bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docetaxel and cyclophosphamide as neoadjuvant chemotherapy in HER2- primary breast cancer.
Authors: Nakatsukasa Katsuhiko , Taguchi Tetsuya , Koyama Hiroshi , Imanishi Seiichi , Sakaguchi Kouichi , Hujita Yoshihumi , Oouchi Yoshimi , Oohashi Mahiro , Okamoto Akiko , Hamaoka Asako , Sugimoto Riho , Tomita Hitomi , Hujiwara Ikuya , Hukuda Kenichirou , Morita Midori , Matsuda Takayuki , Kotani Tatsuya , Kawakami Sadao , Kadotani Yayoi 
Published: February 2017

141 Background: Recently, docetaxel plus cyclophosphamide (TC) has been established as a standard regimen for adjuvant chemotherapy in HER2- operable breast cancer. However, the efficacy and tolerability of TC as neoadjuvant chemotherapy (NAC) remains unclear. We performed a prospective study of TC NAC in HER2- primary breast cancer. Methods: Eligible patients had HER2- invasive breast cancer that measured more than 1cm, less than 7cm and N0~N1 clinically between July, 2011 and February, 2014. Four cycles of TC(75 and 600 mg/m2) were administered intravenously every 3 weeks as NAC. We investigated the pathological complete response(pCR) of primary breast tumors. pCR was defined as no histological evidence of invasive carcinoma, or the appearance of only ductal carcinoma in situ. The cut-off value of Ki67 index between luminal A and luminal B was defined 20%. Results: We enrolled 52 patients. The completion rate for 4 cycles of TC was 94.2% ( 49 of 52). Relative dose intensity was 99.1% for TC therapy. Forty nine patients were classified according to breast cancer subtype before the estimation. Overall pCR rate was 16.3 %( 8 of 49 ) . pCR rate for patients with luminal A ( ER+, Ki67 low and HER2- ), luminal B ( ER+, Ki67 high and HER2- ) and triple negative ( ER- and HER2- ) were 0%( 0 of 12 ), 4.3 %( 1 of 23 ) and 50.0 %( 7 of 14 ), respectively pCR was achieved in almost triple negative patients. Conclusions: The pCR rate of TC was not so high, regardless of the high completion rate. In this study, TC was effective against triple negative subtype, showing a high pCR rates, compared with luminal subtype. In conclusion, the efficacy of TC NAC in HER2- primary breast cancer is limited, and triple negative subtype might be the good target. Clinical trial information: UMIN000013261.
Evaluation of risk factors associated with denosumab induced hypocalcemia.
Authors: Trevino Manllo Sergio Alberto , Khalon Pushpinderdeep , Thind Ravneet , Bhatia Roma , Ali Haythem Y. 
Published: February 2017

144 Background: Denosumab is a monoclonal antibody that neutralizes RANKL preventing osteoclast activation. It has been shown to be superior to zoledronic acid in preventing skeletal-related events in breast cancer with bone metastases. Hypocalcemia has been reported as a common side effect. The aim is to evaluate the risk factors associated with denosumab induce hypocalcemia. Methods: Retrospective study in which 144 charts were reviewed. Baseline characteristics: age, gender, race, type of cancer, calcium, phosphate, vitamin D, PTH, creatinine levels, GFR and corrected calcium were obtained. Tumors were classified in hormone sensitive versus non-sensitive. Charts were reviewed to evaluate for the development and severity of hypocalcemia as defined by the international review criteria. A multivariant analysis to evaluate the relationship between hypocalcemia and the variables of interest was done. Results: Hypocalcemia was observed in 71 of 144 patients. Grade 2 hypocalcemia was the most common. Significantly lower levels of GFR at baseline were detected in patients withhypocalcemia. Hormone responsive tumors were significantly less likely to develop hypocalcemia. Conclusions: Despite adequate supplementation of vitamin D and calcium, hypocalcemia is a common side effect of Denosumab. Careful monitoring of calcium levels is necessary especially in chronic kidney disease and hormone insensitive tumors. [Table: see text]
Impact of chemotherapy and radiation therapy on local control and survival of metastatic breast cancer to the brain: Single-institution review of 792 cases.
Authors: Bugano Diniz Gomes Diogo , Deeba Rita Elias , Valero Vicente , Moulder Stacy L. , Arun Banu , Alvarez Ricardo H. , Hsu Limin , Ibrahim Nuhad K. 
Published: February 2017

