bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized phase II study of two doses of pixantrone in patients with metastatic breast cancer (N1031, Alliance).
Authors: Sideras Kostandinos , Moreno-Aspitia Alvaro , Tenglin Richard Charles , Liu Heshan , Lingle Wilma L. , Reinholz Monica Madden , Halling Kevin C , Chen Beiyun , Gross Gerald G. , Mowat Rex Bradford , Dakhil Shaker R. , Perez Edith A. 
Published: March 2020

1083 Background: Pixantrone (Pix) is a novel aza-anthracenedione with structural similarities to mitoxantrone and promising activity against non-Hodgkin’s lymphoma. Due to the lack of iron binding it is theorized to exhibit less cardiotoxicity than the anthracyclines. Methods: N1031 is a phase II RCT of 2 schedules of Pix, in pts with MBC. Group A pts received 180mg/m2 IV q3 wks, and group B pts 85mg/m2 IV on days 1, 8, 15 q4 wks. Eligibility included prior exposure to anthracyclines and/or taxanes, and 1 to 3 regiments in the metastatic setting (minimum of 2 if no prior adjuvant therapy given). Due to lack of long term cardiac safety data no more than 12 cycles were allowed. Frequent cardiac imaging was performed per protocol. Primary endpoint was RR and secondary endpoints included PFS, OS, safety, and QOL. Planned sample size was 25 pts per group. Results: In total 46 pts were evaluable (23 per group), mean age 55.5 yrs (range 38-79), 37% PS 0, 52% PS 1, and 11% PS 2. 80% of pts had prior exposure to doxorubicin, 72% had prior (neo)-adjuvant therapy, 76% were ER+ and 57% received prior HT. Number of prior metastatic regiments was: 1 (28%), 2 (61%) and 3 (11%). Most common adverse events (%) of any grade were: alopecia (74), anemia (74), fatigue (85), nausea (67), ANC decrease (87), and skin disorder (41). Grade 3-4 adverse events (%) at least possibly attributed to Pix and occurring in at least 2 pts were: ANC decrease (57), fatigue (9), increased AST (4%). One pt from each group (4%) had a grade 3 decrease in EF. There were no major differences between the two groups except for more oral mucositis in group A (35% vs 4%). Median number of cycles was 3 in group A (range 1-12) and 2 in group B (range 1-8). There was only 1 confirmed tumor response per group (4%,95% CI: 0.1-22%) prompting early termination of the trial. The median PFS was 2.7 mo (95% CI: 1.8-3.8), and the median OS was 8.9 mo (95% CI: 7.5-N/A). Conclusions: Pixantrone has insufficient activity in patients with MBC exposed to prior anthracyclines and/or taxanes. Adverse events were similar to prior experience with Pix. There were no major differences between the 2 schedules of administration. There was no significant cardiac toxicity seen in this trial. Correlative studies are underway.
Methallotionein expression and outcome in patients with metastatic breast cancer (MBC).
Authors: Rios-Perez Jorge Arturo , Abedin Sameem , Rosenzweig Margaret Quinn , Jung Su Yon , Bhargava Rohit , Brufsky Adam 
Published: March 2020

1085 Background: Platinum-based agents are important components of therapy of metastatic breast cancer (MBC) and triple negative breast cancer. Their use can be limited by development of resistance. Metallothioneins (MT) are low molecular weight proteins believed to bind bivalent metal ions such as platinum and zinc. MT expression has been associated with decreased survival in breast cancer patients. A proposed mechanism confers resistance to platinum-based agents by their inactivation or limitation of their activity by MT binding. Methods: MT expression in 99 women with MBC (selected at random from our database of 800 women with MBC) was determined from primary breast cancer tissue (n=80) or metastatic tissue n=19). MT expression was determined by immunohistochemistry, and graded as negative, weak, moderate or strong. Clinical data was obtained through our database and supplemented by chart review. Overall survival from breast cancer diagnosis (OS), progression free survival for first metastastic regimen (PFS), and time from first metastasis to death or last update (metastatic survival, MS), were calculated through December 2011 using the log rank test. Results: Consistent with prior studies, moderate to strong MT expression was associated with decreased 5-year OS (p=.03). There was no correlation between MT expression and PFS or MS in this cohort. Surprisingly, MT expression at any degree was strongly associated with better MS in patients with MBC that received carboplatin-based regimens in the first line (n=25, p=.0005) or at any line (n=41, p=.0437). Conclusions: Consistent with prior studies, MT expression was associated with decreased survival in patients with MBC. Surprisingly, MT expression was associated with longer MS in patients with MBC that received carboplatin. These findings are inconsistent with the hypothesis that MT expression causes chemoresistance to platinum based agents in patients with metastatic breast cancer. Further studies are needed to elucidate the mechanisms behind these findings.
