bluuebunny/crossref_metadata_2025 huggingface dataset:
Declines in physical function from androgen deprivation therapy (ADT) in men with nonmetastatic prostate cancer: A matched cohort study
Authors: Breunis H. , Timilshina N. , Tomlinson G. , Naglie G. , Tannock I. , Fleshner N. , Krahn M. , Duff Canning S. , Warde P. , Alibhai S.
Published: August 2020

9526

Background: Although prolonged use of ADT is hypothesized to adversely affect physical function, few studies have examined this relationship longitudinally using objective measures of physical function. Methods: Men age 50+ with non-metastatic prostate cancer (PC) starting continuous ADT were enrolled in this prospective longitudinal matched cohort study. Physical function was assessed with the six-minute walk test (6MWT), grip strength, and the Timed Up and Go (TUG) test, representing endurance, upper extremity strength, and lower extremity strength, respectively. Self-reported physical function was measured with the Medical Outcomes Study SF-36. Assessments were done at baseline, 3 months, 6 months, and 12 months. Two control groups, matched on age, education, and baseline function were also enrolled. One control group had PC but did not receive ADT, and the other group did not have PC. Linear mixed effects regression models were fitted adjusting for baseline covariates. Results: 85 patients on ADT, 86 PC controls, and 86 healthy controls were enrolled. All 3 groups were similar in age (mean age 69.1 y, range 50–87) and physical function (all ANOVA p>0.05). The 6MWT distance improved in both control groups (p=0.05 and 0.05 for PC and healthy controls, respectively) but remained stable in the ADT group (p=0.96)). Grip strength declined in the ADT group (p=0.04), remained stable in the PC control group (p=0.31), and improved in the healthy control group (p=0.008). TUG scores remained stable over time and across groups (p>0.10). SF-36 physical function declined in the ADT group (p<0.001) but increased in both control groups (p<0.001). Negative effects on outcomes were noted within 3–6 months of starting ADT and were larger with older age. Conclusions: Endurance, upper extremity strength, and self-reported physical function are affected within 3–6 months of starting ADT, particularly in older men. Declines persist at 12 months after adjustment for baseline function and covariates. Exercise intervention studies to counteract these losses are warranted.

No significant financial relationships to disclose.
Efficacy of venlafaxine for the prevention and relief of acute neurotoxicity of oxaliplatin: Results of EFFOX, a randomized, double-blinded, placebo-controlled prospective study
Authors: Durand J. P. , Deplanque G. , Gorent J. , Montheil V. , Raymond E. , Scotte F. , Mitry E. , Goldwasser F.
Published: August 2020

9533

Background: Neurosensory toxicity of oxaliplatin is dose-limiting and presents as two distinct clinical syndromes: acute symptoms and cumulative peripheral neuropathy. Methods: From October 2005 to May 2008, patients (pts) presenting oxaliplatin-induced acute neurotoxicity were randomized in a double-blinded study, to receive either arm A: venlafaxine hydrochloride (Effexor, Wyeth Pharmaceuticals Inc.) 50 mg 1 hour prior oxaliplatin infusion and venlafaxine extended release 37.5 mg b.i.d. from day 2 to day 11, either arm B : placebo. The primary endpoint was percentage of pts without acute neuropathy. The study was designed to detect, with 54 pts, a difference of 25%. The neurotoxicity was evaluated using a numeric rating scale of symptoms relief and the Neuropathic Pain Symptom Inventory (Pain 2004;108(3):248–57). Results: 45 pts were included (male : 24; median age : 67.5). Most pts had colo-rectal cancer (75.6%). The two most used chemotherapy regimens were FOLFOX (82.2%) and GEMOX (11.1%). Median number of cycles administered at inclusion was 5. In January 2009, 16 pts out of 22 in arm A (venlafaxine) and 21 pts out of 23 in arm B (placebo) were evaluable. Venlafaxine reduced the incidence of neurosensory acute symptoms : 35.3 % in arm A vs 76.2% in arm B (p=.023, Fisher's exact test). Side effects were emesis (4 pts) and somnolence (3 pts). Conclusions: Venlafaxine is effective for prevention and relief of oxaliplatin-induced acute neurotoxicity.

No significant financial relationships to disclose.
The efficacy, tolerability, and speed of onset of fentanyl pectin nasal spray (FPNS) in the treatment of breakthrough cancer pain (BTCP): A multicenter, placebo-controlled, double-blind, two-phase crossover study
Authors: Gabrail N. Y. , Burton A. W. , Reyes E. , Nguyen A. , Taylor D. R.
Published: August 2020

