Image analysis-based tumor infiltrating lymphocytes measurement predicts breast cancer pathologic complete response in SWOG S0800 neoadjuvant chemotherapy trial.

We assessed the predictive value of an image analysis-based tumor-infiltrating lymphocytes (TILs) score for pathologic complete response (pCR) and event-free survival in breast cancer (BC). About 113 pretreatment samples were analyzed from patients with stage IIB-IIIC HER-2-negative BC randomized to neoadjuvant chemotherapy ± bevacizumab. TILs quantification was performed on full sections using QuPath open-source software with a convolutional neural network cell classifier (CNN11). We used easTILs% as a digital metric of TILs score defined as [sum of lymphocytes area (mm2)/stromal area(mm2)] × 100. Pathologist-read stromal TILs score (sTILs%) was determined following published guidelines. Mean pretreatment easTILs% was significantly higher in cases with pCR compared to residual disease (median 36.1 vs.14.8%, p < 0.001). We observed a strong positive correlation (r = 0.606, p < 0.0001) between easTILs% and sTILs%. The area under the prediction curve (AUC) was higher for easTILs% than sTILs%, 0.709 and 0.627, respectively. Image analysis-based TILs quantification is predictive of pCR in BC and had better response discrimination than pathologist-read sTILs%.

Geographical Disparities and Factors Associated With the Decision to Decline Chemotherapy in Breast Cancer.

PURPOSE: Social determinants of health have been linked to treatment-related disparities in breast cancer. We analyzed data from a large national registry to explore factors related to accepting or declining recommended chemotherapy and whether patients' decisions vary geographically across the United States. METHODS: We used the National Cancer Database to study treatment decision making in patients with advanced breast cancer (American Joint Committee on Cancer clinical stage III-IV) between 2004 and 2017. We focused the analysis on patients who were recommended chemotherapy by their physicians but who declined this treatment. Multivariate logistic regression analysis was performed. RESULTS: A total of N = 215,284 patients with stage III and IV breast cancers were included. Patients in the New England region were more likely to refuse chemotherapy compared with the rest, with patients in the East South Central regions (AL, KY, MS, and TN) and West South Central (AR, LA, OK, and TX) noted to be least likely to refuse chemotherapy. Factors related to a higher rate of refusal by patients included older age > 70 years; hormone receptor-positive tumors; and having higher comorbidity. Patients identified as Hispanic, those who are privately insured, and patients at academic institutions were less likely to decline chemotherapy. CONCLUSION: This analysis identified a significant difference in rates of refusal of recommended chemotherapy by geographical location, insurance status, and treatment facility after adjusting for known social determinants of health. Further understanding of the factors affecting treatment decisions would be important to improve the efficacy of care delivery in patients with cancer and reduce reversible causes of disparity.

Clinical and Demographic Factors, Treatment Patterns, and Overall Survival Associated With Rare Triple-Negative Breast Carcinomas in the US.

