bluuebunny/crossref_metadata_2025 huggingface dataset:
Unknown primary cancer (UPC): Accuracy of tissue of origin prediction by molecular profiling
Authors: Greco F. A. , Spigel D. R. , Yardley D. A. , Erlander M. , Ma X. , Hainsworth J. D.
Published: August 2020

11070

Background: Molecular profiling may be useful to identify the primary site and direct therapy for patients (pts) with UPC. Since most UPC pts never have a primary site identified, the accuracy of molecular profiling diagnoses are difficult to verify. We identified a group of UPC pts who had a primary site subsequently identified during their clinical course, and performed a 92-gene real time polymerase chain reaction (RT-PCR) assay (Arch Pathol Lab Med 130:465, 2006) on tissue from the initial diagnostic biopsy. We then compared the RT-PCR diagnosis with the subsequent clinical diagnosis. Methods: 38 of 501 UPC pts (7%) seen between 2000 and 2008 had their primary tumor subsequently identified during life. 24 of the 38 pts had tissue biopsies (excluding FNA cytology) and are the subject of this study. The RT-PCR assay was performed on unstained slides from the formalin-fixed, paraffin-embedded (FFPE) initial diagnostic biopsy, and the assay predictions were compared to the actual primary sites (found later). No clinical or pathologic data (other than sex, biopsy site, and 1 H&E stained slide) were used in the prediction of the primary site. Results: 16 of 24 assays were successful (8 had no tumor or RNA in the material). 11 of 16 predictions of the site of origin (68%) were correct, corresponding to the actual primary sites found 3–58 months (median 8.5 months) after the initial diagnosis of UPC. Primary sites correctly identified included breast 2, ovary/peritoneal 4, NSCLC 1, colorectal 2, gastric 1, melanoma 1. 3 predictions were inaccurate (colorectal, testicular, sarcoma) in patients with gastroesophageal, pancreas and NSCLC, respectively. 2 assays were unclassifiable. Conclusions: RT-PCR performed on FFPE initial diagnostic tissue was accurate in predicting the primary site of origin in 11 of 16 pts with UPC who eventually had their primary site identified clinically. These data provide a direct validation of the reliability of this RT-PCR assay in predicting the primary site in pts with UPC. When used in concert with clinical features and IHC stains, molecular profiling may provide the basis for more successful site-directed therapy for many of these pts. Prospective studies of RT-PCR in UPC are ongoing.

[Table: see text]
Early assessment of response to aromatase inhibitor (AI) therapy
Authors: Linden H. M. , Kurland B. F. , Livingston R. B. , Ellis G. K. , Gadi V. K. , Specht J. M. , Gralow J. R. , Mankoff D. A. , Peterson L. M. , Schubert E. K.
Published: August 2020

11075

Background: Early decline in proliferative index (Ki-67) predicts response to endocrine therapy. For estrogen receptor positive (ER+) tumors, a low Ki-67 two weeks into endocrine therapy also predicts response (Dowsett JNCI 2007). FDG PET is promising for evaluating early response to systemic therapy and has the advantage of being non-invasive and of providing simultaneous quantitative measures at multiple tumor sites in vivo. We tested the association between FDG PET SUV and Ki-67 after two weeks of aromatase inhibitor (AI) therapy, and their prediction of response. Methods: Patients undergoing AI therapy were eligible for enrollment in the imaging study, and underwent a two week “run-in” of AI monotherapy prior to continued monotherapy or the addition of chemotherapy. Patients underwent baseline FDG PET, and Ki-67 was measured in tumor biopsy specimens. Following two weeks of therapy FDG PET and biopsy were again performed. Patients on AI therapy only were followed for clinical response. Results: A total of 21 patients enrolled in the study. 16/21 (76%) of patients had a greater than 20% decline in FDG SUV, including 11 with analyzable serial biopsy, all with 2-week Ki67 ≤5%. Of the 5 patients who did not show greater than 20% decline in FDG SUV, all 3 with serial biopsy had 2-week Ki67 of ≥20%. Subsequent response to AI was evaluable at 4–6 months in 8 patients who underwent AI monotherapy (5 R, 3 PD). All 5 responders showed decline of at least 20% in FDG SUV (30% - 60% decline), and 2/3 with PD did not (no change, 3% decline, 29% decline). Conclusions: We observed substantial changes in Ki-67 and FDG SUV following 2 W of targeted therapy. Decline in FDG SUV in patients on single agent AI predicted response in almost all cases. Serial FDG PET appears promising as an early indicator of response to AI therapy.

No significant financial relationships to disclose.
Use of CXCR4 as a prognostic marker for disease-specific survival and pattern of recurrence following resection of hepatic colorectal metastases
Authors: Yopp A. C. , Shia J. , Allen P. J. , DeMatteo R. P. , Jarnagin W. R. , Fong Y. , Blumgart L. , D'Angelica M. I.
Published: August 2020