Amrubicin as second- or third-line treatment for patients with HER2-negative metastatic breast cancer (MBC): A phase II trial of the Sarah Cannon Research Institute (SCRI).
Authors: Barton John H. , Raefsky Eric , Harwin William N. , Inclan Alejandro A. , Miletello Gerald , Hainsworth John D. , Burris Howard A. , Yardley Denise Aysel 
Published: March 2020

1086 Background: Anthracyclines demonstrate significant activity in breast cancer, but the potential for cardiotoxicity is dose-limiting. Amrubicin is a novel anthracycline with broad-spectrum preclinical activity and low potential for cardiotoxicity. We present phase II results from a phase I/II trial of amrubicin as second/third- line therapy for HER2- negative MBC. Methods: Women with measurable HER2-negative MBC with 1 or 2 prior chemotherapy regimens for metastatic disease and normal LVEF were eligible. Prior anthracycline- containing adjuvant therapy was allowed. Amrubicin 110 mg/ m2 IV every 3 weeks was administered until disease progression or intolerable toxicity. Tumor assessments were performed every 6 weeks and LVEF assessments every 12 weeks. The primary endpoint was progression free survival (PFS); a median PFS ≥ 4.5 months was considered a study result meriting further development of amrubicin. Results: 48 evaluable patients (pts) were treated from 1/2010 to 9/2011. Baseline characteristics included median age 57; 23% were triple-negative; 33% had 2 prior chemotherapy regimens for MBC; 38% had anthracycline- containing adjuvant therapy. Median treatment duration was 6 weeks (2 cycles), range 1- 12+ cycles. 8 pts (17%) had objective RECIST responses (1 CR, 7 PR); 5 of the 8 responders had received anthracycline-containing adjuvant therapy. 24 additional pts (50%) had stable disease at first reevaluation. The median PFS for all patients was 2.8 months (95% CI 1.6- 4.0 months); median PFS was similar for pts with 1 vs 2 previous regimens for MBC (95% CI 2.5 vs 4.0 months). 24% of pts were progression-free at 6 months. Neutropenia was the most common grade 3/4 toxicity (63%; 6% febrile neutropenia). No grade 3/4 non- hematologic toxicity occurred in > 5% pts. No cardiotoxicity occurred. Only 1 pt discontinued amrubicin due to toxicity (grade 2 fatigue). Conclusions: Amrubicin had good tolerability, no cardiotoxicity and was active as a second/third-line treatment for HER2- negative MBC, including pts previously treated with adjuvant anthracyclines. The median PFS was comparable to other standard single agents in the MBC setting.
Quantitative measures of FDG PET after neoadjuvant chemotherapy to predict breast cancer patient survival.
Authors: Currin Erin-Siobhain Ross , Dunnwald Lisa K , Doot Robert K , Schubert Erin K , Kurland Brenda F , Mankoff David A. , Specht Jennifer M. 