Importance: Triple-negative breast cancers are known collectively to demonstrate a more aggressive clinical course and earlier recurrence than cancers of other histological subtypes. However, the literature on rare triple-negative breast cancers and the association of histological type with survival and risk of metastasis is sparse. Objective: To present the clinical and demographic characteristics, treatment patterns, and overall survival (OS) for histologically rare (<10% of breast cancers) triple-negative breast cancer types: medullary carcinoma, adenoid cystic carcinoma, and metaplastic breast carcinoma. Design, Setting, and Participants: This cohort study was performed in the US using data reported by the National Cancer Database between 2010 and 2016. Confirmed cases of medullary carcinoma, adenoid cystic carcinoma, and metaplastic breast cancer were analyzed. Univariable analyses and multivariable Cox regression models were performed. Data analysis was performed from April to May 2020. Main Outcomes and Measures: The primary outcome was 5-year OS. Secondary outcomes included site of metastasis, effect of immunohistochemistry, management, and 2-year mortality. Results: A total of 8479 patients with breast cancer (mean [SD] age; 62.6 [14.3] years; 8435 women [99.48%]) were analyzed. Metaplastic carcinoma was the most commonly diagnosed histological type in this cohort, with 6867 patients (81%), followed by 1357 (16%) with adenoid cystic carcinoma and only 255 (3%) with medullary carcinoma. Medullary carcinoma presented earlier in life, at a median (interquartile range) age of 53 (45-62) years, compared with 62 (53-72) years for patients with adenoid cystic carcinoma and 63 (52-74) years for patients with metaplastic carcinoma. The proportion of tumors with triple-negative immunohistochemistry varied by histological type for medullary carcinoma (57 patients [22.4%]), adenoid cystic carcinoma (653 patients [48.1%]), and metaplastic carcinoma (3637 patients [53.0%]). Patients with adenoid cystic carcinoma were less likely to receive radiotherapy (711 patients [52.4%]) and chemotherapy (175 patients [12.9%]) compared with patients with medullary carcinoma (radiotherapy, 156 patients [61.2%]; chemotherapy, 190 patients [74.5%]) and metaplastic carcinoma (radiotherapy, 3416 patients [49.7%]; chemotherapy, 4709 patients [68.6%]). The 5-year OS rate was superior for patients with medullary (91.7%) and adenoid cystic carcinoma (88.4%) compared with patients with metaplastic carcinoma (63.1%). The 5-year mortality rate for adenoid cystic carcinoma was 8.33% vs 36.91% for metaplastic carcinoma. Conclusions and Relevance: Nationally, over the course of 7 years, medullary carcinoma was most common and metaplastic carcinoma had the worst 5-year OS among the rare histological breast cancer subtypes analyzed. Factors associated with a poor prognosis for metaplastic carcinoma included advanced stage, lung metastasis, older age, and not receiving chemotherapy or radiation therapy. Future research focusing on rare subtypes of breast cancer is desirable and could inform the optimal management of these relatively understudied carcinomas.

Endocrine Therapy Plus Anti-HER2 Therapy as Adjuvant Systemic Therapy for Luminal HER2-Positive Breast Cancer: An Analysis of the National Cancer Database.

BACKGROUND: Guidelines regarding the usage of adjuvant systemic therapy in patients with small human epidermal growth factor receptor 2 (HER2)-positive and estrogen receptor/progesterone receptor-positive (luminal HER2 positive) tumors are nonspecific. Outcomes of chemotherapy followed by endocrine therapy (ET), with or without anti-HER2 therapy, vs ET alone (no chemotherapy) have not been widely studied in this disease subtype. We sought to examine the usage and outcomes of adjuvant systemic therapy (ET vs chemotherapy with or without trastuzumab) in stage I luminal HER2-positive breast cancer (BC), based on the large National Cancer Database. METHODS: We conducted a retrospective analysis of patients with luminal HER2-positive stage I BC, diagnosed between 2010 and 2015, in the United States, using univariable and multivariable logistic regression analyses. The Kaplan-Meier method estimated overall survival (OS). RESULTS: A total of 37 777 patients were included in the analysis; of these, n = 32 594 (86%) received adjuvant ET and n = 5183 (14%) received chemotherapy. Around 40% of all patients received anti-HER2 therapy (trastuzumab). Patients who received trastuzumab had a better 5-year OS (93.4% vs 92.0%, P = .0002) compared with those who did not. Patients who received anti-HER2 therapy plus ET had the best OS rate at 5 years (93.5%, confidence interval [CI]: 89.2%-98%, P < .0001) compared with those receiving anti-HER2 therapy plus chemotherapy (92.7%, CI: 89.4%-96.1%, P < .0001). CONCLUSIONS: Most patients in the United States, with stage I luminal HER2 positive BC, received ET, not chemotherapy but most of them do not receive anti-HER2 therapy resulting in inferior outcome. Future trials exploring the de-escalation of systemic adjuvant therapy for early-stage luminal HER2-positive BC to ET plus anti-HER2 therapy would be desirable.

Elucidating Determinants of Survival Disparities Among a Real-world Cohort of Metastatic Breast Cancer Patients: A National Cancer Database Analysis.