9535

Background: Breakthrough cancer pain (BTCP) affects up to 95% of patients with cancer pain but oral fentanyl formulations do not consistently match the typical time course of BTCP, which is rapid in onset and lasts for 30–60 min. To tailor fentanyl delivery for the treatment of BTCP, a new nasal formulation of fentanyl (fentanyl pectin nasal spray [FPNS]) has been developed to provide both rapid and controlled nasal delivery of fentanyl. Methods: A randomised, placebo-controlled, double-blind (DB) study assessing the efficacy and tolerability of FPNS was conducted in 114 cancer patients experiencing 1–4 BTCP episodes/day while taking ≥60 mg/day of oral morphine (or equivalent) for cancer pain. Patients who completed a titration phase (N=83) continued to a DB phase where 10 episodes of BTCP were treated with the effective dose identified during titration (7) or placebo (3). Pain intensity (PI) was measured using an 11-point categorical scale and pain relief (PR) using a 5-point scale, both PI and PR were measured at 5, 10, 15, 45 and 60 min post-dose. The primary endpoint was the Summed Pain Intensity Difference at 30 min (SPID30min). Secondary efficacy endpoints included Pain Intensity Difference (PID) from baseline, PI and PR. Safety was assessed by adverse events (AEs) and both objective and subjective nasal assessments. Results: Compared with placebo, FPNS significantly improved mean SPID30min scores (P<0.0001) and significantly improved SPID scores as early as 10 min (P<0.05) and up to 60 min (P<0.0001). Significant differences in favour of FPNS were found in PI as early as 5 min (P<0.05). Similar benefits were also seen with PID, with a trend at 5 min (P=0.07) that was significant from 10 min onward (P<0.01). PR was significant from 10 min (P<0.001) and at all time points to 60 min (P<0.001). Only 5.3% of patients withdrew from titration due to AEs; no significant nasal effects were reported. Conclusions: FPNS provided rapid and effective analgesia in BTCP and was generally safe and well tolerated.

[Table: see text]
Perceptions on caring for adult survivors of childhood cancer in the primary care setting
Authors: Sima J. , Perkins S. M. , Haggstrom D. A.
Published: August 2020

9568

Background: Encouraging cure rates for childhood cancers have resulted in a population of adult childhood cancer survivors (CCS) that are at risk for late effects of cancer-directed therapy. Late effects often occur when CCS are older and receive routine medical care from internists and family practitioners. Our study identifies facilitators and barriers to providing optimal late effects screening as well as evaluating information sources primary care providers (PCPs) perceive as useful, including cancer treatment summaries, survivorship care plans, and Children's Oncology Group (COG) guidelines. Methods: We sampled 1,500 randomly selected general internal medicine and family practice physicians from the American Medical Association Physician Masterfile for a nationwide mail survey. We received 351 surveys with data. Using chi-squared tests or t-tests to compare responders and non-responders we found a higher response rate for family practice (30.2%) compared to general internal medicine (16.5%) (p<.0001). Results were tabulated for descriptive purposes and linear regression and logistic regression were used for the multivariable modeling. Results: Most (84–86%) PCPs stated that they had never received a cancer treatment summary or survivorship care plan; despite this, greater than 90% thought these documents would be useful. Most PCPs (93%) had never used COG guidelines, but 86% agreed that they would follow their recommendations. A minority of PCPs perceived that their medical training was adequate to recognize late effects of chemotherapy (27.6%), cancer surgery (36.6%), and radiation therapy (38.1%). Conclusions: PCPs have a low level of awareness about the medical problems of CCS; receive inadequate training to recognize late effects; and infrequently utilize, cancer treatment summaries, survivorship care plans, and COG guidelines. By evaluating the perceptions of PCPs, we have identified problematic areas for future investigation and have begun to lay the groundwork for incorporating follow-up care for CCS into routine general medical practice.

No significant financial relationships to disclose.
Incidence of acute kidney injury in cancer patients: A population-based cohort study in Denmark
Authors: Christiansen C. F. , Johansen M. B. , Christensen S. , Langeberg W. , Fryzek J. P. , Toft Sørensen H.
Published: August 2020

9570

Background: Although cancer patients may be at increased risk for acute kidney injury (AKI), which could then reduce their likelihood of receiving optimal therapeutic management and supportive care, the occurrence of AKI among newly diagnosed cancer patients has not been well-described. Therefore, we examined the incidence of AKI within the first year after cancer diagnosis to estimate the magnitude of this risk and better understand which patients are at greatest risk. Methods: Using the population-based Danish Cancer Registry, we conducted a retrospective cohort study of 4,427 men and women from North Jutland, Denmark (population 500,000) diagnosed with cancer from 2002 to 2003 (non-melanoma skin cancer excluded). AKI was defined according to the Risk/ Injury/ Failure/ Loss/ End-stage-renal-disease (RIFLE) criteria. We included Risk or worse: at least a 1.5 times increase in serum creatinine (sCr) from baseline. SCr levels were obtained from the Regional Laboratory Database, which collects all biochemical analyses for hospital laboratories. Baseline sCr was defined as the lowest sCr in the year before cancer diagnosis. We compared this value to the highest sCr on record during the first year following cancer diagnosis to identify those who experienced an AKI. Results: Median age for the cohort was 68.6 years, 50.9% were men, and the most common cancer sites were lung (14.2%), breast (13.7%), prostate (9.8%), colon (9.6%), rectum (5.1%), and bladder (6.3%). During the first year, 973 (22.0%) members of the cohort experienced an AKI, corresponding to an overall incidence rate of 326 per 1,000 person-years (95% confidence interval (CI) 306–347). Incidence was highest among patients aged 80 years or older (531 per 1,000 person-years, 95% CI 464–606) and in those with cancer of the liver (1,221, 95%CI 676–2,205), pancreas (1,472, 95%CI 1,130–1,917), or kidney (1,254, 95%CI 974–1,616), or with multiple myeloma (855, 95%CI 538–1,356). Conclusions: To protect against AKI, we must first identify those at risk. Our study showed that over 20% of cancer patients may experience acute kidney injury in the first year after diagnosis. Older patients and those with cancer of the liver, pancreas, or kidney, or with multiple myeloma are especially at risk for AKI.

