bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P2-10-08: Understanding potential gaps in treatment discussions between caregivers/patients with advanced breast cancer and oncologists
Authors: Mayer Musa , Coons Helen L , Jones Stephen , Percassi Deana
Published: May 2015

Approximately 232,670 cases of breast cancer will be diagnosed in the US in 2014, of which 86,088 (37%) cases will involve cancer that has spread regionally or metastasized. The 2013 Global Count Us, Know Us, Join Us survey found that 53% of women with advanced breast cancer (ABC; breast cancer that has spread to distant parts of the body) surveyed in the US wish they had more time to discuss their needs during clinic visits, and 60% believe their cancer treatment options are limited. To better understand unmet patient needs and potential communication gaps in treatment discussions with physicians, surveys were developed for women with ABC, their caregivers, and oncologists.

The Make Your Dialogue Count survey will be conducted online, by paper, and by telephone in the US from June through August 2014. Survey respondents must be (1) women ≥21 years of age diagnosed with ABC; (2) their caregivers who attend at least half the clinic visits; or (3) licensed US medical oncologists who treat ≥5 women with ABC per month. Patient and caregiver data were not weighted. Oncologist data regarding geographic region and years in practice by gender were weighted to align with actual proportions in the population.

Final results of the full survey are expected by September 30, 2014. The Make Your Dialogue Count survey will explore issues such as the emotional impact of diagnosis of ABC; the doctor-patient relationship, including the quality of communications and information exchange during clinic visits; and the effect of side effects on treatment choice and satisfaction, from the perspectives of patients, their caregivers, and oncologists.

Findings from the Make Your Dialogue Count survey will provide insight into the doctor-patient relationship from multiple perspectives. Comparing responses given by patients, caregivers, and oncologists can identify potential communication gaps that could be affecting the quality of care provided. Considering the number of women living with ABC, our findings could help oncologists to meet the emotional and informational needs of their patients, and provide patients with the supportive treatment environment they seek and the most relevant disease and treatment information possible.

Citation Format: Musa Mayer, Helen L Coons, Stephen Jones, Deana Percassi. Understanding potential gaps in treatment discussions between caregivers/patients with advanced breast cancer and oncologists [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-10-08.
Abstract P2-12-15: Perception of women after undergoing microbiopsy following a positive breast cander screening
Authors: Carly Birgit , Aimont Mireille , Beauloye Nicolas , Liebens Fabienne
Published: May 2015

Background: Some authors have challenged the benefit of breast cancer mammographic screening due to high prevalence of overdiagnosis and overtreatment.

Purpose: To assess the anxiety and stress of women undergoing a microbiopsy following a false positive breast cancer screening and to evaluate whether this experience refrains them from continuing breast cancer screening.

Methods: 296 patients underwent breast microbiopsy for positive breast cancer screening B1, B2 and B3 lesions in our Breast Center between 2011 and 2013. Patients undergoing microbiopsy for B4 and B5 lesions were excluded from the study. The patients were thereafter interviewed by our two psychologists by phone within a time range of 6 to 18 months following the biopsy.

Results: 201 women answered the questionnaire (68% response). 5.5% had a breast lesion at risk and 75% had a benign lesion. Half of the women rated their anxiety as high (7-8 on a scalebetween 0 – 10) and 15% as very high (9-10/10) before the biopsy. While waiting for the result, 42% rated their anxiety as high (7-8/10) and nearly a third as very high (9-10/10). But 80% accepted to continue breast cancer screening and 90% would accept to undergo again a microbiopsy if necessary.

Conclusion: microbiopsy provides high stress in most patients undergoing it. Nevertheless, 90% of those who had a false positive results accept it and are willing to undergo a biopsy again if necessary.

Citation Format: Birgit Carly, Mireille Aimont, Nicolas Beauloye, Fabienne Liebens. Perception of women after undergoing microbiopsy following a positive breast cander screening [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-12-15.
Abstract P2-13-10: Assessment of diagnostic and therapeutic value of ductoscopy biopsy in single intraductal papillary lesion compared with open surgery
Authors: Xu Zheli , Xing Wanying , Li Qiang , Xing Deli , Gu Yiqi
Published: May 2015

Purpose

Papillary lesions (PL) account for 1–2 % of all breast neoplasms and fiberoptic ductoscopy is a practical and direct method compared with open biopsy in diagnosis and treatment of intraductal papillary lesions. This study aimed to assess efficacy of ductoscopy in the diagnosis and management of single intraductal papillary lesion.

Methods

A total of 232 patients at China-Japan Union Hospital of Jilin University who were diagnosed with single intraductal papillary lesion by fiberoptic ductoscopy were enrolled from March 2011 to November 2013. All patients underwent ductoscopic papillomectomy before open surgery. The final pathologic diagnoses were made by using specimen from both ductoscopic papillomectomy and surgeries. Any intraductal papillomatous lesion or surface abnormalities were considered as positive findings during ductoscopy.

Results

Histopathologic investigations of surgically excised or ductoscopically removed lesions revealed that 217 out of 232 cases were positive. In 187 cases pathological changes were only found in ductoscopic papillomectomy specimen, while the number of cases which was only found in open biopsy was 24. In 6 cases ductoscopic papillomectomy and surgeries specimen both showed positive.

