bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P4-06-28: Doxorubicin induces cellular senescence in human breast cancer cells and sensitizes them to cytotoxic T-lymphocytes
Authors: Inao T , Iida Y , Kotani H , Harada M
Published: May 2019

[Background]“Cellular senescence” is a state in which cells undergo irreversible cell cycle arrest in response to various cellular stresses. Senescence is induced in not only normal cells but also cancer cells when anti-cancer agents trigger DNA damage. Recent studies have revealed additional feature of senescent cells: increased secretion of various secretory proteins, such as inflammatory cytokines, chemokines, growth factors, and MMPs. This newly recognized senescent phenotype, termed senescence-associated secretory phenotype (SASP), reportedly contribute to tumor recurrence and promotion. Alternatively, senescent cancer cells could be good targets in anti-cancer immunotherapy because they are cell cycle-arrested.

[Objective]In this study, we determined whether ”cellular senescence” could be induced by a chemotherapeutic drug doxorubicin (DXR) and whether senescent cancer cells might increase their susceptibility to cytotoxic T-lymphocytes using human breast cancer cells.

[Methods and Results]A triple-negative (negative for ER, PR, and HER2) human breast cancer cell line (MDA-MB-231) was used. This cell line was treated with DXR for 2 days and examined for their appearance microscopically. The DXR treatment (500 nM) decreased their proliferating ability and increased their cell size. Colony formation assay revealed that cancer cells significantly decreased the number of colonies even with lower doses (3 nM) of DXR. In immunoblot assay, the DXR treatment increased the protein expression of p21, which inhibits cell cycle. In a flow cytometric assay after staining with SPIDER-β-gal, the DXR treatment (500 nM) increased the expression of β-gal in MDA-MB-231 cells. The induction of SA-β-gal in DXR-treated cancer cells were also confirmed by confocal imaging. In addition, the DXR treatment (500 nM) for 2 days beforehand increased their subsequent ability to produce IL-6 and IL-8. Although the DXR treatment (500 nM) decreased the expression of epidermal growth factor receptor (EGFR) on cancer cells, this treatment sensitized them to anti-EGFR chimeric antigen receptor (CAR) T-lymphocytes in apoptosis assay.

[Conclusion]These results suggest that a chemotherapeutic drug DXR can render MDA-MB-231 cells to be senescent and increase their sensitivity to antigen-specific cytotoxic T-lymphocytes. These findings may provide a rationale of combination of chemotherapy and T cell-based anti-cancer immunotherapy.

Citation Format: Inao T, Iida Y, Kotani H, Harada M. Doxorubicin induces cellular senescence in human breast cancer cells and sensitizes them to cytotoxic T-lymphocytes [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-06-28.
Abstract P4-07-10: Epithelial-mesenchymal transition sensitizes breast cancer cells to paraptosis-mediated cell death via the fungus-derived sesterpenoid, Ophiobolin A
Authors: Reisenauer K , Tao Y , Ingros A , Philip T , Evidente A , Kornienko A , Romo D , Taube J
Published: May 2019

The epithelial-mesenchymal transition (EMT) enables the dissociation of cancer cells from the primary tumor by facilitating tolerance to lack of cell-adhesion, decreasing cellular division and increasing motility of individual cells, which leads to an invasive phenotype that links EMT to metastasis. Furthermore, EMT results in the acquisition of stem-cell markers and an increased ability to initiate tumor growth, supporting the concept that EMT may contribute to the development of a small, persistent sub-population of the tumor called cancer stem cells (CSCs). Cells that have undergone EMT have characteristically suppressed cell cycles, making them resistant to commonly used chemotherapies that target DNA replication or microtubule dynamics, processes essential to replicating cells. Nonspecific treatments can also rely on inducing apoptotic cell death; however, recent debates challenge the efficacy of apoptosis in solid tumors, citing high rates of acquired resistance. Utilizing a compound that induces alternative cell death, namely paraptosis, becomes attractive when these other treatments fail. Relying on an activated gene expression program, paraptosis results in the swelling of the mitochondria and endoplasmic reticulum and Apaf-1-independent alternative caspase-9 activity. Treating with paraptosis-inducing compounds such as Ophiobolin A (OpA) specifically targets otherwise-insensitive CSC and EMT cells to re-sensitize bulk tumor populations to chemotherapies. We describe EMT as a key driver of enhanced sensitivity to paraptosis-induced cell death following short-term treatment with OpA or other paraptosis-inducing compounds. Further, paraptosis selectively eliminates the CSC sub-population by reducing stem cell activity and highlights the potential of this pathway in breast cancer treatment.

Citation Format: Reisenauer K, Tao Y, Ingros A, Philip T, Evidente A, Kornienko A, Romo D, Taube J. Epithelial-mesenchymal transition sensitizes breast cancer cells to paraptosis-mediated cell death via the fungus-derived sesterpenoid, Ophiobolin A [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-07-10.
Abstract P4-08-18: Not presented
Authors: Liu Y , Chen S , Jiang Y , Wu J , Shao Z
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Liu Y, Chen S, Jiang Y, Wu J, Shao Z. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-18.
Abstract P4-08-31: Withdrawn
Authors: Loughman T , Wang C-JA , Dynoodt P , Fender B , Lopez-Ruiz C , Barron S , Stapleton S , O'Leary D , Fabre A , Quinn C , Nodin B , Jirström K , Bracken A , Gallagher WM
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Loughman T, Wang C-JA, Dynoodt P, Fender B, Lopez-Ruiz C, Barron S, Stapleton S, O'Leary D, Fabre A, Quinn C, Nodin B, Jirström K, Bracken A, Gallagher WM. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-31.
Abstract P4-08-32: Derivation and validation of a novel prediction model in breast phyllodes tumors after surgery
Authors: Song E , Chao X , Nie Y , Jin X , Tan C , Cui J , Hu H , Yao H
Published: May 2019

Aim

This study aimed to develop a nomogram based on clinicopathological features to evaluate the recurrence probability of breast phyllodes tumors following surgery. The criteria for atypia, mitoses, overgrowth, and surgical margin (AMOS) were also validated.