[Table: see text]
Characterization of human skeletal muscle in weight-losing pancreatic cancer patients
Authors: Brell J. M. , Hardacre J. , Schulak J. , Onders R. , Stellato T. , Sanabria J. , Schulchter M. , Strickland L. , Sprosty R. , Pink J.
Published: August 2020

9571

Background: Decreased body mass (cachexia) is a common cause of functional decline in pancreas carcinoma (PC) and other malignancies. The etiology is unknown. Characterization of human PC skeletal muscle, in regard to proteolysis and gene expression, compared to control muscle may reveal information about pathophysiology. Methods: Biopsies of rectus abdominus muscle were performed in weight-losing PC patients all stages (A) during cancer-related surgery and in cancer-free controls undergoing ventral hernia repair (B). Caspase-3, pAkt, and urinary 3-methylhistidine (u3-MH) were assessed by Western blot and high-performance liquid chromatography. Fat-free mass (FFM), body mass index (BMI), and time to progression were recorded. Muscle from five patients (median weight loss 21%) and five controls were analyzed for gene expression patterns using Affymetrix Human Genome U133 A 2.0 array chip. Two hundred differentially over- and under-expressed genes were examined in group A for potential association with cachexia. RT-PCR confirmation of six candidate genes was performed. Results: Thirty-eight patients were enrolled. Median weight loss in group A (N=27) was 14.5% (5% - 34%). No differences were noted between groups in caspase-3 and pAkt expression. Baseline u3-MH (p=0.86) and FFM (p= 0.28) did not differ; baseline BMI was lower in group A (p=0.04). BMI follow-up measurements (N=17) were significantly decreased (p=0.0005). In 65% patients, progressive disease was noted within median time of 3 months. RT-PCR established up-regulation of CHRNA1 and LMO7, but not GDF8. mRNA down-regulation for TRIM63, IGF-BP6, and MYH-1 was confirmed. Conclusions: Muscle proteolysis in human PC skeletal muscle was not demonstrated, perhaps due to unmeasurable proteolysis or use of non-informative endpoints. BMI decreased in group A with PD; further studies need tight control of BMI variables. New hypotheses about cachexia include neuromuscular junction dysfunction, as CHRNA1 has specific role in ion channel gating; this is disrupted in the paraneoplastic Eaton-Lambert syndrome. This is first study analyzing human muscle in weight-losing PC and proves symptom management multidisciplinary research is feasible in academic setting. Supported by American Cancer Society pilot grant.

No significant financial relationships to disclose.
Prognostic significance of the “surprise” question in cancer patients
Authors: Moss A. H. , Lunney J. R. , Culp S. , Auber M. , Kurian S. , Rogers J. , Dower J. , Abraham J.
Published: August 2020

9588

Background: In patients with advanced cancer, failure to accurately estimate and communicate prognoses can lead to overly aggressive care at the end of life with less attention to important palliative care issues such as pain and symptom management and patients’ values and goals for care. The “surprise” question—would I be surprised if this patient died in the next year?—has been recognized as an innovation to improve end-of-life care in the primary care population by identifying patients with a poor prognosis who are appropriate for palliative care. It has not been previously tested in cancer patients. The purposes of this study were to determine the feasibility and outcomes of the use of the “surprise” question in a cancer center population. Methods: Between July and November 2007, oncologists prospectively classified consecutive breast, lung, and colon cancer patients being seen at the Mary Babb Randolph Cancer Center of West Virginia University into “Yes” and “No” groups based on the surprise question. Patients were followed and their status at the end of one year-alive or dead-was determined along with patient demographics, type of cancer, and stage at presentation. A multivariate Cox proportional hazards regression analysis was used to identify variables associated with patient death. Results: Oncologists classified 826 of 853 prospective patients (97%), with 131 (16%) classified into the “No” group and 695 (84%) into the “Yes” group. At the end of the year, 71 patients had died; 41% of the “No” patients compared to 3% of the “Yes” patients (P <.001). The surprise question ‘No‘ response was more predictive of patient death than stage of cancer, cancer type, or age (hazard ratio 7.53, P value <.001). The “Yes” patients lived longer than the “No” patients (359.8±32.8 days versus 270±131.5 days, P <.001). The sensitivity of the surprise question “No” response was 75% and the specificity was 90%. Conclusions: We conclude that the surprise question is a simple, feasible, and effective tool to identify cancer patients with the worst prognoses who should receive the highest priority for palliative care interventions, particularly advance care planning.

No significant financial relationships to disclose.
Evaluating cancer patient satisfaction before and after daily multidisciplinary care for thoracic surgery inpatients
Authors: Adolph M. D. , Taylor R. M. , Ross P. M. , Vaida A. M. , Moffatt-Bruce S. D.
Published: August 2020

9605

Background: Significant subpopulations of cancer inpatients in the SUPPORT trial were dissatisfied with their pain control. (Desbiens, Wu et al. 1996) The hospitalized thoracic surgical patient is a person at risk for uncontrolled symptoms and burdens due to advanced cancer at time of presentation. Methods: This is a retrospective, observational, study of 1188 thoracic surgery patients undergoing elective surgical procedures for lung cancer at an NCI-approved cancer hospital over a 3-year period. Patients with primary and secondary lung cancer, undergoing elective thoracic surgery procedures were evaluated before (n=660, “Period 1”) and after (n=528, “Period 2”) an 8-month, daily, collaborative multidisciplinary Intervention Period to improve pain control and to facilitate transition for discharge. The collaborative process also identified thoracic surgical patients who needed more complex symptom management and additional support for advanced disease. Patient satisfaction with pain therapy and referrals to hospice were analyzed before and after the intervention period. Results: Pain satisfaction scores improved from baseline in each sequential period (Period 1 = 9.0 SD 1.71, Intervention Period = 9.4 SD 1.37, and Period 2 = 9.5 SD 1.03, p<0.0001). The percentage of patients referred to hospice increased from 0.15% to 1.7% (p<0.0001). Conclusions: Innovative collaboration between thoracic surgery specialists and a palliative medicine service improved patients’ satisfaction with pain control. The collaborative relationship resulted in an increase in referrals to hospice for patients with advanced cancer. These improvements were sustained by the thoracic surgery service after a daily collaborative intervention period ceased.