Conclusions

The accuracy of ductoscopy biopsy in diagnosis was 88.9% (193/217) and specificity was 100%. In 187 out of 217 cases (86.2%) ductoscopic papillomectomy alone could completely remove the lesion. Ductoscopy is an effective tool for diagnosis and treatment of single intraductal papillary lesion.

Citation Format: Zheli Xu, Wanying Xing, Qiang Li, Deli Xing, Yiqi Gu. Assessment of diagnostic and therapeutic value of ductoscopy biopsy in single intraductal papillary lesion compared with open surgery [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-13-10.
Abstract P2-13-14: Does therapeutic mammoplasty reduce mastectomy rates?
Authors: Pollard Jennifer , Wong Pang , Mansell James , Murray Juliette , Lannigan Alison , Doughty Julie , Romics Laszlo , Stallard Sheila , Wilson Christopher
Published: May 2015

Introduction: Therapeutic mammoplasty (TM) is increasing in popularity as a method for enhancing breast conserving surgery. Studies have shown it’s oncologically safe, whilst improving cosmetic outcome1,2,3. Therapeutic mammoplasty has been gaining popularity in West of Scotland over the past five years. Initially it was thought this may reduce requirement for mastectomy and immediate reconstruction. We have recorded type of surgery patients would have required had they not been suitable for TM, looking at changing demographic of surgical workload.

Methods: Prospective data collected about patients undergoing TM in West of Scotland since 2011 in Victoria Infirmary, Western Infirmary and in NHS Lanarkshire. We reviewed clinical indications for TM, surgical alternative, Body Mass Index (BMI) and smoker status.

Results: Seventy-nine patients were identified. In 67 cases, alternative surgical option of mastectomy or standard conservation was recorded. Mean BMI was 29. 41% of patients had contralateral surgery for symmetry at the same time. In 28 cases (35%) TM avoided need for mastectomy. In 39 cases (49%) it was felt that cosmetic result would be improved by TM compared with standard conservation. During the study period, rates of mastectomy with immediate reconstruction as a proportion of total number of treated cancers have remained similar.

Conclusions: Whilst introduction of therapeutic mammoplasty in our region has improved options offered to patients and likely cosmetic outcomes, it has not had a major impact in reducing mastectomy rates or demand for immediate reconstruction. It has probably increased surgical workload of plastic surgeons as these cases are often performed as joint procedures.

References:

1. Iwuchukwu OC, Harvey JR, Dordea M, Critchley AC, Drew PJ. The role of oncoplastic therapeutic mammoplasty in breast cancer surgery – A review. Surgical Oncology. 2012;21:133-141

2. McCulley SJ, Macmillan RD. Planning and use of therapeutic mammoplasty – Nottingham approach. British Journal of Plastic Surgery. 2005;58:889-901

3. Clough K, Lewis J, Couturand B, Fitoussi A, Nos C, Falcou M. Oncoplastic techniques allow extensive resections for breast-conserving therapy of breast carcinomas. Annals of Surgery. 2003;237(1):26-34.

Citation Format: Jennifer Pollard, Pang Wong, James Mansell, Juliette Murray, Alison Lannigan, Julie Doughty, Laszlo Romics, Sheila Stallard, Christopher Wilson. Does therapeutic mammoplasty reduce mastectomy rates? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-13-14.
Abstract P2-13-16: Intraoperative ultrasound guided wire bracketing of nonpalpable breast lesions for excision
Authors: Rock David T , Stewart Aimee L , Sandadi Samith
Published: May 2015

Background. Mammographic wire localization is the primary means of localizing nonpalpable breast lesions for excision. Unfortunately, that procedure is associated with patient discomfort and vasovagal responses, scheduling difficulties, and problems with inaccurate wire placement or wire displacement. In addition, the wires often enter far from the target and take an indirect course resulting in high positive margin rates. We reviewed our experience with intraoperative ultrasound guided bracketing of nonpalpable lesions to determine if the accuracy of the excision and patient factors could be improved.

Methods. Patients that underwent intraoperative ultrasound guided wire bracketing were identified by electronic chart review. After the patient was anesthetized, high frequency linear array ultrasound was used to identify the target lesion. Under direct ultrasound visualization, the lesions were bracketed with 4 hook-wires placed perpendicular to the chest wall at the radial and antiradial margins of the lesion. Excision of the lesion was then performed with circumferential dissection around all 4 localization wires.

Results. Intraoperative localization was planned on 80 patients. The lesion was identified by preoperative ultrasound in 76 of those patients (95%). The remaining patients required mammographic localization. In 67 patients (88%) the lesion was identified for bracketing, in the remaining 11 patients the biopsy clip was seen by ultrasound and bracketed. Only 2 patients had positive margins (no tumor touching ink) requiring re-excision (2.6%).

Conclusions. The results of our experience show that intraoperative ultrasound guided wire bracketing is a reliable alternative to mammographic localization and is associated with a lower positive margin rate than reported for mammographic wire localization with a single wire. In addition, patient comfort is improved, cost is reduced, and there are no scheduling issues. The technique is especially useful for oncoplastic excisions where the incision is remote from the target lesion.

