bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P4-18-03: Measuring what is important to patients in clinical trials: Hearing the patient's voice
Authors: Spears PA , Devine P , Finestone S
Published: March 2017

Patients who participate in clinical trials are important to clinical research and contribute to the advancement of medical discoveries. However, typical clinical trials do not always capture information that is important to patients: how they feel, function and survive. The only way to accurately measure how a patient feels or functions is to ask them. This can be done through the administration of health related questionnaires that are filled out by the patient without interpretation from anyone else; these are referred to as Patient Reported Outcomes (PROs). Although, PRO assessments have been used in clinical trials for the past 30 years through the collection of global quality of life (QOL) and later health related QOL (HR-QOL) measurements, the information has been too broad and has not been precise enough to use in drug approvals, descriptive drug label information or to inform other patients.

There is an effort to change the paradigm of PRO assessment to measure the information most relevant to patients in clinical trials. This includes measuring treatment toxicity, symptom burden and physical function. This is relevant information that other patients want to know about a specific treatment for a specific disease to help them in their treatment decision making. The voice of the patient is critical to assess these items, through PRO measurements. In order to ensure that PRO questionnaires are filled out during a clinical trial, there are ways to make them more acceptable to patients by involving patients in their development (what questions are asked/how many questions are asked/when they are given to patients/how they are given to patients). Patients can inform study teams on the acceptability, understandability and relevance of the questions being asked. Patients can be a key contributor to clinical trial development by identifying the questions that are most important to them and the best way to ask these questions during a clinical trial.

Patient advocacy and educational organizations like Cancer Information & Support Network (CISN) are advocating for changes in PRO collection in clinical trials. Based on information collected from many survivors, caregivers and advocates, a patient-centric clinical trial development model will be proposed. The model includes the involvement of patients as key stakeholders early in clinical trial development to incorporate PROs into clinical trials that are acceptable for patients to complete and the outcomes are meaningful and matter to future patients.

Citation Format: Spears PA, Devine P, Finestone S. Measuring what is important to patients in clinical trials: Hearing the patient's voice [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-18-03.
Abstract P4-18-05: Male breast cancer— infusing a little blue into the sea of pink
Authors: Wagner H , Boyages J
Published: March 2017

Male breast cancer (MBC) is a rare disease dominated by a sea of pink. Issues faced by men with this disease include delayed diagnosis, lack of male-specific information, stigma about having a "female disease" and often under-treatment.

MBC is often treated as a female breast cancer but differences between the two are starting to emerge. Men are often older at diagnosis and sometimes considered "too old" for more aggressive treatments such as chemotherapy. Drugs such as aromatase inhibitors may not be as effective in men as in women but are often prescribed. Drugs such as tamoxifen can cause side-effects such as weight gain, hot flushes, loss of libido and impotence.

Support for patients with MBC is less advanced than that for female breast cancer. A Man's Pink, a MBC advocacy organization, mission is to promote MBC awareness, increase early detection, optimize and increase the survival rates for men diagnosed with breast cancer. Male Breast Cancer: Taking Control (BC Publishing, Boyages, 2015) empowers patients to understand their diagnosis and treatment.

Apart from incidence data, prognosis and treatment options, this talk will focus on how a website (www.malebreastcancer.ca) dedicated to MBC can help dismiss some of the myths and help overcome stigmata for men facing difficulties at diagnosis, treatment and recovery.

Our goal is to promote awareness to assist with earlier diagnosis and treatment to improve survival rates and the journey for men in their battle with breast cancer.

Citation Format: Wagner H, Boyages J. Male breast cancer— infusing a little blue into the sea of pink [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-18-05.
Abstract P4-21-03: A randomized phase II study of Ki-67 response-guided preoperative chemotherapy for HER2-positive breast cancer
Authors: Takahashi M , Nishiyama Y , Hara F , Naito Y , Baba M , Sasaki M , Sato M , Watanabe K , Uemura Y , Yamaguchi T , Mukai H
Published: March 2017

As for the HER2-positive breast cancer, there are many cases to be effective for neoadjuvant chemotherapy in comparison with other intrinsic subtypes. However, pCR is not provided by neoadjuvant chemotherapy in all cases. [Aim] This study evaluated the effectiveness of a therapeutic strategy that switches chemotherapy, based on Ki-67 tumor expression after initial therapy, relative to that of standard chemotherapy in patients with HER2-positive breast cancer. [patients and methods] Patients were randomly assigned to the control arm or the Ki-67 response-guided arm (Ki-67 arm). Primary tumor biopsies were obtained before treatment, and after three once-weekly doses of paclitaxel and trastuzumab to assess the interim Ki-67 index. In the control arm, paclitaxel and trastuzumab was continued for a total of 12 doses, regardless of the interim Ki-67 index. In the Ki-67 arm, subsequent treatment was based on the interim Ki-67 index. Early Ki-67 responders continued to received paclitaxel plus trastuzumab for a total of 12 doses, while early Ki-67 non-responders were switched to epirubicin plus cyclophosphamide every 3 weeks for three cycles with once-weekly trastuzumab for a total of 12 doses. The primary endpoint was the pathological complete response (pCR) rate. [Results] When 237 patients were enrolled, an interim analysis was conducted in 200 patients. There was almost linear correlation between the Ki-67 reduction rate at interim assessment and the pCR rate. The pCR rate in Ki-67 early non-responders in the Ki-67 arm (23.6%; 95% CI, 12.4 to 34.9) was inferior to that in the control arm (44.1%; 31.4 to 56.7; p=0.025). A strong correlation was not found between the Ki-67 reduction rate and the clinical response rate (Spearman's correlation coefficient 0.22).