11081

Background: Expression of the chemokine receptors CXCR4 and CCR7 has been associated with metastases and poor prognosis in primary tumors but their relevance in colorectal liver metastases (CLM) is unclear. This study examines the relationship between tumor chemokine receptor expression, pattern of recurrence and outcome after resection of hepatic metastases.Methods: Eighty patients with metastases from colon or rectal primary tumors who underwent a R0 partial hepatectomy from February 2002 to April 2004 were studied prospectively. Immunohistochemical staining was performed on the formalin-fixed, paraffin-embedded tissues of hepatic metastases using antibodies specific for CXCR4, CXCL12 and CCR7. The correlation between the CXCR4, CXCL12 and CCR7 expression and clinicopathological factors was evaluated.Results: Median follow-up was 42.9 months. Positive expression of CXCR4, CXCL12 and CCR7 was seen in 49 (61%), 23 (29%) and 48 (60%) of tumor specimens, respectively. Clinical risk score greater than 2 and high CXCR4 expression were associated with a shorter disease-specific survival (DSS) and a reduced recurrence-free survival (RFS) following partial hepatectomy for CLM (p<0.05) by multivariate analysis. CCR7 and CXCL12 expression, hepatic artery infusion pump chemotherapy, systemic chemotherapy and site of primary disease did not influence DSS or RFS. Fifty-three (68%) of the patients recurred; 11 with liver only recurrences, 25 with lung only recurrences and 18 with multiple sites of recurrences. High expression of CXCR4 is associated with widespread multiple sites of recurrence ( Table ).Conclusions: CXCR4 expression in colorectal hepatic metastases adds prognostic information with regards to DSS, RFS and patterns of recurrence and may play role in clinical decision making regarding chemotherapy and surgical interventions. CXCR4 expression may also provide additional prognostic information beyond the already validated clinical risk score. [Table: see text]

No significant financial relationships to disclose.
Influence of inflammation-based prognostic score on mortality of patients undergoing chemotherapy for far advanced or recurrent unresectable colorectal cancer
Authors: Ishizuka M. , Nagata H. , Takagi K. , Kubota K.
Published: August 2020

11084

Background: Recent studies have revealed that the Glasgow prognostic score (GPS), an inflammation-based prognostic score that includes only C-reactive protein (CRP) and albumin, is a useful tool for predicting postoperative outcome in cancer patients. However, few studies have investigated the GPS in patients undergoing chemotherapy for far advanced or recurrent unresectable colorectal cancer (AR-UCRC). Objective: To demonstrate the influence of the GPS for prognostication of patients undergoing chemotherapy for AR-UCRC. Methods: The GPS was calculated as follows: patients with both an elevated level of CRP (>1.0 mg/dl) and hypoalbuminemia (<3.5 g/dl) were allocated a score of 2, and patients showing one or none of these blood chemistry abnormalities were allocated a score of 1 or 0, respectively. Results: One hundred twelve patients who had undergone chemotherapy for AR-UCRC with regimens such as such as FOLFIRI (5-fluorouracil [5-FU]/l-leucovorin [LV]/irinotecan hydrochloride [CPT-11]) or FOLFOX (5-FU/LV/oxialiplatin [L-OHP]) were evaluated retrospectively. Kaplan-Meier analysis and log rank test revealed that GPS2 predicted a higher risk of mortality than GPS0 or 1 (P <0.0001). Univariate analyses revealed that the neutrophil ratio (P = 0.0411), CA19–9 (P = 0.0473), CRP (P = 0.0477), albumin (P = 0.0043) and GPS (0,1/2) (P < 0.0001) were associated with mortality. Multivariate analyses using these five factors revealed that only GPS (0,1/2) (odds ratio, 6.071; 95% C.I., 1.625–22.68; P = 0.0073) was an independent risk factor of mortality. Conclusions: GPS is considered the most important and independent predictor of mortality in patients undergoing chemotherapy for AR-UCRC.

No significant financial relationships to disclose.
Time dependence of prognostic values of gene-expression signatures for breast cancer
Authors: Lau K. F.
Published: August 2020

11085

Background: Gene-expression signatures were shown to be prognostic and predictive for breast cancer but their performances over time have not been investigated. Methods: Recurrence score (RS) of oncotype, 70-gene profile (SGP) of Mammaprint, intrinsic subtype (IS) and wound signature (WS) were analyzed using a single dataset of 295 samples from Fan et al. (Fan et al. N Engl J of Med 2006; 355:560–9). Time-varying coefficient Cox models were used to estimate the time-dependent hazard ratios (HR) for relapse-free survival (RFS). Annualized RFS hazard rates were estimated using cubic splines. Concordance between RS and SGP was calculated for different intrinsic subtypes in all 295 samples and was evaluated in a subset of 173 ER+ samples not in the training set of SGP for unbiased comparison. Results: For the high risk groups of RS, SGP, IS and WS, hazard rates peaked around the 2nd year from surgery and decreased rapidly over time. For the low risk groups, hazard rates also peaked around the 2nd yr but remained fairly constant over time. Hazard ratios of high vs. low risk groups of RS at yr 2, 5 and 10 were 17.0 (8.4–34.0), 4.0 (2.0–8.0), 1.7 (0.83–3.4). For intermediate vs. low risk groups of RS, the corresponding HRs were 2.7 (1.1–7.0), 5.0 (1.1–7.4), 1.6 (0.63–4.2). Poor vs. good groups of SVP had HRs of 7.4 (4.5–12.1), 3.6 (2.2–5.9), 2.0 (1.2–3.3) at yr 2, 5, 10. HRs of Luminal B (LB), Basal-like (BL), HER2/ER- (HER2), Normal-like (NL) vs. Luminal A (LA) of Intrinsic Subtypes were 6.8 (4.0–11.5), 5.7 (3.2–10.0), 7.6 (4.0–14.1) and 1.7 (0.9–3.3) at yr 2. HRs at yr 5 were 4.0 (2.3–6.8), 0.7 (0.4–1.2), 1.1 (0.6–2.0) and 2.3 (1.2–4.4) respectively. For WS, HRs at yr 2, 5, 10 were 6.3 (3.3–11.9), 2.9 (1.6–5.6) and 2.2 (1.2–4.1) respectively. Concordance rates of RS and SVP were 1.0, 0.91, 0.86, 0.72 and 0.62 for BL, HER2, LB, LA, NL of Intrinsic Subtypes. In 173 ER+ samples not present in the SGP training set, concordance rate between RS and SVP was 0.77 (Cramer's V = 0.56); the same as in the whole set of 225 ER+ patients (Fan et al. N Engl J of Med 2006; 355:560–9). Conclusions: Prognostic values of gene-expression signatures decrease over time. They can best predict breast cancer relapse during the first 5 years. Concordance between RS and SPV is highest in the basal-like tumors and lowest in the Luminal B and Normal-like subtypes.