BACKGROUND: Disparities in breast cancer survival by race/ethnicity and socioeconomic status have been reported. However, it is unclear if these findings are reproducible among subpopulations. This study aimed to assess if socially oriented factors are predictive of overall survival (OS) among patients with hormone receptor-positive (HR+), human epidermal growth factor 2-positive (HER2+) metastatic breast cancer (MBC). PATIENTS AND METHODS: We analyzed patients with MBC included in the National Cancer Database diagnosed with HR+ and HER2+ disease treated between 2010 and 2015. Multivariate analyses describe the association between non-clinical prognostic factors and OS. A matched analysis, which balanced prognostic factors between whites and African Americans (AA), was also conducted. RESULTS: Of the 6200 patients analyzed, the majority were 50 years or older, white, and treated with hormonal therapy. Disparities in OS were observed; multivariate analysis revealed diminished survival was associated with low income (< $38K vs. ≥ $63K, hazard ratio [HR], 1.30; P < .001), having government insurance (government vs. private, HR, 1.55; P < .001), living closer to one's treatment facility (< 4 miles vs. ≥ 18 miles, HR, 1.16; P = .04), and being AA (AA vs. white, HR, 1.20; P = .006). The mortality disparity attributed to race was insignificant in the matched analysis (AA vs. white, HR, 1.13; 95% confidence interval, 0.98-1.30; P = .09). CONCLUSIONS: This study confirms that the known sociodemographic disparities in OS among patients with MBC are similar within the HR+/HER2+ subpopulation. The discordance of outcomes between matched and unmatched analysis demonstrate that there is a highly vulnerable subgroup of AAs. Further investigation is required to determine if the identified associations are independently causal of poor prognosis.

Long-Term Effect of a Nonrandomized Psychosocial Mindfulness-Based Intervention in Hispanic/Latina Breast Cancer Survivors.

Background: There is a paucity of research on the long-term impact of stress-reduction in Hispanic/Latina breast cancer (BC) survivors, a growing minority. In this article, we assess the long-term efficacy of an 8-week training program in mindfulness-based stress reduction (MBSR) on quality of life (QoL) in Hispanic BC survivors. Methods: Hispanic BC survivors, within the first 5 years of diagnosis, stages I to III BC, were recruited. Participants were enrolled in bilingual, 8-week intensive group training in MBSR and were asked to practice a- home, daily. They were also provided with audio recordings and a book on mindfulness practices. Patient-reported outcomes for QoL and distress were evaluated at baseline, and every 3 months, for 24 months. Results: Thirty-three self-identified Hispanic women with BC completed the MBSR program and were followed at 24 months. Statistically significant reduction was noted for the Generalized Anxiety Disorder measure (mean change -2.39, P=0.04); and Patient Health Questionnaire (mean change -2.27, P=0.04), at 24 months, compared with baseline. Improvement was noted in the Short-Form 36 Health-related QoL Mental Component Summary with an increase of 4.07 (95% confidence interval = 0.48-7.66, P=0.03). However, there was no significant change in the Physical Component Summary. Conclusions: Hispanic BC survivors who participated in an 8-week MBSR-based survivorship program reported persistent benefits with reduced anxiety, depression, and improved mental health QoL over 24 months of follow-up. Stress reduction programs are beneficial and can be implemented as part of a comprehensive survivorship care in BC patients.

Real-world Treatment Patterns and Outcomes in HR+/HER2+ Metastatic Breast Cancer Patients: A National Cancer Database Analysis.