Published: March 2020

1088 Background: In patients with locally advanced breast cancer (LABC), qualitative FDG positivity following neo-adjuvant chemotherapy (NC) has been shown to be inversely associated with survival (Emmering, Annals Oncol, 2008). We investigated quantitative measures of post-therapy FDG uptake, namely standardized uptake value (SUV) and glycolytic flux (Ki), as predictors of breast cancer survival. Methods: Forty-seven patients with LABC underwent dynamic FDG PET scans close to or at the end of NC and prior to surgical resection. Post-therapy FDG uptake at the primary tumor site was measured by mean SUV from 45-60 minutes after FDG injection, maximum SUV (SUVmax) from 50-55 minutes, and FDG glycolytic flux (Ki). Pathologic response (PR) was assessed for at the time of surgical resection. Cox proportional hazards models were used to estimate associations between log-transformed measures of post-therapy FDG uptake, PR and outcome. Results: Median SUVmax was 1.9 (0.9 – 9.2) and median Ki was 2.2 (0.02 – 47.7) mL/min/g. Median follow-up for relapse was 5.7 years with 11 events and 6.3 years for survival with 10 deaths. PR was not significant for DFS (p = .39) or OS (p= .48). Post-therapy FDG uptake measures showed a statistically significant ability to predict survival. SUVmax predicted DFS (p=0.02) and OS (p=0.01). Ki was associated with DFS (p <0.01) and OS (p <0.01). PET measured hazard ratios were not attenuated in multivariate analysis controlling for known prognostic markers such as primary tumor PR and nodal status. However, multivariate survival models appeared highly influenced by one patient with the shortest survival time (1.3 years) and highest SUVmax and Ki. Without this patient, Ki remained a borderline independent predictor of DFS (p= .08) and OS (p= .07), but SUVmax was no longer significant for DFS (p= .32) or OS (p=0.26). Conclusions: Our analysis suggests that quantitative measures of post-therapy FDG PET provide information beyond PR for predicting which LABC patients are at highest risk for relapse and death. This information may be useful in directing post-surgery treatment. Supported by NIH grants CA42045, CA138293, and CA148131.
Is there a need for sentinel lymph node biopsy in microinvasive breast cancer?
Authors: Kapoor Nimmi S. , Shamonki Jamie , Yoon Jeong Lim , Chung Cathie T. , Giuliano Armando E. 
Published: March 2020

1105 Background: There is limited data on the long-term outcome of patients with microinvasive breast cancer. Moreover, predictors of lymph node involvement and the impact of multifocal microinvasion are not well understood. We examined the occurrence of nodal metastasis and the significance of multifocality on disease recurrence. Methods: Patients with T1mic breast cancer, defined as tumors ≤1mm, surgically managed at our institute between 1995-2010 were identified. Specimen slides were independently reviewed. Multivariable analysis (MVA) was used to predict lymph node involvement and disease recurrence. Results: Fifty-two patients with T1mic breast cancers were identified. Median patient age was 53 (range 30-92), median size of in-situ disease was 3cm (range 0.1-12cm). Ten patients (19.2%) had multiple foci of microinvasion (range 2-7). The majority of tumors were high-grade (76.9%). When the invasive tumor component was evaluated, 31 of 41 (73.8%) were ER positive, 40.5% were HER2+(15/37), and only one was ER-/PR-/HER2-. Twenty-nine patients (55.8%) had breast conserving surgery and 23 had mastectomies. Lymph nodes were assessed in 48 patients; there was 1 macrometastasis (2.1%), 4 micrometastases (8.3%) and 4 (8.3%) with isolated tumor cells. Seven of 9 patients with lymph node involvement underwent adjuvant chemotherapy. Univariable analysis showed that ER(-) invasive disease and high-grade DCIS tumors were more likely to have involved lymph nodes. On MVA, only negative ER status was a significant predictor of lymph node metastasis (p<0.02). At median follow-up of 83 months (range 6-172 months), 3 patients (6.3%) had disease recurrence (1 local, 1 distant, 1 local and distant) at 8, 17, and 130 months from presentation. All patients with recurrence had negative lymph nodes and only one focus of microinvasion. No factors predicted disease recurrence. Conclusions: Microinvasive breast cancer clearly has the ability to metastasize and recur, but in this series only 2% of patients presented with nodal macrometastasis. The evaluation of lymph nodes in T1mic cancer is unnecessary in the majority of patients. In our cohort, neither lymph node status nor multifocal microinvasion predicts recurrence.
