bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docetaxel and cyclophosphamide as neoadjuvant chemotherapy in ER+ HER2- breast cancer.
Authors: Yagata Hiroshi , Yamauchi Hideko , Yoshida Atsushi , Hayashi Naoki , Kajiura Yuka , In Reika , Kitano Atsuko , Tsugawa Koichiro , Nakamura Seigo 
Published: March 2020

590 Background: Recently, docetaxel plus cyclophosphamide (TC) has been established as a standard regimen for adjuvant chemotherapy in operable breast cancer. However, the efficacy of TC as neoadjuvant chemotherapy remains unclear, especially in hormone-responsive breast cancer. We prospectively evaluated the response to TC neoadjuvant chemotherapy in patients with ER+ HER2- operable breast cancer. Methods: Eligible patients had ER+ and HER2- invasive breast cancer that measured more than 2 cm in diameter or was node-positive clinically between March 2009 and February 2011. Four cycles of TC (75 and 600 mg/m2) were administered intravenously every 3 weeks as neoadjuvant chemotherapy, followed by breast and axillary surgery. We investigated the clinical response on MRI and the pathological complete response (pCR) of primary invasive breast tumors. Results: We enrolled 43 patients in 45 lesions. Allred score of ER was 7 to 8 in 40 lesions, 6 in 3 lesions and 4 in 2 lesions. PgR was 7 to 8 in 31 lesions, 5 to 6 in 6 lesions, 3 to 4 in 5 lesions, and 0 in 3 lesions. Nuclear grade was 1 in 31 lesions, 2 in 7 lesions, and 3 in 7 lesions. MIB-1 index was median 22% (range, 6 to 71%) in 40 measurable lesions. Clinical response (CR and PR) was observed in 33 lesions (73%) and SD in 12 lesions without any lesions of clinical PD. pCR was achieved in only 1 lesions (ER 8, PgR 3, Nuclear grade 3, MIB-1 index 32.6%). Conclusions: Neoadjuvant TC produced a good clinical response in ER+ HER2- operable breast cancer, while the pCR rate was very low, regardless of the characteristics of cancer cells. Therefore, pCR is not an appropriate prognostic factor in women with ER+ HER2- operable breast cancer who receive neoadjuvant TC. Whether clinical response is related to survival should be addressed in future studies. The efficacy of neoadjuvant TC in ER+ HER2- operable breast cancer is very limited, and more effective regimens are needed to achieve higher pCR rates.
A short-term neoadjuvant pilot study comparing exemestane and letrozole in postmenopausal women with estrogen receptor-positive HER2-negative breast cancer.
Authors: Miura Daishu , Iwatani Tsuguo , Kawabata Hidetaka 
Published: March 2020

591 Background: Current approaches of neoadjuvant endocrine therapy (NAET) are focusing on biomarker analysis of the diagnostic specimens. One of the important things in neoadjuvant treatment is to determine the in-vivo responsiveness to the agent. Little is known regarding biomarker changes in specific agents and the association with biomarker changes and treatment duration. A pilot study was conducted to investigate the differences of biomarker changes in short-term NAET (letrozole vs. exemestane) and also the difference in treatment durations of each AI. Methods: Totally 120 samples from 60 postmenopausal women with ER positive HER2 negative stage 1-3 breast cancers in NAET comparing letrozole (LET) and exemestane (EXE) were analyzed with pre- and post-treatment mRNA expression of ERα, ERβ, PR, HER2, Ki67, PIK3CA, and MAPK using QuantiGene Assay. Thirty-one patients took letrozole 2.5mg daily and 29 did exemestane 25mg daily until the surgery (median duration 22 days). Statistical tests were two-sided. Results: Clinical characteristics were well balanced between the two treatment arms. Median % changes of Ki67 were -58%, ERα -44%, ERβ +93%, and PR -69% in LET and Ki67 -59%, ERα -30%, ERβ +135%, PR -72% in EXE. There were no significant differences of these marker changes between two agents. Dividing into 4 groups in treatment duration, 10-14 days (q1), 15-21 days (q2), 22-28 days (q3), and over 29 days (q4), LET had 2 peaks in Ki67 decreases (-69% (q1), -28% (q2), -78% (q3), -59% (q4)), whereas EXE had a peak in q2 (-62%, -77%, -49%, -26%). Ki67 increasing cases including primary resistance and tachyphylaxis were 5 (16%) in LET (3 in q2 and 2 in q4) and 3 (10%) in EXE (one of each in q2-4). All 8 cases had increases of ERβ, PIK3CA, and MAPK. Conclusions: Although both LET and EXE for short duration had significantly decreased Ki67 mRNA level irrespective of treatment duration, no significant differences was found between two agents. Tumor resistance with AIs may be associated with the other pathways.