pCR rate among Ki-67 early non-responders and responders TotalpCR nn%95%CIKi-67 early non responderControl arm59264431.4-56.7 Ki-67 response guided arm55132312.4-34.9Ki-67 early responderControl arm21104726.3-69.0 Ki-67 response guided arm2084018.5-61.5

Conclusions: The pCR rate in the Ki-67 arm was inferior to that in the control arm. A therapeutic strategy that switches chemotherapy, based on Ki-67 tumor expression after initial therapy, was not effective. The standard chemotherapy protocol remains as the recommended strategy for patients with HER2-positive breast cancer.

Citation Format: Takahashi M, Nishiyama Y, Hara F, Naito Y, Baba M, Sasaki M, Sato M, Watanabe K, Uemura Y, Yamaguchi T, Mukai H. A randomized phase II study of Ki-67 response-guided preoperative chemotherapy for HER2-positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-03.
Abstract P4-21-21: Her2 is not a cancer subtype but rather a driver found in all intrinsic subtypes and highly enriched in molecular apocrine tumors
Authors: Daemen A , Manning G
Published: March 2017

Her2-enriched (Her2E) breast tumors defined by molecular profiling are discrepant from Her2-amplified tumors defined by clinical assessment – over half of all Her2-amplified tumors are not Her2E, while one-third of Her2E tumors are not Her2-amplified. We explored this discordance using genomic profiles of 4,000 breast tumors. We find clear support that Her2 amplification is a discrete cancer driver event and not a subtype, with little genomic impact other than in expression of genes on the amplicon. Many Her2-amplified tumors clearly belong to the basal, luminal A, or luminal B subtypes.

After accounting for the Her2 amplicon, most tumors classified as Her2E appear to be molecular apocrine, expressing high levels of androgen receptor and low to moderate levels of ER. The high rate of Her2 amplification in this group (63%) suggests that additional growth drivers are required for molecular apocrine tumors.

Her2 amplification is also a driver across subtypes of several non-breast tumor types. Her2 is amplified in 2% of 5,400 non-breast tumors, spanning 23 tumor types. The Her2 region in non-breast cancers shows a similar range of amplification and breadth of the amplicon, and a comparable rate of overexpression of genes within the amplicon for most Her2A tumors.

These discoveries reveal therapeutic opportunities for combining anti-Her2 therapy with endocrine or anti-androgen agents for breast cancer, and for expanding anti-Her2 therapy to other tumor types.

Citation Format: Daemen A, Manning G. Her2 is not a cancer subtype but rather a driver found in all intrinsic subtypes and highly enriched in molecular apocrine tumors [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-21.
Abstract P5-03-06: Clinical value of 89Zr-trastuzumab PET in HER2-positive breast cancer patients with a clinical dilemma
Authors: Schröder CP , Bensch F , Brouwers AH , Lub-de Hooge MN , de Jong JR , van der Vegt B , Sleijfer S , de Vries EG
Published: March 2017

Background: Information on human epidermal growth factor receptor 2 (HER2) is essential for management of metastatic breast cancer (mBC). In patients suspected of HER2-positive mBC, standard work up may fail to clarify whole body HER2 status. We aimed to assess whether 89Zr-trastuzumab PET can support treatment decisions in patients posing this clinical dilemma.

Methods: 89Zr-trastuzumab PET was performed as described earlier (Gaykema et al, Clin Cancer Res 2014) in patients in whom standard work up with bone scan, FDG PET, CT and if feasible a biopsy, failed to evaluate HER2 status of their disease. 89Zr-trastuzumab PET was defined positive, when at least a dominant part of the tumor load showed substantial tracer uptake (Gebhart et al, Ann Oncol 2015), when tumor tracer uptake in single lesions (except brain) was ≥ normal liver uptake or when brain metastases had a tracer uptake > background. Circulating tumor cell (CTC) analysis prior to tracer injectionwas performed using the CellSearch System (Janssen Diagnostics LLC) and CTC HER2 status was assessed immunofluorescently. Questionnaires about treatment decisions were completed before, directly after and ≥3 months after 89Zr-trastuzumab PET.

Results: Twenty patients were enrolled: 8 with two primary cancers (HER2-positive and HER2-negative BC or BC and non-BC), 7 with metastases inaccessible for biopsy, 4 with prior HER2-positive and HER2-negative metastases, 1 with primary BC with equivocal HER2 status (average 4.23 HER2 gene copies/nucleus). 89Zr-trastuzumab PET was positive in 12 patients, negative in 7 and equivocal in one patient. In 15/20 patients 89Zr-trastuzumab PET supported treatment decision. The scan altered treatment of 8 patients, increased physicians' confidence without affecting treatment in 10, and improved physicians' understanding of disease in 18 patients. Ten patients had 1-99 CTCs, 6 with HER2 expression. There was no correlation between HER2 expression by CTCs and 89Zr-trastuzumab PET results or subsequent treatment decision.