Post-neoadjuvant chemotherapy sentinel node biopsy and axillary sampling for node negative (N0) axilla.
Authors: Parmar Vani , Nair Nita S. , Hawaldar Rohini W , Vanmali Vaibhav , Prabhu Aruna Laxman , Kaushik Rucha Vishal , Shet Tanuja , Desai Sangeeta , Badwe Rajendra A. 
Published: March 2020

1108 Background: Post neoadjuvant chemotherapy (NACT) sentinel node biopsy (SNB) is not a standard of care due to the wide variability in false negative rate (FNR), varying from 5.7% to 33%. In operable breast cancer (OBC), FNR of less than 10% is acceptable. We attempted to find out the reliability of low axillary sampling(LAS), with dissection limited below the first intercostobrachial nerve, to correctly identify the node negative axilla in the post NACT clinically node negative (N0) patients. Methods: Women with large operable (LOBC) and locally advanced breast cancer (LABC), post-NACT clinically N0, underwent concomitant blue dye-colloid guided SNB and LAS. The identification rate, FNR, and negative predictive value (NPV) of both procedures were compared. Results: Post-NACT 209 eligible women underwent combined LAS and SNB procedure. At presentation, the tumors were large (median 5.0 cm) with 70% clinically palpable nodes. All patients received 4 cycles of neo-adjuvant anthracycline-based chemotherapy and were clinically node negative after chemotherapy. SNB was defined as blue and/or hot node plus palpable node(s). A blue or hot node (median 2 nodes) was identified in 93.8%, and median of 5 sentinel nodes were removed. The false negative rate of SNB was 15.3% (95% CI 8.7%-25.3%). The LAS technique comparatively had nodal yield in 98.5% with median 8 nodes removed; and FNR 8.5% (95% CI, 4.2%-16.6%, p=0.19). Comparative NPV for LAS and SNB were 94.6% and 91.8% respectively. Conclusions: Axillary sampling results for FNR and NPV are similar if not superior to SNB and could be a reliable method of axillary nodal evaluation in advanced breast cancers following neo-adjuvant chemotherapy.
Magnetic resonance imaging (MRI) evaluation of pathologic complete response (pCR) in different breast cancer subtypes after neoadjuvant chemotherapy (NAC).
Authors: Gonzalez-Cortijo Lucia , Hornedo Javier , Sainz de la Cuesta Ricardo , Hernandez-Cortes Gines , Perez-Carrion Ramon , Gonzalez Federico , Acevedo Agustin , del Cerro Elia , Linares Susana , Maldonado Antonio , Cabrera Antonio , Counago Felipe , Diaz-Gavela Ana , Rodriguez-Marquez Cristina , Henriquez Alexandra , Murillo Raquel , Martin del Yerro Jose Luis , Sanz Ignacio , Recio Manuel , Martinez de Vega Vicente 
Published: March 2020

1111 Background: MRI is being used to address treatment response to NAC in breast cancer patients. However, its ability to predict pCR in histologically different tumors remains unclear. We tried to investigate the usefulness of MRI in evaluation of pCR in different breast cancer subtypes after treatment with NAC. Methods: Serial MRI studies were acquired before, during and after NAC in 75 evaluable patients. MRI interpretation included lesion size, morphology and dynamic enhanced evaluation imaging with initial and late enhancement. On the basis of the final MRI, response was determined to be a clinically complete response (CCR) when no residual tumor and no late enhancement were found. By using inmunohistochemistry and fluorescence in situ hybridization (FISH) for human epidermal growth factor receptor 2 (HER2/neu) amplification, tumors were divided into three subtypes: triple negative, HER2 positive, and estrogen receptor (ER) positive/HER2 negative. Every patient received chemotherapy with taxanes and anthracyclines and HER2 positive tumors were treated with trastuzumab. All patients received surgery. pCR was defined as no residual invasive tumor in the surgical specimen. Ductal carcinoma in situ residual disease was considered pCR. Results: 22 of 75 patients (29%) achieved a CCR on the final MRI. Of 22 patients with CCR all 22 (100%) were confirmed pathologically. 19 were pathologic complete responses and 3 showed in situ microscopic residual disease. 12 (55%) were HER2 positive tumors, 4 (18%) were triple negative tumors and 6 (27%) were ER positive/HER2 negative tumors. The negative predictive value of MRI for predicting pCR after NAC was 100%. Conclusions: Absence of both residual tumor and late enhancement in MRI predict pCR with high accuracy in triple negative, HER2 positive and ER positive/HER2 negative breast cancer after NAC.