No significant financial relationships to disclose.
Correlation of HuR cytoplasmic expression in pancreatic cancer and overall patient survival when treated with gemcitabine in the adjuvant setting
Authors: Brody J. , Dasgupta A. , Costantino C. L. , Kennedy E. , Yeo C. J. , Witkiewicz A. K.
Published: August 2020

11097

Background:The Hu/ELAV mRNA binding protein HuR is normally localized to the nucleus and is activated upon stress. Previously, we observed that HuR expression is predominantly cytoplasmic in aggressive forms of pancreatic ductal adenocarcinomas (PDA). Additionally, we have shown that overexpression of HuR in pancreatic cancer cell lines renders them hypersensitive to gemcitabine (GEM). GEM is the standard first line therapy used against PDA. This study was designed to determine the relationship between endogenous HuR expression levels and patient outcome. Methods: We analyzed tissue from 29 resected PDA patients who did not receive neoadjuvant therapy. We determined the intensity of cytoplasmic HuR expression. All patients received adjuvant GEM, alone or in combination with radiation therapy or other chemotherapeutics. Correlation between HuR expression levels and overall survival was evaluated. Results: The median overall survival was 20.6 months, with 18 deaths observed. Median overall survival for low HuR expression was 15.3 months. Median overall survival for high HuR expression was not reached at a follow up of 40 months. A univariate Cox regression model gives a hazard ratio of low to high HuR of 3.36 (p=0.025) [95% CI 1.09–10.35]. Adjusting for age, sex, and radiation therapy in this patient group gives an adjusted hazard ratio of 5.04 (p = 0.03) [95% CI 1.15–22.02]. This indicates a 5-fold increase in risk of death in patients with low HuR levels compared to high HuR levels among patients receiving GEM. Conclusions: This is the first report of a correlation between levels of cytoplasmic HuR expression and overall survival in GEM treated patients. Together with our previously reported experimental data, HuR is regulating the key metabolic enzyme for GEM activation (deoxycytidine kinase). Therefore, HuR is a marker for therapeutic efficacy of GEM based regimens and is a candidate target for the optimization of GEM based treatment strategies. [Table: see text]

No significant financial relationships to disclose.
P53 mutation and differential response to neoadjuvant chemotherapy in women with locally advanced breast cancer: Results from the I-SPY trial (CALGB 150007/1500012 and ACRIN 6657)
Authors: Pradhan S. M. , Carey L. , Edmiston S. , Hylton N. , Parrish E. , Moore D. , Conway K.
Published: August 2020

11099

Background: Independent of other factors, p53 status may influence sensitivity to anthracycline (A)- and taxane (T)-based chemotherapy. We investigated p53 as a predictive marker of differential neoadjuvant chemoresponse by examining change in MRI longest diameter (LD) during sequential A- then T-based chemotherapy in a prospective clinical trial. Methods: 171 patients (pts) with newly diagnosed locally advanced breast cancer received neoadjuvant A- then T-based chemotherapy. LD were obtained pretherapy, between regimens, and posttherapy but prior to surgery. P53 mutation analysis was performed on pretherapy tissue using gene chip technology, SSCP, and sequencing. Subtypes were by IHC: LumA (ER/PR+/HER2-), LumB (ER/PR+/HER2+), Basal (triple negative), HER2 (HER2+/ER/PR-). Results: 99 pts had p53 mutant (M) tumors and 72 were wildtype (WT). M and WT did not differ by age, menopausal status, or HER2. M were significantly more common among basal (71%) and HER2 (59%) than Lum A (24%). Anthracycline response did not differ between WT and M within subtypes. Within HER2, Basal, and LumB, WT had higher taxane- and overall responses than M; within LumB these were statistically significant (p=0.03 and 0.05 respectively). Conclusions: P53 mutation status may affect chemosensitivity even within hormone receptor/HER2 subsets. In this dataset response to anthracycline appeared independent of p53 status within subtypes, while WT tumors responded better to taxanes and overall in LumB, with a similar trend among basal and HER2. Mutational subset and correlative analyses with gene expression, molecular subtyping, and IHC data are ongoing and will be presented. [Table: see text]

No significant financial relationships to disclose.
CD24 expression and breast cancer stem cell phenotype
Authors: Rappa G. , Anzanello F. , Lorico A.
Published: August 2020

11106

Background: Several studies suggest the existence of breast cancer-initiating cells (BCIC), responsible for tumor development and progression. Initial reports that only the CD44+CD24−/low subpopulation contains BCIC have been challenged by subsequent studies. We examined the relationship between CD24 and biological properties of breast cancer cells. Methods: MA-11 breast carcinoma cells, originating from bone marrow micrometastases, are CD44+ and have an heterogeneous expression of CD24 (214,000/cell; range 0–1,120,000). We have previously reported that upon in vitro culture as mammospheres under stem cell-like conditions, MA-11 cells acquired increased tumorigenicity and a CD44+CD24−/low phenotype. We have now investigated the relationship between CD24 expression and tumorigenicity in the MA-11 model. Results: Upon passage of MA-11 mammospheres in adherent culture, cells rapidly re-expressed CD 24. The rapid increase in CD24 was consistent with antigen up-regulation, not selection of CD24−/low cells. Exposure of adherent MA-11 cells to imatinib for 72h resulted in a reversible decrease in CD24 from 214,000 to 15,800/cell. CD44+CD24−/low cells, sorted by flow cytometry, generated CD44+CD24high, and CD44+CD24highgenerated CD44+CD24−/low. Immediately after sorting, >90% CD44+CD24−/low cells were in G0/G1. After 24–48 h in culture, cell cycle distribution, growth rate and invasiveness of the sorted cell populations were equivalent. Upon injection and s.c. growth, CD24 expression of CD44+CD24−/low populations and clones increased from 10,000 to 220,000/cell. Similarly, CD44+CD24−/low clones derived from human MCF-7 breast carcinoma cells formed tumors containing >99% CD44+CD24high cells. The average number of CD24 per cell was equivalent for tumors formed upon injection of CD44+CD24−/low, CD44+CD24+, mammosphere-derived cells or parental adherent MA-11 cells. The tumorigenic potentials of sorted CD44+CD24−/low, CD44+CD24−/lowsub-populations and clones in nu/nu mice were equivalent. Conclusions: CD44+CD24−/low breast cancer cells are not associated with increased tumorigenicity; the high CD24 level of mouse xenografts derived from both CD44+CD24−/low and CD44+CD24hi breast cancer cells suggests an important role for CD24 in tumor growth.