Conclusion: 89Zr-trastuzumab PET, but not CTC analysis, supports clinical decision making in BC patients in whom standard work up fails to evaluate HER2 status. (Funded by the Dutch A Sister's Hope).

Citation Format: Schröder CP, Bensch F, Brouwers AH, Lub-de Hooge MN, de Jong JR, van der Vegt B, Sleijfer S, de Vries EG. Clinical value of 89Zr-trastuzumab PET in HER2-positive breast cancer patients with a clinical dilemma [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-03-06.
Abstract P5-04-01: Cell cycle dynamics at single cell level dictates response to CDK4/6 inhibition
Authors: Asghar U , Barr A , Cuts R , Beaney M , Babina I , Sampath D , Lacap J , Crocker L , Young A , Nerukar A , Pearson A , Herrera-Abreu M , Bakal C , Turner N
Published: March 2017

This abstract was withdrawn by the authors.
Abstract P5-06-09: Cyclin d1 binding to chromatin and the induction of chromosomal instability requires the fuzzy domain
Authors: Pestell RG , Di Sante G , Di Rocco A , Pupo C , Crosariol M , Tompa P , Tantos A , Wang C , Yu Z , Vadlamudi R , Mann M , Casimiro MC
Published: March 2017

The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates the retinoblastoma (Rb) and the nuclear respiratory factor 1 (NRF1) proteins to regulate nuclear DNA synthesis and mitochondrial biogenesis. Cyclin D1 is required for oncogene-dependent growth and genetic ablation of the murine cyclin D1 gene resulted in resistance to Ras or ErbB2-induced mammary tumorigenesis and APC-induced gastrointestinal tumorigenesis. Cyclin D1 overexpression occurs in human breast, prostate, lung, and gastrointestinal malignancies and its abundance is induced at the level of transcription, translation and through post-translational modifications. Cyclin D1 plays a key role in transcriptional regulation inducing gene expression governing chromosomal instability (CIN) and cell-cycle progression. Cyclin D1 is also known to bind TF regulatory regions in chromatin immuno-precipitation (ChIP) assays. Genome wide analysis of cyclin D1 occupancy using ChIP-Seq identified binding sites including both the coding and non-coding genome with enrichment for genes regulating CIN and the G2/M phase (Top2A, AurkB, Cenpp, Mlf1ip, Zw10, Ckap2) consistent with enrichment of cyclin D1 at G2/M and the finding that cyclin D1 induces CIN. We sought to identify the molecular mechanisms governing the recruitment of cyclin D1 in the context of local chromatin to promote CIN. In order to define the domain of cyclin D1 involved in aneuploidy and tumorigenesis, we transduced and assessed the induction of aneuploidy in MEF cells using cyclin D1 wt (wt), cyclin D1 C-terminus domain (C4), cyclin D1 mutant lacking of the E-box motif (ΔE) or ctrl. We also searched for potential histone protein interaction motifs in cyclin D1 and determined the epigenetic motif recognized by cyclin D1 using a histone peptide array. The recognition of an epigenetic code by cyclin D1 may facilitate genome wide expression changes during cell-cycle progression and tumorigenesis. We finally identified a “fuzzy” domain of cyclin D1 which is required to local chromatin access for regulatory promoter regions governing and promoting CIN.

Citation Format: Pestell RG, Di Sante G, Di Rocco A, Pupo C, Crosariol M, Tompa P, Tantos A, Wang C, Yu Z, Vadlamudi R, Mann M, Casimiro MC. Cyclin d1 binding to chromatin and the induction of chromosomal instability requires the fuzzy domain [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-06-09.
Abstract P5-07-04: Transition from a pre-malignant lesion to cancer does not require stemness of the cancer-originating cells in the lesion
Authors: Bu W , Li Y
Published: March 2017

The precancerous lesion is the final step before malignancy, and is thus a key step to cancer prevention. Precancerous lesions are heterogeneous harboring distinct subsets of cells from stem cells to differentiated cells. Whether the stem cells or other subsets in these precancerous lesions are responsible for the eventual cancer remains unanswered. Here, we report that in the precancerous lesions of the MMTV-Wnt1 model of basal-like breast cancer, there exist the stem cell-enriched keratin 6a+ subset and more differentiated WAP+ cell subset. We demonstrate that both mutated Ras and B-Raf can robustly transform both cell subsets into cancer. These data suggest that multiple cell subsets in precancerous early lesions can evolve into cancer. This finding indicates that cancer prevention should target both self-renewing cells and other cell subsets in developing precancerous lesions in high-risk individuals.