Method

Data from 334 patients with breast phyllodes tumors, who underwent surgical treatment at Sun Yat-sen Memorial Hospital from January 2005 to December 2014, were used to develop a prediction model. Additionally, data of 36 patients from Peking University Shenzhen Hospital and data of 140 patients from Sun Yat-sen University Cancer Center during the same period were used to validate the model. The medical records and tumor slides were retrospectively reviewed. The log-rank and Cox regression tests were used to develop a clinical prediction model of breast phyllodes tumors as well as validating the AMOS criteriaAll statistical analyses were performed using R and STATA.

Results

Of all 334 patients included in the study, 224 had benign, 91 had borderline, and 19 had malignant tumors. The local and distant recurrence rate was 17.7%. The 1-,3-, and 5-year cumulative recurrence-free survival was 98.5%, 97.9%, and 96.8%, respectively. Surgical margin, mitoses, and tumor border were identified as independent risk factors for breast phyllodes tumors. A nomogram was developed based on these three variables. The C-index of internal and external validation was 0.71and 0.67, respectively. The area under the curve of AMOS criteria was 0.59.

Conclusions

The present study model presented a more concise and objective variables to evaluate the recurrence-free survival of patients after surgery compared with that using the AMOS criteria, which is more appropriate for clinical practice and also allows for a more accurate prediction.

Citation Format: Song E, Chao X, Nie Y, Jin X, Tan C, Cui J, Hu H, Yao H. Derivation and validation of a novel prediction model in breast phyllodes tumors after surgery [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-32.
Abstract P4-09-07: Higher risk of metachronous contralateral breast cancer in patients with invasive lobular breast cancer
Authors: Akdeniz D , Kramer I , van Deurzen CH , Schaapveld M , Westenend PJ , Voogd AC , Jager A , Steyerberg EW , Sleijfer S , Schmidt MK , Hooning MJ
Published: May 2019

Background: Risk of metachronous contralateral breast cancer (CBC) is an important health issue in primary breast cancer (PBC) survivors. Individualized CBC risk prediction can help identify patients at high or low risk who may or may not benefit from additional surveillance and treatment. For lobular PBC, inconsistent results have been reported on an association with increased risk of CBC. We investigated CBC risk in lobular versus ductal PBC using a large nationwide dataset and taking into account age at PBC and (neo-)adjuvant systemic therapy effects.

Patients and Methods: We selected women diagnosed between 2003 and 2010 with early invasive lobular, lobular mixed with other types, or ductal PBC from the Netherlands Cancer Registry. Categorical and continuous characteristics between the 3 groups were compared using the chi-square statistics and the Kruskal-Wallis test, respectively. Competing risk analyses were applied to determine CBC incidence. Multivariable subdistribution hazard ratios (SHRs) were adjusted for primary tumor stage, age at PBC diagnosis, radiotherapy, (neo-)adjuvant chemotherapy and endocrine therapy.

Results: We selected 74,373 women aged >18 years with lobular (n=8,903), lobular mixed (n=3,512), and ductal (n=62,230) PBC. Women with lobular PBC were older at diagnosis than women with lobular mixed or ductal PBC (61 vs. 58 vs. 58 years, respectively), more often had ER-positive PBC (95.7% vs. 94.1% vs. 79.6%) and were more often systemically treated with only endocrine therapy (30.7% vs. 24.9% vs. 19.7%), while less often treated with only chemotherapy (4.2% vs. 5.3% vs. 15.4%).

Ten-year cumulative CBC incidences in women with lobular, lobular mixed or ductal PBC were 3.2%, 3.6% and 2.8% when treated with systemic therapy (chemotherapy and/or endocrine therapy) and 6.6%, 7.7% and 5.6% without systemic therapy, respectively. Multivariable SHRs were 1.19 (95% CI: 1.05-1.34) for lobular and 1.39 (95% CI: 1.17-1.65) for lobular mixed versus ductal PBC; for women <50 years, risk differences were larger: 1.60 (95% CI: 1.26-2.05) and 1.43 (95% CI: 1.00-2.06), respectively.

Conclusion: Lobular histology and lobular mixed histology are independent risk factors for CBC development, and should be considered as prognostic factors when refining CBC risk prediction models.

