bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and cost outcomes associated with multiple open procedures following percutaneous breast biopsy in Medicare patients.
Authors: Nichols Christine Ida , Kimball Chloe C , Vose Joshua
Published: September 2018

e12083

Background: Percutaneous core-needle biopsy (PCNB) is the standard of care to diagnose suspicious lesions of the breast. Dependent upon histology, many women require additional open procedures for definitive diagnosis and excision. However, there remains little nationally-representative research on the proportion of women undergoing multiple open biopsy or lumpectomy procedures and the associated incremental burden to the health system. Methods: This study used Medicare 100% Standard Analytic Files (2010–2014) to identify patients undergoing PCNB in an outpatient setting. Patients included females aged ≥65; continuous Medicare enrollment; no history of cancer, chemotherapy, radiation or breast cancer surgery in the prior year. Open procedures were defined as an open biopsy or lumpectomy. Study follow-up was defined as 90 days from initial PCNB or until the day prior to chemotherapy, radiation, or mastectomy—to limit analysis to diagnosis-related payments. Payments were defined as Medicare payments. Results: 110,944 patients were identified; the mean age was 73.5; 74.1% underwent only PCNB, 23.8% had one open procedure and 2.1% had multiple open procedures. Among the PCNB-only cohort, 2.7% had multiple PCNBs; among those with subsequent open procedures, 4.1-4.4% had multiple PCNBs (P < .001). Incidence of all-cause complications was significantly lower among those with no open procedure (8%) versus those with one (11%) or more (20%, P < .001). Mean incremental breast-related payments were $3003 greater among those with one open procedure versus none ($4526 v $1523, P < .001), and $1978 greater among those with multiple open procedures ($6504 v $4526, P < .001). Prior receipt of multiple PCNBs and diagnosis of breast cancer were significantly positively correlated in logistic regression with having multiple open procedures, while age ≥ 80 was a negative predictor. Conclusions: There continues to be a percentage of women that require multiple open procedures following initial biopsy. These results suggest that incomplete excision at the first open procedure remains a meaningful concern, and merits further investigation into methods to ensure excisional completeness.
Targeted intraoperative radiotherapy tumor bed boost during breast conserving surgery after neoadjuvant chemotherapy in hormone receptor positive HER2 negative breast cancer.
Authors: Kolberg Hans-Christian , Loevey Gyoergy , Akpolat-Basci Leyla , Stephanou Miltiades , Fasching Peter A. , Untch Michael , Bulsara Max , Vaidya Jayant S. , Liedtke Cornelia
Published: September 2018

e12090

Background: Targeted intraoperative radiotherapy (TARGIT – IORT) as a tumor bed boost during breast conserving surgery is an established option for women with early breast cancer. In a previous study our group could show a beneficial effect of TARGIT-IORT on overall survival after neoadjuvant chemotherapy compared to an external boost in an unselected cohort. In this study we present an analysis of the hormone receptor positive HER2 negative subgroup. Methods: In this non-randomized cohort study involving 46 hormone receptor positive HER2 negative patients after NACT we compared outcomes of 21 patients who received a tumour bed boost with IORT (TARGIT-IORT) during lumpectomy versus 25 patients treated in the previous 13 months with external (EBRT) boost. All patients received whole breast radiotherapy. Disease free survival (DFS) and overall survival (OS) were compared. Results: There were no statistical differences between the two groups regarding tumor size, grading, nodal status and pCR rates. Median follow up was 49 months. Whereas DFS was not significantly different between the groups the 5-year Kaplan-Meier estimate of OS was significantly better by 21% with IORT: TARGIT-IORT 0 events 100%, EBRT 5 events 79%, log rank p = 0.028. Conclusions: Although our results have to be interpreted with caution due to a possible selection bias and the small numbers, we could show that the improved OS as previously demonstrated in our dataset for TARGIT-IORT during lumpectomy after neoadjuvant chemotherapy as a tumor bed boost compared to an external beam radiotherapy boost is driven by the hormone receptor positive HER2 negative subgroup. These data give further support to the inclusion of such patients in the TARGIT-B (Boost) randomised trial that is testing whether IORT boost is superior to EBRT boost and to the analysis of subgroups based on tumor biology in this trial.
The radiation doses to the heart and the left anterior descending coronary artery for various modes of radiation treatment of the breast cancer patients.
Authors: Maslyukova Elizaveta , Korytova Luiza , Bondarenko Anna , Zhabina Razifa , Korytov Oleg , Odintsova Svetlana
Published: September 2018

e12092

Background: The comparison of the radiation load to the organs at risk for three modes of radiation treatment of the breast cancer patients. Methods: The research includes the dosimetric radiation treatment plans for the 20 breast cancer patients with the left-side localization. They all underwent a computed tomography (CT) scan in standard supine position in free-breathing (FB), supine position with Active Breathing Control (ABC) device in deep inspiratory breath hold, and prone position in free-breathing (PP). Three-dimensional treatment plans were made for all 3 CTs. The dose valuations for 3D-planning were carried out for three CT- series. For each mode of radiation, the doze-volume parameters of organs at risk were estimated. Results: For all cases the contoured heart volume varied from 477 см3 - 1056 см3, with medium volume 769 см3. The best marks such as V25heart, medium doses to the heart and LAD, were achieved with on ABC methods (V25heart 4,26%, Dmean heart 3,13Gy, DmeanLAD 13,8Gy) in comparison FB (V25heart 9,49%, Dmean heart 4,97Gy, DmeanLAD 19,55Gy) and PP (V25heart 12,8%, Dmean heart 9,06Gy, DmeanLAD 24,18 Gy) (V25heart P = 0.00153, Dmean heart: P =0,000; Dmean LAD: P = 0.00088), when both the breast and the axillary nodes were included in the volume. The advantage of the dosimetric indexes for FB and ABC did not change while axillary and supraclavicular nodes were added to the radiation volume ABC (V25heart 3,49%, Dmean heart 3,08Gy, DmeanLAD 13,88Gy) in comparison with FB methods (V25heart 7,91%, Dmean heart 4,99Gy, DmeanLAD 19,89Gy) (V25heart P = 0.00205, Dmean heart: P =0,004; Dmean LAD: P = 0.03). Conclusions: Radiation treatment in the position on the back with controlled delay of breath on inspiration height contributed to the statistically significant reduction of the heart volume exposed to more than 25 Gy (V25heart), mean dose to the heart and mean dose to LAD.
Treatment and risk of mortality for 58,953 cases of stage 1, ER+/PR+/HER2- breast cancer in four mutually exclusive race/ethnicities.
Authors: Caggiano Vincent , Parise Carol
Published: September 2018