No significant financial relationships to disclose.
Impact of molecular subtype on presenting characteristics of T1a,b tumors
Authors: Wiechmann L. , Jacks L. , Patil S. , Stempel M. , Morrow M.
Published: August 2020

11111

Background: Gene expression profiling of breast cancers has identified molecular subtypes (Lum A and B, basal, HER2) which impact upon the risk of both local and distant recurrence. There is interest in the impact of molecular subtype on outcome in T1a,bN0M0 tumors, a group thought to have good prognosis and to be amenable to breast conservation. The purpose of this study was to determine if presenting features of T1a,b tumors differ among molecular subtypes. Methods: Subtypes were classified using IHC as Lum A (ER±PR pos, HER2 neg); Lum B: (ER±PR pos, HER2 pos); HER2: (ER+PR neg, HER2 pos); or Basal: ER, PR, and HER2 neg. Data was obtained from a registered database which included patients treated in our institution between 1/98 and 6/07. Of 7906 eligible patients, 6016 were classifiable into molecular subtypes and 1974 tumors (32.8%) measured 10 mm or less. The Chi square test and ANOVA were used for statistical analysis. Results: Data are shown in Table 1 . Patients overexpressing HER2 were significantly younger, had more nodal involvement, multicentric/multifocal (Multi) disease, extensive intraductal component (EIC), and lymphovascular invasion (LVI) (all p<0.0001). On multivariate analysis the HER2 subtype had an odds ratio of 2.5 for Multi versus Lum A/B, but HER 2 was not predictive of nodal status. Conclusions: Even in small breast cancers, presenting features vary with molecular subtype. Unlike Multi, the higher incidence of positive nodes in HER2 patients is explained by traditional prognostic features such as grade, age, and size rather than subtype, suggesting that evaluation of traditional prognostic factors remains valuable in the molecular era. [Table: see text]

No significant financial relationships to disclose.
Methylation profile of human breast cancer: A possible biomarker for the detection of circulating tumor cells
Authors: Marzese D. M. , Gago F. E. , Vargas-Roig L. M. , Roqué M.
Published: August 2020

11112

Background: Genetic and epigenetic events are complementary mechanisms involved in breast carcinogenesis. One of the most common epigenetic mechanisms by which genes are silenced is the aberrant methylation of their promoter CpG islands, i.e. hypermethylation in promoters of Tumor Suppressor Genes. The identification of circulating tumor cells (CTCs) in the blood of cancer patients, based on their aberrant methylation profile, appears as a potential tool for early detection and provides therefore the promise of a non-invasive and affordable cancer detection test. Methods: The methylation status of 26 cancer-related regions was studied, using Methyl Specific-Multiplex Ligation dependent Probe Amplification (MS-MLPA) assay in invasive breast tumors (n=24), axillary lymph nodes (n= 5), and normal breast tissue (n=2). A nested-Methyl Specific PCR (Nested-MSP) was designed for one of the methylated regions in the tumor suppressor gene rassf1A, to identify CTCs in peripheral blood samples. Blood samples from non tumor individuals were used as control. Results: We observed aberrant methylation of one or more of the 26 studied gene regions in all the breast cancer samples. The profiles were specific for each tumor. The more frequently aberrant methylated genes were: rassf1A promoter (62.5%), esr1 (54.17%), apc (54.17%) and rassf1A exon 1 (50%). Absence of aberrant methylation was confirmed in normal breast tissues. The specific methylation profile of tumors could be used to identify the metastasis origin in a patient with a left-sided breast tumor and bilateral tumor invasion of axillary lymph nodes. MS-MLPA revealed identical aberrant methylation patterns in both lymph nodes, revealing a left-sided origin of the right-sided lymph node. For the detection of CTCs in blood, a Nested-MSP on rassf1A was designed. This method allowed the detection of CTCs in the peripheral blood of a cancer patient by their aberrant rassf1A methylation. A healthy age-matched control blood sample revealed absence of CTCs. Conclusions: The identification of the methylation profile of the tumor by MS-MLPA allowed to establish the metastasis origin of invaded axillary lymph nodes and to detect CTCs in peripheral blood of a cancer patient.