Citation Format: Bu W, Li Y. Transition from a pre-malignant lesion to cancer does not require stemness of the cancer-originating cells in the lesion [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-07-04.
Abstract P5-07-09: Stem cell-like transcriptional reprogramming in metastatic resistance
Authors: Pujana MA , Mateo F , Arenas EJ , Gomis R
Published: March 2017

Whether an aggressive phenotype is promoted through adaptation or resistance to target inhibition remains poorly understood. Here, complementary studies in human tumors, xenograft models and cell lines reveal transcriptional reprogramming that supports metastasis in response to PI3K/mTOR inhibition. This feature is driven by stem cell-like transcription factors. These factors functionally cooperate to promote transcriptional up-regulation of key mTOR pathway components and of metastasis mediators. Their expression is also associated with stem cell-like and metastasis signatures in tumors, and their depletion impairs the metastatic potential of breast cancer cells.Whether an aggressive phenotype is promoted through adaptation or resistance to target inhibition remains poorly understood. Here, complementary studies in human tumors, xenograft models and cell lines reveal transcriptional reprogramming that supports metastasis in response to PI3K/mTOR inhibition. This feature is driven by stem cell-like transcription factors. These factors functionally cooperate to promote transcriptional up-regulation of key mTOR pathway components and of metastasis mediators. Their expression is also associated with stem cell-like and metastasis signatures in tumors, and their depletion impairs the metastatic potential of breast cancer cells.

Citation Format: Pujana MA, Mateo F, Arenas EJ, Gomis R. Stem cell-like transcriptional reprogramming in metastatic resistance [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-07-09.
Abstract P5-08-01: Quantifying the contribution of earlier detection and advances in treatment on the gain in life expectancy for US breast cancer patients since 1975: Prospective cohort study of about 470,000 women in US SEER cancer registries
Authors: Soneji SS , Beltrán-Sánchez H
Published: March 2017

This abstract was withdrawn by the authors.
Abstract P5-08-09: Use of oral contraceptives and risk of breast cancer in BRCA1 and BRCA2 mutation carriers: An international prospective cohort study; for the studies of EMBRACE, GENEPSO, HEBON, kConFab and BCFR
Authors: Schrijver LH , Olsson H , Antoniou AC , Milne RL , Phillips K-A , Andrieu N , Easton DF , Goldgar D , Engel C , Kast K , Roos-Blom M-J , Mooij TM , Hopper JL , van Leeuwen FE , Terry M-B , Rookus MA
Published: March 2017

This abstract was withdrawn by the authors.
Abstract P5-08-17: Breast cancer in octagenerians: A community hospital experience
Authors: Gadiyaram V , Caldwell D
Published: March 2017

Background : Breast cancer incidence increases with age. However Elderly patients are undertreated and underdiagnosed affecting their overall survival with limited availabilty of clinical trial data

Patients and Methods : We used the data from our cancer registry to evaluate the cases of breast cancer diagnosed between the years 2005-2010 with follow up data available to date to examine the method of diagnosis(mammogram vs palpable abnormality ), Age at diagnosis, Stage at diagnosis, Type of surgery (BCT Vs Mastectomy ), Receptor status(ER/PR/Her 2 neu) and treatment's received ( Hormonal therapy , Radiation therapy and chemotherapy) and average survival after the diagnosis of breast cancer. Data regarding the causality of death was not readily available as part of the registry data.

Results : A total of 495 breast cancer cases diagnosed in the years between 2005-2010 wee identified ., Median age at diagnosis was 85 with ages ranging from 81-102 .Out of the 495 patients 55 % were diagnosed with a mammogramand 41 % by palpable abnormality. Patients were diagnosed at Stage 0,1,2,3,4 (12%,45 %,7% ,3 %. 55% underwent Lumpectomy and 31 % underwent Mastectomy .82 % and 18 % ER negative. Her 2 data was only available in 59 patients, out of those tested only 4 Her 2 positive. , Radiation(34 %) /Chemo(6 %)/ Hormone(34%) ,Radiation/Chemo 2 % ,Radiation/Hormone 18%, Chemo/Hormon 2% , 41 % didn't proceed with any treatments.Median survival was 54 months and Average survival was 56 months. Median survival 54 months and average survival was 56 months, With 203 patients alive at the end of 5 years with mortality of about 62 %. However we do not have the data of causality of death in these patient .

Comparison between Age Groups : See table below

Comparision of data b/n Age groupsAge at Diagnosis80-8485-8990 +No of patients24419256Mammogram13810532Palpable Lump947924Lumpectomy1576724Mastectomy803026Average Survival in months84.54848.5

Conclusion: Even though Surgery was performed in most the patients , Only 50 % or lesser number of patients had Adjuvant treatment with Endocrine , Radiation and chemotherapy. Based on the data even though most patient were diagnosed with early stage breast cancer , had significantly poor survival with median survival of about 54 months . With Survival dramatically dropped from 84 months to 48 months in patient 85 + years of age.

Citation Format: Gadiyaram V, Caldwell D. Breast cancer in octagenerians: A community hospital experience [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-08-17.
Abstract P5-08-21: The effect of family history on screening procedures and prognosis in breast cancer patients – Results of a large population-based case–control study on breast cancer
Authors: Seiffert K , Thoene K , zu Eulenburg C , Rudolph A , Schmalfeldt B , Flesch-Janys D , Chang-Claude J , Witzel I
Published: March 2017

Background:

Patients with a first- or second-degree family history of breast or ovarian cancer participate more frequently in breast cancer screening procedures. A benefit of additional screening visits has been documented in high-risk patients with (e.g. BRCA 1, BRCA 2 gene mutations). However, the potential benefit of additional screening examinations in moderate risk patients (patients with a history of breast cancer in one or two family members) remains unclear.