Citation Format: Akdeniz D, Kramer I, van Deurzen CH, Schaapveld M, Westenend PJ, Voogd AC, Jager A, Steyerberg EW, Sleijfer S, Schmidt MK, Hooning MJ. Higher risk of metachronous contralateral breast cancer in patients with invasive lobular breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-09-07.
Abstract P4-10-02: Impact of raloxifene adherence in breast cancer risk
Authors: Chavez-MacGregor M , Lei X , Zhao H , Bevers TB , Brewster A , Giordano SH
Published: May 2019

BACKGROUND: Raloxifene is a selective estrogen receptor modulator that has demonstrated to reduce breast cancer risk and reduce the incidence of vertebral fractures. Based on these effects, raloxifene is used as a risk reduction agent and to prevent osteoporosis in postmenopausal women. Little is known about the raloxifene adherence rates or the relationship between adherence and breast cancer incidence.

METHODS: Women 60 years or older without a breast cancer history were identified in the MarketScan database (2008-2015). We identified women who received raloxifene by searching for prescription claims. Proportion of days covered (PDC) were calculated, adherence was defined as a PDC >80% in the first year after initial prescription claim. We identified factors associated with adherence. ICD-9 codes were used to identify incident cases of invasive breast cancer and cumulative incidence rates were calculated. A multivariable Cox model with propensity score method (matching variables included year of claim, age, comorbidities and family history of breast cancer) was used to evaluate the association between raloxifene adherence and breast cancer risk. All statistical tests were two-sided.

RESULTS: A total of 16,179 women were included in the analysis. We identified that during the first year of treatment 6,716 (40.2%) women had a PDC >80% and thus were considered to be adherent. Factors associated with increased adherence included the use of generic drug, mail order of 90 days supply and family history of breast cancer (all p<0.001). Using propensity score matching, the 5 year-cumulative incidence of invasive breast cancer was 1.5% among those not adherent and 0.9% among those adherent to raloxifene (p=0.01). Similarly, the 9 year-cumulative rates were 3.6% and 1.9% respectively (p=0.01). After adjusting for potential confounders, patients that were adherent to raloxifene during the first year of treatment had a lower risk of invasive breast cancer compared to those that were non-adherent (HR=0.64; 95%CI 0.04-0.9).

CONCLUSIONS: Among women 60 years of age or older receiving raloxifene, adherence to therapy was associated with lower risk of invasive breast cancer. Efforts to ensure adherence and compliance are crucial so patients can receive full benefit from this therapy.

Citation Format: Chavez-MacGregor M, Lei X, Zhao H, Bevers TB, Brewster A, Giordano SH. Impact of raloxifene adherence in breast cancer risk [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-10-02.
Abstract P4-10-03: Tobacco exposure and breast cancer
Authors: Dreher N , Layton TM , Parker BA , Shibley WP , Acerbi I , Wallace AM , Blair S , Pierce JP , Glantz S , Guydish J , Hiatt R , van 't Veer L , Esserman L ,   Athena Breast Health Network Investigators and Advocate Partners
Published: May 2019

Background: Smoking is a known risk factor for various types of cancer, and breast cancer patients who smoke are known to have higher breast cancer mortality. However, few studies have found an association between smoking and breast cancer incidence or tumor biology. The Athena Breast Health Network distributes an intake questionnaire at the UCSF and UCSD breast care centers which can be used to investigate links between tobacco exposure and the characteristics of incident breast cancer.

Methods: Intake questionnaires were distributed to all new patients at the UCSF and UCSD breast care centers from December 2012 to May 2018. Patients who completed the questionnaire with a known diagnosis of breast cancer were compared to those without in a case-control study. Breast cancer diagnoses were determined by ICD9 diagnosis codes from the patients' medical records. The association of smoking and breast cancer prevalence and biology was analyzed using generalized linear models and Fisher tests in R.

Results: Of the 7727 patients who completed the Athena intake questionnaire at UCSF and UCSD, 5499 consented to have their data used for research. A first analysis was conducted on 4175 UCSF patients alone: 2186 of the UCSF patients who had completed the questionnaire had a documented breast cancer diagnosis, vs 1989 with no known diagnosis at the time of this analysis. 1096 of the 4175 UCSF patients reported having ever smoked, including 73 who had accrued 30 or more pack years. Complete pathology data was available for 1120 cancer patients. Controlling for age, more patients with invasive breast cancer reported having ever smoked, with an odd's ratio (OR) of 2.32 (p = .0043). By including DCIS, the OR drops slightly to 2.26 (p = .0058). Taking alcohol consumption into account as a confounder lowered the OR to 2.19 (p = .0454). Overall, the risk of breast cancer increases with each additional pack year (OR = 1.08, p = .0211), independent of age. There are no significant differences in tumor biology for any smoking group.

Conclusions: A history of smoking is associated with an increased risk of developing breast cancer and is directly related to cumulative pack years exposure. This association should be further validated in cohort studies.

Citation Format: Dreher N, Layton TM, Parker BA, Shibley WP, Acerbi I, Wallace AM, Blair S, Pierce JP, Glantz S, Guydish J, Hiatt R, van 't Veer L, Esserman L, Athena Breast Health Network Investigators and Advocate Partners. Tobacco exposure and breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-10-03.
Abstract P4-10-10: Assessment of short inter-pregnancy interval in breast cancer diagnosed during pregnancy
Authors: Diaz-Perez H , Del Toro-Mijares R , Lopez-Martinez EA , Muñoz-Lozano JF , Fonseca A , Platas A , Martinez-Cannon BA , Barragan-Carrillo R , Castro-Carrasco J , Limon-Gomez S , Villarreal-Garza C
Published: May 2019

Background: The relationship between pregnancy and breast cancer (BC) risk is not fully understood. Most of the literature has described this interaction in terms of the age at first pregnancy and the number of full-term pregnancies. During the prospective accrual of the “Joven & Fuerte” young women with BC program in Mexico, we identified patients with pregnancy-associated BC (PABC) that experienced a short inter-pregnancy interval (SIPI) (<18 months between a live birth and the beginning of a following pregnancy). To our knowledge, there are no descriptions of the interaction between SIPI and PABC.

