Jessica Goldberg

Nomogram for Predicting the Risk of Local Recurrence After Breast-Conserving Surgery for Ductal Carcinoma In Situ

PURPOSE While the mortality associated with ductal carcinoma in situ (DCIS) is minimal, the risk of ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) is relatively high. Radiation therapy (RT) and antiestrogen agents reduce the risk of IBTR and are considered standard treatment options after BCS. However, they have never been proven to improve survival, and in themselves carry rare but serious risks. Individualized estimation of IBTR risk would assist in decision making regarding the various treatment options for women with DCIS. PATIENTS AND METHODS From 1991 to 2006, 1,868 consecutive patients treated with BCS for DCIS were identified. A multivariate Cox proportional hazards model was constructed using the 1,681 in whom data were complete. Ten clinical, pathologic, and treatment variables were built into a nomogram estimating probability of IBTR at 5 and 10 years after BCS. The model was validated for discrimination and calibration using bootstrap resampling. RESULTS The DCIS nomogram for prediction of 5- and 10-year IBTR probabilities demonstrated good calibration and discrimination, with a concordance index of 0.704 (bootstrap corrected, 0.688) and a concordance probability estimate of 0.686. Factors with the greatest influence on risk of IBTR in the model included adjuvant RT or endocrine therapy, age, margin status, number of excisions, and treatment time period. CONCLUSION The DCIS nomogram integrates 10 clinicopathologic variables to provide an individualized risk estimate of IBTR in a woman with DCIS treated with BCS. This tool may assist in individual decision making regarding various treatment options and help avoid over- and undertreatment of noninvasive breast cancer.

Clinicopathologic Features and Long-Term Outcomes of 293 Phyllodes Tumors of the Breast

BackgroundPhyllodes tumors (PT) are rare fibroepithelial neoplasms of the breast with unpredictable behavior. We reviewed our single institution experience with PT over 51 years to identify factors predictive of local recurrence (LR) and metastasis.MethodsFrom 1954 to 2005, a total of 352 cases of PT were identified; 293 had follow-up. All available pathology slides (90%) were rereviewed for margins, borders, fibroproliferation in the surrounding breast tissue, stromal pattern, stromal cellularity, frequency of mitoses, and necrosis.ResultsAll cases occurred in women, with a median age of 42, with 203 originally categorized as benign and 90 as malignant. Median follow-up was 7.9 years. A total of 35 patients developed LR at a median of 2 years. In univariate analyses, a higher actuarial LR rate was associated with positive margins (P = .04), fibroproliferation (P = .001), and necrosis (P = .006). PT classified as malignant did not have a higher risk of LR (P = .79). Five patients developed distant disease at a median of 1.2 years. These patients constituted 71% of the seven patients who had uniformly aggressive pathologic features, including large tumor size (≥7.0 cm), infiltrative borders, marked stromal overgrowth, marked stromal cellularity, high mitotic count, and necrosis.ConclusionsPositive margins, fibroproliferation in the surrounding breast tissue, and necrosis are associated with a marked increase in LR rates. Efforts should be made to achieve negative surgical margins to reduce risk of LR. Death from PT is rare (2%), and only PT that demonstrate uniformly aggressive pathologic features seem to be associated with mortality.

Breast cancer susceptibility testing: past, present and future.

Breast cancer is a genetic disease. The cancer phenotype is defined by a complex interplay between oncogenes, tumor-suppressor genes and epigenetic factors. Only 5–10% of all breast cancers can be attributed to one of several breast cancer familial syndromes, the most common of which is the hereditary breast and ovarian syndrome caused by deleterious mutations of the BRCA1 or BRCA2 tumor-suppressor genes. The functions of the BRCA proteins are not fully understood, although it is clear that they play a role in the control of transcription, regulation of the cell cycle and management of DNA damage. The inheritance of a deleterious BRCA mutation is accompanied by a 50–80% risk of developing breast cancer, 60% risk of developing a contralateral breast cancer and 15–25% risk of developing ovarian cancer. The clinical management of BRCA heterozygotes involves several strategies of primary, secondary and tertiary prevention. These include risk-reducing surgery, chemoprevention, lifestyle changes and increased surveillance. As we move beyond the 10-year anniversary of the discovery of the BRCA genes, we are inevitably led to thoughtful reflection on the impact of these genes in regards to the greater problem of sporadic breast cancer.

The Influence of Margin Width and Volume of Disease Near Margin on Benefit of Radiation Therapy for Women With DCIS Treated With Breast-Conserving Therapy

Objective and Summary Background Data:There remains variation in the use of radiation therapy (RT) in women with ductal carcinoma in situ (DCIS), despite prospective randomized trials documenting its benefit in reducing the risk of ipsilateral breast tumor recurrence (IBTR). Methods:Patients with DCIS treated with excision alone or excision plus RT from 1991 to 1995 were identified. Margin width, number of involved ducts at closest margin, age, presence of palpable mass, presence of lobular neoplasia, nuclear grade, and necrosis were tested in uni- and multivariate analysis for association with risk of IBTR and added value of RT. Results:Two hundred ninety-four patients with a median follow-up of 11 years had actuarial 10- and 15-year overall IBTR rates of 22% and 29%, respectively. For lesions excised with margins of <1 mm, 1 to 9 mm, and ≥10 mm, the actuarial 10-year IBTR rates were 28%, 21%, and 19%, respectively. RT reduced adjusted IBTR rates by 62% (P = 0.002) for all patients; 83% for lesions with <1 mm margins (P = 0.002), 70% for 1 to 9 mm (P = 0.05), and 24% (P = 0.55) for ≥10 mm. After adjustment for other variables, higher volume of disease near the margin was associated with risk of IBTR in the no RT group (HR = 3.37, P = 0.002) and greater benefit of RT (HR 0.14; P = 0.004). Conclusion:Effect of RT on IBTR risk is influenced by both margin width and number of involved ducts at nearest margin. Patients with higher volume of disease near the margin derive a greater benefit from the addition of RT. Despite margins of ≥10 mm, the risk of IBTR remains substantial in patients with DCIS.