Citation Format: David T Rock, Aimee L Stewart, Samith Sandadi. Intraoperative ultrasound guided wire bracketing of nonpalpable breast lesions for excision [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-13-16.
Abstract P2-13-27: Nipple sparing mastectomy: Risks of wound complication in the setting of neo-adjuvant or adjuvant chemotherapy and/or radiation therapy
Authors: Samuel Selyne , Viscusi Rebecca , Waer Amy , Gonzalez Victor , Chalasani Pavani , Hurst Craig , Larson Ethan , Livingston Robert , Ley Michele
Published: May 2015

Background: Surgical care of breast cancer has evolved significantly over the past 40 years. Nipple sparing mastectomy (NSM) and skin sparing mastectomy (SSM) have become an increasingly used surgical management for women with malignant breast disease. To date, there are limited recommendations about the role of NSM in patients receiving aggressive adjuvant therapy. The purpose of this investigation is to determine whether NSM in the setting of neo-adjuvant or adjuvant chemotherapy and/or radiation therapy increased the risks for wound complications.

Methods: A retrospective chart review of nipple sparing mastectomies at a single institution was performed from 2007 to 2014. Multiple data points including neo-adjuvant or adjuvant chemotherapy and/or radiation therapy, obesity, smoking history, and type of reconstructive surgery were examined in detail.

Results: We counted the procedures by breasts affected and identified 76 NSM in the time period which met criteria. Of the 76 NSMs, 27 breasts received neo-adjuvant(20) or adjuvant chemotherapy and/or radiation(7) therapy. 21 breasts in the NSM group developed wound complications including skin flap necrosis (5), total nipple necrosis and loss (11) hematoma (2) infection(2) and seroma(1). The complications were seen in 11 in the non adjuvant treated setting (14%) and 9 (33%) in the adjuvant therapy setting.

Conclusions: Nipple sparing mastectomy are emerging as safe and adequate options for the management of malignant breast disease. Our results show there is a significant risk of wound complication associated with neo-adjuvant and adjuvant chemotherapy and radiation therapy in the setting of nipple sparing mastectomy. We are pursuing the development of new surgical techniques and guidelines to reduce these risks in these high risk patients.

Citation Format: Selyne Samuel, Rebecca Viscusi, Amy Waer, Victor Gonzalez, Pavani Chalasani, Craig Hurst, Ethan Larson, Robert Livingston, Michele Ley. Nipple sparing mastectomy: Risks of wound complication in the setting of neo-adjuvant or adjuvant chemotherapy and/or radiation therapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-13-27.
Abstract P2-14-06: Prediction of local recurrence following mastectomy
Authors: Al-Himdani Sarah , Timbrell Simon , Tan Kian , Morris Julie , Bundred Nigel
Published: May 2015

Background: Rates of local recurrence following mastectomy vary considerably in the literature, ranging from 1.7% to 11.5%. Previous studies have attempted to identify risk factors for recurrence and whether these relate to aggressive disease or to inadequate local treatment. We aimed to identify local recurrence rates at our institution to determine risk factors associated with local recurrence.

Methods and materials: A retrospective study of all women undergoing mastectomies for unilateral T1-T3 breast cancer between 2000-2005 was undertaken. Kaplan-Meier curves were created and the log-rank test calculated to assess for differences between groups. The incidence of local, regional and systemic recurrence was identified at 5 and 8 years post-mastectomy. Incomplete excision/margin involvement was defined as margins 1mm or less. Demographic, biological and treatment-related factors associated were used to identify predictors of local recurrence.

Results: In total, 581 women were studied (mean age: 59; range: 22-96); 462 simple mastectomies (SM) and 106 skin-sparing mastectomies (SSM) which included 199 (34%) screen-detected and 382 (66%) symptomatic cancers. Mean follow up was 6.7 years (range: 5-12.4) and longest was 12.4 years. SSM patients had a lower mean age (p=<0.001), with a smaller tumour size (p=0.022), fewer positive lymph nodes (p=<0.001) and less co-existing ductal carcinoma in situ (DCIS) (p=<0.001) than SM patients. Recurrence rates for SM were 5.6% and 6.9% and for SSM, recurrence rates were 5.7% and 9.0% at 5 and 8 years respectively. Recurrence in node negative patients was 2.2% at 5 years. Predictors of local recurrence were node positivity (HR 8.03; 95% CI 3.2-20) and margin involvement/close margins (HR 3.34; 1.64-6.8).

Conclusion: No significant difference between recurrence rates in SSM and SSM groups was identified. The presence of over four positive lymph nodes and incomplete excision margins indicates an increased risk of recurrence and in these patients, immediate SSM reconstruction should be considered prudently.

Citation Format: Sarah Al-Himdani, Simon Timbrell, Kian Tan, Julie Morris, Nigel Bundred. Prediction of local recurrence following mastectomy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-14-06.
Abstract P2-14-10: Technical results and complication rates after nipple-sparing mastectomy and direct-to-implant breast reconstruction using porcine acellular dermal matrix for implant coverage
Authors: Reitsamer Roland , Peintinger Florentia
Published: May 2015

Objective:

To evaluate the feasibility and complication rates of nipple-sparing mastectomy (NSM) and direct-to-implant breast reconstruction using a porcine acellular dermal matrix (ADM) for implant coverage.