Objective: We aim to assess the occurrence of SIPI in patients with PABC, as well as describe their clinical features at presentation.

Results: We included patients accrued in the “Joven & Fuerte” program from August 2014 and June 2018 at three Mexican cancer centers. A total of 375 patients ≤40 years-old with newly-diagnosed BC were assessed. 37 patients were diagnosed with PABC (10%), 21 during pregnancy and 16 after pregnancy. 6/37 (16%) patients with PABC experienced a SIPI, all diagnosed during pregnancy (28% of 21). The main clinicopathological features are described in the table 1.

Table 1.Clinicopathological features of patients with PABC and SIPICaseAge at BC diagnosis (years)IPI (months)Pregnancy trimester at diagnosisStageBC subtype131183rdIIBNot available23262ndIIIAHR neg, HER2 pos337143rdIIAHR neg, HER2 pos436152ndIVHR pos, HER2 neg53142ndIIIAHR pos, HER2 neg63142ndIIICNot available

Conclusion: According to the phenomena seen in this cohort of young BC patients, we hypothesize that SIPI may increase the incidence and/or modify the clinical outcomes of PABC. The evidence from clinical and laboratory data suggest that the mechanisms that could alter the interaction include, but are not limited to, the prolongation of the exposure to high concentrations of estrogens or their genotoxic metabolites, interaction with the effect of progesterone and other pregnancy-associated hormones on breast tissue, and immunologic factors. To date, to our knowledge there is no evidence about the effect of SIPI in PABC. Thus, research in this area should be encouraged, particularly in vulnerable women in limited-resource settings, where SIPI is, unfortunately, a common occurrence, and might represent a risk factor for BC/PABC.

Citation Format: Diaz-Perez H, Del Toro-Mijares R, Lopez-Martinez EA, Muñoz-Lozano JF, Fonseca A, Platas A, Martinez-Cannon BA, Barragan-Carrillo R, Castro-Carrasco J, Limon-Gomez S, Villarreal-Garza C. Assessment of short inter-pregnancy interval in breast cancer diagnosed during pregnancy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-10-10.
Abstract P4-12-01: Not presented
Authors: Werutsky G , Villareal-Garza C , Moreno HG , Cartagena AA , Campos-Gomez S , Reyes RO , Lence JJ , Liedke P , Reinert T , Binotto M , Dybal V , Martinez-Mesa J , Freitas RD , Nunes Filho PR , Zaffaroni F , Barrios CH
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Werutsky G, Villareal-Garza C, Moreno HG, Cartagena AA, Campos-Gomez S, Reyes RO, Lence JJ, Liedke P, Reinert T, Binotto M, Dybal V, Martinez-Mesa J, Freitas RD, Nunes Filho PR, Zaffaroni F, Barrios CH. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-12-01.
Abstract P4-12-02: Age-related distress in 3352 breast cancer patients
Authors: Hill A , Obenchain R , Clark K , Loscalzo M , Mortimer J
Published: May 2019

Purpose: Age-related biopsychosocial distress in breast cancer patients has been poorly studied and understood. The breast cancer experience may be different based on chronological age, which may be a surrogate marker of biologic, psychological, social, and functional age. This study reports patient-reported biopsychosocial problem-related distress in breast cancer patients.

Methods: All new patients seen at the City of Hope breast cancer clinic undergo a validated comprehensive biopsychosocial screening prior to their first visit with a medical/surgical oncologist. This touchscreen driven technology queries patients on their physical symptoms, psychosocial concerns, informational and resource needs, interests in clinical trials, and other breast cancer specific concerns. This IRB approved study was conducted in 3,352 patients evaluated from 2009 to 2017. Screening occurred immediately prior to meeting with the physician so that the information could be integrated into the clinical encounter.

Results: The age-related groups included 268 Adolescent and young adult (AYA) patients ages 18-39, 2,244 middle aged adults 40-64 years, and 840 older adults ages 65+ years. Regardless of age, four of the top seven highly distressing problems were the same: worry about the future, side effects of treatment, sleep and fatigue. AYA patients and middle aged adults, but not older adults, identified finances and being anxious or fearful among their top five causes of distress. Middle aged adults and older adults, but not AYA patients, identified physical pain among their top seven causes of distress. Interestingly, both AYA and older adults, but not middle aged adults, identified getting information about complementary and alternative practices as a top source of distress. Although a serious problem across all age categories, thoughts of ending one's life and seriously considering taking one's life were the least common problems identified.

Conclusions: In this series with 3,352 patients, biopsychosocial concerns raised with a diagnosis of breast cancer were similar regardless of age. However, patients under the age of 65 may worry more about finances and patients over the age of 40 may worry more about physical symptoms such as pain. Both AYA patients and older adults cited distress learning about complementary and alternative practices, suggesting a need for providers to address this, especially in these patient populations. Thoughts of ending one's own life were uncommon, which is relevant in a state with the End of Life Option Act.