Real-world aromatase inhibitor use and failure in women with metastatic ER+/HER2- breast cancer.
Authors: Landsman-Blumberg Pamela , Namjoshi Madhav , Thomson Erin , Johnson William 
Published: March 2020

593 Background: Aromatase Inhibitors (AIs) have replaced tamoxifen as first-line therapy for postmenopausal women with metastatic, ER+ breast cancer (BC). However, little information is available on the real-world use of AIs. The objectives of this retrospective claims study were to compare demographic, clinical and treatment characteristics of postmenopausal women with metastatic ER+/HER2- BC treated with AIs and experiencing 0, 1, 2 or ≥ 3 AI failures (AIF). Methods: Women ≥ 55 years old, newly diagnosed with metastatic BC (index) were identified in the 2006-2010 Thomson Reuters MarketScan databases and followed until chemotherapy or 03/31/2011. ER+/HER2- disease was defined as any endocrine therapy (ET: tamoxifen, fulvestrant) or AI (anastrozole, letrozole, or exemestane) use and no trastuzumab or lapatinib use in the 6-month pre-or variable post-index periods. Those with any post-index AI use were retained for study. AIF post-index was defined as a switch to an alternative AI, ET or chemotherapy, or AI discontinuation with no further BC treatment. Patients were stratified by number of post-index AIF: 0, 1, 2 or ≥ 3. Results: Among 4,274 patients identified, 61% had ≥ 1 AIF (1: 80%, 2: 15%, ≥3: 5%). There was no difference in pre-index AI use across AIF cohorts: 0, 1, 2, and ≥3 (54%, 52%, 48%, 56%; p=0.073). AIFs increased with Medicare-eligibility (51%, 56%, 60%, 61%) and bone metastases at index (48%, 53%, 62%, 63%). Among those with ≥1 AIF, median follow-up (FU) increased with each failure but there was no notable pattern to reason for FU end. Median FU of the 0 AIF cohort (408 days) fell between those of the 1 and 2 AIF cohorts, 335 and 517 days. Anastrozole was the most common first line treatment for all cohorts except ≥ 3 AIFs where letrozole was most common. Pre-index and first line fulvestrant use both increased with the number of post-index AIFs: 0.3%, 1.9%, 2.0%, 5.0% and 0.7%, 2.5%, 4.0%, 14.9% respectively. There was no association between number of AIFs and chemotherapy use (36%, 29%, 38%). Conclusions: Over 60% of women with ER+/HER2- metastatic BC treated with AIs failed at least 1 and 20% of those failed ≥ 2. Surprisingly, increased rates of prior fulvestrant treatment appear associated with increasing numbers of AIF.
Limited efficacy and significant toxicities of lapatinib (Lap) plus chemotherapy as neoadjuvant therapy (NAC) for HER2-positive inflammatory breast cancer (IBC) patients (Pts).