Methods:

Patients were recruited in 2002–2005 within a large population-based case–control study on breast cancer in Germany (3,813 cases and 7,341 age-matched healthy controls). Univariate and multivariate analyses were performed to evaluate the effect of family history on breast cancer risk, participation in screening procedures, tumor size and prognosis.

Results

A higher breast cancer risk was observed in patients with a positive family history (1 affected family member: OR 1.32, p<0.001). Patients with a 1st degree positive family history received a higher number of mammograms (MG) (>10 MG: 42.7% vs. 24.9%, p<0.001) and showed a higher rate of imaging-detected tumors (mammogram or ultrasound) (45.8% vs. 31.9%, p<0.001) compared to patients without positive family history. Positive family history (OR 1.45 pT1 vs. ≥pT2, p<0.001) and higher number of mammograms (≥10 mammograms: OR 2.29 pT1 vs. ≥pT2) were associated with smaller tumor size at initial diagnosis. Additionally, there was a significant association between mammogram regularity (HR 0.72, p<0.001) and imaging-assisted tumor detection (HR 0.66, p<0.001) with improved overall survival. However, no significant association between a positive family history of breast cancer and survival could be seen.

Discussion:

Patients with a family history of breast cancer participated more frequently in screening procedures and had a higher rate of image-detected tumors with smaller size at initial diagnosis, compared to patients without affected family members. Breast cancer screening procedures were significantly associated with improved survival.

Citation Format: Seiffert K, Thoene K, zu Eulenburg C, Rudolph A, Schmalfeldt B, Flesch-Janys D, Chang-Claude J, Witzel I. The effect of family history on screening procedures and prognosis in breast cancer patients – Results of a large population-based case–control study on breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-08-21.
Abstract P5-10-03: Racial disparities in breast cancer diagnosis-to-treatment waiting times in South Carolina
Authors: Babatunde OA , Adams SA , Eberth J , Sercy E , Hebert J
Published: March 2017

This abstract was withdrawn by the authors.
Abstract P5-11-05: Examining bone degeneration as a side effect of treatment in premenopausal breast cancer patients
Authors: Kim M , Kim HJ
Published: March 2017

Background: Although it is widely known that adjuvant treatments cause osteoporosis in postmenopausal women, the effect of treatment and the exact degree of bone loss in premenopausal women is not well understood. For this reason, this study examined the relationship between the changes of bone mineral density(BMD) and the types of treatment in premenopausal breast cancer patients.

Method: This retrospective study looks at preoperative and annual spine bone densitometry tests conducted on breast cancer patients during their observational period following initial treatment for their diagnosis. 461 premenopausal patients who received treatment from January 2006 to April 2007 were the study cohort because of the availability of bone mineral density (BMD) data (L-spine and femur T scores) for a two-year period. The data from the patients were separated into groups according to their treatment plans: observation, adjuvant chemotherapy, adjuvant chemotherapy followed by use of Tamoxifen, and GnRHa(Gonadotropin Releasing Hormone agonist) followed by Tamoxifen.

Results: Of the 461 patients, 21 received no treatment aside from surgery, 75 received only Tamoxifen, 34 only chemotherapy, 166 chemotherapy and Tamoxifen, and 165 Zoladex and Tamoxifen. The no treatment group demonstrates the standard annual change in BMD. At first year, the chemotherapy only group and tamoxifen after chemotherapy group showed significant bone loss in the first year (p<0.005, both). The patients who received tamoxifen alone or tamoxifen with goserelin showed decrease BMD but not significant. After 2 years, tamoxifen with goserelin group showed significant decreased BMD in both spine and femur (p<0.001, p=0.001, both). Chemotherapy group showed partial recovery from the first year bone loss. Conclusion: The patients who received chemotherapy or GnRHa as treatment showed the greatest degree of bone degeneration but at different periods. However, Tamoxifen used along with these treatments seemed to lessen the extent of bone degeneration. Significant bone loss from hormone treatment occurred two years after surgery as compared to one year for chemotherapy.

Citation Format: Kim M, Kim HJ. Examining bone degeneration as a side effect of treatment in premenopausal breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-11-05.
Abstract P5-11-06: BEAUTY and the breast: Is adjuvant chemotherapy the right time for a beauty boost? Results of a randomised controlled trial
Authors: Saghatchian M , Lacas B , Deneuve J , Bouvet N , Mokdad-Adi M , Ghouadni A , Amiel P , Charles C , Boinon D , Delaloge S , Dauchy S
Published: March 2017

This abstract was not presented at the symposium.
Abstract P5-11-11: A phase I safety study of topical calcitriol (BPM31543) for the prevention of chemotherapy-induced alopecia (CIA)
Authors: Goldfarb SB , Konner J , Stevens J , Brouwer S , Narain NR , Ye R , Ravipaty S , Sarangarajan R , Akmaev VR , Jimenez JJ , Belum VR , 'Kitts S , Ciccolini K , Berman B , Lacouture ME
Published: March 2017

Background: Chemotherapy induced alopecia (CIA) may lead to significant psychosocial and quality of life issues. Currently there are no FDA approved oral or topical agents available to prevent CIA. In murine studies, topical calcitriol reduced CIA, due to arrest of cell cycle in healthy hair follicles, and reduction in the sensitivity of follicular epithelium to chemotherapy.