Citation Format: Hill A, Obenchain R, Clark K, Loscalzo M, Mortimer J. Age-related distress in 3352 breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-12-02.
Abstract P4-12-03: Prospective study: Impact of adjuvant chemotherapy with anthracyclines and taxanes in cognitive skills
Authors: Bella SR , Ferrari AI , Baiud MC , Cortes MN , Llugdar JR , Vigil ME
Published: May 2019

Introduction

Adjuvant chemotherapy is one of the outstanding treatments in the treatment of breast cancer. Many of its side effects are well known, while others are under study, as cognitive impairment.

One/eight women have breast cancer, which often affects a young population. Cognitive disorders produced by chemotherapy were studied with controversial results.

It seems convenient to study whether chemotherapy produces a cognitive impairment in a homogeneous group of patients receiving adjuvant chemotherapy with concomitant anthracycline cyclophosphamide followed by weekly paclitaxel (AC-T) in a prospective design.

Methods

Included patients had early-stage breast cancer (Stage I-II) and received AC-T (Anthracycline 60 mg/sqm - cyclophosphamide 600 mg/sqm and sequential weekly paclitaxel 80 mg/sqm) following surgery and before radiation therapy, as indicated. Her 2 positive patients also received adjuvant Trastuzumab therapy.

The cognitive deficit was estimated through the Addenbrooke's Cognitive Examination test, taken the day of the beginning of treatment, and at 3, 6 and 12 months later.

Beck Depression Inventory Test was used to assess depression. It was taken at the beginning of treatment and at 12 months later.

Control group was built by healthy people, which were examined with the same test just once.

Results

From October 2016 to April 2014, 108 patients were included in chemotherapy group and 50 in a healthy control group. 51 patients completed 12 months follow up examination.

Significant differences were found between patients and control group in attention, concentration, verbal fluency, language, visuospatial abilities and memory parameters.

These parameters were found impaired at the beginning of the treatment, having a favorable evolution at twelve months, with a complete resolution.

Orientation did not suffer significant changes during all study.

27/108 patients were found to be depressed at the beginning of treatment, with a favorable evolution of this parameter at twelve months.

Control group did not suffer from any cognitive deficit or depression.

Conclusions

In this prospective study, patients suffered cognitive deterioration at the beginning of treatment, which was recovered at the twelve-month follow-up.

Given the prevalence of depression in the chemotherapy group patients at the beginning of treatment versus the control group, this is probably the cause of the cognitive disorder.

Citation Format: Bella SR, Ferrari AI, Baiud MC, Cortes MN, Llugdar JR, Vigil ME. Prospective study: Impact of adjuvant chemotherapy with anthracyclines and taxanes in cognitive skills [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-12-03.
Abstract P4-12-04: Use of complementary and integrative medicine therapies in Chilean patients with breast cancer. Experience of a private center: prevalence and characteristics of patients
Authors: Salas C , Lopez G , Cadiz F , Barriga C , Gonzalez P , Acevedo S , Raimilla P , Pincheira P , Naing A , Quiroga M
Published: May 2019

Background: During the last decade several studies have been reported that the use of complementary and integrative medicine (CIM), defined as health care methods generated outside of standard Western, or conventional clinical practices has been increasing among breast cancer patients in developed countries. However, there is little information about the use of CIM in developing countries. Chile currently has no published statistics on the use of CIM in breast cancer.

Methods: We conducted a cross-sectional survey between March and June 2017 in breast cancer patients treated in Clinica Alemana de Santiago to determine the prevalence of CIM use and the types of preferred CIM. We also analyzed associations between CIM and several variables including sociodemographic variables, the reasons that motivated the use of CIM and the subjective benefits that patients attributed to CIM. Statistical analysis included two tailed t–test for continuous variables, Fischer's exact test for categorical variables and logistic regression for association between CIM use and other variables.

Results: 288 patients answered the survey. Among them, 98.9% were women, mostly between 41 and 50 years (40.4%). 44.9% (n = 129) reported using CIM. No association was found between the use of CIM and sociodemographic variables (sex, age, education, income). Most used CIM types were: vitamins / minerals (50.4%), herbs (48.8%), special diets (42.6%), meditation/prayers (37.2%). The reasons for CIM use were "to do everything possible" (72%), "improve immunity" (67.8%), "reduce side effects of treatment" (32.7%), recommendation by family member or friend (32.7%). Regarding CIM habits, 50.8% of patients reported having started CIM use at the time of diagnosis and only 51.6% reported about CIM use to their attending physician. Most patients reported benefits associated to CAM use (61%) but no differences were found in reported quality of life.

Conclusions: Great amount of the patients reported using CIM and half of them mentioned that they shared this information with their attending physician. It is necessary incorporate to medical routines questions regarding CIM use and to educate the patients regarding the safe use of CIM and the possible interactions of these approaches with conventional clinical practices.