No significant financial relationships to disclose.
Inflammation genes and pain severity in lung cancer patients
Authors: Reyes-Gibby C. C. , Shete S. , Wu X. , Kurzrock R. , Spitz M.
Published: August 2020

9618

Background: While studies suggest that variants in infammation genes explain individual variation in pain severity, these studies only assessed one or a few candidate genes. Given that pain is a complex trait, multiple genes with relatively small effects are likely to influence vulnerability to pain. In this study, we evaluated a comprehensive panel of 59 single nucleotide polymorphisms (SNP) in 37 inflammation genes in newly diagnosed non-Hispanic Caucasian lung cancer patients (n=667) and assessed their association with pain severity. We also assessed the extent to which clinical and demographic factors explain pain severity in this population. Methods: Patients rated their pain “during the past week” on an 11-point numeric scale, (0= ‘no pain’ and 10= ‘pain as bad as you can imagine’) at presentation, prior to initiating cancer therapy. A score > 7/10 was considered to indicate severe pain. Logistic regression analyses were conducted to assess the extent of association between genetic polymorphism and pain severity. All SNPs were genotyped using SNPlex. Results: Results showed that 16% of the sample reported severe pain. As expected, severe pain was more prevalent among those with advanced stage of disease (OR=2.34; 95% CI=1.50–3.65), younger age (OR=0.47; 95%CI=0.30–0.75), depressed mood (OR=3.68; 95%CI=1.96–6.93) and fatigue (OR=3.68; 95% CI=1.96–6.93). Of the 59 SNPs, we initially found SNPS in 6 genes [IKB 3’-UTR(C/T), TNFA -308GA, TNFB Arg13Cys, IL2-330T/G, IL8–251 T/A, COX2 3’-UTR(T/C)] to be significantly associated with severe pain. Controlling for clinical and demographic variables, we found that carriers of CC alleles for COX2 3’-UTR T/C (OR= 3.24; 95% CI=1.12, 9.39) and carriers of TT alleles for IL2-330T/G (OR=1.68; 95%CI=1.04, 2.73) persisted as significant correlates of severe pain. Conclusions: Because genetic polymorphisms are stable markers, understanding the extent to which genetic variability plays a role on cancer-related pain may prove useful in identifying patients at high-risk for pain development and importantly, could help in understanding patients who might benefit most from symptom intervention, and ultimately in developing personalized and more effective pain therapies.

No significant financial relationships to disclose.
Pattern of utilization of pegfilgrastim in patients with chemotherapy-induced neutropenia: A retrospective analysis of administrative claims data
Authors: Skarin A. T. , Vekeman F. , Laliberté F. , Afonja O. , Lafeuille M. , Barghout V. , Duh M. S.
Published: August 2020

9624

Background: Pegfilgrastim is a long-acting granulocyte colony-stimulating factor (G-CSF) used to prevent or treat febrile neutropenia associated with myelosuppressive anticancer therapies. According to the prescribing information, pegfilgrastim should not be administered within 14 days before or 24 hours after cytotoxic chemotherapy because of the potential for myeloid toxicity. This study examined use patterns of pegfilgrastim in real-life practice. Methods: Analysis of health insurance claims data in 2000- 2007 from > 35 large health plans across the US was conducted. Patients who had a cancer diagnosis and chemotherapy within 120 days of their first pegfilgrastim injection were identified. The proportion of pegfilgrastim injections that were followed by administration of chemotherapy within 11 and 9 days was calculated. Analysis was also stratified by cancer type [Non-Hodgkin's lymphoma (NHL), lung, breast]. Results: A total of 13,526 cancer patients received 57,118 pegfilgrastim injections. NHL, lung, and breast cohorts comprised 2,722, 2,772, and 4,955 patients, respectively. Mean age (SD) was 55.0 (11.6) and women represented 65.9% of study population. Among all cancer types, 19.2% of pegfilgrastim injections had a chemotherapy claim within the following 11 days. This pattern of use was the highest in NHL (18.9%), followed by lung (17.1%), and breast (16.2%). Similar results were observed in the 9-day sensitivity analysis (see Table ). Conclusions: Based on the retrospective analysis of this administrative claims database, the use of pegfilgrastim within 11 days of an administration of chemotherapy was observed in 15–20% of cases which is inconsistent with the recommended guidelines. Pegfilgrastim use in these situations may have the potential to increase sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy. Further research is being conducted to assess the related clinical and economic impact of this pattern of usage. [Table: see text]

[Table: see text]
Use of physical activity as a health tool for cancer patients and oncologists
Authors: Karvinen K. , DuBose K. D. , Allison R. R.
Published: August 2020

