Zeina Nahleh

SWOG S0800 (NCI CDR0000636131): addition of bevacizumab to neoadjuvant nab-paclitaxel with dose-dense doxorubicin and cyclophosphamide improves pathologic complete response (pCR) rates in inflammatory or locally advanced breast cancer

SWOG S0800, a randomized open-label Phase II clinical trial, compared the combination of weekly nab-paclitaxel and bevacizumab followed by dose-dense doxorubicin and cyclophosphamide (AC) with nab-paclitaxel followed or preceded by AC as neoadjuvant treatment for HER2-negative locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). Patients were randomly allocated (2:1:1) to three neoadjuvant chemotherapy arms: (1) nab-paclitaxel with concurrent bevacizumab followed by AC; (2) nab-paclitaxel followed by AC; or (3) AC followed by nab-paclitaxel. The primary endpoint was pathologic complete response (pCR) with stratification by disease type (non-IBC LABC vs. IBC) and hormone receptor status (positive vs. negative). Overall survival (OS), event-free survival (EFS), and toxicity were secondary endpoints. Analyses were intent-to-treat comparing bevacizumab to the combined control arms. A total of 215 patients were accrued including 11xa0% with IBC and 32xa0% with triple-negative breast cancer (TNBC). The addition of bevacizumab significantly increased the pCR rate overall (36 vs. 21xa0%; pxa0=xa00.019) and in TNBC (59 vs. 29xa0%; pxa0=xa00.014), but not in hormone receptor-positive disease (24 vs. 18xa0%; pxa0=xa00.41). Sequence of administration of nab-paclitaxel and AC did not affect the pCR rate. While no significant differences in OS or EFS were seen, a trend favored the addition of bevacizumab for EFS (pxa0=xa00.06) in TNBC. Overall, Grade 3–4 adverse events did not differ substantially by treatment arm. The addition of bevacizumab to nab-paclitaxel prior to dose-dense AC neoadjuvant chemotherapy significantly improved the pCR rate compared to chemotherapy alone in patients with triple-negative LABC/IBC and was accompanied by a trend for improved EFS. This suggests reconsideration of the role of bevacizumab in high-risk triple-negative locally advanced breast cancer.

Abstract P3-11-16: S0800: Nab-paclitaxel, doxorubicin, cyclophosphamide, and pegfilgrastim with or without bevacizumab in treating women with inflammatory or locally advanced breast cancer (NCI CDR0000636131)

Background. Locally advanced breast cancer (LABC) and inflammatory breast cancer (IBC) remain difficult challenges despite progress in multimodality treatment. The SWOG trial S0800 (clinicaltrial.gov NCT00856492) compared bevacizumab in combination with weekly nab-paclitaxel followed by dose-dense AC to nab-paclitaxel followed or preceded by AC as neoadjuvant treatment for HER2-negative IBC/LABC. The rationale was based on the proposed role of angiogenesis, potential role of improved flow and oxygenation in enhancing the delivery of chemotherapy agents, and the proapoptotic effect with certain chemotherapeutic agents, particularly taxanes. Methods. This was a randomized open-label Phase II trial with an accrual goal of 200 patients equally allocated to either bevacizumab (Arm 1) or no bevacizumab.Two patients were ineligible and five withdrew consent leaving 208 for analysis. The no bevacizumab group was further randomized to two sequences (Arm 2: nab-paclitaxel - AC+PEG-G versus Arm 3: AC+PEG-G- nab-paclitaxel) with 50 patients expected in each sequence. The primary endpoint of this study was pathologic complete response (pCR) defined as no evidence of invasive tumor at the primary site and axillary lymph nodes in the surgical specimen. The power for the primary comparison of bevacizumab (bev) versus no bevacizumab (no bev) ignoring sequence was 80% with a 1-sided α = 0.10. Randomization was stratified by hormone receptor status and type of disease (IBC or LABC). Results 215 patients were accrued May 2010 - September 2012. Most had LABC (88%) versus IBC (12%) and most tumors were hormone-receptor (HR) positive (67%). Fourteen (7%) patients had no definitive surgery (included as no pCR); 135 (65%) had residual disease (no pCR) and 59 (28%) had pCR. The bevacizumab pCR rate was higher (35/96; 38%) than that in the non-bevacizumab arms (24/112; 21%) (exact p=0.021; stratified p=0.015). In HR-positive disease there was slight improvement that was not statistically significant (bev 25% vs. non-bev 18%; p=0.41) while the difference was larger in HR-negative disease (bev 59% vs. non-bev 28%; p=0.014). In LABC the overall pCR rate was 29% with a higher rate in the bevacizumab patients (37% vs. 22%; p=0.035). For IBC there was improvement (30% vs. 14%), but not statistically significant (p=0.61) in a small sample. Overall, Grade 3 and 4 events were common in both (bev 67%; non-bev 65%), but did not differ by treatment. There were 21 deaths with 3-year overall survival (OS) of 87% and 83% for bevacizumab and non-bevacizumab, respectively (log-rank p=0.57). Conclusion Compared with combination anthracycline-taxane neoadjuvant chemotherapy, the Bev-Nab-paclitaxel-AC regimen significantly improved pCR rate overall, primarily for triple negative (TNBC) patients. This neoadjuvant regimen could be a good choice for TNBC/IBC . The observed pCR rate in ER negative disease (59%) suggests that the addition of bevacizumab to a standard chemotherapy backbone may improve outcome in this subset, and justifies further testing of such an approach. Correlative science studies to further delineate the biology of TNBC and the effects of bevacizumab are ongoing. Citation Format: Zeina A Nahleh, William E Barlow, Daniel F Hayes, Anne F Schott, Julie R Gralow, Edith A Perez, William M Sikov, Sudhathi Chennuru, Hamid Mirshahidi, Sarah Vidito, Danika L Lew, Lajos Pusztai, Robert B Livingston, Gabriel N Hortobagyi. S0800: Nab-paclitaxel, doxorubicin, cyclophosphamide, and pegfilgrastim with or without bevacizumab in treating women with inflammatory or locally advanced breast cancer (NCI CDR0000636131) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-11-16.