Citation Format: Salas C, Lopez G, Cadiz F, Barriga C, Gonzalez P, Acevedo S, Raimilla P, Pincheira P, Naing A, Quiroga M. Use of complementary and integrative medicine therapies in Chilean patients with breast cancer. Experience of a private center: prevalence and characteristics of patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-12-04.
Abstract P4-13-04: Not presented
Authors: Cazzaniga ME , Blasi L , Pronzato P , Giordano M , Garrone O , Donadio M , Del Mastro L , Livi L , Natoli C , Michelotti A , Turletti A , Riccardi F , De Laurentiis M , Marchetti P , Montemurro F , Romagnoli E , De Placido S , Biganzoli L , Bologna A , Bria E , Mustacchi G
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Cazzaniga ME, Blasi L, Pronzato P, Giordano M, Garrone O, Donadio M, Del Mastro L, Livi L, Natoli C, Michelotti A, Turletti A, Riccardi F, De Laurentiis M, Marchetti P, Montemurro F, Romagnoli E, De Placido S, Biganzoli L, Bologna A, Bria E, Mustacchi G. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-13-04.
Abstract P4-14-04: Time course changes in serum FSH, estradiol, and menstruation restoration in premenopausal patients with breast cancer taking adjuvant tamoxifen after completing chemotherapy: A report from the ASTRRA study
Authors: Kim HJ , Noh WC , Nam SJ , Park B-w , Lee ES , Im SA , Jung YS , Yoon JH , Kang SS , Park KH , Lee S-J , Jung J , Lee MH , Cho SH , Kim SY , Kim H-A , Han S-H , Han W , Hur MH , Ahn SH
Published: May 2019

BACKGROUND

Assessment of restoration of ovarian function after chemotherapy is critical with respect to the initiation of different types of endocrine treatment in young high risk breast cancer patients

METHODS

In total, 1289 women who remained premenopausal or resumed premenopausal status after chemotherapy were randomized to receive 5 years of tamoxifen or 5 years of tamoxifen plus 2 years of ovarian suppression. The patients who did not resume menstruation were followed up for 2 years with tamoxifen treatment after finishing chemotherapy. Prospectively collected consecutive post-chemotherapy hormone and menstruation data were available for 705 breast cancer patients who enrolled tamoxifen-only treatment group or did not resume menstruation during follow up. This analysis evaluated the proportion of patients with pre-menopausal FSH levels (<30 mIU/ml), E2 levels (340 pg/ml), and menstruation at any time point during treatment with tamoxifen.

RESULTS

During 5 years of tamoxifen treatment after chemotherapy for premenopausal breast cancer patients, 62% of patients resumed menstruation. Menstruation returned in 92% of patients under 35 years old but only in 31% of patients over 45 years old. Ovarian function, defined by serum FSH and E2 levels, resumed in 94% and 65% of patients, respectively, over 5 years. Most patients achieved ovarian function restoration during the first 2 years after chemotherapy, with 47.1% resuming menstruation and 86.2% and 50.3% achieving pre-menopausal FSH and E2 levels, respectively, in the first 2 years. Clinical factors related to menstruation restoration were younger age (HR = 6.38, 95% CI 1.33-3.47), 6 month hormone profile after chemotherapy (FSH<30: HR=1.67, 95% CI 1.28-2.17; E2 >40: HR=2.96, 95% CI 2.25-3.89), and anthracycline without taxane chemotherapy (HR=1.63, 95% CI 1.25-2.13).

CONCLUSIONS

During 5 years of tamoxifen treatment after chemotherapy, half of patients experienced menstruation restoration, including most very young patients under 35 years. The majority of patients experienced menstruation restoration in the first 2 years of tamoxifen treatment.

Citation Format: Kim HJ, Noh WC, Nam SJ, Park B-w, Lee ES, Im SA, Jung YS, Yoon JH, Kang SS, Park KH, Lee S-J, Jung J, Lee MH, Cho SH, Kim SY, Kim H-A, Han S-H, Han W, Hur MH, Ahn SH. Time course changes in serum FSH, estradiol, and menstruation restoration in premenopausal patients with breast cancer taking adjuvant tamoxifen after completing chemotherapy: A report from the ASTRRA study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-14-04.
Abstract P4-15-03: Not presented
Authors: Yu K-D , Shao Z-M
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Yu K-D, Shao Z-M. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-15-03.
Abstract P4-15-04: Neoadjuvant endocrine therapy for ER+ DCIS can lead to disease regression and allows BCS in up to a third of patients with disease >40mm at diagnosis
Authors: Cartlidge CW , Johns N , Hackney RJ , Turnbull AK , Dixon JM
Published: May 2019

Background: The role of neoadjuvant endocrine therapy (NET) for ER+ DCIS is an area of evolving study. It may allow down-sizing prior to surgery, converting DCIS requiring mastectomy to disease suitable for breast conservation surgery (BCS). Here we report the results from the first European single-institution series of its type.

Methods: Data were prospectively collected from patients diagnosed with ER+ DCIS and treated with NET prior to surgery, at a single unit between 2009 -2015. The size of the tumour on initial imaging (mammography) was compared to the size of the tumour on final imaging and pathology using RECIST criteria to determine disease progression. Blocks from initial core biopsy and final pathology are being interrogated by immunohistochemistry and DNA and RNA comparisons.

Results: 42 patients diagnosed with ER+ DCIS received NET with median age at diagnosis of 63y (range 37-94y). 7/42 premenopausal women were treated with tamoxifen, 35/42 post-menopausal women were treated with letrozole.

36/42 (85.7%) patients underwent surgery with 18/36 (50%) requiring mastectomy and 18/36 (50%) treated by BCS. 3/18 (16.7%) of the BCS patients required re-excision for positive margins. The median time to operation was 72d (range 15-308d). In total 12/42 (28.6%) had invasive disease on final pathology.