Treatment patterns and outcomes are unclear for metastatic breast cancer (MBC) patients diagnosed with hormone receptor-positive (HR+), human epidermal growth factor 2-positive (HER2+) disease. This study aimed to: (1) examine the utilization of first-line therapy among HR+/HER2+/MBC patients and (2) compare overall survival (OS) between the identified regimens. We analyzed National Cancer Database patients (HR+/HER2+/MBC) who were treated between 2010 and 2015. Multivariable logistic and Cox regression were used to: (1) identify independent predictors of treatment receipt and (2) determine significant prognostic factors for OS. Kaplan-Meier method and log-rank test were used to estimate and evaluate OS, respectively. Propensity scores were added to all multivariate OS models, thereby accounting for bias in treatment receipt. Of 6,234 patients analyzed, 3770 (60.5%) received hormonal therapy and 2464 (39.5%) received chemotherapy. Receipt of hormonal therapy was associated with older age, grade 1/grade 2 disease, no visceral involvement, higher comorbidity scores, and being white. Multivariate analysis suggest patients receiving hormonal therapy + anti-HER2 experienced improved OS, when compared to chemotherapy + anti-HER2 (HR: 0.74, p = 0.004). Overall, the cohort receiving hormonal therapy + anti-HER2 reported the highest 5-year OS (hormonal + anti-HER2: 47.5% vs. chemotherapy + anti-HER2: 39.8% vs. hormonal: 38.5% vs. chemotherapy: 36.3%, p < 0.001). Our findings suggest de-escalated therapy may be the preferred and potentially more effective care path for HR+/HER2+/MBC patients, signaling a need for randomized studies.

Immune profiling of pre- and post-treatment breast cancer tissues from the SWOG S0800 neoadjuvant trial.

BACKGROUND: How the immune microenvironment changes during neoadjuvant chemotherapy of primary breast cancer is not well understood. METHODS: We analyzed pre- and post-treatment samples from 60 patients using the NanoString PanCancer IO360™ assay to measure the expression of 750 immune-related genes corresponding to 14 immune cell types and various immune functions, and assessed TIL counts and PD-L1 protein expression by immunohistochemistry. Treatment associated changes in gene expression levels were compared using t-test with Bonferroni correction. TIL count, PD-L1 protein and immune metagenes were compared using Wilcoxon test. Baseline immune markers were correlated with pathologic complete response (pCR) using estrogen receptor and treatment arm adjusted logistic regression. RESULTS: At baseline, high TIL counts and high expression of chemoattractant cytokines (CCL21, CCL19) and cytotoxic T cell markers were associated with higher pCR rate. High expression of stromal genes (VEGFB, TGFB3, PDGFB, FGFR1, IGFR1), mast and myeloid inflammatory cell metagenes, stem cell related genes (CD90, WNT11, CTNNB1) and CX3CR1, and IL11RA were associated with residual disease (RD). After treatment, in cases with pCR, TIL counts and most immune genes decreased significantly. Among RD cases, TIL counts and PD-L1 expression did not change but cellular stress and hypoxia associated genes (DUSP1, EGR1), and IL6, CD36, CXCL2, CD69 and the IL8/VEGF metagene increased. CONCLUSIONS: Activated T cells in the tumor microenvironment are associated with pCR whereas stromal functions are associated with residual disease. Most immune functions decrease during neoadjuvant chemotherapy but several immunotherapy targets (PD-L1, IL6, IL8) remain expressed in RD suggesting potential therapeutic strategies.

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.

Single arm phase II study of oral vitamin B12 for the treatment of musculoskeletal symptoms associated with aromatase inhibitors in women with early stage breast cancer.

Breast cancer patients receiving endocrine therapy with aromatase Inhibitors (AIs) often experience musculoskeletal and joint-related side effects. The purpose of this study was to evaluate the effect of Vitamin B12 supplements on musculoskeletal symptoms such as pain and arthralgias induced by AIs and to correlate response with serum and inflammatory biomarkers. Upon receiving approval by the Institutional Review Board (IRB), the majority of the patients consented into the study were treated at the Texas Tech Breast Care Center. Included were patients who had a diagnosis of invasive breast cancer (Stages I-III), and were experiencing significant musculoskeletal symptoms associated to AIs. Only patients with an average pain score ≥ 4, as assessed by the Brief Pain Inventory-Short Form (BPI-SF) questionnaire, were included in the study. Participants received 2500 mcg of sublingual vitamin B12 daily for 90 days. Assessments at baseline and at 3 months included: BPI-SF pain scores, the impact on quality of life determined by Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES), and correlative serum markers relative to baseline (a pre-post study). A total of forty-one patients were enrolled. Average pain scores were improved by 34% (P < .0001) at 3 months compared to baseline. In addition, a 23% improvement in worst pain was noted (P = .0003). Analysis of the results for the FACT-ES scoring showed improvement on all scales. No significant adverse events were observed. Decrease in pain score was correlated with increased serum B12 levels. This study suggests that Vitamin B12 reduces pain and improves quality of life for patients taking AIs who experienced AI-related musculoskeletal symptoms. If confirmed in large randomized prospective trials, Vitamin B12 would be a safe and cost-effective option for the treatment of AI-related musculoskeletal symptoms.