Physical symptom profile for adult cancer inpatients at a Lebanese cancer unit

BACKGROUNDnHospital-based palliative care programs in Lebanon are nonexistent in a structured form. One of obstacles is the lack of knowledge about symptom prevalence and burden of cancer patients in Lebanon.nnnMETHODSnThis is a cross-sectional observational study where 100 adult cancer patients admitted to the American University of Beirut Medical Center inpatient unit completed a survey to assess 20 physical symptoms according the National Cancer Institutes Common Terminology Criteria for Adverse Events 4.0 (NCI-CTCAE 4.0) guidelines.nnnRESULTSnHematologic, gastrointestinal, breast, and lung cancers were the most common. Mean age was 51.5 years; 51% were female. 74% of patients with solid tumors had metastatic disease. Treatment approaches were palliative chemotherapy, followed by curative chemotherapy and best supportive care. The most common symptoms were fatigue, appetite loss, nausea, and pain; most distressing were nausea, pain, and fatigue. Nausea and vomiting were more prevalent among females than males. Females reported more severe vomiting than males, but males had more intense pain. Overall symptom burden difference was statistically significant across age groups, with the 51-60 year group having the most symptoms, but not among different genders. Difference was significant among different treatment intents, with the best supportive care group having most symptoms.nnnCONCLUSIONnFatigue should be better addressed as a legitimate symptom. Subgroup differences must be considered when managing gastrointestinal symptoms. Pain should be more effectively managed, and vulnerable subgroups such as the 51-60 year age group and those on best supportive care should receive special consideration.

Comparative Outcome of Computed Tomography-guided Percutaneous Radiofrequency Ablation, Partial Nephrectomy or Radical Nephrectomy in the Treatment of Stage T1 Renal Cell Carcinoma.