Methods: A prospective dose escalation study is being performed in up to 31 women with breast cancer, gynecologic cancer and sarcomas. Each patient is applying 1mL of BPM31543 to her scalp bid, ≥ 5 days prior to initiation of taxane-based chemotherapy for at least 3 months or until the completion of chemotherapy. The study cohorts are: 5/10/20/40/60/80μg/mL. The first 5 cohorts are completely enrolled and the final cohort is currently being enrolled. Each patient undergoes pk analysis, adverse event (AE) monitoring, patient self-assessment diaries (1-10 scale), and blinded photographic assessments. Efficacy and pK data are still being collected and analyzed for the patients on study, but will be available by December.

Results: Twenty-four subjects have been enrolled so far (evaluable at this time, n = 13). Pk data (n = 16; 5-40μg/mL) showed inter-individual variability, but no significant dose-dependent increase in systemic absorption (range, < 20-110 pg/mL). Treatment-related AEs (probably/possibly) were mild/moderate in nature and included scalp pain (n = 1; 5 μg/mL), elevated vitamin D levels in 1 patient (20μg/mL) and passage of renal calculus in another (n = 1; 40μg/mL). All subjects reported changes in overall hair fullness, thickness, and volume of hair during chemotherapy. At the 5/10 μg/mL dose level, ≥ 75% hair loss was reported in 85% of patients. At the ≥ 20 μg/mL dose level, ≥ 75% hair loss was seen only in 43% of patients. Hair loss/ thinning caused all subjects to change their hair style (onset, week 2; peak, weeks 5-6).

Conclusions: Data have shown that the twice daily application of BPM31543 in patients receiving taxane-based chemotherapy was safe and well-tolerated. Efficacy data from the preliminary analysis was promising and led to the amendment of the study to evaluate two additional higher dose cohorts: 60 and 80 μg/ml.

Citation Format: Goldfarb SB, Konner J, Stevens J, Brouwer S, Narain NR, Ye R, Ravipaty S, Sarangarajan R, Akmaev VR, Jimenez JJ, Belum VR, 'Kitts S, Ciccolini K, Berman B, Lacouture ME. A phase I safety study of topical calcitriol (BPM31543) for the prevention of chemotherapy-induced alopecia (CIA) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-11-11.
Abstract P5-15-15: Phase II study of navelbine plus carboplatin followed by oral navelbine in patients with metastatic/recurrent triple negative breast cancer previously treated with anthracycline and taxane
Authors: El-Sadda W , Abdel Halim I , El-Ibrashi M
Published: March 2017

This abstract was not presented at the symposium.
Abstract P5-15-18: MERIBEL STUDY: Single-agent eribulin as first-line therapy for taxane-resistant HER2[-] metastatic breast cancer (MBC) patients (pts)
Authors: Ortega V , Antón A , Garau I , Afonso N , Calvo L , Fernández Y , Martinez-Garcia M , Blanco E , Zamora P , García M , Illarramendi JJ , Rodríguez CA , Aguirre E , Pérez J , Cortés J , Llombart A
Published: March 2017

This abstract was withdrawn by the authors.
Abstract P5-16-01: A randomised phase III trial comparing two dose-dense, dose-intensified approaches (ETC and PM(Cb)) for neoadjuvant treatment of patients with high-risk early breast cancer (GeparOcto)
Authors: Schneeweiss A , Möbus V , Tesch H , Hanusch C , Denkert C , Lübbe K , Huober J , Klare P , Kümmel S , Untch M , Kast K , Jackisch C , Ingold-Heppner B , Thomalla J , Blohmer J-U , Rezai M , Nekljudova V , von Minckwitz G , Loibl S
Published: March 2017

This abstract was withdrawn by the authors.
Abstract P5-16-25: Serum 25-hydroxyvitamin D levels and oncologic outcomes of breast cancer patients receiving neoadjuvant chemotherapy
Authors: Park S , Lee JS , Kim JH , Lim SM , Park HS , Kim SI
Published: March 2017

Background:According to prior studies, the role of serum vitamin D3 has been inconsistentand clinical implications of 25-hyrdoxyvitamin D (25-OHD) have been little studiedin breast cancer patients receiving neoadjuvant chemotherapy (NCT).

Objectives: The aims of study were to investigate changes in 25-OHD levels before and after NCT and to determine the association of 25-OHD and oncologic outcomes including pathological complete response (pCR) in breast cancer patients.

Patients and Materials: From January 2010 to December 2013, serum 25-OHD levels at pre- and post-NCT were measured in 377 breast cancer patients. The association of serum 25-OHD levels with clinicopathological data including breast cancer subtypes, pCR and survival were retrospectively analysed. Delta 25-OHD was calculated as serum 25-OHDlevels before minus after NCT.

