Abstract
Background: Inflammatory breast cancer (IBC) is the most aggressive form breast cancer. NST, followed by local therapy (surgery and radiation therapy), is considered the current standard ...therapy for IBC. Among noninflammatory breast cancers, sensitivity to NST differs based on ER and HER2 status. However, whether the sensitivity to NST also differs in primary IBC based on ER status or other prognostic factors has not been studied in a large cohort.
Methods: We retrospectively reviewed 1078 patients (pts) newly diagnosed with IBC from April 1989 to January 2011. Of these, 838 pts met our inclusion criterion of stage III disease at diagnosis, and 713 of these pts had received NST and surgery. Among this population, 545 pts had information available on both ER and HER2 status. We compared pathological complete response (pCR) rates (defined as no evidence of invasive disease in the breast and ipsilateral axillary limph nodes) and clinical characteristics between ER and HER2-status subgroups and analyzed their clinical outcome. We used the Kaplan-Meier method to estimate the median recurrence-free survival (RFS) after surgery and overall survival (OS), and the Cox proportional hazards regression model to test the statistical significance of potential prognostic factors in each group.
Results: Overall 177 pts had ER+HER2− tumors; 75, ER+HER2+; 134, ER-HER2+; and 159, ER-HER2−. NST consisted of anthracycline-based A alone, a taxane T alone or with A+T; HER2 targeting therapies (H) were administered to 117 patients with HER2-positive breast cancer after 1998. Overall pCR rate was 14.7%. pCR rates are shown by marker subtype and NST received in the table below. pCR rate, nuclear grade, vascular invasion, clinical response to NST, adjuvant treatment, radiation therapy, and adjuvant hormonal therapy differed significantly among subgroups.
The median RFS and OS for all patients was 19.2 and 33.2 months, respectively. In multivariate analysis, BMI, ER status, lymphatic invasion, radiation therapy, and pCR rate were associated with RFS, and ER status, vascular invasion, radiation therapy, and pCR rate were associated with OS. Except in the ER+HER2− group, pCR was associated with better prognosis compared to non-pCR. Adjuvant hormonal therapy improved RFS both in ER+HER2+ and ER+HER2− groups, but did not improve OS in the ER+HER2+ group. Among 209 patients with HER2+ IBC, 134 received HER2 targeting therapies in neoadjuvant or adjuvant chemotherapy, and had a trend to improvement in RFS compared to chemotherapy alone (p = 0.082). The ER-HER2− group showed poorest outcome compared to other subgroups (P < 0.001).
Conclusions: Sensitivity to NST differs depending on the ER and HER2 status in IBC pts. pCR rates based on these subgroups appear to be low. There is a need more effective treatments in the neoadjuvant and adjuvant therapies for all subgroups of IBC.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-10-05.
Micromechanical and electronic devices are a potential application for nanohoneycomb‐structured diamond films, which were produced by oxygen plasma etching with porous anodic alumina films as masks ...to give highly ordered hexagonal hole arrays with high aspect ratios. The high refractive index and high transparency of these structures make them suitable for photonic bandgap materials.
Scaling of an efficient and compact diode-end-pumped Nd:YAG laser was demonstrated by two-dimensional phase-locked arrays. The arrays of stable resonators were formed by multiple thermal lenses ...induced by the simultaneous end-pumping of laser-diode-coupled fibers. Because of partial overlap of each transverse mode, the output was phase locked. Various configurations of pumping fibers were tested to study phase locking. It was found that minimization of the coherently coupled intensity between adjacent array elements have good prediction for phase difference between modes. When the plane parallel cavity as long as 30 mm was pumped by 2*2 laser diode coupled fibers, phase-locked 1.8-W continuous wave 1.06- mu m output was obtained with 55% slope efficiency. 1.2-W single longitudinal mode output with single-lobe beam profile was obtained by using a spatial phase filter and the twisted mode method.< >
Recent studies have shown 70-80% of gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphomas regressing in response to eradication of Helicobacter pylori (H. pylori). Genetic mechanism of ...regression of gastric MALT lymphoma after H. pylori eradication remains unclear. To clarify the issue, we evaluated microsatellite instability (MSI) at 12 microsatellite loci in 15 patients with gastric low-grade MALT lymphoma, who received eradication therapy of H. pylori. H. pylori infection was observed in all the patients. After eradication therapy of H. pylori, patients were observed for a median of 21 months (range, 6-49 months). Eradication was achieved in all the patients. Nine of the 15 (60%) patients showed complete regression (CR), 3 (20%) partial regression (PR), and 3 (20%) no change (NC). MSI was detected in 3 of the 15 (20%) patients with low-grade MALT lymphoma. Compared with response to eradication therapy of H. pylori, MSI was detected in 1 of the 12 (8%) CR and PR patients, and in 2 of the 3 (67%) NC patients. Especially, MSI at D18S61 was detected in 2 of the 3 (67%) NC patients but in none of the 12 CR and PR patients. There was a significant difference between frequency of MSI at D18S61 in NC patients and that in CR and PR patients (p<0.05). These data suggest that MSI at D18S61 may be associated with lack of regression of gastric MALT lymphoma after H. pylori eradication.