e12101

Background: The estrogen receptor positive (ER+), progesterone receptor positive (PR+), human epidermal growth factor 2 negative (HER2-) subtype is the most common. Cases of stage 1, ER+/PR+/HER2- are most often treated with hormone therapy alone, although this is not universal. The purpose of this study was to determine if there were differences in mortality for patients with stage 1, ER+/PR+/HER2- breast cancer given no treatment, chemotherapy alone, or both chemotherapy and hormone therapy when compared with hormone therapy alone for four mutually exclusive race/ethnicities. Methods: We identified 58,953cases of Stage 1, ER+/PR+/HER2- first primary female invasive breast cancer from the California Cancer Registry 2000-2014. Cases were stratified into white (n = 41,716), black (n = 2,310), Hispanic (n = 8,186) and Asian/Pacific Islander (API) (n = 6,741). Treatment was categorized as none, hormone therapy alone, chemotherapy alone, or both chemotherapy and hormone therapy. Kaplan Meier survival analysis and Cox Regression were used to assess the risk of mortality associated with treatment using hormone therapy alone as the reference category. Treatment was considered a risk for mortality and hazard ratios (HR) and 95% confidence intervals reported if the Wald χ2 was statistically significant (p < 0.05). Models were adjusted for age, grade, socioeconomic status, and tumor size. Separate analyses were conducted for each race/ethnicity. Results: White women, having no treatment (HR = 1.33; 1.14-1.54), or chemotherapy alone (HR = 1.49; 1.10-2.00) was associated with an increased risk of mortality. For API women, having the combination of chemotherapy and hormone therapy was associated with increased risk of mortality (HR = 2.47; 1.34-4.56). For black and Hispanic women, there was no difference in risk of morality for any combination of treatment when compared with hormone therapy. Conclusions: The effectiveness of treatment modalities for the Stage 1, ER+/ER+/HER2- subtype varies considerably by race/ethnicity.
Long-term risk of second malignancies in women with ductal carcinoma in situ or early-stage invasive breast cancer after breast conservation treatment.
Authors: Kushner Carolyn J. , Hwang Wei-Ting , Solin Lawrence J. , Vapiwala Neha
Published: September 2018

e12103

Background: Women with ductal carcinoma in situ (DCIS) or early stage breast cancer have a good prognosis after breast conservation treatment (BCT), and are at risk for second malignant neoplasms (SMNs). The long-term risk of SMNs is not well established and carries important public health implications. Methods: A total of 755 women with DCIS or stage I-II invasive breast cancer underwent breast-conserving surgery followed by definitive breast irradiation between 1995 and 2001. Systemic therapy (chemotherapy and/or hormonal therapy) was given to 73% of the patients. We have previously described patient demographics and 15-year oncologic outcomes in detail (Vapiwala, Cancer, 2017). The patient records were reviewed for development of SMNs. SMNs of any anatomic site (other than contralateral breast cancer and basal/squamous cell carcinoma of the skin) were included for analysis. The Kaplan-Meier method was used to determine the rate of SMNs over time. Median follow-up was 13.8 years. Results: The 5-, 10-, and 15-year rates of developing any SMN were 3.6% (95% CI 2.4-5.3%), 7.8% (95% CI 6.0-10.2%), and 12.7% (95% CI 10.2-15.8%). The most common SMNs were uterine (n=12), leukemia/lymphoma (n=11), melanoma (n=10), ovarian (n=9), and lung (n=7). Conclusions: Development of SMNs is a substantial risk for a protracted period of time following BCT. Clinical patterns of specific SMN histologies, locations and time course of development suggest potential opportunities for screening and treatment to guide patient survivorship clinics and protocols.
Surgical management associates independently with improved survival among de novo stage IV breast cancer patients without liver or brain metastasis.
Authors: Geng Cuizhi , Zhang Wenjin , Li Zhensheng
Published: September 2018