No significant financial relationships to disclose.
The individuality of tumor-stroma interaction in non-small cell lung cancer: Insights from functional and molecular analyses
Authors: Gottschling S. , Kuner R. , Granzow M. , Chang Xu E. , Muley T. , Hoffmann H. , Dienemann H. , Eckstein V. , Ho A. D. , Thomas M. , Meister M.
Published: August 2020

11115

Background: Tumor-stroma interaction plays a significant role for malignant growth. Results from prostate and breast cancer rodent models show cancerogenic properties of tumor-associated and genetically altered stromal cells (SC) when combined with initiated or normal epithelium (Olumi et al., Cancer Res 1999, Kuperwasser et al., PNAS 2004). However, data on the mechanisms and sequels of tumor-stroma interaction in lung cancer are scanty. Methods: Here, we analyzed the functional and molecular sequels of cross-talk between the non-small cell lung cancer (NSCLC) cell lines A549, H23, and H1703 and primary stromal cells (SC) derived from matched normal lung tissue and tumors of newly diagnosed NSCLC patients. Tumor cells were kept in a non-contact co-culture system with SC and analyzed for alterations in proliferation, colony formation, migration, adhesion, invasion, chemosensitivity and gene expression by Affymetrix HG U133 Plus 2.0 arrays. Results: Exposure to SC altered cellular functions and gene expression profiles related to tumor growth, metastasis and response to therapy. Each cell line showed individual alterations that were hierarchically governed by the (1) type of tumor cell, (2) the SC donor and his histology (3) and the local origin of the SC (normal lung tissue vs. tumor-associated). Conclusions: This in vitro model demonstrates an individual pattern of tumor-stroma interaction in NSCLC that is determined by both, the properties of the tumor cells and those of the stromal environment. Thus, biomarker programs in NSCLC should also consider the stromal compartment.

No significant financial relationships to disclose.
Weekly paclitaxel and capecitabine in HER2-negative metastatic breast cancer (MBC): A multicenter GINECO randomized phase II comparing two paclitaxel-capecitabine schedules
Authors: Lortholary A. , Hardy-Bessard A. C. , Bachelot T. , Dalivoust P. , de Rauglaudre G. , Alexandre J. , Bourgeois H. , Jaubert D. , Paraiso D. , Largillier R.
Published: August 2020

1114

Background: Paclitaxel (Ta) and capecitabine (Xel) are synergistic in vitro. Compared to a continuous weekly Tax combined with a classical 14 days (d)/21 Xel administration (Elza-Brown et al., ASCO 2000), we have explored the combination of Xel 5d/week (wk) and weekly Ta 3 wk out 4 in the objective to increase the efficacy/toxicity ratio of the TaXel combination. Methods: Patients (pts) in first or second-line of MBC, previously treated with anthracyclins + docetaxel were randomized either to A: Ta (60 mg/m2/w) + Xel (2000 mg/m2/d x 14 d/21) or to B: Ta (80 mg/m2/w) + Xel (2000 mg/m2/d x 5 d/wk) 3wk out 4. Results: From January 2006 to January 2008, 130 pts were accrued (A 66, B 64). Pts characteristics were well balanced between the two arms including median age (58 yrs), histologic type and grade, hormone receptor-positive tumor (80%), previous treatment, visceral disease (72%), number of sites (>1; 63%), ECOG PS (0; 42%, 1; 58%). Pts received a median of 6 cycles (1–23) with a received/planned mean dose of 89.3% for Ta in both arms and of 74 and 76% for Xel respectively in arm A and B. Haematological toxicity (Tox) was low in both arms with neutropenia Gr 3 in only 8% of cycles, G-CSF support in 2% of cycles, and infection G3 in 5 pts. Alopecia G2 was less frequent in arm A (29 vs 60%). Other Tox were similar in both arms: [G2/3 (%) cutaneous (35/17), pain (36/9), fatigue (26/13), neuropathy (20/3), diarrhea (15/6), mucositis (8/2), vomiting (9/1)] but treatment interruption due to Tox was more frequent in A (A 19, B 7 pts) (p = 0.02). Response rate was 52% (B) versus 44% (A). A progression-free survival advantage was seen for B over A (366 vs 272 days, p = 0,15) including in the triple negative pt subset (n = 26 pts) (197 vs 150 days, p = 0.07). Conclusions: The intermittent regimen (3 wk out 4) of weekly paclitaxel and capecitabine 5 d/week is a well accepted, safe and effective TaXel schedule and might be a chemotherapy regimen of choice in MBC including triple negative patients.

No significant financial relationships to disclose.
Phase II trial report of the new neoadjuvant chemotherapy with S-1 and docetaxel for advanced breast cancer
Authors: Okazaki K. , Kira M. , Yamai H. , Nakagawa Y. , Nagao T. , Kenzaki K. , Bando Y. , Morimoto T. , Kondo K. , Tangoku A.
Published: August 2020

1121

Background: Primary chemotherapy with anthracycline and taxanes is a gold standard regimen which realize pathologically complete response in 20% of patients with advanced breast cancer. However, sequential administration of anthracycline and taxanes induces serious side effects. This regimen is therefore difficult to use for higj-risk patients. S-1 is a new oral anti-tumor drug, which is composed of 5-fluoro-1-(tetrahydro -2- furanyl)-2, 4(1H, 3H)-pyrimidinedione (Tegafur, FT), 5-chloro-2, 4- dihydroxypyridine (Gimeracil, CDHP) and potassium 1, 2, 3, 4-tetrahydro-2, 4-dioxo-1, 3, 5-triazine-6-carboxylate (potassium Oteracil, Oxo). Combined treatment with docetaxel and S-1 yielded significant response in patients with gastric cancer with minimal side effects due to biochemical modulation of both CDHP and Oxo. The purpose of this study was to evaluate the efficacy and toxicity of docetaxel in combination with S-1 for advanced breast cancer. Methods: Patients with advanced breast cancer (Stage IIA to IV) were treated with i.v. docetaxel (40mg/m2) on day 1 and oral S-1(80mg as FT/m2/day) on days 1 to 14 every 3 weeks for 8 courses. The clinical response was evaluated every 3 months with MMG, MRI, ultrasonography and CT scan based on RECIST criteria. The patients underwent surgery after completion of chemotherapy. Pathologic examination was performed with thin-sliced specimens. The specimens were also reserved for genetic analysis. Written informed consent was obtained from all patients or family members after the Ethics Committee of Tokushima University Hospital approved the study protocol. Results: Twenty-two patients completed the therapy and underwent surgery. Four cases (18.2%) of pathologic complete response (pCR) were recognized on pathologic examination. The response rate was 90.9% and 95.5% of the patients could preserved their breast. Bone marrow suppression was substantial, and low-grade anorexia, nausea, and peripheral neuropathy were observed. Conclusions: The new regimen of S-1 combined with docetaxel is expected to exhibit satisfactory efficacy in treating advanced breast cancer as primary chemotherapy. Genetic analysis will be performed to examine and to find biomarkers for measurement of the efficacy of this therapy.