Abstract
Background: The rate of pathologic complete response (pCR) to neoadjuvant systemic treatment (NST) of patients with a body mass index (BMI) of ≥25 has been reported to be significantly lower ...than that of patients with a BMI <25. However, only patients with a BMI of ≥30 have been found to have worse overall survival (OS) than patients with a BMI <25. Several studies have shown that an increasing body weight after surgery is a poor prognostic factor for OS. Whether a higher BMI after NST and before surgery truly predicts response to chemotherapy or outcomes remains unclear. We hypothesized that higher BMI will be associated with lower rates of pCR and long-term clinical outcomes. The purpose of this study was to determine whether a change in BMI from baseline to after NST and definitive surgery affects pCR and OS in patients with inflammatory breast cancer (IBC) or locally advanced non-IBC.
Material and Methods: We retrospectively reviewed the medical records of 263 patients with primary IBC and 865 patients with stage III non-IBC who underwent standard NST consisting of anthracyclines and/or taxanes with or without concurrent trastuzumab followed by definitive surgery at our institution between November 1, 2006, and December 31, 2012.
Results: The median follow-up time for survivors was 19.8 months (0.1-69.9 months). One hundred forty-five (55.1%) IBC and 566 (65.7%) non-IBC were hormone receptor-positive and 91 (34.6%) IBC and 198 (22.9%) non-IBC were human epidermal growth factor receptors (HER2)-positive. One hundred forty-four (54.8%) IBC and 446 (51.9%) non-IBC were postmenopausal. Of the 1128 patients included in the study, 223 (19.8%) achieved pCR, including 42 (16.0%) IBC and 181 (20.9%) non-IBC. The median change in BMI during NST of the patients who achieved pCR (0.1) was significantly higher than that of the patients who did not achieve pCR (-0.1; p = 0.04). The pCR rate of the patients whose BMIs had positive change post NST (23.2%) was higher than that of the patients whose BMIs were lower after NST (18.2%), but this difference was not significant (p = 0.054). Multivariate analysis did not reveal positive change in BMI post NST to be a significant predictor of pCR.
Univariate analysis with the log-rank test revealed that higher BMI change from pre NST as a categorical variable (BMI change >0 vs. ≤0) predicted increased OS in all patients (p = 0.005) and in IBC patients (p<0.001). After adjust for other clinical variables, none of the BMI-related measures (i.e., baseline BMI, BMI at surgery, and BMI change during NST) predicted OS. Although univariate analysis revealed that BMI change as a continuous variable predicted OS in IBC patients (p = 0.031), after adjust for other clinical variables BMI change no longer predicted OS. None of the BMI measures as continuous or categorical variables predicted recurrence-free survival.
Conclusion: In patients with stage III breast cancer, a higher BMI after NST than at baseline does not predict lower pCR rate or decreased survival after adjust for other clinical variables.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD2-4.
Abstract
Background: Very little is known about the survival of patients with inflammatory breast cancer (IBC) and distant metastasis. Furthermore, the American Joint Committee on Cancer ...classification of breast cancer does not recognize metastatic IBC as a distinct entity within stage IV. We hypothesized that the survival of patients with IBC and distant metastasis is worse than the survival of patients with stage-matched non-IBC.