e12106

Background: To examine the independent effect of surgical management of the primary tumor and axillary lymph node on survival in patients with de novo Stage IV breast cancer (BC) Methods: 113 patients with de novo stage BC between 2010 to 2013 were followed up to Oct. 1, 2016. Multivariable Cox proportional hazard models were constructed to assess the effect of mastectomy (MAS) and axillary lymph node dissection (ALND) on overall survival (OS) after univariate analyses and K-M curves. Non-treatment covariates included age, BMI, menopause, Stage T, Stage N, ER, PR, HER2, Ki67>14% status, and metastasis sites (lung, liver, bone, brain and others). Chemotherapy, hormonal, target treatement and radiotherapy before the disease progression were others. Results: Mean age 52 (24 - 84) years old, metastasis site by bone 53% (60), lung 32% (36), liver 32% (36), brain 2% (2), and other 23% (23). Median survival 21.4 months. All 42% (48) surgical patients had simultaneous MAS and ALND. Younger (mean 49 vs. 54) and fewer post-menopause (42% vs. 62%) were significantly noticed in surgical patients with median survival 37.8 vs. 14.2 months of others. Multivariable analysis showed OS favorable HRs 0.53 (95% CI 0.24 - 1.17, p=0.12) of surgery and HR 0.48 (0.22 - 1.04, p=0.06) of hormonal drug, and significant HR 0.10, (0.02 - 0.52, p<0.01) of target therapy, insignificant effects of chemotherapy HR 0.60(0.26 - 1.42, p=0.25) and radiotherapy HR 0.70 (0.33 - 1.50, p =0.36). Unfavorable metastasis sites were identified as brain and liver at multivariable model for subgroup analysis. K-M curves estimated median survival 29.3 vs. 14.4 months (favorable vs. unfavorable patients). Both univariate and multivariate analyses showed the significant effect of surgery in favorable subgroup (N=76) with HR 0.30 (0.16 - 0.56, p <0.01) and 0.33 (0.11 - 0.98, p=0.05) on OS, respectively. In unfavorable subgroup (N=37), the results were insignificant effect of surgery on OS with HR 0.75 (0.37 - 1.55, p=0.54) and 1.60 (0.33 - 7.81, p=0.56). Conclusions: Surgical management associated independently with improved survival among de novo stage IV BC patients without liver or brain metastasis.
Sentinel lymph node biopsy using indocyanine green fluorescence navigation method after neoadjuvant chemotherapy for patients with clinically node-positive breast cancer.
Authors: Yamagami Kazuhiko , Matsumoto Hajime , Hashimoto Takashi , Yanai Seiji , Yuen Sachiko , Kuramitu Hitomi , Ichinose You , Deai Teruyuki , Toi Masakazu
Published: September 2018

e12108

Background: Sentinel lymph node biopsy (SNB) for initially clinically node-positive (cN1) after neoadjuvant chemotherapy (NAC) is controversial. Even if approximately 40% of node positive disease converts to node negative after NAC, SNB using blue dye (BD) and/or radioisotope (RI) agent showed the high false-negative rate (FNR) (SENTINA, ACOSOG Z1071). These trials showed the accuracy of SNB was closely related to the number of sentinel lymph nodes (SNs) removed. We presented the efficacy of indocyanine green (ICG) fluorescence navigation method for SNB in clinically node-negative (cN0) patients (ASCO2008). The ICG method can provide higher numbers of SNs and it helps to identify lymph nodes with the remained metastases. Methods: Of 1900 patients (Jan. 2010 - Dec. 2016), 242 women with cN0 or cN1 received NAC: Group 0 (cN0 before NAC, n=150), Group 1 (cN1 converted ycN0 after NAC, n=71) , Group 2 (cN1 remained ycN1 after NAC, n=21). Node status was evaluated by ultrasound. All patients underwent SNB using both ICG- and BD-method together. Fluorescence images were obtained by a CCD camera with a cut filter as a detector, light emitting diodes at 760nm as the light source. ALND was performed in Group1 and Group 2. Results: Pathological complete nodal response rate (pcNRR) was 48.4%. Table shows the number of SNs removed by ICG or BD. SNs detection rates (ICG, BD): Group 0 (98.7%, 84.7%), Group 1 (98.6%, 83.1%), Group 2 (85.7%, 47.6%). Resulting of a FNR (ICG, BD): Group 1 (5.7%, 15.3%), Group 2 (22.2%, 60.0%). Conclusions: The pcNRR and a FNR of BD in Group 1 were similar to those of SENTINA or ACOSOGZ 1071 trials. In patients who converted from cN1 to ycN0, the fluorescent ICG method showed a high detection rate of SNs and a low FNR. [Table: see text]
Characterization of the tumor immune microenvironment (TIM) with multiplex immunohistochemistry (mIHC) in patients with breast cancer following treatment with MK-2206.
Authors: Marks Douglas Kanter , Gartrell Robyn Denise , El Asmar Margueritta , Hart Thomas , Lu Yan , Esancy Camden , Hibshoosh Hanina , Connolly Eileen , Kalinsky Kevin , Saenger Yvonne M.
Published: September 2018

e12109

Background: The PAM (PI3K/Akt/mTOR) signaling pathway has been implicated in the oncogenesis of multiple solid malignancies, including breast cancer (BC). Our aim is to characterize the TIM in a series of patients with operable stage I-III BC treated with MK-2206, an allosteric Akt inhibitor within a presurgical trial. In NCT01319539 , patients received 2 doses of MK-2206 with first dose at day -9 and second at day -2 from surgery. Methods: mIHC was performed using immune biomarkers (DAPI, CD3, CD8, CD4, FOXP3, CD68, Pancytokeratin) on full section (4uM) tissue slides from core biopsy specimens and postsurgical specimens of 10 patients - 5 treated with MK-2206, 5 paired controls. Images were taken using Vectra, a novel pathology workstation and analyzed using inForm software to perform cell classification and phenotyping. T- tests were used to compare biomarker changes before and after MK-2206. Results: Our preliminary analysis demonstrates that patients treated with MK-2206 exhibited an increase in median cytotoxic T-cells (CD3CD8+) density, as compared to the control population , which was statistically significant (87% vs.0.2%, p < 0.05). We did not identify a change in macrophage (CD68) or T helper/T reg (CD4/CD4FOXP3+) density following MK-2206 treatment in this small cohort. We are currently expanding our myeloid panel as well as performing additional tissue analysis to validate our findings. As data is exploratory no correction was made for multiple comparisons. Conclusions: Tumor infiltrating lymphocytes (TILs) are both prognostic of overall survival as well as predictive of response to neoadjuvant chemotherapy in BC. At present, there are currently both FDA approved therapies, as well as agents in clinical development that exert antineoplastic activity through the PAM pathway. Investigations that endeavour to understand the impact of these therapies on the tumor immune microenvironment may lead to both an increased understanding of the bioactivity of these agents and potentially identify aspects of the immune response which can be exploited in future therapeutics.
Concurrent use of capecitabine with radiation therapy and survival in breast cancer (BC) after neoadjuvant chemotherapy.
Authors: Liu Ying , Catanese Benjamin Peter , Chin Christine , Lee Shing , Zhan Serena , Kalinsky Kevin , Connolly Eileen
Published: September 2018

