCC.Evidence acquisitionThis paper is based on a presentation given at the 6th Meeting of the European Society of Oncological Urology 2009, held in Istanbul, Turkey. Data were retrieved from recent review articles, original articles, and abstracts on the treatment of advanced and metastatic RCC.Evidence synthesisThe potential role of adjuvant vaccines in treatment of patients with advanced RCC after nephrectomy has been suggested. With regard to the newly developed targeted agents for treatment of metastatic clear-cell RCC, sunitinib and bevacizumab plus interferon-α (INF-α) seem promising as first-line therapy for good- and intermediate-risk patients. Temsirolimus appears to be effective as first-line treatment in metastatic RCC (mRCC) patients with poor prognosis. Sorafenib and everolimus should be considered as second-line therapy in mRCC patients. Some targeted therapies have also demonstrated clinical activities in patients with metastatic non–clear-cell RCC. Although grade 1 and grade 2 treatment-related adverse events were common with targeted therapies, most were manageable. The effect of targeted agents in earlier stage disease is currently under investigation. Cytokine therapy was associated with a modest survival benefit in mRCC. A combined analysis, however, suggested that cytoreductive nephrectomy might improve survival in patients with mRCC treated with interferon immunotherapy.ConclusionsMore research on the use of adjuvant vaccines in treating patients with advanced RCC is warranted. Although the management of metastatic disease has undergone a revolution in recent years, a lot of questions still need to be answered.     

Use of Breast Imaging After Treatment for Locoregional Breast Cancer (AFT-01)

Background

Annual mammography is recommended after breast cancer treatment. However, studies suggest its under-utilization for Medicare patients. Utilization in the broader population is unknown, as is the role of breast magnetic resonance imaging (MRI). Understanding factors associated with imaging use is critical to improvement of adherence to recommendations.

Methods

A random sample of 9835 eligible patients receiving surgery for stages 2 and 3 breast cancer from 2006 to 2007 was selected from the National Cancer Database for primary data collection. Imaging and recurrence data were abstracted from patients 90 days after surgery to 5 years after diagnosis. Factors associated with lack of imaging were assessed using multivariable repeated measures logistic regression with generalized estimating equations. Patients were censored for death, bilateral mastectomy, new cancer, and recurrence.

Results

Of 9835 patients, 9622, 8702, 8021, and 7457 patients were eligible for imaging at surveillance years 1 through 4 respectively. Annual receipt of breast imaging declined from year 1 (69.5%) to year 4 (61.0%), and breast MRI rates decreased from 12.5 to 5.8%. Lack of imaging was associated with age 80 years or older and age younger than 50 years, black race, public or no insurance versus private insurance, greater comorbidity, larger node-positive hormone receptor-negative tumor, excision alone or mastectomy, and no chemotherapy (p?<?0.005). Receipt of breast MRI was associated with age younger than 50 years, white race, higher education, private insurance, mastectomy, chemotherapy, care at a teaching/research facility, and MRI 12 months before diagnosis (p?<?0.05).

Conclusion

Under-utilization of mammography after breast cancer treatment is associated with sociodemographic and clinical factors, not institutional characteristics. Effective interventions are needed to increase surveillance mammography for at-risk populations.ClinicalTrials.gov Identifier: NCT02171078.

     

Accelerated Partial-Breast Irradiation Versus Whole-Breast Irradiation for Early-Stage Breast Cancer Patients Undergoing Breast Conservation, 2003–2010: A Report from the National Cancer Data Base

Background

Previous studies have demonstrated an increase in the utilization of accelerated partial-breast irradiation via brachytherapy (APBI-b), but larger, more contemporary studies examining overall APBI use are lacking.

Methods

A total of 575,438 nonneoadjuvant American Joint Committee on Cancer stage 0 to II breast conservation patients were selected from the National Cancer Data Base from 2003 to 2010 who underwent either whole-breast irradiation or APBI.

Results

Overall, 59,396 patients (10.3 %) underwent APBI. The use of APBI for the entire cohort increased from 3.4 % in 2003 to 12.8 % (p < 0.001) in 2008 and then decreased to 12.4 % in 2010. Three-dimensional conformal radiation increased from 0.8 to 2.2 %, intensity-modulated radiotherapy increased from 0.7 to 1.3 %, and brachytherapy (APBI-b) increased from 2.0 to 8.9 %. The most significant factors associated with APBI use were patient age and facility location. Patients 80–89 years old were 3.8 times more likely to undergo APBI compared to patients 30–39 years old (odds ratio [OR] 3.77, 95 % confidence interval [CI] 3.45–4.10, p < 0.001). Patients living in the West census region were 2.0 times more likely to undergo APBI compared to patients living in the Northeast (OR 2.0, 95 % CI 1.93–2.15, p < 0.001). Using the American Society of Radiation Oncology (ASTRO) guidelines, among patients with noninvasive cancer who received APBI, 95.6 % were categorized as “cautionary” and 4.4 % as “unsuitable.” Of the invasive patients, 43.8 % were categorized as “suitable,” 47.0 % as “cautionary,” and 9.2 % as “unsuitable.”