Authors: Alvarez Ricardo H. , Cristofanilli Massimo , Ensor Joe , Lucci Anthony , Yang Wei Tse , Le-Petross Huong T. , Reuben James M. , Babiera Gildy , Huo Lei , Gong Yun , Woodward Wendy A. , Parker Charla A. , Willey Jie S. , Buchholz Thomas A. , Ueno Naoto T. , Valero Vicente 
Published: March 2020

594 Background: IBC is a rare disease but the most aggressive form of locally advanced breast cancer with a higher frequency of HER2 neu amplification (HER2+) compared to non-IBC. The EGFR pathways are also important therapeutic targets in IBC. (Zhang D, 2009). Lap is an oral reversible dual kinase inhibitor of epidermal growth factor receptor of EGFR and HER2. Our objective was to determine the efficacy of Lap in combination with paclitaxel as NAC in pts with previously untreated HER2+ IBC. The primary end-point was to determine the rate of pathological complete response (pCR) defined as no residual invasive disease in the breast and the axillary lymph nodes or Residual Cancer Burden (RCB) of 0. (Symmans FW, 2008). The second endpoint was to assess general safety and cardiac toxicity of this combination therapy. Methods: From October 2008 to May 2011, 15 chemo-naïve pts were treated with Lap 1,250 mg/day as a single agent for 2 weeks, followed by 12 weeks of paclitaxel (80 mg/m2 weekly) plus Lap (1,000 mg/day), and finally with 4 cycles of FEC-75 mg/m2 regimen plus Lap (1,000 mg/day) before surgery. Among 12 first pts enrolled, 6 pts had grade 3 diarrhea (CTCAC v3.0) and the protocol was amended to reduce the Lap dose to 750 mg/day. After modified radical mastectomy (MRM), patients received radiation therapy and one year of adjuvant trastuzumab. Results: Median age was 53.8 (range, 39 -70), performance status was 0 (13 pts), 1 (2 pts), 4 pts had metastatic disease at diagnosis. 10 of 15 pts had MRM. One pt achieved pCR. Five pts did not complete the NAC due to grade 2 cardiomyopathy (1), liver dysfunction (2), diarrhea (1), and insurance denial after pt started treatment (1). The trial was stopped early due to severe toxicity (>15%) and lack of efficacy. Conclusions: Lap in combination with chemotherapy as NAC has a limited anti-tumor activity in pts with HER2+ IBC with a pCR rate of 6.6%. Lap and paclitaxel was associated with severe diarrhea toxicity and required multiple dose reductions of Lap. With the recent promising results in HER2+ NAC studies, the role of Lap should continue to be explored in combination with other anti-HER2 agents in IBC patients.
Neoadjuvant chemotherapy versus neoadjuvant hormonal therapy in postmenopausal women with ER-positive, HER2/neu negative locally advanced breast cancer.
Authors: Ambros Tadeu Frantz , Reis Isildinha M. , Bagga Dilprit , Villasboas Jose Caetano , Blieden Clifford , Sujoy Victoria , Wright Jean L. , Saigal Kunal , Fernandez Carmen Gomez , Hurley Judith 
Published: March 2020

595 Background: Postmenopausal women with large ER+/HER-2 negative tumors frequently receive neoadjuvant chemotherapy (NC), but pathological complete response (pCR) rates are low. Neoadjuvant hormonal therapy (NH) may offer benefit in this setting. Methods: Retrospective review of medical records from University of Miami/Jackson Memorial Hospital from 1998-2011. Primary outcomes: pCR (absence of invasive tumor in breast and lymph nodes at surgery), recurrence free survival (RFS) and tumor size reduction evaluated through comparison of palpable breast mass size at presentation with pathological tumor size in surgical specimen, and categorized as good response (GR) ≥ 30% reduction or no response (NR) < 30%. The Kaplan-Meier method and the log-rank test were used in the analysis of RFS. Results: Data from 151 post-menopausal women with ER+/HER-2 negative BC who received NC (57%) or NH (43%) was analyzed. Median follow-up among alive patients with no evidence of disease was 5.4 years in NC and 2.9 years in NH. Mean age was higher in the NH group (63.3 vs 56.1, p<0.0001). There were no racial or ethnic differences between the groups. Clinical stage was comparable in NC and NH (IIA 5.8% vs 9.2%, IIB 25.6% vs 20%, IIIA 37.2% vs 29.2%, IIIB/IIIC 31.4% vs 41.5%, p=0.775). Tumor histology was predominantly ductal in both groups (NC 85.7% and NH 78.5%, p=0.247). pCR was similar in NC and NH (4.7% vs 0%, p=0.078) along with RFS (median 8.5 yrs vs 6.0 yrs, p=0.946). In the NC group, GR was significantly more frequent (77.9% vs 60%, p=0.017). Among patients in the NH group, having GR was predictive of longer RFS (5-year rate 83.7% vs 50.5%, p=0.014). Breast only pCR occurred at equivalent rates between NC and NH (9.3% vs 3.1%, p=0.189) as did the absence of lymph node metastasis (29.1% vs 26.2%, p=0.606). In the NH cohort 38.5% received no adjuvant chemotherapy. Conclusions: NH provides an effective alternative to NC and, if there is a GR, may preclude the need for chemotherapy in over one third of postmenopausal women with large ER positive/HER-2 negative breast cancer.