e12117

Background: Capecitabine has been studied as a radiosensitizer in rectal cancer, but its role in BC is unclear. Our study seeks to examine the association of concurrent capecitabine/radiation therapy (RT) on survival in women with BC and residual disease after neoadjuvant chemotherapy (NAC). Methods: In a retrospective study of women with stage I-III BC who received Adriamycin/Taxane-based NAC from 2010-2016, we identified 21 women administered concurrent capecitabine/RT. To assess differences in survival, we selected a clinical control cohort (n = 64) based on criteria used to select patients for capecitabine/RT including pathological stage II/III disease and non-HER2+ tumor subtype. We also created a matched cohort (2:1), matching on tumor subtype, pathological stage, and age ( < 50 or 50+ years). Differences in progression-free survival (PFS), using STEEP criteria, and overall survival (OS), using all-cause mortality, between those who received capecitabine/RT and controls were assessed. Results: Of the 21 women who received capecitabine/RT, the majority were 50+ years (n = 12), pathological stage III (n = 15), and hormone receptor positive/HER2 negative BC (n = 20). Compared with clinical controls, women who received capecitabine/RT had larger disease (p = 0.041) and a higher pathological stage (p = 0.067), but there were no other differences. In those receiving capecitabine/RT, there were 9 recurrences (3 local, 6 distant) compared with 14 recurrences (4 local, 10 distant) in the clinical controls and 10 recurrences (all distant) in the matched controls. In multivariate models, capecitabine/RT was associated with worse PFS (HR 3.04 95% CI 1.24-7.43 p = 0.015) and OS (HR 4.29 95% CI 1.45- 12.6 p = 0.008), after adjusting for clinical size and pathologic stage. In the 2:1 matched cohort, capecitabine/RT was also associated with worse PFS (HR 2.96 95% CI 1.20-7.29 p = 0.018) and OS (HR 5.61 95% CI 1.76-17.9 p = 0.004). Conclusions: Capecitabine/RT after NAC is associated with worse PFS and OS using two control populations, suggesting capecitabine/RT should be discouraged in BC.
Survival advantage associated with neoadjuvant chemotherapy compared to neoadjuvant hormonal therapy in postmenopausal women with hormone receptor positive breast cancer: A National Cancer Data Base study.
Authors: Basnet Alina , Wang Dongliang , Sivapiragasam Abirami
Published: September 2018

e12119

Background: Neoadjuvant endocrine therapy (NET) and neoadjuvant chemotherapy (NCT) are both considered effective strategies in postmenopausal, hormone receptor positive breast cancer patients. Small prospective studies show comparable response rates and breast conservation rates. Using National Cancer Data Base (NCDB) we report overall survival (OS) differences between these two strategies with subgroup analysis by Estrogen Receptor (ER), Progesterone Receptor (PgR) status. Methods: We extracted data on hormone receptor positive breast cancer patients without metastasis in women aged ≥ 50 from the NCDB registry (2004-2014). We excluded patients who did not receive adjuvant endocrine therapy after NCT and patients who received adjuvant chemotherapy after NET as this could affect OS. We calculated OS using Kaplan Meier analysis with hazard ratio (HR) from cox regression model. Subgroup analysis was performed by ER, PgR status. Results: Out of 2,246,279 patients, 30,348 patients met our inclusion criteria. 7836 received NET and 22512 received NCT. OS rate was 70.8% vs 81.7% at 5 yrs and 42.5% vs 62.1% at 9 yrs for NET and NCT respectively with adjusted hazard ratio (HR) of 1.818; 95% CI (1.657-1.996). OS outcome for ER+/PgR+ group was 72.3% vs 83.5% at 5 yrs and 43.5% vs 64% at 9 yrs for NET and NCT respectively with adjusted HR of 1.807; 95% CI (1.624-2.010). OS for ER+/pgR- group was 62.9% vs 76.8% at 5 yrs and 33.1% vs 54.2% at 9 yrs for NET and NCT respectively with adjusted HR of 1.890; 95% CI (1.549-2.306). Our analysis also revealed that 5591 T1 patients received neoadjuvant therapy among which 2541 received NET and 3050 received NCT. Conclusions: We find a significant survival advantage in patients treated with NCT as opposed to NET. All subgroups showed imporved OS with NCT compared with NET. Limitations that should be considered in this registry based study are: not accounting for Her-2 status, differences in surgical technique, duration and choices of adjuvant chemotherapy and radiotherapy options.
Comprehensive assessment of cancer stem cell like cells in prediction of pathologic complete response to preoperative dual anti–HER2 therapy for HER2–positive primary breast cancer.
Authors: Espinosa Fernandez Jose Rodrigo , Yamauchi Teruo , Imamura Chiyo K. , Yamauchi Hideko , Jinno Hiromitsu , Takahashi Maiko , Kitagawa Yuko , Nakamura Seigo , Lim Bora , Krishnamurthy Savitri , Reuben James M. , Liu Diane D , Tripathy Debu , Chen Helen X. , Takebe Naoko , Saya Hideyuki , Ueno Naoto T.
Published: September 2018