No significant financial relationships to disclose.
Effect of fulvestrant treatment on serum VEGF levels in hormone-sensitive metastatic breast cancer patients
Authors: Camerini A. , Garrone O. , Valsuani C. , Puccetti C. , Rondini M. , Donati S. , Siclari O. , Barni S. , Pronzato P. , Amoroso D.
Published: August 2020

1124

Background: Fulvestrant (F) is a pure antiestrogen agent available for the hormonal treatment (HT) of post-menopausal ormone-sensitive advanced breast cancer (ABC). We previously reported (ASCO 2007 abs1085) a lipid lowering effect of F possibly related to an action on progesterone (P) receptor. Aim of the study is to analyze the effect of F treatment on serum VEGF levels that may represent an effect of P pathway alteration. Methods: 21 pts (median age 75 yrs [range 43–82]) with hormone-sensitive ABC were enrolled. All patients were heavily pretreated receiving a median of 2 [1–4] HT-lines and 2 [1–5] CT-lines before F. Last HT before F administration was exemestane in 8/21, letrozole in 9/21, anastrozole 3/21, and tamoxifene in 1/21. Treatment-related data, including response according to RECIST criteria and toxicity, were collected. Fulvestrant was administered as standard monthly 250 mg injection. Peripheral venous blood samples were collected before F administration, every 3 months, and at discontinuation time. VEGF levels were evaluated by ELISA and expressed as absolute absorbance values. Baseline values were always compared to the last available sample. Results: At report time pts received a median of 4 F injections (range 3–8). We observed a PR in 3/21, SD in 7/21, and PD in 11/21 pts with a clinical benefit of 45% and a median TTP of 4.5 [3–9] months. Serum VEGF levels significantly decreased during F treatment (156.8 ± 28.5 vs. 122.2 ± 14.5 A; p = 0.01). VEGF reduction was independent from clinical benefit (186.4 ± 44.6 vs. 131.1 ± 21.8 A, p = 0.04 in pts with CB and 158.9 ± 52.5 vs. 125.0 ± 27.9 A, p = 0.1 ns in pts without CB), type of last HT or treatment duration. Conclusions: We observed a reduction of serum VEGF levels associated with F treatment in our study population. Our data seem to strengthen the hypothesis of a possible effect of F on P pathway affecting both lipid metabolism and VEGF production regulation.

No significant financial relationships to disclose.
Changes in survival from metastatic breast cancer during the last twenty-years: A population based study in Northern Italy
Authors: Cortesi L. , Cirilli C. , Rashid I. , Artioli E. , Federico M.
Published: August 2020

1125

Background: A significant improvement in overall survival was observed in the last two decades in patients with breast cancer due to early diagnosis and more effective therapies. However, a significant improvement in metastatic setting has been questioned. Our population based study was aimed to investigate the outcome of metastatic breast cancer from 1988 to 2005. Methods: Women with stage IV de novo or relapsed breast cancer diagnosed between 1988 and 2005 were identified by the Modena Cancer Registry (MCR). For all patients overall survival (OS) was measured from the date of first distant metastases to the date of death from any cause or last follow-up and compared across groups for four periods of similar duration time: 1988–1993 (A), 1994–1997(B), 1998–2001(C), 2002–2005(D). Results: Among 8,654 patients with breast cancer identified by the MCR, 409 had an initial metastatic disease (4.8%) and 693 (8.4%) had a distant recurrence. Median age at onset was 66 versus 59 years in de novo vs relapsed disease (p = 0.001). Significant differences for postmenopausal age (80% vs 71%) and for positive estrogen receptors (72% vs 63%) were registered in de novo and relapsed disease, respectively (p = 0.001). After a 27 months median follow-up for initial metastatic disease, the five-year OS was 12%, 14%, 9%, and 13% in the A, B, C, and D periods, respectively, (p = 0.5). Conversely, in relapsed breast cancer, after a 29 months median follow-up, a significant survival improvement was observed between the first and the other three periods, being the 5 year-survival rate after recurrence 10%, 22%, 30%, and 25%, respectively (p = 0.001). A survival improvement was seen in the last ten years for relapsed breast cancer using aromatase inhibitors (p < 0.0001) while for initial metastatic disease the same treatment provided a better outcome only in the last 4 years (p < 0.0001). Conclusions: Data from our study show that the outcome of initial metastatic breast cancer is still discouraging, despite the availability of several new drugs in recent years. A limited improvement was observed in relapsed breast cancer with the aromatase inhibitors introduction. In any case, the finish line is still far away, and robust investments in basic and translational research are still absolutely necessary.