9634

Background: Regular physical activity can be beneficial to health for both patients and their providers. Research suggests that health care providers can potentially provide an important role in changing patients’ health behaviors. The purpose of this study is to (a) explore factors that influence whether or not oncologists recommend physical activity to their patients and (b) to examine physical activity levels of oncologists. Methods: 199 practicing medical and radiation oncologists throughout the United States responded to a mailed survey (response rate = 30%). Oncologists self-reported their physical activity promotion practices, their own physical activity behaviors, and provided demographic and practice related information. Results: Approximately 64% of oncologists reported inquiring about their patients’ physical activity on most or all visits. Further, 57% of oncologists reported regularly meeting American College of Sports Medicine guidelines for physical activity (i.e., 150 minutes of moderate or 60 minutes of vigorous physical activity per week). Potential predictors of physical activity promotion (i.e., age, ethnicity, number of years practicing, tumor types treated and own physical activity participation) were tested using univariate statistics. A logistic regression analysis indicated that number of years practicing (OR = 2.84, 95% CI = 1.465–5.521) and their own physical activity participation (OR = 1.87, 95% CI = 1.025–3.426) were both significant and independent predictors of physical activity promotion. No other factors were identified as predictors of physical activity promotion. Conclusions: Approximately half of oncologists do not meet public health physical activity guidelines and fewer than two thirds regularly inquire about the physical activity levels of their patients. Data from this study suggest that these findings are linked: inactive oncologists tend to promote physical activity less to their patients. More physical activity adoption by oncologists may ultimately lead to increased activity levels in their patients, leading to greater health benefits for both patients and providers.

No significant financial relationships to disclose.
Is best supportive care really best supportive care?
Authors: Lee R. , Von Roenn J.
Published: August 2020

9639

Background: With the growth of palliative medicine over the past decade, the paradigm of supportive care has evolved to create new standards for cancer patients. The aim of this study was to define “best supportive care” (BSC) during clinical trials of advanced solid tumors. Methods: Systematic review of the literature using Medline and the Cochrane Central Register of Controlled Trials databases. These were searched for randomized controlled trials in which anticancer therapy was compared with a BSC only arm. Results: A total of 43 studies met our inclusion criteria (publication dates, 1980–2008) with the following cancer types: 22 lung cancer, 6 colorectal, 6 pancreas, 2 gastric, and 7 other cancer types. Thirty-eight studies (88%) provided some definition of supportive care and sixteen studies (37%) used the term BSC. The average survival across treatment arms was 27.5 weeks. All but one study described the use of palliative therapies at the discretion of the treating physician without standardization. Over half of all studies (56%) specifically mentioned analgesics and radiotherapy (RT) for pain control. Other specific interventions listed were steroids (14), antibiotics (10), psychological support (10), nutritional support (9), blood transfusions (8), anti-emetics (6), and anti-depressant or anxiolytic medications (3). One-third of trials (15) reported an equivalent clinical evaluation schedule for both the BSC and treatment arms. Quality of life (QoL) was measured with a validated instrument (e.g., QLQ-30) in 55% of trials and 37% compared the utilization of at least one palliative treatment between groups. Trials using the term BSC were more likely to provide multidisciplinary therapy beyond RT and analgesics (50% vs. 19%; p<0.05). Conclusions: The management of subjects in a BSC arm of clinical trials are highly variable. Overall, the trials compare treatment versus no treatment as subjects in the BSC group likely did not receive care according to current palliative medicine standards. Future randomized clinical trials with a BSC arm should provide a comprehensive, multidisciplinary approach that is consistent with practice guidelines. A standardized BSC approach developed with palliative medicine specialists is warranted for further study.

No significant financial relationships to disclose.
Chromosome enumeration probe 17 (CEP) ratio to predict chemosensitivity in HER-2 overexpressing breast cancer
Authors: Miura D. , Saitoh Y. , Iwatani T. , Kawabata H. , Inoshita N.
Published: August 2020

e11600

Background: Precise assessment of HER-2 is critical in breast cancers and predicts benefit of trastuzumab (T). Although subset analysis of CALGB 9840 suggests benefit in FISH-negative patients with chromosome 17 polysomy (C17), clinical significance of C17 in FISH-positive patients is still less known. To analyze the epidemiologic feature of C17 in Japanese patients, consecutive operable breast cancer patients during 05–07 treated in single institution were studied. Methods: HER-2 status of consecutive 307 patients excluding DCIS and whose specimens were poor quality for study, were analyzed with Pathvysion (FISH). We defined HER- 2 (+) and C17 as HER-2/chromosome 17 ratio ≥ 2.2 and CEP ratio ≥ 2.2, respectively. Pathological response following neoadjuvant chemotherapy (NACT) was assigned according to the Japanese Breast Cancer Society (G3; no invasive or in situ residual tumor in the breast, G2; up to two thirds of primary cancer cells having pathologically severe changes or disappearance, G1; up to one third to two thirds of primary cancer cells having pathologically severe changes or disappearance). Results: HER-2 (+) was found in 22% (67/307) and C17 in 25% (77/307). Twenty-four of 67(36%) in HER-2 (+) had C17 and 53 of 240 (22%) in HER-2 (-) did C17. Among HER-2 (+), 23 cases received T-contained regimens as NACT (FEC/EC followed by PAC+T in 18 and DOC+CPA+T in 5). Six of 9 (67%) with C17 had G3 and 2 of 14 (14%) with non-C17 did G3. CEP ratio significantly predicts to have G3 (p=0.02) but HER-2/chromosome 17 ratio by logistic regression analysis. Conclusions: C17 was found in 25% of Japanese operable breast cancer patients of which was similar to that of CALGB. CEP ratio is a good predictive marker for chemo- sensitivity in HER-2 (+) subset.