Conclusions

The utilization of APBI has stabilized at approximately 12 % starting in 2008. The majority of APBI is delivered using APBI-b, with patient age being the most significant factor associated with APBI use.     

Chemotherapy in Old Women with Breast Cancer: Is Age Still a Predictor for Under Treatment?

Breast cancer affects mostly older women but there are no guidelines especially devoted to adjuvant chemotherapy for this population. In this context, this study was carried out in a population‐based cohort of French elderly women with breast cancer, to check adherence to the existing national guidelines according to the women's age, taking into account the evolution of the situation over time for women requiring chemotherapy. Between October 2006 and December 2008, all consecutive women included in the French Health registry for a biopsy‐proven primary nonmetastatic breast cancer, aged 65–80 years at diagnosis, and living in South Eastern France, were asked to participate in a cohort study. Medical information was collected from physicians. The study population was restricted to the 223 women who were recommended adjuvant chemotherapy according to national guidelines. Those who received chemotherapy were compared to those who did not receive this treatment. Among these 223 women 55% had received chemotherapy. Only three women refused the treatment. Less than 8% have had a geriatric assessment before treatment decision and only two were proposed to participate in a clinical trial. After adjustment for comorbidity score, tumor characteristics, socio‐demographic characteristics, and year of diagnosis, increasing patient age was independently associated with decreased guideline concordance for adjuvant chemotherapy. Women aged 75–80 years received chemotherapy more than four times less often than women aged 65–74 years. However, the percentage of women who received chemotherapy increased from 33% to 58% between 2006 and 2008, in parallel with the setting up of Onco‐Geriatric Coordination Units in the area. In France, chronological age remains a barrier to receive chemotherapy for older breast cancer women but the establishment of a formal collaboration between oncologists and geriatricians seems to be an effective way to improve care delivery in this population.     

Macrophages in Breast Cancer: Do Involution Macrophages Account for the Poor Prognosis of Pregnancy-Associated Breast Cancer?

Macrophage influx is associated with negative outcomes for women with breast cancer and has been demonstrated to be required for metastasis of mammary tumors in mouse models. Pregnancy-associated breast cancer is characterized by particularly poor outcomes, however the reasons remain obscure. Recently, post-pregnancy mammary involution has been characterized as having a wound healing signature. We have proposed the involution-hypothesis, which states that the wound healing microenvironment of the involuting gland is tumor promotional. Macrophage influx is one of the prominent features of the involuting gland, identifying the macrophage a potential instigator of tumor progression and a novel target for breast cancer treatment and prevention. Financial Support: This work was supported in part by grants from The Avon and Mary Kay Ash Foundations, and DOD BC060531 to PS and a DOD Predoctoral Grant BC073482 to JO.     

Treatment of Metastatic Breast Cancer With Somatostatin Analogues—A Meta-Analysis

Background: Somatostatin analogues appear to have antiproliferative effects in breast cancer by inhibiting various hormones. Several small phase 1 and 2 clinical trails have evaluated the efficacy of somatostatin analogues, but the results are varied. The purpose of this study was to use the technique of meta-analysis to determine the effect of somatostatin analogues on tumor response, toxicity, and serum hormone levels in women with metastatic breast cancer.Methods: All published and unpublished trials were reviewed. Meta-analysis was preformed by best linear unbiased estimate regression with observations weighted inversely to their variance. Significance was considered at P < .05.Results: Fourteen studies (N = 210) were included. Positive tumor response was reported in 87 patients (41.4%). Mean duration of response was 3.9 months. Response was best when somatostatin analogues were given as first-line therapy (69.5% versus 28.5%, P < .006) and in patients with 2 metastases (45.0% versus 5.6%, P = .3). Mild side effects occurred in 47 of 185 patients (25.4%). Therapy was associated with a decrease in serum insulin-like growth factor (IGF-1) and an increase in growth hormone.Conclusions: In patients with metastatic breast cancer, treatment with somatostatin analogues was associated with a tumor response of over 40% with few side effects. Best results were achieved when somatostatin analogues were given as first-line therapy.     

Is Routine Intraoperative Frozen-Section Examination of Sentinel Lymph Nodes in Breast Cancer Worthwhile?