Methods:

NSM and direct-to-implant breast reconstruction using a porcine ADM for implant coverage was performed in a series of 91 breasts in 63 patients. Technical results, complications, and cosmetic results were collected from patient records.

Results:

Short-term complications within one month comprised minor complications as minimal nipple necrosis in 13.2%, and infection in 1.1%. Major complications, as hemorrhage with surgical evacuation in 4.4%, and implant loss due to skin breakdown in 4.4%, totaled in 8.8%. Within three months after primary surgery 3 further severe complications with reoperation ocurred. In 87.9% no second surgical intervention was necessary and cosmetic results were good or excellent. After a mean follow-up of 12 months (range 5 - 35 months) no further complications could be observed. Patient satisfaction was high for 92.3% of the patients and subjective cosmetic result was excellent in 90.1% and satisfactory in 2.2%.

Conclusion:

Direct-to-implant breast reconstruction using a porcine ADM for implant coverage after NSM is an innovative approach resulting in a high patient satisfaction. The technique is challenging but feasible and complication rates are acceptably low.

Citation Format: Roland Reitsamer, Florentia Peintinger. Technical results and complication rates after nipple-sparing mastectomy and direct-to-implant breast reconstruction using porcine acellular dermal matrix for implant coverage [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-14-10.
Abstract P3-02-05: Qatar experience of Standard risk breast cancer screening program (BCSP)
Authors: Bujassoum Salha , Alassam Reena , Bugrein Hekmat , Elmistiri Mufid
Published: May 2015

Background

Qatar has one of the highest age-adjusted breast cancer incidences in the Arab world. Although this is much lower than the incidence in the West. Breast cancer incidence in Qatar was 45 per 100,000 in 2003-2007.These higher incidence rates in Qatar are mainly due to the growing population. The prevalent age group, for Qatari and non-Qatari patients, was 40-50 years old. This suggests that the age-specific incidence of breast cancer in Qatari women is unlike the pattern usually seen in Western nations where median age at diagnosis is 61 years, moreover the diagnosis is often at advanced stages of breast cancer. These factors led to establishment the first hospital based (BCSP) in Qatar. It uses a distributed model of mammography service. The program launched 2008, accepts eligible asymptomatic women at ages 40 - 69 years.

Methods

A retrospective study was done during the period from April 2008 –December 2013.

Our aim is to describe our experience of (BCSP) in Qatar and to monitor performance indicators. Our (BCSP) includes an office call and recall as well as triple assessment. We also discuss positive cases in multi-disciplinary meeting.

Results

Total number of screened women was 4264 with an increasing participation, year by year. Out of these, Qatari patient’s accounts for 1145, and non Qatari for 3119. The age group of cases was (43-51). Total breast biopsies were 82, of which 45 were positive of breast carcinomas, (37) invasive ductal carcinoma, (8) noninvasive ductal carcinoma. The Invasive cancer detection rate was 8.2 %. The positive predictive value (PPV) was 46%. Sensitivity value has improved from 51% in 2008 to 70% in 2012 as well as specificity value that has increased from 77% in 2008 to 83% in 2012.

Conclusion

Public acceptance of (BCSP) in Qatar gradually increased and detection rates are higher than western countries. We’re detecting biologically aggressive tumors at younger age groups. We’ve a unique population and we need to utilize our data and evidence based medicine to guide policy makers and women to make the correct decision towards (BCSP).

Citation Format: Salha Bujassoum, Reena Alassam, Hekmat Bugrein, Mufid Elmistiri. Qatar experience of Standard risk breast cancer screening program (BCSP) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-02-05.
Abstract P3-04-02: Multiple subtypes of triple negative breast cancer are dependent on androgen receptor
Authors: Barton Valerie N , D'Amato Nicholas C , Gordon Michael A , Jacobsen Britta M , Richer Jennifer K
Published: May 2015

Triple negative breast cancer (TNBC) constitutes 10-20% of invasive breast carcinomas and has the lowest five-year survival rate. Currently, there are no targeted therapies for TNBC. Recent studies demonstrate that the androgen receptor (AR) is expressed in up to a third of TNBC. AR is highly expressed in the "luminal AR (LAR)" molecular TNBC subtype, but is also present in other TNBC subtypes and may present an opportunity for targeted therapy. We hypothesized that AR+ TNBC critically depend on AR and that AR inhibition will decrease tumor burden in preclinical models of breast cancer. To determine the extent to which AR+ TNBC depend on AR, we inhibited AR activity with the AR antagonist enzalutamide (ENZ) and shRNAs against AR in multiple TNBC subtypes. Treatment with ENZ prevented AR nuclear localization in response to DHT in multiple TNBC cell lines, reduced baseline proliferation in 2D culture (p<0.05), and decreased anchorage independent growth in soft agar (p<0.01). AR knockdown significantly reduced proliferation (p<0.001) and increased apoptosis (p<0.001) compared to cells transduced with a non-targeting control. In addition to reduced proliferation, AR knockdown or treatment with ENZ altered cellular morphology from stellate to round in Matrigel and significantly decreased migration (p<0.05) and invasion (p<0.001) of cell lines spanning multiple TNBC subtypes. Microarray profiling and ELISA of TNBC lines treated with DHT and ENZ suggested that AR regulation of the EGFR ligand amphiregulin (AREG, p<0.05) is a mechanism by which AR influences proliferation, migration and invasion in TNBC. Indeed, treatment with exogenous AREG rescued decreased proliferation, migration and invasion of AR knockdown cell lines (p<0.05). In vivo, ENZ significantly decreased tumor viability (p=0.008) and increased necrosis (p=0.009) in SUM159PT xenografts. Our findings suggest that AR influences both proliferation and invasion of AR+ TNBC cells representing multiple TNBC subtypes and provide promising preclinical data on the efficacy of ENZ in AR+ TNBC. Thus, inhibition of AR by anti-androgens such as ENZ may represent an effective targeted therapy for TNBC.