e12123

Background: Chemotherapy for breast cancer destroys non–stem cells while sparing cancer stem cells (CSCs). In contrast, anti–HER2 therapy may eliminate resistant cells because HER2 may be a key driver of CSCs. CSC biomarkers have been found to be prognostic of poor outcome and predictive of resistance to therapy. However, there are no comprehensive studies of the impact of anti-HER2 therapies on CSC–related biomarkers. We conducted a prospective biomarker determination study of breast CSCs characterized by CD44v expression and increased aldehyde dehydrogenase 1 (ALDH1) enzymatic activity or expression. Methods: In a prospective trial (ClinicalTrials.gov: NCT01688609), 18 patients with operable primary HER2+ breast cancer (≥T2 excluding inflammatory, any N; median age of 54 yrs) were treated with preoperative anti–HER2 therapy following the NeoALTTO trial dual therapy arm regimen, with a goal of identifying novel predictive biomarkers for pCR. Proportions of tumor cells with CSC characteristics, defined as CD44v+ and ALDH1+, were estimated at baseline, at 6 weeks (after therapy with lapatinib/trastuzumab) and at 18 weeks (after therapy with lapatinib/trastuzumab and paclitaxel) to assess adaptive response. We determined changes in the quantity and characteristics of CSC–related biomarkers during preoperative therapy and correlated them to tumor response. Results: Out of 18 patients, 8 (44%) had a pCR; 5 of these 8 patients (62%) were positive for CD44v staining on tumor cells at baseline and none were positive on the 6–week biopsy. In contrast, 6 of the 10 patients without pCR exhibited persistent levels, or enrichment of CD44v proportion and expression at 6 and 18 weeks (p = 0.0128). ALDH1 expression and other biomarkers were not statistically significant predictors of pCR. Conclusions: Enrichment of CD44v+ tumor cells after double anti–HER2 therapy may predict poor response to dual anti–HER2 therapy with cytotoxic chemotherapy. A second biopsy after the start of preoperative therapy may reflect biological changes useful for the guidance and application of therapeutic strategies for patients with HER2+ breast cancer. Clinical trial information: NCT01688609.
Impact of neoadjuvant HER2-directed therapy on HER2 status in breast cancer.
Authors: Manguso Nicholas , Johnson Jeffrey , Basho Reva Kakkar , McArthur Heather L. , Tanaka Hisashi , Giuliano Armando E.
Published: September 2018

e12130

Background: Neoadjuvant chemotherapy (NAC) with HER2-directed therapy has become standard-of-care for most women with potentially curable HER2-positive (HER2+) breast cancer and is associated with a high pathologic complete response (pCR) rate. The HER2 status of residual disease after NAC is not well characterized and could potentially inform clinical decisions about additional systemic therapy. We describe tumoral HER2 status before and after NAC with HER2-directed therapy. Methods: An institutional database was screened to identify patients with stage 1-3 HER2+ breast cancer by fluorescence in situ hybridization (FISH) and/or immunohistochemistry (IHC) who received NAC with HER2-directed therapy followed by resection between 2011 and 2015. Clinicopathologic data was collected. Change in HER2 status by FISH and IHC following treatment was described. Results: 99 patients were identified. Median age was 49 years (range 26-85). Pre-treatment median HER2/CEP17 copy number ratio (CNR) for all tumors was 6.3 (range 1.9-20.7) by FISH and 84 (84.8%) tumors were IHC 3+. 44 (44.4%) patients achieved a pCR. Of the 55 patients with residual disease, 35 had sufficient residual tumor to evaluate HER2 status and 14/35 (40%) were HER2- by FISH and IHC (table). Tumors converting from HER2+ to HER2- had lower pre-treatment median HER2 copy numbers (11.9, range 4.6-22) compared to tumors that remained HER2+ (18.3, range 5.1-48.6; p=0.04) after neoadjuvant therapy. Additionally, pre-treatment median HER2/CEP17 CNR was lower among tumors that converted from HER2+ to HER2- (3.0, range 2.2-8.2) compared to those remaining HER2+ (6.8, range 2-15.7; p=0.02). Conclusions: While pCR rates are high with NAC and HER2-directed therapy, many patients still have residual tumor. In this cohort, 40% of patients with evaluable residual disease after NAC had HER2+ tumors that became HER2-. HER2 conversion was associated with lower pre-treatment HER2 copy numbers and HER2/CEP17 CNR. Conversion from HER2+ to HER2- in patients undergoing neoadjuvant therapy may have clinical significance and biological implications. [Table: see text]
Obesity and survival in the neoadjuvant breast cancer setting: Role of tumor subtype and race.
Authors: Liu Ying , Catanese Benjamin Peter , Saraf Anurag , Lee Shing , Zhang Yuan , Connolly Eileen , Kalinsky Kevin
Published: September 2018

e12136

Background: Obesity may adversely influence survival in breast cancer; however, studies are conflicting and limited in the neoadjuvant setting. Results may also vary by tumor subtype and race/ethnicity. Our study seeks to examine associations between obesity and survival in women receiving neoadjuvant chemotherapy (NAC) and the role of tumor subtype and race/ethnicity. Methods: In a retrospective review of women with operable invasive breast cancer administered Adriamycin/Taxane-based NAC at a single intuition from 2004-2016, we identified n = 273 women with completed BMI data at diagnosis. Obesity was defined as body mass index (BMI) > = 30. We assessed associations between obesity and progression-free survival (PFS), using STEEP criteria, and overall survival (OS), using all-cause mortality, both overall and stratified by tumor subtype in three groups: Hormone Receptor Positive (HR+)/HER2- (n = 135), HER2+ regardless of hormonal status (n = 94), and Triple Negative Breast Cancer (TNBC) (n = 44), examining race/ethnicity (Non-Hispanic White, Black and Hispanic) in each subtype. Results: There were 60 events and 33 deaths observed. Overall, obesity was associated with worse PFS (HR1.71 95% CI 1.03-2.85, p = 0.04) and a trend towards worse OS (HR 1.70 95% CI 0.86-3.37, p = 0.13). In HR+/HER2- disease, there was an interaction between obesity and hormonal therapy. In those receiving only tamoxifen (n = 35), obesity was associated with worse PFS (HR 2.96 95% CI 1.02-8.6, p = 0.047) and OS (HR 14.3 95% CI 1.67-123.1, p = 0.015). In those receiving an aromatase inhibitor (AI) (n = 96), there was no association between obesity and survival, p > 0.05. In TNBC, obesity was associated with worse PFS (HR 2.62 95% CI 1.03-6.66, p = 0.043) and OS (HR 3.00 95% CI 0.95-9.51, p = 0.062). In HER2+ disease, obesity was associated with worse PFS (HR 3.37 95% CI 0.97-11.72, p = 0.056) but not OS (HR 1.35 95% CI 0.22-8.19, p = 0.75). Race/ethnicity was not significantly associated with survival in any tumor subtype, and there were no interactions between race/ethnicity and obesity with survival. Conclusions: Obesity negatively impacts survival in all tumor subtypes, including TNBC, and may be influenced by hormonal therapy class in HR+/HER2- disease.
From the CLEOPATRA study to real life: An observational study from 11 Italian Centres; Preliminary report from the G.O.N.O. SUPER trial.
Authors: Garrone Ornella , Saggia Chiara , Beano Alessandra , Cicchiello Federica , Milani Andrea , Bertolini Ilaria , Coltelli Luigi , La Verde Nicla Maria , Collovà Elena , De Conciliis Enrico , Pedani Fulvia , Vandone Anna Maria , Donadio Michela , Cazzaniga Marina Elena , Michelotti Andrea , Merlano Marco Carlo
Published: September 2018