2/36 (5.6%) patients had a pathological complete response (PCR), 14/36 (38.9%) had a partial response (PR), 17/36 (47.2%) had stable disease and 3/36 (8.3%) had larger disease on pathology than imaging; this is a common feature of many lower grade DCIS lesions.

26/42 (61.9%) patients initially had DCIS >40mm (largest 240mm) and yet 9/26 (34.6%) of these patients still underwent successful BCS.

There was a significant correlation between length of endocrine therapy and reduction in size of disease. Immunohistochemical and molecular analyses are ongoing.

Conclusions:

•NET is an effective treatment for ER+ DCIS. It reduces the rate of re-excision to 16.7% in this series - substantially lower than the national (UK) figures for DCIS at 30%.

•It produces path CRs (5.6%) and high response rates that relate to the duration of treatment.

•This unique study shows that the optimal duration of NET is of the order of 6 months, achieving high rates of conversion for mastectomy to BCS.

Citation Format: Cartlidge CW, Johns N, Hackney RJ, Turnbull AK, Dixon JM. Neoadjuvant endocrine therapy for ER+ DCIS can lead to disease regression and allows BCS in up to a third of patients with disease >40mm at diagnosis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-15-04.
Abstract P4-16-08: A regional audit of 6-hour monitoring for administration related reactions during the first administration of subcutaneous trastuzumab
Authors: Karmali S , Hughes N , Kinneally A , Kroes J , Cook J , Killian M , Shafiq T , O'Mahony D , Bird B , O'Connor M , O'Reilly S , Galiauskas R , Murphy CG
Published: May 2019

Introduction

In 2012, Subcutaneous Trastuzumab (TSC) was introduced as an alternative to Intravenous Trastuzumab (TIV) for HER2+ breast cancer. The pivotal HannaH study demonstrated that TSC was non-inferior to TIV, was preferred by patients, and serious administration related reactions (ARRs) were not reported. However, the Summary of Product Characteristics (SPC) advises that patients be observed for ARRs for 6 hours post-first administration (and 2 hours post-subsequent administrations), similar to TIV.

Aim

To assess the frequency and tolerability of ARRs during the 6-hour observation period post first administration of TSC in patients with HER2+ breast cancer.

Method:

A retrospective audit of TSC was conducted in Southwest Ireland across five centers from 2014-2016. Patient charts were reviewed to record ARRs reported on the first-administration or at subsequent visit. In addition a subset of patients were interviewed regarding their recollection of ARRs with first or subsequent injections.

Results:

The study is ongoing having identified 192 patients. These centers have administered 2111 TSC injections in total, associated with 4998 hours of observation as per SPC. From the 385 injections given over the first two TSC administrations, 13 injections (3.4%) were associated with ARRs within 24 hours. Nine patients (2.3%) experienced injection site reactions immediately post injection, one injection site pain (0.3%), and one experienced petechiae on subsequent exposure (0.3%). Three patients experienced pyrexia and dry cough 24 hours post-injection and were hospitalized for respiratory tract infection. There were no reactions experienced between 2 and 6 hours post-first injection. There were no serious ARRs. Telephone interviews are ongoing and these results will be reported.

Conclusion:

ARRs related to TSC are usually immediate, mild and self-limiting. Observing patients for 6 hours post-first injection and 2 hours post-subsequent injections represents an inefficient use of healthcare resources.

Citation Format: Karmali S, Hughes N, Kinneally A, Kroes J, Cook J, Killian M, Shafiq T, O'Mahony D, Bird B, O'Connor M, O'Reilly S, Galiauskas R, Murphy CG. A regional audit of 6-hour monitoring for administration related reactions during the first administration of subcutaneous trastuzumab [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-16-08.
Abstract P5-03-04: Targeting the tumor microenvironment by CXCR4 inhibition to abrogate trastuzumab resistance in HER2-positive breast cancer
Authors: Liu S , Xie SM , Yang-Kolodji G , Tripathy D
Published: May 2019

Background: Despite the fact that trastuzumab alongwithotherHER2-targetingdrugshavesignificantlyimprovedthe survival of patients with HER2 overexpression breast cancers (HER2+BC), resistance to trastuzumab is a clinical challenge in HER2+BC. Discerning actionable mechanisms of resistance to trastuzumab remains an important unmet need. WepreviouslyreporteddysregulationofCXCR4involvedintrastuzumab-resistance,butitscausal roleandthe associated mechanismsremainunknown.

Methods We established trastuzumab-resistant (TR) human breast cancer HER2+ cell lines by continuously exposing cells to trastuzumab (20 μg/ml) for at least 6 months. CXCR4 expressionwasassessed in TR cells or parental cells with Westernblot.QuantitativedensitometricanalysisofthedensitywasperformedwithAlphaViewSAsoftware.Relevant cell phenotypes were measured, including mammosphere formation, in vitro antibody-dependent cellular cytotoxicity (ADCC) assay, and cell invasion induced by 10% fetal bovine serum with or without 100ng/ml stromal cell-derived factor-1α (SDF-1α, CXCL12), the ligand of CXCR4. ANOVAwasusedtotest differencesbetweenmorethantwogroups,whilethedifferencesbetweentwogroupswereassessedbasedon pairedt-test.