Study of quadrant high-dose intraoperative radiation therapy for early-stage breast cancer

Partial breast irradiation has been tested in limited pilot studies and shown to provide acceptable cosmesis, minimal toxicity and adequate local control. The aim of this study was to determine the feasibility of using quadrant high‐dose intraoperative radiation therapy (IORT) for the treatment of early‐stage breast cancer.

Concurrent lobular neoplasia increases the risk of ipsilateral breast cancer recurrence in patients with ductal carcinoma in situ treated with breast‐conserving therapy

Multiple clinicopathologic factors have been analyzed for their association with an increased risk of ipsilateral breast tumor recurrence (IBTR) after women receive breast‐conserving treatment (BCT) for ductal carcinoma in situ (DCIS). The reported incidence of proliferative lesions, such as atypical ductal hyperplasia (ADH), columnar cell changes (CCC), and lobular neoplasia associated with breast cancer, has been as high as 23%; however, the relevance of these lesions on the natural history of DCIS and the risk of IBTR remains unknown.

Palliative Care and Symptom Management in Older Patients with Cancer

Older patients with cancer are best served by a multidisciplinary approach with palliative care (PC) playing an integral role. PC focuses on symptom control irrespective of its cause and should not be associated only with terminal care. It provides an additional layer of support in the care of patients with cancer with an emphasis on quality of life. This article discusses the evaluation and management of pain and other common nonpain symptoms that occur in elderly patients with cancer, as well as end-of-life care.

Outcomes of ICU Admission of Patients With Progressive Metastatic Gastrointestinal Cancer

Background: Data on the outcomes of intensive care unit (ICU) admissions for patients with advanced incurable chemoresistant solid tumor malignancies, and the benefits of subsequent/post-ICU anticancer treatments are limited but have end-of-life and ethical implications. Methods: An institutional database was queried to identify patients of the gastrointestinal (GI) medical oncology service of Memorial Sloan Kettering Cancer Center with ≥1 ICU admission during 2014. Records were reviewed for evidence of cancer control from cancer treatment after the ICU admission. Results: Twenty-eight patients who had progressed beyond at least first-line chemotherapy for metastatic GI adenocarcinoma were admitted to the ICU for sequelae of progressive clinical deterioration. The most frequent reasons for ICU admission were sepsis (39%) and acute respiratory failure (29%). Ten patients died in the ICU, 3 died during the same hospitalization after ICU discharge, and 15 were discharged from the hospital. Of these 15, the median survival from hospital discharge was 2.2 months and 6 received further chemotherapy but with no evidence of clinical benefit. Of these 6, 3 lived over 5 months but the treatment of 5 entailed recycling of previously ineffective chemotherapy agents (3) or those originally used in the adjuvant setting (2). Two of these patients received liver-directed therapy without benefit. Conclusions: Admissions to the ICU in this cancer population were associated with high morbidity and mortality and did not result in benefit from subsequent cancer treatment. These data can be used to help establish realistic expectations and care goals in previously treated patients having metastatic GI cancer with clinical deterioration.

A novel scoring system to predict survival in patients with advanced pancreatic adenocarcinoma: The Memorial Prognostic Score (MPS).

36 Background: A major limitation of prognostic tools such as the Eastern Cooperative Oncology Group (ECOG), Karnofsky, and Palliative Performance Scale is a reliance on subjective clinical assessment. An objective tool, the Glasgow Prognostic Score (GPS) is derived from C-reactive Protein (CRP) and albumin and has been validated in patients with operable and inoperable malignancies. One disadvantage of this tool is that CRP is not routinely measured in the United States. We examined if the Neutrophil-Lymphocyte Ratios (NLR) (Ahn, H.K., et al., Neutrophil-Lymphocyte Ratio Predicts Survival in Terminal Cancer Patients. J Palliat Med, 2016) could be substituted for CRP in the GPS to predict survival in patients with advanced pancreatic adenocarcinoma. METHODS A retrospective chart review identified patients at MSKCC with pathology-confirmed stage IV pancreatic adenocarcinoma diagnosed between 2011 to 2014. Pre-treatment absolute neutrophil count, absolute lymphocyte count, and albumin were extracted. The NLR for each patient was calculated and assigned: NLR ≤ 4 g/dl = 0, NLR > 4 g/dl = 1; serum albumin > 4 g/dl = 0, and serum albumin < 4 g/dl = 1. Combining NLR and albumin scores resulted in a composite MPS score of 0-2, similar to GPS. We evaluated the association of the MPS with overall survival. RESULTS N = 833 patients were identified with median survivals summarized in the table below. A log-rank test showed statistically significant differences in survival between MPS groups (p<0.00005). The MPS on univariate analysis had a HR of 1.36 (95% CI 1.23 - 1.50, p<0.0005) associated with overall survival. CONCLUSIONS The MPS, a novel composite of NLR and albumin, is an objective prognostic tool that divided this sample of patients into three clinically distinct subgroups. Further interrogation will control for performance status, disease characteristics and anti-cancer therapy. [Table: see text].