Comparison of long-term results of endoscopic video-assisted breast surgery (VABS) between transaxillary retromammary approach (TARM) and periareolar approach.
Authors: Yamashita Koji , Haga Shunsuke , Shimizu Kazuo 
Published: March 2020

1112 Background: The breast conserving surgery (BCS) and the sentinel node (SN) biopsy became to be recognized as the standard treatment for early breast cancers. We have reported about cosmetic effectiveness and lower infestation of the video-assisted breast surgery (VABS) for the breast diseases. We devised the trans-axillary retro-mammary (TRAM) approach of VABS. It needs only one skin incision in the axilla and can treat any tumor of the breast without making any injuries on the breast skin. We evaluated the aesthetic results and the curability of this surgical method. Methods: We have performed VABS on 300 patients since December, 2001. The newly devised TARM was performed on 120 patients of early breast cancer, stage I and II. After endoscopic SN biopsy, we elongated the axillary skin incision to 2.5 cm. We dissected major pectoral muscle fascia to detach retromammary tissue behind the tumor. We cut the mammary gland with clear surgical margin, and removed it through the axillary port. The breast reconstruction was made by filling absorbable oxydized cellulose. The postoperative aesthetic results were evaluated by ABNSW. Results: BCS was performed on 286 patients (26 after preoperative chemotherapy) and skin-sparing mastectomy on 14. There was no serious complication after surgery. Surgical margin was minimally positive in 2. The original shapes of the breast were preserved well. The follow-up is 126 months at maximum and 74 months on average. There is 3 locoregional recurrences and 14 distant metastases. 5-year survival rate is 97.3%. With regard to TARM, The skin incision only in the axilla made better looks and shapes of the breast. It could be applied for tumors in any area of the breast without tumor nipple extension. The reconstruction with oxidized cellulose needs no excessive detachment of the skin beyond the surgical margin. The postoperative esthetic results were excellent and better. The sensory disturbance was minimal. All patients expressed great satisfaction. Conclusions: VABS can be considered as a good surgical procedure concerning locoregional control and esthetics. TARM is better on the patients without tumor nipple extension.
Predictors of recurrence in postmastectomy patients with one to three positive lymph nodes.