Prevalence of Low Vitamin D in Patients with Breast Cancer in a Predominantly Hispanic Population at the American-Mexican Border.

INTRODUCTION: Low level of vitamin D (VD) has been linked with a higher risk of cancers. The aim of this study was to assess the prevalence of low VD in patients with breast cancer in a predominantly Mexican Hispanic/Latino patient population, a fast growing and relatively understudied population. MATERIALS/METHODS: We sought to evaluate the serum VD levels in breast cancer patients diagnosed at the Texas Tech University Breast Cancer Center in El Paso, TX, between May 2013 and May2014 via a retrospective chart review of the Electronic Medical Records. RESULTS: We identified a total of 83 consecutive breast cancer patients with available VD levels. Mean age 57 yr, 94% were Hispanics. VD was insufficient (<30 ng/ml) in 86% of patients (95% CI: 0.76-0.92) and it was deficient (<20 ng/ml) in 39% (95% CI: 0.28-0.50). CONCLUSION: VD deficiency is widely prevalent in Hispanic/Latino patients with breast cancer. This is quite alarming in view of possible increased risk of cancer with low VD and potentially worse cancer outcomes. This calls for increased efforts to screen for, diagnose, and treat VD deficiency in this patient population. Further pharmacogenomics studies are warranted to explore the underlying etiology of VD deficiency in this paradoxically sunny region.

Literature Review and Profile of Cancer Diseases Among Afghan Refugees in Iran: Referrals in Six Years of Displacement.

BACKGROUND: There is a paucity of research on the profile of cancers among displaced populations, specifically Afghan refugees in Iran. This study illustrates the pattern of cancers in this population, and highlights the challenges of cancer care in displaced people with the intent that this data will facilitate appropriate allocation of resources to improve care in this population. MATERIAL AND METHODS: This was a retrospective cross-sectional study, in which we collected the demographics and profile of cancers among Afghan refugees from 2005 to 2010 from referrals to the United Nations High Commissioner for Refugees (UNHCR) offices in Iran. Accrued evidence by other studies published between January 1993 and July 2014 pertaining to cancer diagnoses in refugees from Afghanistan, Tibet, Syria, Jordan, and Iraq was reviewed. RESULTS: Cancer diagnoses accounted for 3083 of 23 152 total referrals, with 49% female and 51% male cases; 23.3% were 0-17 years of age, 61.2% were 18-59, and 15.5% were above 60. The most common health referral for females and males (0-17) was malignant neoplasms of lymphatic and hematopoietic tissue, accounting for 34.2%. In the age groups 18-59 and above 60 for both male and females it was malignant neoplasm of the digestive system, occurring in 26.3% and 48.7%, respectively. CONCLUSIONS: In the setting of humanitarian crises especially war, cancer diagnoses among refugees is a major health burden both on the host countries and the international community with serious implications considering the recent growing trend in the Middle Eastern countries. The prevalence of certain cancer diagnoses among refugees, like gastrointestinal, respiratory, breast, and genitourinary cancers necessitates a multidirectional approach, primarily aimed at prevention and early detection. International partnerships are essential for improvement in cancer surveillance service availability, and delivery of the standard of care, in an overall effort to reduce the human cost, monetary, and resource associated burdens of cancer. Recommendations to implement effective prevention and management goals as well as improved record keeping in the refugee setting and the acquisition of secure and sustainable funding sources should be implemented in collaboration with global humanitarian agencies like UNHCR.