Citation Format: Valerie N Barton, Nicholas C D'Amato, Michael A Gordon, Britta M Jacobsen, Jennifer K Richer. Multiple subtypes of triple negative breast cancer are dependent on androgen receptor [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-04-02.
Abstract P3-04-03: PIK3CA mutations in androgen receptor-positive triple negative breast cancer confer sensitivity to the combination of PI3K and androgen receptor inhibitors
Authors: Lehmann Brian D , Bauer Joshua A , Schafer Johanna M , Pendleton Christopher S , Tang Luojia , Johnson Kimberly C , Chen Xi , Balko Justin M , Gomez Henry , Arteaga Carlos L , Mills Gordon B , Sanders Melinda E , Pietenpol Jennifer A
Published: May 2015

Triple negative breast cancer (TNBC) is a heterogeneous collection of biologically diverse cancers, which contributes to variable clinical outcomes. Previously, we identified a TNBC subtype that has a luminal phenotype and expresses androgen receptor (AR+). TNBC cells derived from these luminal AR+ tumors have high frequency PIK3CA mutations. The purpose of this study was to determine if targeting PI3K alone or in combination with an AR antagonist is effective in AR+ TNBC.

Methods: We determined the frequency of activating PIK3CA mutations in AR+ and AR- TNBC clinical cases. Using AR+ TNBC cell lines and xenograft models we evaluated the effectiveness of PI3K inhibitors, used alone or in combination with an AR antagonist, on tumor cell growth and viability.

Results: PIK3CA kinase mutations were highly clonal, more frequent in AR+ vs. AR- TNBC (40% vs. 4%), and often associated with concurrent amplification of the PIK3CA locus. PI3K/mTOR inhibitors had an additive growth inhibitory effect when combined with genetic or pharmacological AR targeting in AR+ TNBC cells. We also analyzed the combination of bicalutamide +/- the pan-PI3K inhibitor GDC-0941 or the dual PI3K/mTOR inhibitor GDC-0980 in xenograft tumor studies and observed additive effects.

Conclusions: While approximately one third of TNBC patients respond to neoadjuvant/adjuvant chemotherapy, recent studies have shown that patients with androgen receptor positive (AR+) TNBC are far less likely to benefit from the current standard of care chemotherapy regimens and novel targeted approaches need to be investigated. In this study, we show that activating PIK3CA mutations are enriched in AR+ TNBC; and, the growth and viability of AR+ TNBC cell line models is significantly reduced after treatment with PI3K inhibitors used in combination with an AR antagonist. These results provide rationale for pre-selection of TNBC patients with a biomarker (AR expression) to investigate the use of AR antagonists in combination with PI3K/mTOR inhibitors.

Citation Format: Brian D Lehmann, Joshua A Bauer, Johanna M Schafer, Christopher S Pendleton, Luojia Tang, Kimberly C Johnson, Xi Chen, Justin M Balko, Henry Gomez, Carlos L Arteaga, Gordon B Mills, Melinda E Sanders, Jennifer A Pietenpol. PIK3CA mutations in androgen receptor-positive triple negative breast cancer confer sensitivity to the combination of PI3K and androgen receptor inhibitors [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-04-03.
Abstract P3-05-21: Investigation into the oncogenic potential of the androgen receptor in aromatase inhibitor resistant breast cancer
Authors: Young Leonie , Creevey Laura , Ali Azlena , Hill Arnold DK , McIlroy Marie
Published: May 2015

The heterogenous nature of breast cancer, exemplified by a wide range of subtype classifications, has been well documented. The identification of the novel molecular apocrine breast tumours (ER-, PR-ve, HER2-ve, AR+), with a gene expression profile reflective of ER+ luminal breast cancer, has led to the proposition of an alternative role for the androgen receptor as a pseudo ER. This proposition was borne out of global expression profiling and AR recruitment of molecular apocrine cells, demonstrating that more than 50% of AR binding to the genome mirrors the pattern of ER binding suggesting that in the absence of ER, AR can mimic ER in its DNA binding capabilities.