Results: Mean ageof study population was 48.7 yearsand mean follow-up periods were 35.9months.Mean baseline serum 25-OHD concentration was 14.60 ng/mL (standard deviation, 7.44) and more than 80% of patients showed insufficient 25-OHD levels. The mean 25-OHDat post-NCT was 12.16 ng/mL (standard deviation, 6.87).There was a significant decrease in serum 25-OHD after NACT (p<0.001).The pCR rates were 25.7% among study cohort.However, 25-OHD levels at baseline and post-NCT were not related to pCR and survival outcomes. No associations were found between pCR and delta 25-OHD. According to stratification by breast cancer subtypes, however, patients with ≥ -2.67 (median value) of delta 25-OHD revealed a trend of higher achievement of pCR and better survival in luminal A subtype. No associations were found among the other subtypes.

Conclusions: Many Korean breast cancer patients showed insufficient serum 25-OHD levels at diagnosis of malignancy and a significant decrease in serum vitamin D3 after NACT was observed.No significant association of 25-OHD 3 with pCR and survival was found. Therefore, correction or maintenance of appropriate serum 25-OHD levels should be focused for bone health as comprehensive management of breast cancer during NCT.In addition, possible oncological aspects of 25-OHD should further researched individually considering breast subtypes.

Citation Format: Park S, Lee JS, Kim JH, Lim SM, Park HS, Kim SI. Serum 25-hydroxyvitamin D levels and oncologic outcomes of breast cancer patients receiving neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-25.
Abstract P5-16-26: National trends in neoadjuvant therapy for breast cancer
Authors: Schnabel F , Schwartz S , Hochman T , Chun J , Goldberg J
Published: March 2017

Purpose:Neoadjuvant therapy has been widely integrated in the treatment of locally advanced breast cancer. Over time, this strategy has been extended to include patients with earlier stage disease to allow for assessment of in vivo response to treatment. The aim of this study was to describe the national trends in neoadjuvant therapy for all invasive breast cancers with a particular focus on triple negative disease and HER2 status.

Methods: The National Cancer Database (NCDB), an oncology outcomes database that collects data from more than 1500 Commission on Cancer (CoC) accredited cancer programs, was queried for all women diagnosed with invasive breast cancer from 2006-2013. Patients with unknown systemic therapy sequence were excluded. Women were classified by whether or not they received neoadjuvant systemic, chemo and/or endocrine, therapy.

Results: We identified 1,221,976 cases that were eligible for this analysis. Of these, 29.7% were HER2 negative, 18.4% were classified as triple negative, and 8.9% received neoadjuvant systemic therapy. The percentage of patients receiving neoadjuvant therapy increased from 7.5% in 2006 to 9.8% in 2012 with a slight decrease to 9.5% in 2013. This increase in the use of neoadjuvant therapy over the time period was statistically significant (p<0.0001). There was a small increase in the percent of patients with HER2 positive status who received neoadjuvant therapy, from 5.7% in 2006 to 6.5% in 2013. During this time period, there was a 9% increase in the percent of triple negative patients who received neoadjuvant therapy (13.1% in 2016 to 22.1% in 2013).

Number and percent of patients who received/did not receive neoadjuvant therapy by year2006 (N=136117)2007 (N=143033)2008 (N=148888)2009 (N=154713)2010 (N=154040)2011 (N=162333)2012 (N=163395)2013 (N=159457)No Neoadjuvant Therapy | 125908 (92.5)131559 (91.98)136593 (91.74)141364 (91.37)139459 (90.53)146500 (90.25)147401 (90.21)144306 (90.5)Neoadjuvant Therapy | 10209 (7.5)11474 (8.02)12295 (8.26)13349 (8.63)14581 (9.47)15833 (9.75)15994 (9.79)15151 (9.5)

Conclusions: Over the time period from 2006-2013, there has been an apparent increase in the percentage of patients who received neoadjuvant therapy. This trend is accompanied by increases in the percentage of TNBC patients and in Her2 positive patients who received neoadjuvant therapy. Other factors and the joint effects of these factors on the observed increase in the use of neoadjuvant therapy are under evaluation to elucidate the basis for this observation in the NCDB data.

Citation Format: Schnabel F, Schwartz S, Hochman T, Chun J, Goldberg J. National trends in neoadjuvant therapy for breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-26.
Abstract P6-01-08: Identifying metastatic drivers in patient derived xenograft models of triple negative breast cancer
Authors: Powell E , Shao J , Tieu T , Peoples M , Bristow C , Manyam G , Cai S , Tu Y , Edwards JR , Heffernan TP , Piwnica-Worms D , Liang H , Piwnica-Worms H
Published: March 2017

Metastases are responsible for the vast majority of deaths due to breast cancer. Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high rates of metastasis and poor response to chemotherapy. We are using patient derived xenograft (PDX) models of TNBC to identify drivers of TNBC metastasis. Using these models, we demonstrated that human breast tumors are capable of completing all stages of the metastatic cascade in mice, and metastatic lesions are observed in organs normally found in patients with metastatic breast cancer including lung, liver, bone, brain and lymph nodes. Lentiviral transduction was employed to express both bioluminescent and fluorescent proteins in three distinct PDX models of TNBC. In this way, metastatic lesions can be isolated using bioluminescent imaging and circulating tumor cells (CTCs) are isolated by flow cytometry. A lung metastasis gene expression signature was generated and comprehensive gain-of-function screens are being conducted in vivo to validate this signature and identify functional drivers of TNBC metastasis.