Results: To better capture the heterogeneity of HER2+BC, we chose two trastuzumab-sensitive cell lines, BT474 (HER2+/HR+) and SKBR3 (HER2+/HR-) and an intrinsically trastuzumab-resistant cell line, HCC1419 (HER2+/HR-). We found much higher CXCR4 expression levels in cells with intrinsically trastuzumab-resistant cells compared to trastuzumab-sensitive cells. Upregulation of CXCR4 expression was found in each of the acquired TR cell lines compared to their parental cells. Dysregulation of CXCR4 significantly enhanced mammosphere formation and cell invasion (P < 0.001, respectively). SDF-1α induced cell invasion and clumping. Down-regulation of CXCR4 with shRNA significantly increased trastuzumab induced–antibody-dependent cellular cytotoxicity (2.17 folds of control cells, P < 0.01). Targeting CXCR4 with its approved inhibitor AMD3100 significantly decreased mammosphere formation and invasion of HER2+BC with TR (P < 0.01; P < 0.0001 respectively).

Conclusion: Our results suggest that the SDF-1-CXCR4 axis plays a critical role in resistance to trastuzumab. Targeting CXCR4 signaling may lead to novel combinational therapies to overcome intrinsic or acquired resistance to trastuzumab in advanced HER2+BC, including postulated effects of trastuzumab on signal transduction, differentiation and immune activation.

Citation Format: Liu S, Xie SM, Yang-Kolodji G, Tripathy D. Targeting the tumor microenvironment by CXCR4 inhibition to abrogate trastuzumab resistance in HER2-positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-03-04.
Abstract P5-03-13: ERVMER34 sensitizes the response of HER2 positive breast cancer to neoadjuvant therapy
Authors: Chi Y , Ji W , Xiu B , Zhang Q , Wu J
Published: May 2019

Although anti-HER2/neu antibody therapy combined with chemotherapy has achieved an outstanding effect, many patients with HER2-positive breast cancer still succumb due to therapeutic resistance. Understanding the mechanisms of therapeutic resistance is of vital importance. In this study, core needle biopsy tissue from HER2-positive patients was collected before neoadjuvant chemotherapy. Differentially expressed RNAs between pCR and non-pCR group have been identified through RNA-seq. Here we found that ERVMER34, an endogenous retroviral envelope protein was significantly inhibited in non-pCR group compared to pCR group. High ERVMER34 expression was associated with good overall survival both in TCGA database and our own patients cohort. Further study showed that ERVMER34 could be glycosylated and secreted to cell supernatant. The IC50 of paclitaxel and trastuzumab in HER2 positive breast cancer cells was decreased by ectopic overexpression of ERVMER34. Furthermore, RNA-seq, FACS assay and western blot revealed that ERVMER34 could promote cell apoptosis and sensitize therapy response through inhibiting mTOR pathway in HER2 positive breast cancer cells. Via mass spectrometry, TRIM21, an E3 ligase was found to interact with ERVMER34 and promoted its ubiquitination degradation. Taken together, these data suggest that ERVMER34 may severve as a novel biomarker to predict therapy response in HER2 positive breast cancer.

Citation Format: Chi Y, Ji W, Xiu B, Zhang Q, Wu J. ERVMER34 sensitizes the response of HER2 positive breast cancer to neoadjuvant therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-03-13.
Abstract P5-03-15: Mechanism of activation of PPP1R1B drug-resistance gene in trastuzumab-resistant Her2+ breast cancer
Authors: Momand J , Murad R , Ma X , Geng S , Mortazavi A
Published: May 2019

Trastuzumab (Herceptin) resistance is a persistent challenge in the treatment of metastatic Her2+ breast cancer, with an average relapse time of 1 year after treatment. Human breast cancer cell-lines (SKBr3 and BT474) selected for trastuzumab resistance have a PPP1R1B gene (chr17:39,626,924-39,636,626) that is transcriptionally activated compared to their drug-sensitive counterparts. PPP1R1B codes for two related protein products, Darpp-32 (long) and t-Darpp (short), that are overexpressed in 50% of clinical breast cancer samples in comparison to normal breast tissue; reintroduction of t-Darpp into drug-sensitive cells confers drug resistance. The mechanism controlling overexpression of these transcripts is unknown. To gain insight into this mechanism we used ATAC-seq to map open chromatin areas in trastuzumab-resistant breast cancer cell lines and compared their open chromatin areas to those in the parental trastuzumab-sensitive counterparts. The PPP1R1B gene consists of 7 canonical exons. In each trastuzumab-resistant line there is two significantly increased open chromatin peaks, one within exon 2 and one within exon 3. We are performing deep sequencing (>200 million reads) to identify transcription factor footprints in these peaks. Furthermore, we performed RNA-seq analysis and identified genes that are similarly regulated in the resistant lines in comparison to their drug-sensitive counterparts. In summary, these results shed light on an area of high clinical importance and point to potential drug targets to be developed to overcome trastuzumab resistance in Her2+ breast cancer.

Citation Format: Momand J, Murad R, Ma X, Geng S, Mortazavi A. Mechanism of activation of PPP1R1B drug-resistance gene in trastuzumab-resistant Her2+ breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-03-15.
Abstract P5-04-19: Withdrawn
Authors: Ghassemifar S , Finn G , Zhang H , Richardson J , Kuesters G , Santillana S , Pipas M
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Ghassemifar S, Finn G, Zhang H, Richardson J, Kuesters G, Santillana S, Pipas M. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-04-19.