Background: Routine intraoperative frozen section (FS) of sentinel lymph nodes (SLN) can detect metastatic disease, allowing immediate axillary dissection and avoiding the need for reoperation. Routine FS is also costly, increases operative time, and is subject to false-negative results. We examined the benefit of routine intraoperative FS among the first 1000 patients at Memorial Sloan Kettering Cancer Center who had SLN biopsy for breast cancer.Methods: We performed SLN biopsy with intraoperative FS in 890 consecutive breast cancer patients, none of whom had a back-up axillary dissection planned in advance. Serial sections and immunohistochemical staining for cytokeratins were performed on all SLN that proved negative on FS. The sensitivity of FS was determined as a function of (1) tumor size and (2) volume of metastatic disease in the SLN, and the benefit of FS was defined as the avoidance of a reoperative axillary dissection.Results: The sensitivity of FS ranged from 40% for patients with T1a to 76% for patients with T2 cancers. The volume of SLN metastasis was highly correlated with tumor size, and FS was far more effective in detecting macrometastatic disease (sensitivity 92%) than micrometastases (sensitivity 17%). The benefit of FS in avoiding reoperative axillary dissection ranged from 4% for T1a (6 of 143) to 38% for T2 (45 of 119) cancers.Conclusions: In breast cancer patients having SLN biopsy, the failure of routine intraoperative FS is largely the failure to detect micrometastatic disease. The benefit of routine intraoperative FS increases with tumor size. Routine FS may not be indicated in patients with the smallest invasive cancers.Presented at the 53rd Annual Meeting of the Society of Surgical Oncology, March 16–19, 2000, New Orleans     

Which Eligible Breast Conservation Patients Choose Mastectomy in the Setting of Newly Diagnosed Breast Cancer?

Purpose  

Breast conserving therapy (BCT) and mastectomy offer equivalent survival for women with newly diagnosed breast cancer (BrCa). Despite this, many women eligible for BCT elect mastectomy. Herein, we identify factors associated with choosing ipsilateral mastectomy instead of BCT when mastectomy is not required.     

Immunomodulation via Chemotherapy and Targeted Therapy: A New Paradigm in Breast Cancer Therapy?

Cytotoxic chemotherapy in the treatment of tumors has traditionally been thought to be immunosuppressive. Increasing evidence suggests the contrary and has introduced the concept of ‘immunogenic’ chemotherapy or, in other words, the concept that the innate and adaptive immune systems are critical in determining the long-term efficacy of some cytotoxic-based (and radiotherapy-based) regimens. The underlying mechanisms how these therapies can stimulate an antitumor immune response have been demonstrated recently. In this article, we review the background of this new paradigm and how combinations of traditional agents with the new immunotherapeutic therapies may significantly advance our treatment of breast cancer.     

Diet and Breast Cancer: Can Dietary Factors Influence Survival?

Breast cancer accounts for over one third of invasive cancers in women. Earlier detection and improved initial treatments have resulted in an increasing number of women who have completed standard treatments but who remain at risk for breast cancer recurrence or early death. Epidemiological studies have linked diet composition with prognosis, and many women attempt to modify their diets and improve nutritional status following diagnosis. The hypothesis that dietary factors may reduce risk for secondary cancer events and increase survival in this population is currently under study in two large randomized clinical trials: the Women's Intervention Nutrition Study (WINS) and the Women's Healthy Eating and Living (WHEL) Study. The WHEL Study is testing the effect of a diet high in vegetables, fruit, and fiber, and low in fat, on disease-free survival in women with early stage breast cancer. Hypothesized mechanisms include effects of diet modification on gonadal hormones, retinoid-like activities of carotenoids, and other protective effects of biologically active dietary constituents.     

Are Breast Cancer Subtypes Prognostic for Nodal Involvement and Associated with Clinicopathologic Features at Presentation in Early-Stage Breast Cancer?

Background

Breast cancer subtypes (BCS) determined from immunohistochemical staining have been correlated with molecular subtypes and associated with prognosis and outcomes, but there are limited data correlating these BCS and axillary node involvement. This study was conducted to assess whether BCS predicted for nodal metastasis or was associated with other clinicopathologic features at presentation.

Methods

Patients with stage I/II disease who underwent breast-conserving surgery and axillary surgical assessment with available tissue blocks underwent a institutional pathological review and construction of a tissue microarray. The slides were stained for estrogen receptor, progesterone receptor, and HER-2/neu (HER-2) for classification into BCS. Nodal involvement and other clinicopathologic features were analyzed to assess associations between BCS and patient and tumor characteristics. Outcomes were calculated a function of BCS.

Results

The study cohort consisted of 453 patients (luminal A 48.6 %, luminal B 16.1 %, HER-2 11.0 %, triple negative 24.2 %), of which 22 % (n = 113) were node positive. There were no significant associations with BCS and pN stage, node positivity, or absolute number of nodes involved (p > 0.05 for all). However, there were significant associations with subtype and age at presentation (p < 0.001), method of detection (p = 0.049), tumor histology (p < 0.001), race (p = 0.041), and tumor size (pT stage, p < 0.001) by univariate and multivariate analysis. As expected, 10-year outcomes differed by BCS, with triple negative and HER-2 subtypes having the worse overall (p = 0.03), disease-free (p = 0.03), and distant metastasis-free survival (p < 0.01).

Conclusions

There is a significant association between BCS and age, T stage, histology, method of detection, and race, but no associations to predict nodal involvement. If additionally validated, these findings suggest that BCS may not be a useful prognostic variable for influencing regional management considerations.