No significant financial relationships to disclose.
Impact of adjuvant aromatase inhibitors on bone mineral density in breast cancer patients
Authors: Lai C. N. , Correa P. D. , Alhasso A.
Published: August 2020

e11616

Aims: It is well known that aromatase inhibitors (AI) are associated with significant reduction in bone mineral density (BMD) through suppression of estrogen production. This effect has been confirmed in several studies. It is considered important that we evaluate our patients and assess their baseline BMD in the adjuvant setting in relation to the use of AIs. Methods: 122 patients on adjuvant AI were evaluated retrospectively. AIs were used either as upfront, early switch or extended adjuvant therapy. BMD (T score for hip and lumbar spine) was evaluated using DEXA scanning at baseline and annually thereafter. Risk factors for osteoporosis were assessed prior to each scan. Results: Mean baseline T scores for lumbar spine and hip were - 0.95 and - 0.79 respectively. The corresponding T scores after 1 year of treatment were -1.06 and -0.92 respectively. This represents 10.6% and 17.4% reduction in T scores for the spine and hip. 24 patients (19.7%) required anti osteoporosis therapy on the basis of their baseline T Score and they were predominantly osteoporotic. 77 patients had chemotherapy as well and had a more significant reduction in their T scores (29% reduction at the hips) in comparison to non chemotherapy patients. Patients on upfront AIs had lower baseline mean T scores (- 0.932 at hip and - 1.119 at L- Spine) and at follow up (- 1.066 at hip and -1.165 at L spine) in comparison to those on the switch approach (baseline: - 0.666 hip, - 0.816 spine; follow up: - 0.809 hip, - 0.974 spine) Conclusions: AIs are associated with decreased BMD particularly for patients who had chemotherapy. Normal T scores at baseline are reassuring and in the absence of other risk factors probably do not require further scanning. Those with low T scores (<-1.5) will require continued follow up, however, the optimal scanning interval is not yet fully established and longer follow up is required.

No significant financial relationships to disclose.
Single-center experiences of neoadjuvant systemic therapy in breast cancer: Individualization of the treatment
Authors: Gumus M. , Ustaalioglu B. O. , Seker M. , Bilici A. , Salman T. , Sönmez B. , Aliustaoglu M. , Eser M. , Salepci T. , Yaylaci M.
Published: August 2020

e11628

Background: Neoadjuvant chemotherapy is one of the standard treatment options for patients with locally advanced breast cancer for twenty five years. In this study, we evaluate results of neoadjuvant chemotherapy in breast cancer patients. Methods: We retrospectively analyzed 68 patients with locally advanced breast cancer. Anthracycline/taxane-based chemotherapy regimens were prescribed mostly for neoadjuvant chemotherapy. Before chemotherapy was given, patients were examined for distant metastasis by radiologic methods thereafter if patient had distant metastasis, they were excluded. Patients with breast cancer received neoadjuvant chemotherapy were analyzed according to age, menopausal status, type of surgery, response to the treatment, histopathological properties and survival. After 3 to 6 cycle of chemotherapy patients were reevaluated by clinically and radiologically for response. Surgery was performed for appropriate patient thereafter adjuvant locoregional and systemic chemotherapy were continued. Results: Median age was 47 (29–43) years. 17,6 % of them were younger than 35 years and 42,6 % were premenopausal. Median follow-up time was 19 month. After 3 to 6 cycle of neoadjuvant chemotherapy 64 of patients responded to therapy (94,1 %). Breast conserving surgery was performed for 15,6 % patients. In histopathologic analysis most of patients were invasive ductal carcinoma and there was lymph node invasion for 84,9 %. Estrogen and progesterone receptor status were negative for 18,6 % of patients and cerbB2 was positive for 14,8 % of patients. Median disease free survival time was 44 month (SE: 9; 95% CI: 25–62) but median overall survival time could not be reached. Three years disease free survival rate and overall survival rate were 55,3% and 90,1% respectively. According to Cox regression analyses; we did not find any demographic and pathologic characteristic of breast cancer that is related to prognosis. Conclusions: In recent years neoadjuvant chemotherapy in breast cancer is increasingly being used for early stage disease. Further study will be facilitated establishment of guidelines for preselecting patients for neoadjuvant chemotherapy and will provide beneficial effect on treatment option and survival.

No significant financial relationships to disclose.
Early-stage male breast cancer: A 10-year experience
Authors: Gercovich N. , Gil Deza E. , Russo M. , Garcia Gerardi C. , Diaz C. , Morgenfeld E. , Rolnik B. , Emina J. , Rivarola E. , Gercovich F. G.
Published: August 2020