146 Background: There are various treatment modalities for metastatic breast cancer to the brain (MBC-b), with wide variation of reported outcomes. Methods: There were 1,513 patients (pts) with MBC-b treated at MD Anderson Cancer Center October 2009-December 2012. We reviewed medical records of the first consecutive 1015 and included 792 with confirmed brain metastases (BM). A Cox multivariate model was used to identify the effect of treatment on time-to-progression in the brain (TTP-b) and overall survival (OS). Results: Disease subtypes: ER+/HER2- (27%); ER+/HER2+ (16%); ER-/HER2+ (18%); ER-/HER2- (29%), missing (10%). Number of BM: 1 (20%), >1 (73%), missing (7%). Local treatment: metastasectomy (S) (13%), radio-surgery (SRS) (12%), whole-brain radiation (WBRT) (57%), combination of S/SRS with WBRT (11%), no treatment (7%). Systemic treatment: Any (64%), HER2 directed (24%). Median OS was 11.33 months(m) (4.4-25.8). Clinical characteristics associated with OS in multivariate analysis: ER+, HER2+, age < 60, ECOG 0-1, single BM, controlled systemic disease at time of BM and <3 treatment lines before BM. After correction for covariates, use of systemic therapy was associated with longer OS (HR 0.35 CI 0.20-0.60, p < 0.001) regardless of subgroup: HER2+ (19.9 vs 3.5m), ER+/HER2- (12.7 vs 2.2m), ER-/HER- (10.5 vs 2.3m). In pts receiving trastuzumab at diagnosis of BM, continuation of HER2 therapy increased OS (HR 0.44 CI 0.25-0.77, p = 0.004) regardless of agent used (lapatinib vs trastuzumab p=0.7). OS was the same for S and SRS (p=0.7) and either one increased OS (HR 0.41 CI 0.21-0.79 p=0.008). WBRT prolonged OS in multiple BM (HR 0.61 CI 0.38-0.96); Median TTP-b was 11.07m (5-24). WBRT added to S/SRS had longer TTP-b than either modality alone (17.6m vs 10.4m HR 0.56 CI 0.37-0.85 p=0.006). Use of systemic therapy after diagnosis of BM increased TTP-b (11.8 vs 5.1m HR 0.55 CI 0.33-0.92 p = 0.024), but there was no difference between agents used (lapatininib vs trastuzumab p=0.79; capecitabine vs others p= 0.96). Conclusions: WBRT improved local control when done after S/SRS. The use of chemotherapy after local therapy improved time to progression in the brain and survival.
Subsequent endocrine therapy after resistance to ethinylestradiol treatment for the late-stage metastatic breast cancer: A retrospective cohort study.
Authors: Yamashita Toshinari , Yamamoto Yutaka , Ibusuki Mutsuko , Inao Touko , Hayashi Mitsuhiro , Sueta Aiko , Takeshita Takashi , Kuroi Katsumasa , Iwase Hirotaka 
Published: February 2017

148 Background: Aromatase inhibitor (AI) is a most commonly used as the endocrine therapy in postmenopausal hormone-dependent breast cancer. Paradoxically, estrogen additive therapy using ethinylestradiol can be useful after long-term estrogen deprivation therapies with AI. Furthermore, there is a possibility of the beneficial effect of AI or fulvestrant as a subsequent endocrine therapy after EE2 failure. Methods: Ethinylestradiol (EE2; 3mg/day, TID) therapy was performed in 20 patients with metastatic breast cancer (median; 62 years-old, the mean observation time: 13.6 months.), who were heavily treated by sequential endocrine therapies (3rd or more line) including cytotoxic chemotherapies. We examined the efficacy of a subsequent endocrine therapy of AI or fulvestrant after becoming resistance to the EE2 therapy in the patients who got the disease control by the prior EE2 therapy. The primary endpoint was clinical benefit rate (CBR) and the secondary endpoint was time to treatment failure (TTF). (Registration number; UMIN 000002831, additional analysis). Results: Median TTF of EE2 treatment was 46 weeks (23-62+, 2 cases were ongoing). The response rate was 41% (9/22), the clinical benefit rate was 50% (11/22). The stable disease (< 6 months) was 18% (4/22) and another 3 cases were judged as progressive disease. Four cases withdrew due to nausea, fatigue and muscle-skeletal pain. In 20 cases progressed after disease control (SD or more) of EE2, a subsequent endocrine therapy, fulvestrant for 10 cases and AI for 10 cases, was performed. Fulvestrant group showed 50% (3 in 6) of CBR and 15 weeks (5-55+) of TTF, and AI-treated group showed 43% (3 in 7) of CBR and 19 weeks (5-33+) of TTF. Two in three cases, who became resistance to anti-estrogen treatment, got long SD by further EE2 re-therapy. Conclusions: Some cases showed clinical benefits of a subsequent therapy by AI or fulvestrant after becoming to EE2 failure. Taken together, sequential use of estrogen and anti-estrogen therapy (vice versa) could be one of the options as a salvage endocrine therapy for the patients with end-stage breast cancer.
Feasibility study of TS-1 additional therapy for the triple-negative breast cancer received neoadjuvant or adjuvant chemotherapy (SBCCSG14).
Authors: Futsuhara Kazushige , Inoue Kenichi , Nagai Shigenori E. , Saito Tsuyoshi , Sakurai Takashi , Kimizuka Kei , Kurozumi Masafumi , Tabei Toshio , Yamada Hirofumi , Kojima Masato , Hata Satoshi , Yamazaki Yasuo ,   Saitama Breast Cancer Clinical Study Group
Published: February 2017