Authors: Moo Tracy-Ann , McMillan Robert , Lee Michele , Stempel Michelle , Patil Sujata , Ho Alice Y. , El-Tamer Mahmoud 
Published: March 2020

1118 Background: Although the role of post mastectomy radiation therapy (PMRT) is well established in women with ≥ 4 positive axillary lymph nodes (ALN), its indications in patients with 1-3 positive ALN is controversial. A recent large meta-analysis suggested a survival benefit in patients with 1-3 positive ALN who received PMRT. However, because recurrence rates in this group are low, identifying a subgroup of patients at higher risk for locoregional recurrence (LRR) could aid decision-making about PMRT. Methods: From an institutional database, 1,333 breast cancer patients who underwent mastectomy between 1996 and 2006 and had 1-3 positive ALN were identified. Among these, T3/T4 tumors and those who received PMRT were excluded. 926 patients were analyzed. The Kaplan-Meier method and Cox regression was used to explore clinicopathologic features that predicted LRR, distant metastases (DM), and recurrence-free survival (RFR). Results: Median follow-up was 7yrs. LRR occurred in 49 patients and DM in 126 patients. LRR and/or DM occurred in 146. On univariate analysis, factors significantly affecting LRR recurrence were increasing tumor size (p=0.04), age <50 (p=0.003), histologic grade (p=0.03), nuclear grade (p=0.008), lymphovascular invasion (LVI) (p<0.0001), and macroscopic ALN metastases (p=0.02). On multivariate analysis, age <50 (p=0.0012) and the presence of LVI (p<0.0001) predicted a higher LRR; increasing tumor size (p=0.0005), age <50 (p=0.04), higher histologic grade (p=0.01), number of positive ALN (p=0.04), LVI (p=0.02), macroscopic ALN metastases (p=0.02), and no chemotherapy (p=0.02) predicted a significantly lower RFR. Conclusions: Pts with T1-2 tumors and 1-3 positive ALN are at low risk of isolated LRR; however, patients <50 and with LVI may have additional risk that warrants consideration of PMRT.
Overuse of sentinel lymph node biopsy with breast conserving surgery for clinical DCIS.
Authors: Jones Natalie Beckman , Ottesen Rebecca A , Niland Joyce C. , Breslin Tara M. , Weeks Jane C. , Hughes Melissa E , Agnese Doreen Marie , Edge Stephen B. 
Published: March 2020

1125 Background: The National Comprehensive Cancer Network (NCCN) guidelines recommend against sentinel lymph node biopsy (SLNB) for ductal carcinoma in-situ (DCIS) treated with breast conservation surgery (BCS). SLNB is appropriate with mastectomy because it precludes subsequent SLNB if invasive cancer is identified. However, SLNB is commonly performed with BCS for DCIS. We hypothesize SLNB use in the setting of BCS for DCIS varies and may be over used in some cancer centers. Methods: We examined 6,070 cases with initial biopsy showing DCIS presenting to 13 institutions participating in the NCCN Breast Outcomes Database from 1998-2009. Receipt of SLNB was defined as SLNB performed at any point in primary treatment for those with a final diagnosis of DCIS or at the first surgical procedure for those upstaged to invasive cancer. Characteristics of patients who did and did not have SLNB were compared using Chi-square tests. Logistic models adjusting for clinical and pathologic variables were performed to assess factors associated with use of SLNB. Results: Of 3,725 treated with BCS, 778 (20.9%) had SLNB. Among 2,345 treated with mastectomy, 1,484 (63.3%) had SLNB. Within BCS, patients presenting with clinical symptoms (vs. screening detected) were more likely to have SLNB (p=0.0006, OR: 1.76; 95% CI 1.31-2.36). For both groups, presence of comedo necrosis, year of diagnosis, and treating institution were predictors of SLNB (p<0.0001). 1,171 (19.3%) were upstaged from DCIS at initial biopsy to invasive cancer on final pathology. 212 (18.1% invasive cancer group) had positive nodes. Use of SLNB increased over time from 1998-2009 in mastectomy group. Among BCS group, SNLB use decreased over the first half of the study period and then remained stable at approximately 15% across all centers. Conclusions: Although use of SNLB has decreased over time, a substantial percentage of patients undergoing BCS for DCIS receive SNLB. Practices vary considerably across centers. SLNB can be performed as a second procedure for those treated with BCS and identified with invasive cancer, thereby avoiding unnecessary risk of significant morbidity. Breast programs should review their practices to curtail the use of unnecessary surgery for women with DCIS.