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.

Molecular markers of epithelial-to-mesenchymal transition are associated with tumor aggressiveness in breast carcinoma.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is a transient process occurring during developmental stages and carcinogenesis, characterized by phenotypic and molecular alterations, resulting in increased invasive and metastatic capabilities of cancer cells and drug resistance. Moreover, emerging evidence suggests that EMT is associated with increased enrichment of cancer stem-like cells in neoplastic tissues. We interrogated the molecular alterations occurring in breast cancer using proposed EMT markers such as E-cadherin, vimentin, epidermal growth factor receptor (EGFR), platelet-derived growth factor (PDGF) D, and nuclear factor κ B (NF-κ B) to decipher their roles in the EMT and breast cancer progression. METHODS: Fifty-seven invasive ductal adenocarcinomas of the breast were assessed for the expression of E-cadherin, vimentin, EGFR, NF-κ B, and PDGF-D using immunohistochemical analysis. Tumors were categorized into three groups: A (ER+, and/or PR+, HER-2/neu-), B (ER+, and/or PR+, HER-2/neu+), and C (triple-negative: ER-, PR-, and HER-2/neu-). Immunostained slides were microscopically evaluated and scored using intensity (0, 1+, 2+, and 3+) and percentage of positive cells, and data were statistically analyzed. RESULTS: Membranous E-cadherin was positive in all 57 cases (100%), whereas cytoplasmic E-cadherin was predominantly positive in groups B and C compared with group A (21%, 7%, and 0%, respectively). All group A cases were negative for vimentin and EGFR. There was statistically significant increased expression of vimentin (P < .0002), EGFR (P < .0001), and NF-κ B (P < .02) in triple-negative cases when compared with groups A and B. CONCLUSIONS: Vimentin, EGFR, and NF-κ B were significantly increased in triple-negative tumors, which is consistent with the aggressiveness of these tumors. These markers could be useful as markers for EMT in breast cancers and may serve as predictive markers for designing customized therapy in the future.

Molecularly targeted therapy in breast cancer: the new generation.

Breast cancer management has become increasingly complex, requiring the integration of data not only from the patient's history and imaging modalities but also from specific tumor biomarkers and gene expression. Targeted and biologic therapies in breast cancer continue to evolve rapidly. The field of molecular targeted therapy has emerged. Its ultimate goal is to personalize and simplify treatment as well as minimize toxicity. This review aims at highlighting the current state-of-the-art in novel molecular targeted therapies for breast cancer based on multi-targeted small molecule tyrosine kinase inhibitors (TKI). The first two agents in this group entering clinic, Lapatinib (GW572016; Tykerb) and SUNITINIB (SU11248; Sutent) are discussed. This review article also includes relevant patents.

Male breast cancer in the veterans affairs population: a comparative analysis.

BACKGROUND: The incidence of male breast cancer (MBC) continues to rise. The Veterans Affairs (VA) Central Cancer Registry (VACCR) provides a unique source for the study of MBC. The objective of this retrospective analysis was to compare the characteristics and outcome of patients with MBC and patients with female breast cancer (FBC) in the VA population. METHODS: VACCR data were used to analyze the database of VA patients who had breast cancer diagnosed between 1995 and 2005. It includes 120 VA medical centers. Primary site codes were identified for breast cancer (500-508). Data were entered and analyzed using biostatistical software. RESULTS: In total, 3025 patients' records were reviewed, and 612 patients who had MBC were compared with 2413 patients who had FBC. The mean age at diagnosis was 67 years for patients with MBC and 57 years for patients with FBC (P < .005). More patients with MBC were black, and patients with MBC presented with higher disease stage and more lymph node-positive disease. The dominant histology in MBC was ductal carcinoma. No difference in grade or laterality was observed. Estrogen and progesterone receptor-positive tumors were more common in MBC compared with FBC. Overall, patients with MBC received less chemotherapy, whereas no statistical difference was observed in the use of hormone treatment. The median overall survival for patients who had MBC was 7 years compared with 9.8 years for patients who had FBC (log-rank test; P < .005). There was no statistically significant difference in median survival for patients with stage III disease and stage IV disease. However, the median survival differed significantly for patients with stage I disease and stage II disease. In lymph node-negative patients, the median survival was 6.1 years for patients with MBC and 14.6 years for patients with FBC (P < .005), whereas the median survival did not differ significantly in lymph node-positive patients. Using Cox regression analysis age, sex, clinical stage, and lymph node status were independent prognostic factors for survival, whereas race, histology, and grade were not. CONCLUSIONS: To the authors' knowledge, this is the largest series of MBC and FBC to date in the veterans population. The results suggested the presence of differences in the biology, pathology, presentation, ethnicity, and survival between patients with MBC and patients with FBC in the VA population. It is noteworthy that the survival of patients with MBC was inferior for those with early-stage disease and lymph node-negative tumors, suggesting that there are differences between the sexes in the pathogenesis and biology of breast cancer. In patients with hormone receptor-positive MBC, survival was inferior despite similar hormone treatment practices between MBC and FBC. This observational study calls for a better understanding of this disease that would allow new opportunities for specific therapeutic intervention.