162 Background: Prospective randomized clinical trials have demonstrated a significant advantage from postoperative adjuvant chemotherapy for patients with breast cancer. However, triple-negative breast cancer is high rate of early recurrence. Therefore, patients who do not achieve pathological complete response (pCR) for neoadjuvant chemotherapy have worse long-term survival than patients who achieve pCR. Treatment after adjuvant chemotherapy and neoadjuvant chemotherapy is not established yet. We notice that TS-1 improve early recurrent rate of breast cancer. TS-1 proved good response for advanced breast cancer and long-term therapy is possible. We planned the study for the purpose of inspecting it about the safety, completion and efficacy of giving TS-1 after standard therapy of triple negative breast cancer for one year. Methods: The patients with stage ±/II/ III triple negative breast cancer received neoadjuvant or adjuvant chemotherapy and surgery and/or radiotherapy. Furthermore, the cases of neoadjuvant chemotherapy did not achieved pCR. After that, dose of TS-1 is 80mg/m² administered orally daily for 2 weeks followed by a 1-week rest period given as 3-week cycles. Results: 63 patients were enrolled, including 44 patients received neoadjuvant chemotherapy and 19 patients received adjuvant chemotherapy. The average age is 50 years (28-68 years). 38 cases (60.3%) brought oral administration for one year to completion. The reasons of discontinuance were 15 cases of toxicity and 10 cases of recurrence. Average relative dose intensity was 80%. The compliance of TS-1 was 70.1% (222.4 days). Overall survival of 3 years was 86.47%, progression-free survival 50.8%. The overall incidence of toxicity was 54 cases (85.7%), and grade 3 toxicity occurred in 21 cases (33.3%). Conclusions: The compliance of TS-1 was approximately equal to the compliance for gastric cancer in spite of receiving treatments of anthracycline and/or taxane. The toxicity was approximately equal to the results for metastatic breast cancer. TS-1 administered orally for one year was feasible for triple negative breast cancer received standard therapy. Clinical trial information: UMIN000001414.
HER2Δ16 expression in HER2-positive breast cancer.
Authors: De Yao Jocelyn Torres , Sun Danyu , Galehouse Donna , Shorten Scott , Haller Nairmeen Awad , Rehmus Esther Hoogland 
Published: February 2017

31 Background: HER2Δ16 isoform was detected in breast cancer and showed similar increased transforming activity to somatic mutation or deletion activated rat HER2 oncogene with 89% of HER2-positive breast cancer with this mutation developing local lymph node positive disease progression. This is the first study characterizing and determining the prevalence of HER2Δ16 isoform in patients from a NAPBC-accredited cancer center. Methods: 95 HER2-positive breast cancer tissue samples from 2002 to 2008 were obtained from Akron General Medical Center. Total RNA from cancer cells were isolated and RT-PCR was performed using primers to amplify the wild-type HER2 and HER2Δ16 isoform. DNA products from RT-PCR were then loaded in agarose gel electrophoresis with the HER2Δ16 isoform band being shorter compared to the wild type HER2. Results: Preliminary results from our ongoing study showed 39% (12 of 31) of our HER2 samples has HER2Δ16 isoform. Out of the 12 HER2Δ16 isoform samples, 17% are Stage I, 50% are Stage II, 25% are Stage III, and 8% are Stage IV breast cancer at diagnosis. Patient age ranges from 34 to 87, with 50% of the HER2Δ16 isoform patients having lymph–node positive disease at the time of diagnosis. This is in contrast to patients with HER2 wild type for which 26% (5 of 19) are diagnosed with Stage I disease and 42% have lymph node positive disease at the time of diagnosis. Conclusions: Transgenic mice that overexpressed rat HER2 oncogene with small extracellular domain deletion promoted transforming activity of this protein. HER2Δ16 isoform is detected in 39% of HER2 positive breast cancer based on our preliminary results with 50% having lymph node–positive breast cancer on initial diagnosis. Immunohistochemistry and FISH could not distinguish the wild type HER2 from the HER2Δ16 isoform. Further study is recommended for possible prognosticating utility of HER2Δ16 isoform in breast cancer.
The DCIS score: Potential for health care savings?
Authors: Young Rebekah , Kalnicki Shalom , Fox Jana Lauren 
Published: February 2017