Patients and Methods: We retrospectively reviewed 5314 consecutive patients with stage III or IV breast cancer (IBC or non-IBC) who were treated at our institution between 1986 and 2012. A total of 1079 patients presented with IBC (stage III: 861; stage IV: 218) and 4235 non-IBC (stage III: 2781; stage IV: 1454). We compared the time to distant metastasis from initial diagnosis, distant metastasis–free survival (DMFS), and overall survival (OS) in stage-matched patients with IBC or non-IBC.
Results: The median follow-up periods were 3.3 years for patients with stage III disease (range, 0-32.2 years) and 1.8 years for patients with stage IV disease (range, 0-19.9 years). The total number of recorded events (metastasis/death) was 1657 for stage III, while the numbers of deaths for stage III and IV were 1337 and 973, respectively. In patients with stage III, the time to distant metastasis was shorter in IBC than in non-IBC (median 1.3 vs. 1.7 years, P < .001). DMFS and OS were shorter in patients with stage III IBC than in those with stage III non-IBC (2.5 vs. 6.9 years, P < .001; and 4.7 vs. 8.9 years, P < .001; respectively). However, there was no significant difference in OS after development of distant metastasis between stage III IBC and non-IBC (median for both 1.3 years, P = .83). In multivariate analysis, the diagnosis of IBC remained significantly associated with mortality after adjusting for potential confounders. De novo stage IV IBC presented more frequently with multiple sites of metastasis than de novo stage IV non-IBC (P = .02). In patients with de novo stage IV disease, OS was shorter in IBC than in non-IBC (2.3 vs. 3.4 years, P = .004). In the multicovariate Cox model, while ethnicity, tumor grade, hormone receptor status and HER2 status, site of metastasis, number of sites of metastasis, and definitive breast surgery by 1 year were all significant factors in OS for stage IV breast cancer, the diagnosis of IBC conferred a hazard ratio of 1.33 (95% confidence interval: 1.05 - 1.69) in multivariate analysis.
Conclusion: Our findings suggest that IBC patients with metastasis at diagnosis have worse outcomes than stage-matched non-IBC patients. IBC patients presenting with de novo stage IV disease should be considered as a separate subcategory of stage IV in the tumor-node-metastasis classification because their clinical course and prognosis are different from those of patients with stage IV non-IBC.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-12-02.
Abstract
BACKGROUND: Pathological complete response (pCR) after neoadjuvant systemic chemotherapy (NST) is strongly associated with improved long-term clinical outcomes, even among the patients with ...inflammatory breast cancer (IBC). In this study, we examined the clinical factors determining long-term outcome in patients with IBC who did and did not achieve pCR.
METHODS: We identified patients with primary IBC treated with NST who received definitive surgery within 1 year and were evaluable for pathological tumor response, and whose hormone receptor and HER2 status was available at baseline. pCR was defined as no evidence of invasive cancer in the breast and ipsilateral axillary lymph nodes. We also investigated the relationship between clinical outcome and the ratio of positive to excised lymph nodes (lymph node ratio) in the non-pCR group. The Kaplan-Meier method was used to estimate disease-free survival (DFS) and overall survival (OS); groups were compared using the log-rank test. Multivariate Cox proportional hazards models were fit to identify predictors of DFS and OS.
RESULTS: Among 517 patients treated at MDACC between 1998 and 2011, 79 (15.2%) achieved pCR. A total of 50.3% had hormone receptor-positive disease, 37.5% had HER2-positive disease, and 26.3% had triple-negative disease. NST included an anthracycline and a taxane in 72.9% of the patients, an anthracycline only in 17.3% and others in 9.8%. A total of 83.7% of patients received adjuvant radiation therapy. The median follow-up period was 3.9 years in the pCR group and 2.4 years in the non-pCR group. Two-year DFS for pCR and non-pCR groups are 74% and 40%, respectively (p<.0001). In the pCR group, only triple-negative disease was significantly associated with decreased OS (P = 0.006) and DFS (P = 0.024). In the non-pCR group, high lymph node ratio, triple-negative disease, vascular invasion, and positive surgical margins were associated with decreased OS and DFS, and adjuvant radiation and hormonal therapies were associated with increased OS and DFS in the multivariate model. As shown in the table, increased lymph node ratios were associated with increased estimated hazard ratios for OS and DFS in the non-pCR group.