Citation Format: Powell E, Shao J, Tieu T, Peoples M, Bristow C, Manyam G, Cai S, Tu Y, Edwards JR, Heffernan TP, Piwnica-Worms D, Liang H, Piwnica-Worms H. Identifying metastatic drivers in patient derived xenograft models of triple negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-01-08.
Abstract P6-01-14: Dissection of the Abl interactor 1 signaling in metastatic breast cancer cells
Authors: Jiang P , Tang H , Hogan H , Tate S , Ryan W , Paul L , Liu X , Zonghan D
Published: March 2017

Abl interactor 1 (Abi1) is a key component of WAVE regulatory complex (WRC) that regulates actin cytoskeleton reorganization, membrane receptor signaling, and intracellular trafficking. Recent in vitro and in vivo studies as well as the studies of human patient samples suggest that Abi1 may play an important role in breast cancer (BC) metastasis. To determine if Abi1 is deregulated in metastatic breast cancer cells, we compared the expression of Abi1 in a panel of human breast cancer cell lines exhibiting distinct metastatic properties. In comparison with low-metastatic ER+/PR+ BC lines MCF-7 and T47D and a non-transforming mammary epithelial cell line MCF-10A, two ER-BC lines CN34 and MDA 231 and their sublines selected by high metastatic potential to bone (231Bo), brain (231Br and CN34Br), and lung (231LM2) show significantly reduced Abi1 protein levels, with greater reduction found in highly metastatic sublines. It is unlikely that the down-regulation of Abi1 expression in these metastatic BC cells occurs at mRNA level, because RT-PCR analysis shows no significant difference in Abi1 mRNA levels among the cells analyzed. Interestingly, despite a reduction in protein level, the tyrosine phosphorylation of Abi1 was increased in CN34, MDA231, and their metastatic sublines compared to low-metastatic BC cells. The tyrosine phosphorylation of Abi1 is stimulated by epidermal growth factor (EGF) in these cells and Abi1 is recruited to EGF receptor (EGFR) upon EGF stimulation. The deregulation of Abi1 in metastatic BC cells is mediated by Abl tyrosine kinases, as the inhibition of Abl family kinases by imatinib not only attenuates EGF-stimulated Abi1 tyrosine phosphorylation but also rescue the down-regulation of Abi1 protein in metastatic BC cells.

These findings are consistent with a role of the EGFR-Abl-Abi1 signaling in BC metastasis. The studies suggest that this pathway may serve as a biomarker for diagnosis and/or prognosis of metastatic breast cancer. We have identified the tyrosine 213 in Abi1 as a major phosphorylation site stimulated by Abl kinases and have generated a unique conditional Abi1 depletion/re-expression system to dissect how the deregulation of the Abi1 signaling contributes to BC metastasis.

Citation Format: Jiang P, Tang H, Hogan H, Tate S, Ryan W, Paul L, Liu X, Zonghan D. Dissection of the Abl interactor 1 signaling in metastatic breast cancer cells [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-01-14.
Abstract P6-01-15: Novel regulation of breast cancer cell aggressiveness by cancer testis antigen
Authors: Kannan A , Wells RM , Ikebe M , Dasgupta S
Published: March 2017

We recently demonstrated that a vesicular endocytosis associated protein SH3GL2, attenuates spontaneous metastases of breast cancer cells by inducing a mesenchymal to epithelial differentiation and the onset of the intrinsic apoptotic pathway. The present study aims to understand the molecular mechanism behind the SH3Gl2 mediated reduction of spontaneous metastasis of the breast cancer cells.

We employed a cDNA microarray analysis of the SH3GL2-overexpressing breast cancer cells exhibiting reduced pulmonary metastasis and identified a 12.1 fold downregulation of SPANXB1, a cancer-testis antigen that regulates sperm motility. A limited number of studies reported an association between increased SPANXB1 expression and progression of melanoma and hepatocellular carcinoma. Augmented SPANXB1 mRNA and protein expression was evident in primary breast tumors and its upregulation was associated with pulmonary metastasis of breast cancer cells. However, the expression pattern of SPANXB1 and its role in BCa development and progression is unknown. By immunohistochemical analysis, we detected high expression (p=0.002) of SPANXB1 in 78% (18/23) of the primary breast cancer tissues and corresponding lymph node metastases compared to the matched normal breast tissues. A couple of non-tumorigenic human breast epithelial cell lines were stably transformed with SPANXB1 to understand its effect on cellular growth and progression. The SPANXB1-transformed cells exhibited increased invasion (p=0.0001) and epithelial to mesenchymal transition accompanied by an augmented expression ratio of Vimentin/E-Cadherin, molecules regulating differentiation and metastasis. The SPANXB1-transformed cells also exhibited a markedly reduced expression of SH3GL2, implicating a SPANXB1:SH3GL2 crosstalk accompanied by an enhanced production of lactate (p=0.004). Our investigation identifies new breast cancer promoting role of a cancer testis antigen, which bears potential for biomarker and targeted therapeutic development.

Citation Format: Kannan A, Wells RM, Ikebe M, Dasgupta S. Novel regulation of breast cancer cell aggressiveness by cancer testis antigen [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-01-15.