e11630

Introduction: Male breast cancer is very rare, representing only between 0.7% and 1% of all breast cancers, and only half of them are early stage cases. Objective: The present study has been designed with the aim of studying retrospectively the clinical onset and evolution of male invasive breast cancer patients (stages I and II) treated at IOHM between 1997 and 2008. Methods: The records of 3,000 breast cancer cases followed between 1997 and 2008 were searched, looking for male stage I and II breast cancer patients. A database was designed following the recommendations of the Directors of Surgical Pathology of the USA. The information registered encompassed: adjuvant treatments, recurrence date and date of final consultation or death. Results: Twelve pts were identified. Mean age (range)= 66 yo (50–89 yo). Tumoral type= Invasive Ductal Carcinoma 12 pt. Tumoral subtype= NOS 9 pt (75%) Apocrine 2 pt (17%) Micropapillar 1 pt (8%). Nottingham´s grade= Grade 2: 8 pt, Grade 3: 3 pt, N/A=1 pt. Stage= I= 6 pt, II=6 pt. ER (Positve= 9 pt, Negative=1 pt, N/A= 2 pt). PR (Positve= 8 pt, Negative= 2 pt, N/A=2 pt). Her2neu (0+= 3 pt, 1+= 3 pt, 2+= 2 pt, N/A= 4 pt). Surgery= Mastectomy= 11 pt, Lumpectomy 1= pt. Radiotherapy=5 pt. Adjuvance= No=2 pt, Hormonotherapy (HT)= 3 pt, Chemotherapy (CHT) = 3 pt, CHT+HT= 4 pt. Recurrence= Yes= 2 pt, No= 10 pt. Survival: Dead= 1 pt, Alive =11 pt. Mean Time To Progression= Stage I =66 months, Stage II =42 months. Global survival: Stage I =66 months, Stage II =52 months. Conclusions: 1. Twelve stage I and II male breast cancer patients were identified out of 3000 (0.4%) breast cancer cases diagnosed and followed in the past 10 years at the IOHM. 2. Mastectomy was the surgical procedure in 11 of the 12 cases 3. Ten pt underwent adjuvant treatment. 4. With a mean follow up time of 60 months, all stage I patients are alive and there were no recurrences. Two of the 6 stage II pts progressed and one died.

No significant financial relationships to disclose.
Case series: Paclitaxel (P) and pegfigrastim (PF)-induced hypersensitivity pneumonitis (HSP) in breast cancer patients (pts)
Authors: Cream L. , Barochia A. C. , Sivik J. , Kass R.
Published: August 2020

e11631

Background: P, a chemotherapeutic agent, extensively used in management of solid tumors. Although hypersensitivity reactions from P are common; HSP is rarely reported. We report 3 pts with early stage, high risk breast cancer, who developed HSP while receiving dose dense (DD) P with PF support. Methods: C#1 51 yr old woman (W) was diagnosed (Di) with triple negative (TN), infiltrating duct carcinoma (ca) with nodal metastasis. Neoadjuvant chemo (NC) with DD adriamycin 60 mg/m2 (A) and Cyclophosphamide 600 mg/m2 (C) was started. She completed 4 cycles of AC with PF 6 mg SQ given day 2 of each cycle without complications. Several days after her first dose of P with PF, she experienced dyspnea on exertion (DOE) and a non productive cough (NPC). CT of chest (CC) revealed ground glass opacity more in upper lungs, suggestive of HSP, and echocardiogram (echo) was within normal limits (WNL). She rapidly improved with steroid (S). C#2 46 yr w was Di with hormone positive, her 2 negative, infiltrating duct ca with nodal involvement. NC with DD AC followed by P was started. She completed 4 cycles of AC with minimal toxicity followed by DDP. After the third P infusion, she developed NPC with DOE. CC revealed diffuse interstitial prominence and echo was WNL. She rapidly improved with S. C#3 63 yr W was Di with 2.3 cm, TN, invasive duct carcinoma of left breast. NC with DD AC followed by P was started. After 2nd infusion of P, she developed hypoxia and cough; CC revealed diffuse groundglass opacities throughout lungs bilaterally, suggestive of HSP. She rapidly improved with S. Results: All 3 cases occurred in non-smoking pts without known lung/cardiac disease, treated with PF on day 2 of each cycle. Pts had abnormal CCs, were afebrile and responded quickly to steroids. Published DD experience (Citron et al) uses daily filgrastim (F), not the pegylated form which our pts received. We believe that HSP in these pts may be related to long acting growth factor stimulation of white cells and causing reversible HSP. Conclusions: Future prospective studies on taxanes using DD regimens should include a randomized design where pts given PF are compared to pts who receive F.

No significant financial relationships to disclose.
Case report of a 27-year-old male with DCIS
Authors: Hamm C. , Coroneos C.
Published: August 2020

e11635

DCIS in a young male is rarely reported. Our patient is a 25 year old male who presented with symptomatic unilateral gynecomastia. He presented with a strong family history of cancer on both maternal and paternal sides of his family including breast, lung (maternal) and melanoma, colon and pancreatic (paternal). His mother tested negative for BRCA1 and BRCA2. There is no information on the paternal genetic testing. He was treated with left subcutaneous mastectomy. Upon histologic review of the sample, concurrent gyecomastia and ductal carcinoma in situ was discovered. To date, only four cases of gynecomastia and DCIS have been described in younger male patients. Since only 30 - 50% of patients with DCIS eventually develop invasive cancer in the subsequent 10 - 20 years, this figure in the general population may be higher. This case underscores the importance of family history in any patient presenting with a breast mass. Patients must be made aware of the risk, however small it may be and physicians must remain cautious of malignancy in young males with gynecomastia.

No significant financial relationships to disclose.
Triple negative breast cancer: Adjuvant treatment and outcome of 62 patients
Authors: Koussis H. , Scola A. , Maruzzo M. , Ghiotto C. , Orvieto E. , Bozza F. , Zavagno G. , Jirillo A.
Published: August 2020