Symptom management needs of oncology outpatients.

QUESTION: What were the needs of outpatients for symptom management? METHOD: A multidisciplinary team assembled to determine the need for a symptom management clinic. Two surveys were developed for potential users: one for the outpatients and the other for the attending oncologists. INTERVENTION: During a 3-week period, outpatients were approached after registering for the oncology clinic and while waiting for their appointment. Ninety-five percent of the outpatients approached completed the survey. FINDINGS: A total of 112 surveys revealed that outpatients would attend a symptom management clinic for relief of pain (50%), fatigue (40%), nausea/vomiting (30%), and/or sleeping difficulty (30%). A total of 16 surveys completed by oncologists revealed that outpatients could use more assistance with pain (81%), diet (75%), depression (69%), and/or fatigue (56%). Outpatients felt they would benefit from meeting with a nurse (35%), social worker (21%), dietician (18%), and/or pharmacist (18%). While oncologists thought that the following would complement care: dietician (69%), psychologist (69%), nurse (56%), and/or social worker (56%). Fifty-one percent of the outpatients indicated that they would attend a symptom management clinic and all but one oncologist would refer to this clinic. DISCUSSION: While there exists some disconnect between perceived need for symptom management between outpatient and oncologist, it is evident that pain is the symptom of primary concern. An interdisciplinary team of oncologist, nurse, social worker, dietician, pharmacist, and psychologist could collaboratively address the presenting symptoms. Users, both outpatients and oncologists perceive benefit from a collaborative and interdisciplinary symptom management clinic.

Hormonal therapy for male breast cancer: A different approach for a different disease.

Male breast cancer (MBC) is on the rise in the United States [Surveillance, Epidemiology, and End Results (SEER) Program () SEER Stat Database: Incidence-SEER 9 Regs Public-Use; November 2004 submission (1973-2002), National Cancer Institute, DCPPS, Surveillance Research Program, Cancer Statistics Branch, released April 2005, based on the November 2004 submission]; however mortality due to MBC has not changed unlike in its female counterpart [American Cancer Society: Cancer facts and figures 2005. Atlanta (GA): American Cancer Society; 2005]. The rarity of MBC has precluded major progress in the understanding and treatment of this disease. Treatment has often been extrapolated from female breast cancer (FBC) despite distinct clinicopathologic features between the two entities, especially with regards to the role of male hormones and estrogens in this disease. Also, it is uncertain if hormone receptor positive tumors carry the same prognostic implication in MBC as in the female disease. Hormonal therapy has been the mainstay of treatment in MBC with tamoxifen the front-line drug. The role of the newer generation aromatase inhibitors has not been well defined but they are being used in clinical practice for the treatment of MBC, based on accepted data for women with the disease. This commentary focuses on the major hormonal differences between male and female breast cancer that would suggest the need to explore different treatment strategies if significant advances are to be made in the understanding and treatment of this distinct disease.