e12510

Background: Approximately 20% of breast cancers (BC) are HER-2+. Trastuzumab (T) has substantially improved the outcome, both in early and in advanced settings, in HER-2+BC. Pertuzumab (P), combined with T and taxanes, ameliorated progression free survival (PFS) and overall survival (OS) in the phase III CLEOPATRA study. In order to verify the results of the trial in unselected patients (pts), we performed a multicenter, retrospective-prospective, observational study, in HER-2+ metastatic BC (MBC) pts. Methods: We analyze the outcome of all HER-2+ MBC pts treated with P+T and taxanes, as first line therapy since the availability of P in Italy, at 11 general and university hospitals. Results: Up to February 1stdata from 103 HER-2+ MBC pts were recorded. Main pts’ characteristics were: median (M) age 52 y (28-78), m ECOG PS 0 (0-2), ER/PgR positive 68 pts (66%). Most common metastatic sites: liver 51 pts (49.5%), bone 64 pts (62.1%), lung 26 pts (25.2%). Thirty pts (29.1%) had bone and soft tissue disease only; 78 pts (75.7%) had metastatic disease on presentation. m number of metastatic sites was 3 (1-7); 25 pts (24.3%) received neo/adjuvant chemotherapy (CT) + T and 36 pts (34.9%) adjuvant endocrine therapy; 71 pts (69%) and 32 pts (31%) received docetaxel (D) and paclitaxel (P) respectively. m number of CT cycles was 6 for both drugs (D range 3-12; P range 1-18).At the time of the present analysis 12 pts are still on CT and 78 on maintenance; response is available for 91 pts and ORR is 80.2% (22 pts and 51 pts obtained CR and PR respectively), 6 pts experienced PD during CT. Median PFS is 13.9 months (1.5+ - 33.8+).Among hematological toxicities leucopenia (any grade) was recorded in 29 pts (28.1%), g 3 febrile neutropenia in 6 pts (5.8%). No change of left ventricular ejection fraction (LVEF) was recorded during CT; 4 pts interrupted maintenance P due to drop in LVEF and 1 due to rash. Onicopathy, nausea, alopecia, rash and arthro-myalgia were the most common non-hematological toxicities. Conclusions: Our preliminary results highlight the activity and the safety of the combination of CT plus P and T in unselected HER2+ MBC patients. The study is ongoing and updated results will be presented.
Outcomes of Turkish National Breast Cancer Registry.
Authors: Kilickap Saadettin , Gumus Mahmut , Uncu Dogan , Ozkan Metin , Cicin Irfan , Elkiran Tamer E. , Isikdogan Abdurrahman , Karaoglu Aziz , Oksuzoglu Berna , Ozdemir Feyyaz , Turna Hande , Uslu Ruchan , Ozyilkan Ozgur , Erdogan Alper , Goktas Burce , Kara Oguz
Published: September 2018

Background: The aim of this registry was to collect demographic, diagnostic, treatment, and outcome information about Turkish patients with breast cancer (BC). Methods: It was designed as a multicenter, cross-sectional, non-interventional study conducted on new and previously diagnosed BC cases applied to 28 medical oncology outpatient clinics between 2012 and 2015. A total of 16841 male (n = 153) and female (n = 16688) patients > 18 years were included. Results: Mean age of BC patients was 52.0±11.5 years. Among women, 53.7% were postmenopausal, and 24.4% were receiving hormone replacement (HRT) and/or oral contraceptive therapies (OCT). At time of diagnosis, 18.2% of patients presented with Stage 1, 48.5% with Stage 2, 25.5% with Stage 3, and 7.9% with Stage 4 BC. In 79,8% of the patients histopathology was invasive ductal carcinoma. Estrogen (ER) and progesterone receptors (PR) were positive in 74.7%, and 69.4% of patients, respectively. Diagnostic immunohistochemistry (IHC) was performed in 90.4% of patients. HER2+ was found in 30.2% of patients. HER2+ was observed in 27.6% Stage I, 27.6% Stage II, 36.2% Stage III, and in 41.7% Stage 4 BC. ER and PR positivity were 62.4% and 56.4% among HER2+ patients, respectively. Neoadjuvant therapy was administered in 10.6% and adjuvant therapy was administered in 73.2% of patients. Between 2010 and 2015, trastuzumab was administered in 68.3% of adjuvant (n = 1959), and 7.5% of neoadjuvant (n = 215) HER2+ patients. Conclusions: BC is a major health concern. Majority of the patients are diagnosed in stage 2 or 3, therefore screening should be improved to diagnose patients at earlier stages. In HER2 positive patients, neoadjuvant trastuzumab usage is limited despite its known advantages.
Characteristics of HER2 3+ metastatic breast cancer patients with long-term benefit of trastuzumab.
Authors: Tomasevic Zoran , Tomasevic Zorica , Minic Ivana , Kolarevic Daniela
Published: September 2018