Adjuvant lapatinib in women with early-stage HER2-positive breast cancer (HER2+ BC): Analysis of the hormone receptor-negative subgroup of the intent-to-treat (ITT) population of the TEACH trial.
Authors: Smith Ian Edward , Finkelstein Dianne M , O'Shaughnessy Joyce , Moy Beverly , Ejlertsen Bent , Kaufmann Manfred , Buzdar Aman , Fumoleau Pierre , Gradishar William John , Martin Miguel , Boyle Frances , Piccart-Gebhart Martine J. , Pritchard Kathleen I. , Lindquist Deborah , Rappold Erica , Williams Lisa Simone , Liedke Pedro E.R. , Chavarri-Guerra Yanin , Goss Paul Edward 
Published: March 2020

596 Background: TEACH is a randomized, double-blind, placebo (P)-controlled trial evaluating lapatinib (L) in reducing relapse risk in trastuzumab -naive patients (pts) previously treated with chemotherapy for HER2+ BC. The primary results (presented at SABCS 2011) showed a hazard ratio (HR) for disease-free survival (DFS) in L arm compared with P of 0.83 (95% confidence interval [CI] 0.70-1.00; stratified log-rank 2-sided P=.053). The predefined hormone receptor negative subgroup was analyzed, which in contrast to the hormone receptor positive subgroup of the ITT population (N=3147) had a significantly improved DFS. Methods: 3161 HER2+ BC pts (Stage I-IIIc) were randomized 1:1 to L daily or P for 1 year (yr). Primary endpoint was DFS in the ITT population. Central nervous system (CNS) recurrence rate was a secondary endpoint. A subgroup analysis by Cox Proportional Hazards Regression Models was performed for the hormone receptor negative pts from the ITT population. Results: 1288 pts (41%) comprised the hormone receptor negative subgroup of the ITT (L:639, and P:649). Median time from diagnosis to randomization was 2.4 (0.3-15) yrs, median follow-up was 4 yrs. Median age for this subgroup was 53 (24-87) yrs. With 85 events in L arm and 128 in P arm, the HR for DFS for hormone receptor negative pts was 0.68 (95%CI 0.52-0.89) favoring L. Most hormone receptor negative subgroups showed benefit for L: pts up to 1 yr from diagnosis (HR 0.64; 95%CI 0.41-0.99), node negative (HR 0.57; 95%CI 0.35-0.92), premenopausal (HR 0.59, 95%CI 0.37-0.94), and those who received prior anthracycline chemotherapy without taxanes (HR 0.63; 95%CI 0.43-0.92). Node positive patients had a trend to benefit from L (HR 0.74; 95%CI 0.53-1.03). CNS as one site of initial recurrence occurred in 1% in L (n=7) and P (n=8) arms. Conclusions: Lapatinib improved DFS in patients early or late in follow-up from diagnosis of HER2+, hormone receptor negative BC. Similar subset analyses are important in other large adjuvant anti-HER2 therapy trials. Results might provide a better understanding of the subtypes of HER2+ disease and help to further individualized therapy.
Adverse events with pertuzumab and trastuzumab: Evolution during treatment with and without docetaxel in CLEOPATRA.
Authors: Baselga José , Cortes Javier , Im Seock-Ah , Pivot Xavier B. , Clark Emma , Knott Adam , Ross Graham , Swain Sandra M. 