Renal cell carcinoma (RCC) accounts for 3% of all cancers in adults. The indications for Radiofrequency Ablation (RFA) for renal carcinomas include T1a (tumor 4 cm or less, limited to the kidney), elderly patients, renal impairment, comorbidities, poor surgical candidate, and multiple bilateral renal masses. We retrospectively reviewed medical records, specifically investigating the indications, complications and outcomes of RFA and nephrectomy for treatment of RCC in a tertiary medical center with a predominantly Hispanic patient population. Forty-nine patients with RCC were evaluated. Nine patients had RFA, 9 had partial nephrectomy and 31 had radical nephrectomy. All patients among the 3 groups had stage T1N0M0 RCC at diagnosis. Tumor recurrence was observed in 2 (22%) patients that had RFA, one (11%) patient that had partial nephrectomy and no patients that had radical nephrectomy. One patient had recurrence of the tumor at the opposite kidney pole from the initial RFA site 4 years later. This particular patient did not have any tumor recurrence at the site of the initial RFA. A second RFA was performed on the recurrent tumor with no recurrence upon subsequent follow up visits. The second patient had recurrence of the RCC on 1 year follow that was discovered to be sarcomatoid RCC, which is an aggressive type with a poor prognosis. Our results support the clinical utility of RFA in patients with stage T1 RCC who are poor surgical candidates or those with reduced renal function. The clinical utility of RFA as an equally effective approach when compared to partial nephrectomy in patients with stage T1 RCC that meet strict indications for the procedure. The treatment choice should be individualized and based on the characteristics of the renal tumor such as size, location and histological type of RCC. We conclude that RFA presents a safe treatment choice for patients with RCC if long term follow up is maintained.

Perceptions and needs of women with metastatic breast cancer: a focus on clinical trials.

Many patients are living longer with Metastatic Breast Cancer (MBC) than ever before. However, complete responses remain uncommon, and progression of disease is often inevitable. The experience of living with MBC exposes patients to a wide variety of clinical, psychological, social and spiritual issues. Although much research effort has focused on decision-making and coping strategies among women with early breast cancer, relatively little attention has been given to the needs, experiences, and perceptions of women living with MBC. Furthermore, there are major research gaps in understanding and prioritizing the types of psycho-social interventions that would make the most difference in the lives of these patients. Fortunately, the tide is turning. This communication represents a joint effort of the Breast International Group and the National Cancer Institute (NCI)-sponsored North American Breast Cancer Group (BIG-NABCG) to highlight perceptions and needs of patients living with MBC and current obstacles facing them, and recommends strategies for better addressing some of these unmet needs.

Spindle cell carcinoma of the breast: a case report and discussion.

Spindle cell carcinoma of the breast is a rare subtype of metaplastic carcinoma with likelihood of aggressive behavior and lack of specific treatment options. Spindle cell carcinomas of the breast are typically Triple Negative and have distinct clinical, radiographic and pathological characteristics. We present, in this report, the case of a woman diagnosed with spindle cell carcinoma of the breast, and review the literature on this rare but intriguing disease.

Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Pre- and Posttreatment Breast Cancers in the SWOG S0800 Phase II Neoadjuvant Chemotherapy Trial

Our aim was to examine the association of pretreatment tumor-infiltrating lymphocyte (TIL) count and PD-L1 levels with pathologic complete response (pCR) and assess immune marker changes following treatment in tumor specimens from the S0800 clinical trial, which randomized patients to bevacizumab + nab-paclitaxel, followed by doxorubicin/cyclophosphamide (AC) versus two control arms without bevacizumab (varying sequence of AC and nab-paclitaxel). TILs were assessed in 124 pre- and 62 posttreatment tissues (including 59 pairs). PD-L1 was assessed in 120 pre- and 43 posttreatment tissues (including 39 pairs) using the 22C3 antibody. Baseline and treatment-induced immune changes were correlated with pCR and survival using estrogen receptor (ER) and treatment-adjusted logistic and Cox regressions, respectively. At baseline, the mean TIL count was 17.4% (17% had zero TILs, 9% had ≥50% TILs). Posttreatment, mean TIL count decreased to 11% (5% had no TILs, 2% had >50% TILs). In paired samples, the mean TIL change was 15% decrease. Baseline PD-L1 was detected in 43% of cases (n = 5 in tumor cells, n = 29 stroma, n = 18 tumor + stroma). Posttreatment, PD-L1 expression was not significantly lower (33%). Higher baseline TIL count and PD-L1 positivity rate were associated with higher pCR rate even after adjustment for treatment and ER status (P = 0.018). There was no association between TIL counts, PD-L1 expression, and survival due to few events. In conclusion, TIL counts, but not PD-L1 expression, decreased significantly after treatment. Continued PD-L1 expression in some residual cancers raises the possibility that adjuvant immune checkpoint inhibitor therapy could improve survival in this patient population. Mol Cancer Ther; 17(6); 1324–31. ©2018 AACR.