35 Background: The Oncotype Dx Recurrence Score for DCIS (DCIS Score) is a 12-gene assay derived from the original Oncotype DX test. The DCIS Score provides a local recurrence risk estimate at 10 years after lumpectomy for DCIS. Results can guide decisions regarding adjuvant radiation (RT). Foregoing RT can be a source of significant healthcare savings. We investigated the actual healthcare dollar savings to-date in our patients. Methods: We evaluated patients in whom the DCIS Score was ordered (x) and calculated total cost of testing. Potential cost of RT was that of IMRT as reimbursed by Medicare for a 16 fraction course, multiplied by x. Many of our patients with large breasts require IMRT for dose homogeneity and normal tissue parameters. We also calculated potential cost with 3D conformal (3D-CRT). Total potential cost was the sum of testing and treatment costs, determined for each modality. The number of patients ultimately treated (y) was also multiplied by these costs. Total actual cost was the sum of test expenses and actual treatment costs. Savings was the difference between total actual and total potential cost. Results: From 2/2012 to 5/ 2014 the DCIS Score was performed in 38 patients (x = 38). Median age was 66 (40 to 85). Grade was low in 39%, intermediate in 45%, and high in 16%. Fifty percent had necrosis and median size was 0.5 cm (0.1 to 3.1cm). The total cost of testing was $4125 * 38 = $156,750. IMRT reimburses at $23, 000 and 3D-CRT at $11,000. Potential total cost of RT ranged from $418,000 to $874, 000; testing brought total potential costs to $574, 750 to $1,030, 750. Upon receipt of test results, 12 (y) patients ultimately underwent therapy. IMRT was given in 11 patients and 3D-CRT in 1, for a total treatment cost of $264, 000. Therefore, total actual expenditures were $420, 750. Savings amounted to (574, 750 – 420, 750) = $154, 000 to (1,030, 750 – 420, 750) = $610, 000. Conclusions: In the era of rising healthcare costs, it is imperative to examine instances of possible overtreatment. The DCIS Score has the potential to save not only healthcare dollars, but to spare patients radiation side effects, time lost from work, and transportation expenses. While there are costs associated with the assay, if ordered judiciously, these can be offset by the subsequent savings from eliminating treatment.
Genetic counseling and testing of an underserved population at a large city hospital.
Authors: Joseph Kathie-Ann P. , Dhage Shubhada , Rifkind Kenneth 
Published: February 2017

38 Background: Genetic counseling and testing for hereditary breast and ovarian cancer is underutilized in low-income and racial/ethnic women. We examine the number of patients referred for genetic counseling over from 2011-2012, clinic referral pattern, and number of patients tested in a population of largely underserved, immigrant patient population. Methods: The study was conducted in Bellevue Hospital. A retrospective review of patients referred to this institution’s high-risk clinic was analyzed. Demographics, insurance status, BRCA status, if tested, and source of referral were collected. Results: Between 2011-2012, 196 patients were referred for genetic counselling. The majority of the referrals came from specialty clinics: Breast Surgery (42%), Medical Oncology (24%) and Gyn (8.7%). 17.5% were classified as other. One percent of consults came from internal medicine, 0.5% from women’s clinic, 4% were referred from family members. Of those patients counseled, 83 were tested. Breast surgery had the highest yield with 49% of the patients tested, followed by med onc (33%). One patient refused testing. Forty-seven of our patients were able to receive genetic testing through Myriad hardship, thirty-three through Medicaid, two paid by Bellevue Hospital, and one by private insurance. Five patients were BRCA1 positive, five patients were BRCA2 positive (12% of patients tested); An additional five patients were BRCA2 MUS. Racial/ethnic breakdown of the BRCA positive patients were 40% Asian, 20% Latina, 30% African American, 10% White. Four patients had a personal history of BrCa, two patients personal history of OvCa, one patient personal history of BCa/OvCa, and three patients FHBCa/OvCa. Conclusions: Genetic testing for HBOC can be underutilized in low-income and racial/ethnic women due to lack of insurance and lack of education. It is possible to get many high-risk women tested and most patients are receptive to testing when the benefits of testing are clearly explained. Our results indicate that while cancer specialists are referring high-risk patients, there may be room for education on the part of primary care specialists to refer more unaffected high risk patients. This may afford patients the opportunity to make better informed screening and treatment decisions.
Obesity and menopausal status as determinants of procarcinogenic breast inflammation.
Authors: Iyengar Neil M. , Morris Patrick Glyn , Zhou Xi Kathy , Gucalp Ayca , Giri Dilip D. , Harbus Michael , Falcone Domenick J , Vahdat Linda T. , Awad Mahmoud I. , Krasne Margaret D , Subbaramaiah Kotha , Morrow Monica , Hudis Clifford A. , Dannenberg Andrew 
Published: February 2017