Published: March 2020

597^ Background: In CLEOPATRA, the HER2-dimerization inhibitor pertuzumab (P) was combined with trastuzumab (T) and docetaxel (D) in HER2-positive 1st-line MBC. P+T+D significantly improved efficacy compared with placebo (Pla)+T+D while having little effect on safety. Pts were recommended to receive ≥6 cycles of D but could discontinue D prior to Cycle 6 due to poor tolerability or progressive disease (PD) or continue D beyond Cycle 6 at investigators’ discretion. Once D was discontinued, pts received Pla+T or P+T until PD. To understand the full safety profile of the regimen, adverse events (AEs) occurring before and after D discontinuation were analyzed. Methods: Treatment was given q3w (Pla/P: 840 mg loading, then 420 mg; T: 8 mg/kg loading, then 6 mg/kg; D: 75 mg/m2, escalating to 100 mg/m2 if tolerated; de-escalation by 25% allowed). AEs were graded according to NCI-CTCAE v3.0, monitored continuously during the treatment period, and their relationship to study drugs was assessed by investigators. Results: From 808 pts enrolled, 804 were analyzed in the safety population (pts who received ≥1 dose of study treatment). AEs that led to discontinuation of all study treatment were experienced by 5.3% (Pla+T+D) and 6.1% (P+T+D) of pts, whereas discontinuation of D alone due to AEs occurred in 23.2% (Pla+T+D) and 23.6% (P+T+D) of pts. Conclusions: Treatment in both arms was well tolerated. After discontinuation of D, there was a clear reduction in grade ≥3 AEs; however, the incidence of grade ≥3 diarrhea remained slightly elevated with P+T+D. The AE profile of P+T is consistent with that seen in previous Phase II studies (Gianni Lancet Oncol 2012; Baselga JCO 2010). These data suggest that the combination of P+T may also be well tolerated in other breast cancer settings, such as in adjuvant therapy, which is currently under phase III study (APHINITY; NCT01358877). [Table: see text]
Oncologists' and primary care providers' awareness of late effects of cancer treatment: Implications for survivorship care.
Authors: Nekhlyudov Larissa , Aziz Noreen , Lerro Catherine C. , Virgo Katherine S. 
Published: March 2020

6008 Background: There is a growing population of cancer survivors, many of whom may experience late or long-term effects (LEs) of treatment. The goal of our study was to describe and compare primary care providers’ (PCP) and oncologists’ awareness of LEs. Methods: The Survey of Physician Attitudes Regarding the Care of Cancer Survivors was completed by a nationally representative sample of 1,072 PCPs and 1,130 oncologists (cooperation rate 65%). Respondents were asked to report for each of four standard chemotherapy drugs used to treat breast or colorectal cancer the five LEs they had observed and/or had seen reported in the literature. We described and compared the physicians’ responses and, using separate multinomial logistic regression models, determined predictors of their ability to identify the main LEs for all agents, adjusting for physician demographics and practice characteristics. Results: Almost all (95.3%) oncologists identified cardiac dysfunction as a LE of doxorubicin (Adriamycin), and peripheral neuropathy as LEs of both taxol (97.3%) and oxaliplatin (96.6%); while these LEs were identified by only 55.1%, 21.8% and 21.8% of PCPs, respectively. Most oncologists identified premature menopause (71.4%) and secondary malignancies (62.0%) as LEs of cytoxan, compared with only 14.8% and 17.2% of PCPs. Main LEs for all four chemotherapy drugs were identified by 65% (n=741) of oncologists and only 6% (n=60) of PCPs. In adjusted models, oncologists were more likely to identify the main LEs for all chemotherapy drugs if they spent 51-90% (OR 1.87, 95% CI 1.21-2.88) or >90% (OR 1.82, 95% CI 1.08-3.08) of their time on patient care, and less likely if they were not board certified (OR 0.58, 95% CI 0.37-0.89). African American PCPs were less likely to identify the main LEs for all chemotherapy drugs (OR 0.19, 95% CI 0.08-0.45). Conclusions: Oncologists often identified the main LEs of cancer drugs while PCPs did not. While not surprising, these findings emphasize that in the transition of patients from oncology to primary care settings, PCPs should be informed about the LEs of cancer treatment so that they may be better prepared to recognize and address these among survivors in their post-treatment care.
Impact of adjuvant trastuzumab-based chemotherapy in T1ab node-negative HER2 overexpressing breast carcinomas.
Authors: Frenel Jean-Sebastien , Rodrigues Manuel Jorge , Peron Julien , Yann-Alexandre Vano , Wassermann Johanna , Debled Marc , Picaud Francois , Albiges Laurence , Vincent-Salomon Anne , Cottu Paul H. 
