Valentina Aristarco

Dual Effect of Metformin on Breast Cancer Proliferation in a Randomized Presurgical Trial

PURPOSE Metformin is associated with reduced breast cancer risk in observational studies in patients with diabetes, but clinical evidence for antitumor activity is unclear. The change in Ki-67 between pretreatment biopsy and post-treatment surgical specimen has prognostic value and may predict antitumor activity in breast cancer. PATIENTS AND METHODS After tumor biopsy, we randomly allocated 200 nondiabetic women with operable breast cancer to either metformin 850 mg/twice per day (n = 100) or placebo (n = 100). The primary outcome measure was the difference between arms in Ki-67 after 4 weeks adjusted for baseline values. RESULTS Overall, the metformin effect on Ki-67 change relative to placebo was not statistically significant, with a mean proportional increase of 4.0% (95% CI, -5.6% to 14.4%) 4 weeks apart. However, there was a different drug effect depending on insulin resistance (homeostasis model assessment [HOMA] index > 2.8, fasting glucose [mmol/L] × insulin [mU/L]/22.5; P(interaction) = .045), with a nonsignificant mean proportional decrease in Ki-67 of 10.5% (95% CI, -26.1% to 8.4%) in women with HOMA more than 2.8 and a nonsignificant increase of 11.1% (95% CI, -0.6% to 24.2%) with HOMA less than or equal to 2.8. A different effect of metformin according to HOMA index was noted also in luminal B tumors (P(interaction) = .05). Similar trends to drug effect modifications were observed according to body mass index (P = .143), waist/hip girth-ratio (P = .058), moderate alcohol consumption (P = .005), and C-reactive protein (P = .080). CONCLUSION Metformin before surgery did not significantly affect Ki-67 overall, but showed significantly different effects according to insulin resistance, particularly in luminal B tumors. Our findings warrant further studies of metformin in breast cancer with careful consideration to the metabolic characteristics of the study population.

A presurgical study of lecithin formulation of green tea extract in women with early breast cancer

Epidemiologic data support an inverse association between green tea intake and breast cancer risk. Greenselect Phytosome (GSP) is a lecithin formulation of a caffeine-free green tea catechin extract. The purpose of the study was to determine the tissue distribution of epigallocatechin-3-O-gallate (EGCG) and its effect on cell proliferation and circulating biomarkers in breast cancer patients. Twelve early breast cancer patients received GSP 300 mg, equivalent to 44.9 mg of EGCG, daily for 4 weeks prior to surgery. The EGCG levels were measured before (free) and after (total) enzymatic hydrolysis by HPLC-MS/MS in plasma, urine, breast cancer tissue, and surrounding normal breast tissue. Fasting blood samples were taken at baseline, before the last administration, and 2 hours later. Repeated administration of GSP achieved levels of total EGCG ranging from 17 to 121 ng/mL in plasma. Despite a high between-subject variability, total EGCG was detectable in all tumor tissue samples collected up to 8 ng/g. Median total EGCG concentration was higher in the tumor as compared with the adjacent normal tissue (3.18 ng/g vs. 0 ng/g, P = 0.02). Free EGCG concentrations ranged from 8 to 65.8 ng/mL in plasma (P between last administration and 2 hours after <0.001). Free EGCG plasma levels showed a significant positive correlation with the Ki-67 decrease in tumor tissue (P = 0.02). No change in any other biomarkers was noted, except for a slight increase in testosterone levels after treatment. Oral GSP increases bioavailability of EGCG, which is detectable in breast tumor tissue and is associated with antiproliferative effects on breast cancer tissue. Cancer Prev Res; 10(6); 363–9. ©2017 AACR.

A Presurgical Study of Oral Silybin-Phosphatidylcholine in Patients with Early Breast Cancer