Dermatopathic Lymphadenitis Mimicking Breast Cancer with Lymphatic Metastasis: A Case Report and Discussion

Patient: Female, 56 Final Diagnosis: Dermatopathic lymphadenitis Symptoms: Lymphadenopathy Medication: — Clinical Procedure: — Specialty: Oncology Objective: Rare co-existance of disease or pathology Background: Dermatopathic lymphadenitis is a rare benign lymphatic hyperplasia commonly associated with exfoliative or eczematoid dermatitis. Of interest, this condition can be confused with lymphatic metastasis in adults. Case Report: In this report, we describe the case of a 56-year-old woman diagnosed with left breast invasive ductal carcinoma in remission, who presented with dermatopathic lymphadenitis mimicking breast cancer recurrence. Conclusions: Dermatopathic lymphadenitis is a benign entity that needs to be considered in the differential diagnosis of lymphadenopathy. Pursuing extensive workup in asymptomatic patients with a similar presentation and initial negative tests for malignancy recurrence is not recommended.

Overview of Metronomic Chemotherapy in SWOG Breast Cancer Cooperative Group Clinical Trials

Metronomic chemotherapy, defined as continuous or frequent treatment with low doses of anticancer drugs, has been observed to provide excellent safety profiles and has been tested in many tumors. SWOG, formerly the Southwest Oncology Group, has reported extensively on metronomic chemotherapy used in breast cancer. The earliest trials reported on a continuous, or “Cooper-” type, Cyclophosphamide, Methotrexate, 5-Fluorouracil (CMF) regimen in the setting of adjuvant chemotherapy for node-positive breast cancer, in which cyclophosphamide is administered orally on a daily basis and the 5-FU and methotrexate are given by weekly intravenous injection. Subsequently, other regimens have been evaluated. We will, hereby, provide an overview of the main SWOG trials evaluating metronomic chemotherapy in breast cancer.

Abstract P3-07-06: BRCA mutations among Hispanic breast cancer patients of Mexican origin in El Paso, TX

Introduction: El Paso, TX is a large American-Mexican border city of population around 900,000, 85% Hispanic of Mexican origin. Limited cancer research has been conducted in this population. The relative homogeneity of this Hispanic population lends a unique opportunity to study the prevalence of BRCA mutations among Hispanic patients of Mexican origin, to identify reported Mexican founder or recurrent mutations, and to study the breast cancer characteristics in mutation carriers. Methods: Hispanic women with a personal history of breast cancer, who presented consecutively for genetic cancer risk assessment, were enrolled in an Institutional Review Board –approved registry and underwent BRCA testing bases on NCCN guidelines. The characteristics of tumors and patients with positive BRCA mutation were analyzed. Descriptive statistics were utilized . Results : 59 patients were screened; 13 patients (22%) tested positive. Mean age was 50 years; 8 patients (62%) had stages I or II, 2 patients stage III, and 3 unknown. 10 (77%) ductal, 1 (7%) lobular and 2 undetermined; 30% had ER positive tumors versus 61% ER negative; 69% had HER2 –neu negative tumors and 23% HER2-neu positive; 62% were triple negative. Nine patients (69%) were diagnosed with breast cancer at younger than 50 years. Median BMI was 31.78. Ten patients had BRCA1 mutations and 3 BRCA2 mutations. A total of 9 unique deleterious BRCA Mutations were observed, BRCA1 R71G (330A>G);del exons 1-2;C1787S(5478T>A) and G1788D(5482 G>A); C1225X (3794 C>A); A 1708E(5242 C>A); R1751X(5370C>T; and del exons 9-12 and BRCA2 Q742X (2452 C>T); and 3492 insT Conclusion: This study confirms that breast cancer patients with BRCA mutations in the El Paso, TX present at a younger age, and have predominantly triple negative tumors. Of particular interest is 44% (4 of 9) BRCA mutations (BRCA1 exon 9-12 del; C1787S & G1788D and BRCA 2 3492insT; Q742X) identified have been reported as recurrent mutations in Hispanic individuals from Mexico as the country of origin, including BRCA1 ex9-12del, the 1st Mexican founder mutation and 100% of the BRCA2 mutations. A more cost-effective approach to initial screening of Hispanic individuals based on country of origin may be desirable and would potentially decrease the number of cases requiring complete sequencing. Increasing breast cancer awareness and encouraging genetic counseling among high risk younger patients of Mexican descent is also needed.nnCitation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-07-06.