Aromatase Inhibitor (AI) therapy is the gold standard first line therapy for postmenopausal breast cancer. AIs function by abrogating the activity of the enzyme Cyp 19 (aromatase), which is responsible for converting circulating androgens to estrogen. By preventing this conversion step, this eradicates the main steroid driving breast cancer growth and in turn results in a more androgenic environment. We hypothesise that AR may also act as a pseudo ER in our AI resistant (MCF7-letrozole resistant) cells. Preliminary data demonstrates that AR is recruited to some but not all classical ER target genes as well as some AR target genes in MCF7-LetR cells, therefore highlighting the potential of AR to act as an oncogene in this setting. Analysis of AR protein expression also demonstrates higher levels of AR in AI resistant cells versus sensitive cells. In the evaluation of the responsiveness of a range of breast cancer cell lines to the AR antagonist Bicalutamide, it was noted that our AI resistant cells demonstrated responsiveness to Bicalutamide treatment.

RNA sequencing experiments following AR knockdown in AI resistant cells also provide crucial information as to the key genes differentially regulated by AR. Given that resistance to AI therapy is an emerging clinical issue, further elucidation of the potential mechanisms of AI resistance and potential AR targets is highly warranted.

Citation Format: Leonie Young, Laura Creevey, Azlena Ali, Arnold DK Hill, Marie McIlroy. Investigation into the oncogenic potential of the androgen receptor in aromatase inhibitor resistant breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-05-21.
Abstract P3-05-22: PI3K pathway as a novel target in androgen-driven aromatase inhibitor resistant breast cancer
Authors: Young Leonie S , Ali Azlena , Creevey Laura , Bane Fiona , Marzuki Wan Afif , Hill Arnold DK , McIlroy Marie
Published: May 2015

Breast cancer has the highest incidence and second highest mortality rate among all cancers in women worldwide (1). The gold standard treatment for post-menopausal breast cancer is aromatase inhibitor (AI) therapy. Unfortunately, resistance is inevitable in about 30-60% of these patients (2). Research from our lab has previously identified a transcription factor, HOXC11, to be associated with breast cancer resistance and metastases (3). Prosaposin (PSAP) was then identified as a putative HOXC11 target gene in the AI resistant setting. PSAP is a secreted protein that also plays a role in metastatic prostate cancer in both a ligand dependent and independent fashion (4,5).

We have previously shown PSAP to be an androgen responsive gene that can upregulate androgen receptor (AR) expression in a ligand dependent manner in AI resistance. An AR antagonist was effective at slowing down cell proliferation in AI resistant cells in vitro . However, since PSAP can also potentially act in a ligand independent fashion, this current study is focused on evaluating the role of PSAP in PI3K pathway activation in the development of AI resistance. Treatment of cells with recombinant PSAP protein (rhPSAP) resulted in increasing expression of p-AKT in a dose-dependent manner. To target this pathway of resistance, we used a pan-class PI3K/mTOR inhibitor BEZ235 on our AI resistant cells. Functional studies with BEZ235 treatment showed significant reduction in both cell motility as well as cell proliferation. Treatment of AI resistant cells with BEZ235 resulted in decreased expression of p-AKT, with little or no effect on AR expression. These findings suggest that to prevent resistance to AI therapy, combination treatment regimens including AR antagonists plus a PI3K inhibitor may ensure sustained response to therapy.

References:

1. Servick K. Breast Cancer: a World of Differences. Science Magazine. Special Issue. March 2014

2. Kazi AA et al. Breast Nonhypoxic regulation and role of hypoxia-inducible factor 1 in aromatase inhibitor resistant breast cancer. Cancer Research. 2014; 16:R15

3. McIlroy M et al. Cancer Res.2010;70(4);1585-94

4. Koochekpour Set al. Prosaposin is an AR-target gene and its neurotrophic domain upregulates AR expression and activity in prostate stromal cells. J Cell Biochem. 2008; 104: 2272–2285.

5. Koochekpour S et al. Prosaposin is a novel androgen-regulated gene in prostate cancer cell line LNCaP. J Cell Biochem. 2007; 10: 631–641.

Citation Format: Leonie S Young, Azlena Ali, Laura Creevey, Fiona Bane, Wan Afif Marzuki, Arnold DK Hill, Marie McIlroy. PI3K pathway as a novel target in androgen-driven aromatase inhibitor resistant breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-05-22.
Abstract P3-06-13: Prospective cohort study using the breast cancer spheroid model as a predictor for response to neoadjuvant therapy – The SpheroNEO study
Authors: Halfter Kathrin ML , Ditsch Nina , Kolberg Hans-Christian , Fischer Holger , Hauzenberger Tanja , Edler von Koch Franz , Bauerfeind Ingo , von Minckwitz Gunter , Funke Ilona , Crispin Alexander , Mayer Barbara
Published: May 2015

(1) PURPOSE

The aim of the prospective trial was to determine if cell survival in a breast cancer spheroid model following cytostatic treatment in vitro predicts treatment response in breast cancer patients receiving equivalent neoadjuvant therapy.

(2) PATIENTS AND METHODS

Three-dimensional spheroids were directly generated from fresh tumor biopsy samples of 78 patients eligible for neoadjuvant therapy. Cell survival in vitro, as well baseline clinical and pathological characteristics were correlated with the outcome following treatment of each patient to determine the factor(s) most highly associated with pathological complete response (pCR i.e.ypT0/ypN0) at surgery.