40 Background: Chronic inflammation predisposes to several malignancies. We previously demonstrated an obesity → inflammation → aromatase axis in breast tissue. As obesity is a risk factor for postmenopausal (PoM) but not premenopausal (PreM) breast cancer (BC), we examined whether menopause and body mass index (BMI) independently impact breast white adipose tissue (WAT) inflammation. Methods: WAT was prospectively collected from patients (pts) from 04/10 to 08/13. WAT inflammation, detected by CD68 immunohistochemistry, was defined by the presence of dead or dying adipocytes surrounded by an envelope of macrophages known as crown-like structures of the breast (CLS-B). WAT area was measured with NIH Image J. Adipocyte diameter was measured with Canvas 11 Software. Endpoints were 1) CLS-B (+/-) and 2) CLS-B/cm2. Clinicopathologic associations with CLS-B were analyzed by logistic regression and Fisher’s exact test. Results: WAT (237 mastectomies, 13 abdominal reconstructions) was obtained from 238 pts; median age 48 (range 22 to 90). CLS-B occurrence and number of CLS-B/cm2 were greater in overweight/obese (BMI ≥ 25) and PoM pts compared to lean (BMI < 25) and PreM pts (Table). In multivariable analyses, BMI and PoM state were independently associated with CLS-B presence (p <.01 and p = .04) and greater CLS-B/cm2(p < .01 and p = .01). PoM pts had larger mean adipocyte diameter (105.2 +/- 14.0 μ) than PreM pts (95.7 +/-15.6 μ; p < 0.01). In pts with bilateral breast WAT and abdominal WAT, concordant CLS status (+/-) was found in 49/63 (78%) and 10/13 (77%) pts, respectively. Conclusions: Breast WAT inflammation (both presence and severity), which we have previously linked to increased aromatase activity, is associated with both increased BMI and menopause. These findings can explain the increased risk of estrogen receptor–positive BC with obesity and PoM status and may also provide targets for rational therapies. [Table: see text]
Effect of human insulin on breast cancer risk in Taiwanese women with type 2 diabetes.
Authors: Tseng Chin-Hsiao 
Published: February 2017

43 Background: Whether human insulin may induce breast cancer is rarely studied. Methods: The reimbursement databases of all Taiwanese patients with diabetes from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at January 1, 2004 and a total of 482,065 women with type 2 diabetes were followed up for breast-cancer incidence until the end of 2009. Incidences for ever-users, never-users, and subgroups of human insulin exposure (using tertile cutoffs of cumulative dose and cumulative duration of insulin) were calculated and the multivariable-adjusted hazard ratios were estimated by Cox regression. Results: There were 59,830 ever-users and 422,235 never-users, with respective numbers of incident breast cancer of 559 (0.93%) and 4,711 (1.12%), and respective incidence of 207.7 and 215.1 per 100,000 person-years. The overall adjusted hazard ratios (95% confidence intervals) did not show a significant association with insulin [1.098 (0.994-1.212)]. However, significant trends for the different categories of the dose-responsive parameters were observed. Patients in the third tertiles consistently showed a significantly higher risk of breast cancer compared to never-users: 1.339 (1.164-1.540) and 1.331 (1.158-1.531) for ≥ 39,000 units for cumulative dose of insulin, and ≥ 21.8 months for cumulative duration of insulin, respectively. Conclusions: This study discloses a significantly higher risk of breast cancer associated with the use of human insulin, demonstrating a significant dose-responsive relationship.