Published: March 2020

601 Background: HER2 overexpression has been recognized as a pejorative prognostic factor in node negative T1ab (T1abN0) breast tumors. Randomized clinical trials have shown benefit of adjuvant trastuzumab-based chemotherapy (ATBC) for node-positive and/or greater than 1 cm (T1c or more) HER2+ breast carcinomas. There are no prospective efficacy data of ATBC in T1abN0 HER2+ tumors. Methods: We retrospectively evaluated 276 cases of T1ab node-negative HER2+ breast tumors in 8 French Comprehensive Cancer Centers. We assessed clinical, therapeutic features and outcome. We estimated the probability of disease-free survival (DFS), analyzed associations of ATBC, patient and tumor characteristics with DFS and prognosis factors using the log-rank test, multivariate analysis with logistic regression and Cox’s proportional hazards model. Results: Out of the 276 T1abN0 cases, 129 (47%) received ATBC (ATBC+) and 123 (45%) were not treated by either trastuzumab or chemotherapy (ATBC-). Of these 252 ATBC+ or ATBC- patients, decision of ATBC was associated with date of diagnosis (before or after ASCO 2005 Annual Meeting when interim results from three trastuzumab adjuvant trials were reported) and with poor prognosis features: negative hormone receptors (HR-) status, Elston-Ellis high grade, tumor size > 5 mm and age. With a median follow-up of 44 months 16 recurrences were observed (13 in the ATBC- group, 2 in the ATBC+ and 1 with adjuvant chemotherapy alone). Nine recurrences were distant metastases. A survival benefit in ATBC+ was observed with a 99% 40-months DFS versus 93% for ATBC- (logrank p-test = 0.018). In an exploratory analysis, two factors were significantly associated with worst prognosis for ATBC- that were not observed for ATBC+ : HR- status (98% 40-months DFS for ATBC+ patients versus 84% for ATBC- patients; logrank p-test = 0.0003) and presence of lymphovascular invasion (100% 40-months DFS for ATBC+ versus 73% in ATBC- cases; logrank p-test = 0.003). Conclusions: In our seriesATBC is associated with a significant reduction of risk of recurrence of T1abN0 HER2+ tumors. A clear DFS benefit of ATBC was observed in HR- tumors and/or in presence of lymphovascular invasion.
Do insurance status and neighborhood characteristics explain why minorities underutilize NCI cancer centers?
Authors: Huang Lyen C. , Ma Yifei , Ngo Justine V , Rhoads Kim F 
Published: March 2020

6010 Background: National Cancer-Institute (NCI) designated cancer centers provide some of the highest quality cancer care in the US, in part due to the availability of cutting edge technologies and access to cancer clinical trials. Racial/ethnic minorities suffer from persistent disparities in cancer outcomes, and these groups are typically under-represented in clinical trials. This may be due in part to under-utilization of NCI centers by these groups. Methods: A unique dataset linking the California Cancer Registry with California patient discharge abstracts was used to identify patients undergoing resection for a primary diagnosis of colorectal cancer (CRC) (1996-2006). Travel distance to treatment hospital was determined using GIS software. Chi-square analysis correlated patient demographics, clinical characteristics, insurance status, and neighborhood socioeconomics with NCI center use. Multivariable regression models were constructed to predict the likelihood of using an NCI center. Results: 95,994 CRC patients were identified. Median travel distance for care was <5 miles. Only 12,659 (13%) lived within a 5 mile radius of an NCI center; and of those, fewer than 10% used the center for CRC care (n=1130). Black (OR 0.83 95%CI 0.72-0.95) and Hispanic (OR 0.72 95%CI 0.65-0.81) patients were less likely than white patients to use NCI centers. Neighborhood socioeconomics, but not insurance status, were significantly correlated with NCI under-utilization. Asian populations were more likely to use NCI centers than white patients (OR 1.40 95%CI 1.28-1.54). Conclusions: Black and Hispanic patients are less likely to use nearby NCI hospitals for CRC care. Outreach efforts in communities with low socioeconomic status and educational attainment may increase use of NCI centers, improve CRC outcomes, and increase minority enrollment in clinical trials.