No significant financial relationships to disclose.
Contralateral risk-reducing mastectomy in BRCA1/2 mutation carriers and other high-risk women in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab)
Authors: Kiely B. E. , Jenkins M. A. , McKinley J. M. , Friedlander M. L. , Weideman P. C. , Milne R. , McLachlan S. , Hopper J. L. , Phillips K.
Published: August 2020

1509

Background: Contralateral risk-reducing mastectomy (CRRM) reduces contralateral breast cancer (BC) risk by up to 97%. Few studies have examined the prevalence and predictors of CRRM in BC patients at high familial risk of a second primary BC. Methods: Participants were women with unilateral BC and a strong family history of the disease, including BRCA1 and BRCA2 mutation carriers. Data were collected by interview, self-administered questionnaire, and review of pathology and surgical reports. Associations between having CRRM and potential predictors were assessed using multivariate logistic regression. Results: Of 1018 study participants (median follow-up 5.5 years), 154 (15%) underwent CRRM. The median time from initial BC to CRRM was 1 year. More likely to undergo CRRM were women who were younger at the time of their BC diagnosis (odds ratio [OR] = 0.94 per year of age, p < 0.001), those diagnosed more recently (OR = 1.16 per calendar year, p < 0.001), those who underwent mastectomy rather than breast conservation as their initial definitive BC treatment (OR = 5.2, p < 0.001) and those who underwent risk-reducing salpingo-oophorectomy (OR = 3.4, p < 0.001). BRCA1/2 mutation status and tumor characteristics were not independently associated with CRRM uptake. A contralateral BC event occurred in 177 (20.5%) of the 864 women who did not have CRRM, compared with one chest wall event (0.6%) in the 154 women post-CRRM. Conclusions: Younger women with more recently diagnosed BC treated with mastectomy were most likely to elect CRRM. BRCA1/2 mutation status and the competing risk of BC recurrence and death did not appear to influence decision making.

No significant financial relationships to disclose.
A study of lavender and tea tree oils on postmenopausal FSH levels and hot flash severity
Authors: Cohn R. D. , Bornhauser C. , MacManus D. , Sadakane M. , Read W.
Published: August 2020

1516

Background: Products containing lavender and tea tree oil have been linked to prepubertal male gynecomastia.(N Engl J Med 356:479–485) This implies that these products may be phytoestrogens, or plant products with estrogenic effects. Exogenous estrogens increase the risk of developing breast cancer and could counteract benefit from adjuvant hormonal manipulations in women with a history of breast cancer. We designed a study to determine the effects of lavender and tea tree oil on healthy postmenopausal women's FSH as a means to determine the estrogenic effect of both products. Hot flashes are a side effect of decreased endogenous estrogen, and in this study we used hot flash severity as an additional assay of estrogenic effect. Methods: Lavender lotion and tea tree oil products were generously donated by The Body Shop. Nine healthy postmenopausal women suffering from hot flashes were asked to apply lavender lotion and tea tree oil according to product directions for a week each, with a washout period in between. Participants were menopausal with baseline FSH > 26 IU/mL. Serum FSH was obtained at baseline, after each lotion and after the washout period. Participants also recorded daily hot flash number and severity. Average daily hot flash severity was calculated for each patient during each period, with lotion use periods compared to Paired, 2-tailed T-tests were used to compare average hot flash severity for each participant as well as FSH values as compared to the baseline obtained before it. Results: Compliance was excellent. No significant differences were seen between time periods with either product for either measure. In no case did FSH dip to premenopausal levels. No indication of improvement in hot flash frequency or severity was seen. Conclusions: In our population, the lavender and tea tree oil products showed no estrogenic effects. This is similar to clinical trials of phytoestrogens, which as used by humans are not potent enough to affect FSH or hot flash severity. Both lotions can probably be used without increasing the risk of recurrent or de novo breast cancer. We intend one more study period in which participants will use a large daily amount of lavender lotion, again tracking hot flash severity and FSH.

No significant financial relationships to disclose.
Risk of noncompliance due to patient discomfort during screening mammogram
Authors: Mullai N. , Murugesan N. , Burton L. , Goodin V. , Stout A.
Published: August 2020

1522

Background: There is enough evidence supporting the benefits of screening mammograms than any other screening procedure for the early detection of malignancy. Compliance to the screening method is very important to achieve this purpose. There is some concern about future trends in breast cancer mortality as a decline in rates of mammogram screening has been noticed. Pain during mammography has been recognized as a significant deterrent to breast screening. Hence this study was done to evaluate compliance in screening mammogram and to analyze major reasons for noncompliance. Methods: Randomly selected patients visiting the doctor's office for various reasons were asked about mammogram and their experience. Their responses were tabulated and analyzed statistically. Results: Out of 160 people questioned, 155 patients had mammogram regularly at 1–2 year interval and five patients did not. 50% of respondents were 51–70 years of age, 15% were 50 years or under, and 31% were over 70 years. Ninety patients (58%) reported their mammogram experience was unpleasant, causing pain and bruising. In spite of the discomforts reported, 132 (82.5%) patients said they would continue the screening as recommended. However, 28 patients (17.5%) indicated their intention not to get further mammograms based on their painful experience, unless the screening technology was improved. Conclusions: Breast cancer incidence after peaking in 1998 has decreased 9.8% since then with a 12% decline in women aged 50–60. The sharpest decline was noted from 2003 that could be due to the decrease in the hormone replacement therapy after the Women's Health Initiative report. However, it may also reflect some reduction in screening mammograms from 70% (in 2000) to 66% (in 2005) as estimated by National Health Interview Survey. Various causes were attributed for the decline in screening mammogram rate including the discomfort and pain caused by compression during film mammography. More than 1 in 6 patients refusing to undergo further screening is definitely a sign of concern. Better screening methods like patient controlled compression mammogram reported by Duke University Medical Center or other methods are worth investigating, to improve the compliance of the one of the effective preventive measures.