Relationship between node ratio increase and clinical outcome Hazard ratio (95% confidence interval)Increase in node ratio,%OSDFS101.07 (1.02-1.12)1.09 (1.05-1.14)201.15 (1.05-1.25)1.20 (1.11-1.29)301.23 (1.08-1.41)1.32 (1.17-1.48)401.32 (1.11-1.58)1.45 (1.24-1.68)501.42 (1.14-1.77)1.59 (1.31-1.92)
CONCLUSIONS: In patients who do not achieve pCR, high lymph node ratio and positive surgical margins predict poor outcome after NST. Use of an optimized tri-modality treatment plan (chemotherapy, surgery, radiation therapy) is important to achieve the best outcomes in patients with IBC; Surgery including total mastectomy with clear margins and axillary dissection to remove all nodal tissue are critical for achieving optimal clinical outcomes in IBC. Even in the pCR group, some patients with triple negative disease still had a poor prognosis suggesting a need for more effective systemic therapy such as innovative agents tailored to the Lehmann subtypes.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-12-03.
The aim of the present study was to examine the efficacy of the volume-adjusted prostate-specific antigen (PSA) density as a predictor of pathological stage. Among patients who underwent radical ...prostatectomy for clinically organ-confined prostate cancer, we selected patients with PSA levels of 4-10 ng/ml. In these patients with borderline PSA value extent of disease is most difficult to predict. Using the transition zone (TZ) volume instead of the total prostate volume, we compared the ability of PSA to predict the tumor extent.
From April 1992 to November 1996, we examined 61 consecutive patients who underwent radical prostatectomy. Their age ranged from 52 to 78 years. The PSA densities for the total prostate volume (PSAD) and for the TZ volume (PSAT) were calculated by transrectal ultrasound examinations. To compare the usefulness of PSA, PSAD, and PSAT, the area under the receiver-operator characteristic (ROC) curve was calculated for each parameter.
The final pathological stage was pT2N0M0 in 34 patients, pT3N0M0 in 20 patients, and pT3N1M0 in 7 patients. Accordingly, 34 patients (55.7%) had organ-confined prostate cancer. In patients with capsular perforation, the areas under the ROC curve were 0.686 for PSA, 0.665 for PSAD, and 0.860 for PSAT, while in those with seminal vesicle invasion the respective values were 0.712, 0.703, and 0.882. Thus, PSAT was superior to PSA and PSAD in differentiating extracapsular disease.
PSAT provides superior preoperative prediction of extracapsular tumor invasion, which appears to be useful in treatment selection (e.g. total prostatectomy).
High catalytic performance was achieved through the interligand hydrogen bonding interaction.
New asymmetric bis(oxazoline) (Box) ligand bearing amide group at the oxazoline 4-position, (
S,
...S)-2,2′-methylenebis(4-
tert-butylcarbamoyl-2-oxazoline) (
1S
), was designed and synthesized for selective catalytic reaction. The crystal structure of the ternary copper complex, consisting of
1S
and N-benzoyl-N-phenyl-hydroxylamine, demonstrated interligand interactions, such as hydrogen bonding and CH-
π interaction. Catalytic performance of the copper complex with
1S
was investigated for an asymmetric Diels–Alder reaction using benzylidene-2-acetylpyridine and 1,3-cyclohexadiene (CHD). The reaction product was enantio-pure endo-(pyridin-2-yl)(3-phenylbicyclo2,2,2oct-5-ene-2-yl)methanone (BPCD), of which crystal structure was analyzed by the X-ray method. No stereo- and enantio-isomer of BPCD was detected by chiral HPLC analysis. Introduction of hydrogen bonding site into
1S
can promote the Diels–Alder reaction even though using poor reactive CHD. Without
1S
, this reaction did not give any product. Addition of 2-propanol to this reaction system inhibited the formation of BPCD, indicating that the designed interligand interaction sites, especially hydrogen bonding, play an important role for catalytic performance.