(3) RESULTS

Cell survival after treatment in the breast cancer spheroid model proved to be a sensitive and specific predictor for pCR in individual breast cancer patients. A mean cell survival of 21.8% was found in the breast cancer spheroid model for 22 patients with pCR versus 63.8% in 56 patients without pCR (P = .001). A receiver operator characteristic analysis determined an area under the ROC curve of 0.86 (95% CI: 0.77 to 0.96) for cell survival compared to classic factors i.e. negative hormone receptor and positive Her2/neu status, and age ≤ 50 years at primary diagnosis (AUC = 0.80, 95% CI: 0.70 to 0.90). A cutoff of 35% cell survival was proposed, which grouped patients according to likelihood for pCR. Out of the 32 patients with values below this threshold, 21 patients (65.6%) and one patient (2.2%) with a cell survival greater than 35% achieved pCR respectively; (sensitivity 95.5% (95% CI: 0.86 to 1.00); specificity 80.4% (95% CI: 0.70 to 0.91)).The specificity was improved to 81% (95% CI: 58 to 95%) if the patient was treated per-protocol.

A positive correlation was also found between cell survival in vitro and residual tumor size (P = .021), indicating the possibility of the model to predict degree of response.

(4) CONCLUSION

The breast cancer spheroid model is a valuable predictor for treatment outcome in patients undergoing neoadjuvant chemotherapy for primary breast cancer. Preclinical selection of the most efficient drugs is a prerequisite to improve pCR.

Citation Format: Kathrin ML Halfter, Nina Ditsch, Hans-Christian Kolberg, Holger Fischer, Tanja Hauzenberger, Franz Edler von Koch, Ingo Bauerfeind, Gunter von Minckwitz, Ilona Funke, Alexander Crispin, Barbara Mayer. Prospective cohort study using the breast cancer spheroid model as a predictor for response to neoadjuvant therapy – The SpheroNEO study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-13.
Abstract P3-06-20: A seven-gene signature can predict distant recurrence in patients with triple-negative breast cancers (TNBCs) who receive adjuvant chemotherapy following curative surgery of the primary breast cancer
Authors: Park Yeon Hee , Jung Hae Hyun , Do In-Gu , Cho Eun Yoon , Sohn Insuk , Jung Sin-Ho , Kil Won Ho , Kim Seok Won , Lee Jeong Eon , Nam Seok Jin , Ahn Jin Seok , Im Young-Hyuck
Published: May 2015

BACKGROUND: Women with triple-negative breast cancers (TNBCs) represent a significant treatment challenge as they have a relatively poor prognosis and no effective targeted therapy exists. Although TNBCs are often discussed as a single disease entity of breast cancers, in fact they are very heterogeneous. The aim of this study was to investigate candidate genes that might function as biomarkers to differentiate TNBCs among patients, who received adjuvant chemotherapy after curative surgery, into those with high or low risk for distant recurrence.

METHODS: We tested whether the results of a NanoString expression assay that targeted 245 prospectively selected genes and used mRNA extracted from paraffin wax-embedded tumor tissues would predict distant recurrence in patients with TNBC. The levels of expression of seven genes were used in a prospectively defined algorithm to allocate each patient to a risk group (low or high).

RESULTS: NanoString expression profiles were obtained for 203 tumor tissue blocks. Increased expressions of the five genes (SMAD2, HRAS, KRT6A, TP63, and ETV6) and decreased expression of the two genes (NFKB1 and MDM4) were associated favorable prognosis in this patients’ cohort and were validated with cross-validation. The proportions of patients categorized as having low or high risk were 75% and 25%, respectively. The Kaplan–Meier estimates of the rates of distant recurrence at 10 years in the low- and high-risk groups according to gene expression signature were 62% (95% CI, 48.6–78.9%) and 85% (95% confidence interval, CI, 79.2–90.7%), respectively. When adjusting for tumor–node–metastasis (TNM) stage, the distant recurrence-free survival (DRFS)s in the low-risk groups were significantly longer than that in the high-risk group (p<.001) in each of TNM stages I plus II, and III. In a multivariate Cox regression model, the gene expression signature provided significant predictive power jointly with the TNM staging system.

CONCLUSION: A seven-gene signature could be used as a prognostic model to predict DRFS in patients with TNBC who received curative surgery followed by adjuvant chemotherapy.

Citation Format: Yeon Hee Park, Hae Hyun Jung, In-Gu Do, Eun Yoon Cho, Insuk Sohn, Sin-Ho Jung, Won Ho Kil, Seok Won Kim, Jeong Eon Lee, Seok Jin Nam, Jin Seok Ahn, Young-Hyuck Im. A seven-gene signature can predict distant recurrence in patients with triple-negative breast cancers (TNBCs) who receive adjuvant chemotherapy following curative surgery of the primary breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-20.
Abstract P3-06-27: BRCAness is important to identify TNBC subtype resistant to taxanes
Authors: Ishikawa Takashi , Narui Kazutaka , Shimada Kazuhiro , Kida Kumiko , Oba Mari S , Tanabe Mikiko , Ichikawa Yasushi , Sugae Sadatoshi , Endo Itaru
Published: May 2015

BACKGROUND: Triple negative breast cancer (TNBC) is heterogeneous and consists of tumors associated with basal like, BRCA related and cancer stem cell (CSC) phenotypes. Although anti-cancer agents are substantial for treating TNBC, existing ones do not work in some subpopulation in TNBC at all. However, it has not been reported that subdivision of TNBC is useful for choosing ant-cancer agents.