e12523

Background: Because there is no cumulative dose, trastuzumab could be given until disease progression. However, characteristics of patients with long term benefit of trastuzumab treatment are seldom reported. Methods: Trastuzumab become available for HER2 3+ MBC at November 2005 at the Institute for Oncology and Radiology of Serbia. Since then, we have registered 42 patients with HER2 3+ MBC and/or inoperable loco-regional recurrent BC treated with first line trastuzumab for at least 24 months (range 24-123+). Results: Median age was 53 years (range 35-76). 30/42 patients (71%) had ER/PR positive BC. MBC was initial presentation in 14 patients (33%), and as relapse in 28 (67%) patients. Only 7/28 (25%) patients received neoadjuvant/adjuvant trastuzumab, therefore majority have been trastuzumab naive (83.3%). Metastases were present in the liver (9), lungs (9), bones (16), soft tissue (6), CNS (1), while 20 (48%) patients had multiple metastatic sites. After antracyclines based chemotherapy, patients have been treated with first line weekly taxane concurrently with three weekly trastuzumab. After taxanes (up to 24 doses), trastuzumab was continued +/-hormonal therapy. Objective response was achieved in 29 (69%) patients with 17 patients (40%) achieving complete response. Median duration of response was 32+ months; 11 patients are still in remission 5 years after trastuzumab initiation. The longest complete remission duration is 123+ months, in patient with initially inoperable BC and solitary cerebellar metastasis. During observational period 10 patients stopped trastuzumab predominantly because of disease progression (8/42 19%) and 2 (4.8%) because of decreased ejection fraction (EF≤ 50%) that occurred as a rather late effect, after 34 and 49 months of continuous trastuzumab treatment. Three patients are lost from follow-up (7%); 39 (93%) patients included in this analysis are alive, still receiving trastuzumab for median 37 cycles (range 29-172+). Conclusions: A subgroup of patient with HER2 3+ MBC has a long-term benefit of trastuzumab treatment. In this analysis majority (71%) had also ER/PR positive MBC and majority have not been treated with neoadjuvant/adjuvant trastuzumab (83.3%).
Incidence and risk of neutropenia with palbociclib in patients with cancer: A systematic review and meta-analysis.
Authors: Mao Yan , Lu Janice , Wang Haibo , Nie Gang
Published: September 2018

e12530

Background: Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6 and has improved the progression-free survival of estrogen receptor positive, metastatic breast cancer (MBC). Its application in other cancers is also undergoing clinical evaluation. Neutropenia, especially high grade (grade 3 or 4), is one of the major side-effects of palbociclib, and the incidence was reported too vary in different studies. In order to better understand the overall risk of palbociclib associated neutropenia, we conducted a systematic review and meta-analysis. Methods: We conducted a systematic literature search (including Medline, Web of Science to November, 2016 and abstracts presented at the ASCO annual meetings from 2009 to 2016). Eligible studies include prospective clinical trials of patients with cancer treated with palbociclib on a 125mg daily 3/4 week schedule and have available data on neutropenia. The incidence and relative risk (RR) of neutropenia were calculated using a random-effects or fixed-effects model, depending on the heterogeneity of the included studies. Results: Eight studies published between 2012 and 2016 included a total of 1515 patients with cancer were eligible for analysis. For patients treated with palbociclib, the overall incidence of all-grade and high grade neutropenia were 77.4% (95% CI 70.9-82.8%) and 60.9% (57.8–63.8%), respectively. Surprisingly, the incidence of neutropenia was significantly different between MBC patients and non-MBC patients (all grade: RR 1.26 [95% CI 1.01–1.56], p = 0.041; high-grade: RR 1.57 [1.23–2.00], p = 0.000) who received palbociclib. Palbociclib was associated with a significantly increased risk of all-grade neutropenia in patients with cancer with an RR of 15.03 (10.17–22.21, p < 0.001) compared with controls. Conclusions: Patients with cancer who received palbociclib have a significant risk of developing neutropenia, especially MBC patients. It is strongly recommended to monitor these patients who are treated with palbociclib to adjust dose, treatment intervals, and avoid infections.
Dermatologic adverse events in breast cancer patients receiving endocrine therapies.
Authors: Freites-Martinez Azael , Belum Viswanath Reddy , Geller Shamir , Skripnik Anna , Ciccolini Kathryn , Shapiro Jerry , Kitts Sarah , Goldfarb Shari Beth , Lacouture Mario E.
Published: September 2018