No significant financial relationships to disclose.
Results of the first national public breast cancer screening program in the Kingdom of Saudi Arabia
Authors: Omalkhair A. , Tahan F. , Al Naeem A. , Young S. , Musaad S. , Jazieh A.
Published: August 2020

1524

Background: Despite the relatively low incidence in the Kingdom of Saudi Arabia (KSA) compared to Western countries, breast cancer (BC) is the most common cancer among Saudi females for the past 11 consecutive years (National Cancer Registry 1994–2004). The objective of this study is to report the results of the first public national BC screening program in KSA and to evaluate the relationship between imaging and pathological findings and known BC risk factors. Methods: Asymptomatic women 40 years of age or older underwent BC screening at Abdulatif Charitable Cancer Screening Center, Riyadh, KSA. Mammograms were scored using American College of Radiology Breast Imaging Reports and Data System (BIRADS). Correlations between imaging findings and risk factors, as well as pathological findings, were analyzed. Results: A total of 1,215 women were enrolled between September 2007 and April 2008. Median age was 45 years (19–91) and median body mass index (BMI) was 31.6 kg/m2 (16.7–58). A total of 16 cases of cancer were diagnosed (80% are less than stage IIB). No cancer was diagnosed in 942 women with R1/R2 scores and only one case of cancer was diagnosed in 228 women with R0/R3 scores. However, among 26 women with R4/R5 scores, 50% had malignant disease and 35% had benign lesions (odds ratio = 1.96; 95% confidence interval = 1.5, 2.6) (p < 0.0001). No correlation between known risk factors and imaging score or cancer diagnosis. Conclusions: The public acceptance of BC screening program was encouraging. Longitudinal follow-up and inclusion of more participants will help in better determining the risk factors relevant to our patient population.

No significant financial relationships to disclose.
Frequency of late-stage breast cancer diagnoses despite high mammography screening rates in an HMO
Authors: Haque R. , Schottinger J. E. , Kanter M. H. , Avila C. C. , Contreras R. , Gordon M. A. , Quinn V. P.
Published: August 2020

1526

Background: Kaiser Permanente Southern California (KPSC) led the nation in screening women for breast cancer (BCa) with a mammography rate of nearly 90% in 2007 according to 2008 Healthcare Effectiveness Data and Information Set (HEDIS) measures. Despite successes in improving screening rates in this health plan that serves 3+ million diverse members, the percentage of women diagnosed with late stage BCa (stage III, IV) remained stable, varying from 12.9% (N∼323) in 2003 to 10.8% (N∼270) in 2007. To identify patient and health care factors associated with late stage diagnosis and the impact of its enhanced screening implementation guidelines, KPSC undertook this study. Methods: This cross-sectional study included a cohort of 10,580 BCa patients from 2003–2007. We compared women diagnosed with late stage disease versus those with early stage disease (stages I, II). P values (2-sided) were based on the chi-square distribution. Adjusted odds ratios and 95% confidence intervals were estimated using unconditional logistic regression. Results: Factors that were positively associated with late stage diagnosis in the univariate analyses included age, lack of recent mammography screening, worse tumor features, 80+ years of age, minority race, lower geocoded household income, increased healthcare visits, and use of Pap testing (P < 0.01 for all variables). Factors significantly associated with late stage diagnosis in the multivariate model included only lack of recent mammography screening (OR = 1.35, 95% CI: 1.14–1.58) and worse tumor features including high grade (grade 3, OR = 2.58, 95% CI: 1.96–3.40), positive lymph nodes (OR = 53.49, 95% CI: 39.90–71.72), and HER-2+ tumors (OR = 1.40, 95% CI: 1.13–1.72). Conclusions: Targeting older women, those with lower utilization, and women who did not have a recent mammogram may help further lower the prevalence of late stage diagnoses. However, given the extent of the health plan's previous efforts to enhance BCa screening rates, a ceiling effect may limit additional benefit. Additional efforts to decrease the rate of advanced tumor stage at diagnosis may include improving interpretation of mammograms or earlier detection of aggressive tumors by enhanced BRCA genetic testing.

No significant financial relationships to disclose.
Factors leading to the decision for contralateral prophylactic mastectomy in patients with breast cancer
Authors: Yi M. , Hunt K. K. , Arun B. K. , Bedrosian I. , Gutierrez Barrera A. M. , Kuerer H. M. , Babiera G. , Mittendorf E. A. , Meric-Bernstam F.
Published: August 2020

1528

Background: Women with breast cancer have an increased risk of developing contralateral breast cancer in their lifetime. Thus increasing numbers of women have been electing to undergo contralateral prophylactic mastectomy (CPM) at the time of their initial breast cancer treatment. The objective of this study was to identify factors that determine the decision for CPM in patients at a major cancer center. Methods: 2,544 women with Stage 0-III unilateral primary breast cancer who underwent surgery to the breast at our institution from January 2000 to August 2006 were identified from a prospectively maintained database. Patient and tumor characteristics were evaluated and comparisons were made between patients who did or did not undergo CPM using logistic regression. Results: Of the 2,544 patients, 1254 (49.3%) underwent total mastectomy for their known cancer; 282 (22.5%) of these patients underwent immediate or delayed CPM. Overall, 171 patients (6.7%) had genetic testing; and the use of testing increased in the latter years of the study (3.% in 2000–2002 vs. 8.2% in 2003–2006, p<.0001). 49 of 171 patients had genetic testing prior to surgery. 10 had a deleterious BRCA1/2 mutation, 9 of whom had a CPM (p=.002). 14 patients without a mutation also had a CPM. Multivariate analysis revealed factors associated with use of CPM were: age younger than 50, white race, family history of breast cancer, higher clinical tumor stage, invasive lobular histology, and use of reconstruction (Table). Conclusions: Both patient and tumor characteristics influence selection of CPM. Although the use of genetic testing is increasing, most women elect to undergo CPM without having genetic testing. Evidence-driven models are needed to better inform women of their absolute risk of contralateral breast cancer as well as competing risk from their primary breast cancer in order to empower them in their active-decision-making.

[Table: see text]

No significant financial relationships to disclose.