e11636

Background: Triple negative breast cancer (TNBC) represents around 12–20%. They are high risk in view of poorly differentiated tumor shortened survival, younger age, increased mortality rate in the first 5 years, increased risk of brain metastasis, rapid progression from distant recurrence to death of patients. To provide further insight we have undertaken a comprehensive multi year review of demographics tumor features adjuvant treatment and outcomes in this patients group. Methods: A retrospective analysis of all patients with TNBC treated by adjuvant chemotherapy between January 2000 and June 2008 was done though chart review. Results: Sixty-two patients were seen in our institution. The median age at diagnosis was 57 years (range 27–86 yrs). Forty-three patients underwent conservative breast cancer surgery, mastectomy 19 patients. All patients underwent axillary lymph nodes dissection or sentinel lymph node biopsy. The stage of the disease at diagnosis was: I in 22, IIA in 22, IIB in 8, IIIA in 4, IIIB in 2 and stage 0 in 4 patients. After multidisciplinary evaluation 58 patients received adjuvant treatment with: anthracycline based regimen in 30, anthracycline plus taxane in 4 and 24 patients were treated with Cyclophosphamide, methotrexate and 5-Fluorouracil (CMF) regimen. After median 13 months (4–71), 8 (13.7%) relapses were observed: 6 out 8 were anthracycline based regimen treated. The pattern of disease spread was: local recurrence 5, lymph node 1, liver 2 patients. The median follow-up was 25 months (range 95–1). Conclusions: Treatment options for TNBC are limited because of lack of targeted treatment. Current, old and new drugs alone or in combination (anthracycline, taxanes, platinum salts, bevacizumab, erlotinib, dasatinib, cetuximab) are used in an experimental setting.

No significant financial relationships to disclose.
Pilot study with pegylated liposomal doxorubicin (PLD) and docetaxel as first-line treatment in patients with metastatic breast cancer (MBC)
Authors: Mel J. R. , Ramos M. , Cueva J. , Castellanos J. , Almanza C.
Published: August 2020

e12002

Background: Anthracyclines (AC) and taxanes are the most active cytotoxic agents for the treatment of MBC. The use of AC is limited by their acute toxicities and by their potential to cause cumulative cardiac damage. The development of alternative formulations of AC, such as pegylated liposomal doxorubicin (PLD) with lower toxicity may improve tolerability and efficacy of AC based regimens. This study has been conducted to determine the efficacy and toxicity profiles of docetaxel and PLD as first line treatment in patients (pts) with MBC. Methods: Pts ≥ 18 years with histologically confirmed breast cancer, advanced disease, PS ≥ 60%, LVEF> 50%, adequate bone marrow, renal and hepatic function were included. No prior systemic therapy for MBC was allowed. Pts with brain metastases were excluded. Docetaxel 60 mg/m2 iv followed by PLD 30 mg/m2 iv day 1 every 3 weeks up to 6 cycles were given. Results: Thirty women with a median age of 64 years (40–81) were included. (76.7%) of pts were postmenopausal, Karnofsky PS 100 and 90 were 48% and 21% respectively, 86% of pts had ductal carcinoma. Most common sites of metastasis were lung (57%), liver (47%), and bone (43%). 20/30 (67%) of pts were pretreated, 15 (50%) pts with AC-containing regiment and 17 (57%) with radiotherapy. A total of 157 cycles (median 6, range 2–6) were administered. Median relative dose intensity was 90% for docetaxel and 88% for PLD. Over 28 pts assessable for response, overall response rate was 35.7% (95% CI: 18.0%-53.4%), all of them PR. With a median follow-up of 20.5 months, median time to progression was 8.1 months. Main grade 3 nonhaematological toxicities were PPE (27%), mucositis (27%), and asthenia (17%). No grade 4 nonhaematological toxicities were observed. Main grade 3/4 haematological toxicities were neutropenia (17%), leucopenia (10%), and thrombopenia (6.7%). 4 pts (13%) had febrile neutropenia. Conclusions: Docetaxel and PLD administered every 21 days as first-line treatment in MBC is an active schedule with an acceptable toxicity profile.

No significant financial relationships to disclose.
Predictors of progression of bone metastases in breast cancer patients
Authors: El Ayass W. , Sereika S. , Van Londen G. , Brufsky A.
Published: August 2020

e12011

Background: Breast cancer is mostly diagnosed in elderly women aged >= 65 years and they constitute about 41% of all newly diagnosed cases. Bone metastases is a very common event in these patients especially those with estrogen receptor positive subtypes.Our aim is to identify factors that may be associated with progression of bone metastases in breast bancer (BC) patients with bone metastases only. Methods: Retrospective review of medical records of 50 females with breast cancer with only bone metastases evaluated at Magee Womens Hospital in Pittsburgh, Pennsyvlania, between June 1998 and September 2007. Patients’ progression of their bone disease was followed based on serial bone scans. Candidate predictors considered included: age at breast cancer diagnosis (as a continuous variable and dichotomized at 60 years), age at metastatic BC diagnosis (as a continuous variable and dichotomized at 60 years), time elapsed between breast cancer diagnosis, and metastatic BC diagnosis, ER status, PR status, ER/PR status, HER-2 status, use of radiation, type of bisphosphonate used (since all but two patients had this: aredia use, zometa use), type of disease (IDC, ILC), and stage of disease (I, II, III, IV). Marginal modeling using generalized estimating equations assuming a binomial error distribution was used considering potential candidate predictor variables univariately and then multivariately to identify predictors of progression of bone metastases at a significance level of 0.05. Results: Based on the univariate analysis, age at BC diagnosis (p = 0.03), age at metastatic BC diagnosis (p = 0.03), and being ER+ or PR+ (p = 0.04) were positively predictive of progression, with the latter two being also jointly significant in multivariate analysis. As anticipated, treatment with bisphosphonates and radiation therapy were found to have a protective role against progression. Conclusion: We found that age as a continuous variable and ER/PR + were positive predictors of progression of bone metastases in BC patients. These findings suggest an increased need of individualized treatment especially in elderly to prevent morbidity and lower cost.

No significant financial relationships to disclose.