e12533

Background: Endocrine therapies are known to cause adverse events including hot flashes, arthralgias, and dyspareunia. Dermatologic adverse events (dAE), including alopecia are infrequently reported, despite their potential impact on quality of life (QoL). This study aims to characterize endocrine therapy-related dAE including alopecia, acne, xerosis, and onychodystrophy. Methods: A retrospective chart review (2005-2015) of patients referred to the dermatology service for dermatologic conditions developing during endocrine therapies was performed. Relevant data was abstracted from each patient’s medical record including demographics, primary cancer diagnosis, and dAEs by grade (CTCAE v4.03). The psychosocial impact of alopecia was assessed in a subset of patients using a QoL questionnaire (Hairdex), which includes the following domains: ‘emotions’, ‘functioning’, ‘symptoms’, ‘stigmatization’ and ‘self-confidence’. Results: A total of 74 breast cancer patients treated with endocrine therapies were included (median age 62yrs. [range, 34-85]). Alopecia was the reason for a dermatologic consultation in all patients, and was attributable to aromatase inhibitors (AI) in 49 patients (66.2%) and tamoxifen in 22 (29.3%). The mean duration of treatment at the time of alopecia diagnosis was 24 months (SD ±14.3). In 93.2% of the patients, alopecia was grade 1 in severity, and in 6.8% it was grade 2 (the latter was attributable to AIs only). All grade xerosis was identified in 34 (45.9%), onychodystrophy in 21 (28.4%) and acne in 9 patients (12.2%). In patients who completed the Hairdex questionnaire (n = 44), a high ‘emotions’ (52.6, p < 0.05) and ‘stigmatization’ (46, p < 0.05) domains score were found, while ‘symptoms’ (22.1, p < 0.05) and ‘functioning’ (24.5, p < 0.05) domains score were lower. Conclusions: Endocrine therapies are associated with alopecia and dAEs, with a greater severity with AIs. A psychosocial impact on emotions was seen in patients with alopecia. Moreover, xerosis, acne, and onychodystrophy were also observed. These findings underscore the need for increased attention to dAE in breast cancer patients receiving endocrine agents, in order to maintain quality of life and adherence to therapies.
Safety results of the Canadian Expanded Access Program (EAP) of palbociclib (PAL) plus letrozole (L) in postmenopausal patients (pts) with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) deemed appropriate candidates for first-line (1L) endocrine therapy (ET) with L.
Authors: Joy Anil A. , Verma Shailendra , Provencher Louise , Theall Kathy Puyana , Lu Dongrui (Ray) , Dequen Florence , Rayson Daniel
Published: September 2018

e12534

Background: In the PALOMA-2 study, 1L PAL+L prolonged progression-free survival in women with estrogen receptor-positive/HER2- ABC vs placebo + L (hazard ratio 0.58; P< 0.001). Here we assess a cohort of Canadian pts treated with 1L PAL+L for ABC in an EAP study (NCT02142868). Methods: This was an open-label, single-arm study of US and Canadian postmenopausal women (N = 337) with HR+/HER2- ABC for whom 1L ET with L was deemed appropriate. The primary objective was to allow pt access to PAL in combination with L. PAL (125 mg/d orally [3 wk on, 1 wk off]) was administered with L (2.5 mg orally QD) until PAL was commercially available. Secondary objectives included safety and patient-reported outcomes (PROs). Results: 96/97 (99%) treated/enrolled Canadian pts were assessed for safety and PROs (treated pt characteristics: median age 62.5 y, white/Asian [89%/7%], metastatic sites bone/lung/liver [71%/25%/17%], ECOG PS 0-1/2 [93%/7%], 89% with prior systemic anticancer treatment [tx]). Median exposure was 4 x 28 d cycles of tx, and the median average PAL dose was 125 mg/d. All-causality treatment-emergent adverse events (AEs) were reported in 100% pts; 68% had grade 3/4 events, the most common events were neutropenia (61%), infections (3%), and alanine aminotransferase increase (3%). Grade 4 neutropenia and grade 3 febrile neutropenia were reported in 2% and 1% of pts, respectively. Due to AEs, PAL was temporarily discontinued in 59% and 31% had ≥1 dose reduction. The main reasons pts permanently discontinued from the study were sponsor study termination, 77%; objective progression, 11%; and AE related/unrelated to study drug, 6%/2%. All EQ-5D questions were completed by 96% pts at baseline and 85% by end of tx (EOT). At EOT, the median EQ-5D index and the EQ visual analog scale scores were not significantly changed from baseline. Conclusions: A safe and tolerable profile was observed for PAL+L in 1L treatment of Canadian pts with HR+/HER2− ABC, consistent with other studies. Sponsor Pfizer Clinical trial information: NCT02142868.
Real world experience with exemestane and everolimus for advanced HR-positive breast cancer.
Authors: Wang Ying , Le Dan , Camateros Pierre , Lohrisch Caroline A.
Published: September 2018

e12538

Background: BOLERO-2 demonstrated a significant progression free survival (PFS) advantage for EvEx compared to Ex alone in the treatment of metastatic hormone receptor positive breast cancer (HP-MBC) following failure with aromatase inhibitor (AI) in menopausal patients. Benefits and harms reported in clinical trials do not always mirror real life, thus we examined the frequency of dose modifications for toxicity and PFS in a real-world population. Methods: Women with HP-MBC started on EvEx between Dec. 2, 2013 and Nov. 1, 2015 in any one of five cancer centres in British Columbia, Canada were identified via the provincial pharmacy database. Clinical and prior treatment details, adverse events, and outcomes were compared to those of the BOLERO-2 study participants. Results: We identified151 patients treated with EvEx: median age was 53 (range 25 – 85), and 60 (40%) were ≤49. ECOG performance status was 0-1 in 122 (81%) and 2-3 in 29 (19%). 135 (89%) received prior treatment for MBC, which included non-steroidal AI in 117 (87%) and chemotherapy in 74 (55%). 94 (62%) received EvEx as 3rd line treatment and beyond. Median follow-up was 714 days (range 10 – 1127); 66 (44%) were alive at time of analysis. Dose reductions, interruptions and discontinuations of everolimus due to toxicity occurred in 32%, 31%, and 30%, respectively, higher than reported in BOLERO-2. Median PFS was 6.1 months (95% CI: 4.9 – 7.7) in our cohort, similar to that of the investigator assessed EvEx arm of BOLERO-2. Majority, 52%, of dose reductions/interruptions occurred within the first month of treatment initiation. Conclusions: We observed similar PFS forEvEx in a real world population compared with BOLERO-2. Dose interruptions and reductions were frequent, but may have enabled patients to tolerate therapy for longer. Discontinuation rates for toxicity were high and may limit the efficacy of the combination in the real world. Recent findings of primary prophylaxis against mucositis may help enhance continuation and dose maintenance (Beck et al. JCO 2016). Alternately, starting at a lower dose of Ev and increasing to tolerance may be worth exploring, as despite higher rates of dose modifications, our PFS rate was similar to that in BOLERO-2.