AIM: To examine whether subdividing TNBC is beneficial for tailored chemotherapy and to identify predictive factors for existing anti-cancer agents in TNBC.

METHODS: Sixty-six TNBC cases from a randomized phase II trial comparing TCx6 (TC6) with FEC followed by docetaxel (FEC-D) as neoadjuvant chemotherapy for hormone receptor-negative breast cancer (Kanagawa Breast Oncology Group 1101 Study). TNBC was subdivided by 1) IHC of CK 5/6 and EGFR into basal- and non-basal subtypes, and 2) MLPA of BRCA1 into BRCA1 and non-BRCA1 subtypes. The pCR rates were examined according to each regimen and subtype. 3) The association of grade 3 pCR was examined with Ki-67, p53, aldehyde dehydrogenase (ALDH) 1 and topoisomerase 2A (topoIIα) by IHC and TOP2A by FISH for each regimen.

RESULTS: 1) In basal subtype, the pCR rate was significantly higher for FEC-D (42.9%) compared with TC6 (13.6%) (p=0.033), but it was equivalent in non-basal subtype (FEC-D vs TC: 25.0% vs 36.4%, p=0.554). 2) In BRCA1 subtype, it was more significant (FEC-D vs TC: 53.8 % vs 13.3%, p=0.022). 3) An association between pCR and low ALDH1 expression was found in both FEC-D and TC6 (OR: 3.75 and 2.73). High topo IIα protein expression was associated with pCR in FEC-D (OR: 3.5).

DISCUSSION: TC6 was less effective than FEC-D in basal subtype and BRCA1 subtype, showing that taxanes cannot exert their anticancer role in tumors with BRCA1 dysfunction. Although basal subtype may contain more BRCA1-defective tumors than non-basal subtype, MLPA of BRCA1 was better to identify subtype resistant to taxanes than CK5/6 and EGFR. ALDH1 predicted treatment efficacy, and could therefore represent a marker of resistance to conventional chemotherapy.

Citation Format: Takashi Ishikawa, Kazutaka Narui, Kazuhiro Shimada, Kumiko Kida, Mari S Oba, Mikiko Tanabe, Yasushi Ichikawa, Sadatoshi Sugae, Itaru Endo. BRCAness is important to identify TNBC subtype resistant to taxanes [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-27.
Abstract P3-06-31: Patient-derived xenografts accurately predict patient response in breast cancer patients
Authors: Stow Lisa , Katz Amanda , Irie Hanna , Port Elisa , Stebbing Justin , Ciznadija Daniel , Davies Angela , Paz Keren
Published: May 2015

PURPOSE/OBJECTIVES: A growing body of evidence demonstrates that patient-derived xenografts (PDXs) represent living tumor models that accurately reflect the biology of the primary patient tumor. More importantly, we have previously shown that PDX models show responses to therapeutic agents that are concordant with patient clinical response and can be used to direct personalized cancer treatments (Stebbing, 2014). Here we report the ability of PDX models to predict for patient response to drug treatment in a cohort of breast cancer patients.

MATERIALS/METHODS: Tumors were resected from patients with either primary or metastatic breast cancer and implanted into immunodeficient mice to establish PDX models. Successfully engrafted PDX models were expanded and randomized for drug sensitivity testing. Tumor growth inhibition and tumor regression were captured and results were correlated with a patient’s clinical response. In some cases, PDX results were used to personalize cancer treatment and some patients used PDX-directed treatments over multiple lines of therapy.

RESULTS: A total of 42 tumors from 40 patients were implanted resulting in 21 successfully engrafted PDX models (50% engraftment rate). Notably, engraftment rates were much higher for patients with triple negative breast cancer (TNBC) and resulted in 7 successful PDX models from 8 TNBC patients (87.5% engraftment rate). Drug sensitivity testing was offered to patients with established PDX models. Drugs and drug combinations tested included standard and nonstandard chemotherapy as well as biologics. At that time of this publication, 4 patients (3 TNBC and 1 HER2+) with completed drug sensitivity tests also had clinical data available resulting in 7 clinical correlations; 4 retrospective and 3 prospective. In all 7 cases, the PDX model accurately predicted patient clinical response demonstrating an accuracy of 100%. Five of the drug tests predicted drug sensitivity and 2 tests predicted resistance, indicating the potential of the PDX platform to predict for both sensitivity and resistance to therapy. The 3 prospective correlations resulted in concordant clinical benefit in 2 patients for duration greater than 6 months each.

CONCLUSIONS: These data support the use of the personalized PDX model as a platform for therapeutic decision making that can guide treatment for patients with breast cancer. A prospective clinical trial in TNBC is currently underway.

Citation Format: Lisa Stow, Amanda Katz, Hanna Irie, Elisa Port, Justin Stebbing, Daniel Ciznadija, Angela Davies, Keren Paz. Patient-derived xenografts accurately predict patient response in breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-31.