Silybin-phosphatidylcholine is an orally bioavailable complex of silybin, a polyphenolic flavonolignan derived from milk thistle, endowed with potential anticancer activity in preclinical models. The purpose of this window of opportunity trial was to determine, for the first time in early breast cancer patients, the breast tissue distribution of silybin. Twelve breast cancer patients received silybin-phosphatidylcholine, 2.8 g daily for 4 weeks prior to surgery. Silybin levels were measured before (SIL) and after (TOT-SIL) enzymatic hydrolysis by high-performance liquid chromatography (HPLC)-MS/MS in biologic samples (plasma, urine, breast cancer, and surrounding normal tissue). Fasting blood samples were taken at baseline, before the last administration, and 2 hours later. All patients were fully compliant and completed the treatment program. No toxicity was observed. SIL and TOT-SIL were undetectable in baseline samples. Despite a high between-subject variability, repeated administration of Siliphos achieved levels of TOT-SIL of 31,121 to 7,654 ng/mL in the plasma and up to 1,375 ng/g in breast cancer tissue. SIL concentrations ranged from 10,861 to 1,818 ng/mL in plasma and up to 177 ng/g in breast cancer tissue. Median TOT-SIL concentration was higher in the tumor as compared with the adjacent normal tissue (P = 0.018). No significant change in either blood levels of IGF-I and nitric oxide or Ki-67 in tumors was noted. Silybin-phosphatidylcholine, taken orally, can deliver high blood concentrations of silybin, which selectively accumulates in breast tumor tissue. These findings provide the basis for a future phase II biomarker trial in breast cancer prevention. Cancer Prev Res; 9(1); 89–95. ©2015 AACR.

A randomized, placebo-controlled, phase II, presurgical biomarker trial of celecoxib versus exemestane in postmenopausal breast cancer patients

In breast cancer presurgical trials, the Ki-67 labeling index predicts disease outcome and offers clues to the preventive potential of drugs. We conducted a placebo-controlled trial to evaluate the activity of exemestane and celecoxib before surgery. The main endpoint was the change in Ki-67. Secondary endpoints were the modulation of circulating biomarkers. Postmenopausal women with histologically confirmed estrogen receptor–positive breast cancer were randomly assigned to exemestane 25 mg/day (n = 50), or celecoxib 800 mg/day (n = 50), or placebo (n = 25) for 6 weeks before surgery. Changes in biomarkers were analyzed through an ANCOVA model adjusting for baseline values. Exemestane showed a median absolute 10% reduction in Ki-67 [from 22 (interquartile range, IQR, 16–27), to 8 (IQR 5–18)], and a 15% absolute reduction in PgR expression [from 50 (IQR 3–90) to 15 (IQR −0–30)] after 6 weeks of treatment. Exemestane significantly increased testosterone [median change 0.21 ng/mL, (IQR 0.12–0.35)], decreased SHBG [median change −14.6 nmol/L, (IQR −23.1 to −8.6)], decreased total and HDL cholesterol by −10 mg/dL (IQR −21–2) and −7 mg/dL, (IQR −14 to −2), respectively. Triglycerides were reduced by both agents [median change −0.5 mg/dL (IQR −17.5–13.5) and −8 mg/dL (IQR −28–9) for celecoxib and exemestane, respectively]. Exemestane showed a remarkable antiproliferative effect on breast cancer, whereas celecoxib did not affect breast cancer proliferation. Given the proven preventive efficacy of exemestane, these findings support the use of Ki-67 to explore the optimal exemestane dose and schedule in the prevention setting. Cancer Prev Res; 9(5); 349–56. ©2016 AACR.

Abstract 248: Association of vitamin D related polymorphisms with hereditary breast cancer in 431 patients wild type for BRCA1 and BRCA2 mutations

Background: A high proportion of Breast Cancer (BC) patients with a positive family history is not explained by mutations in BRCA1 and BRCA2 genes and the biology and BC outcome are different compared to patients with BRCA mutations. Low serum 25-hydroxyvitamin D (25(OH)D) has been found to be associated with an increased cancer incidence and poorer prognosis. Single nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) and vitamin D binding protein (VDBP) genes (also called GC (Globulin Complex)), may contribute to final vitamin D activity. The aim of this study is to assess the role of 25(OH)D and VDBP serum levels, VDR and GC SNPs on BC recurrence and survival in a cohort of patients with positive family history, wild type (WT) for BRCA1 and BRCA2. Methods: VDR (ApaI, FokI, TaqI, BsmI) and GC (rs2282679, rs4588, rs7041) SNPs were analyzed, by TaqMan SNP Genotyping Assays (Thermo Fisher Scientific), for 431 WT patients. Serum levels of 25(OH)D and VDBP were measured using an electro-chemiluminescence immunoassay (Abbott) and Human Vitamin D BP Quantikine ELISA kit (RD 95%CI: 0.27-0.68; and CC vs. CT HR=0.66; 95%CI: 0.45-0.99). Finally, low serum VDBP concentrations are significantly associated with a higher risk of BC recurrence (VDBP 321: HR=1.79; 95%CI: 1.03-3.13) and 25(OH)D>30 ng/ml in late summer/autumn vs Conclusions: 25(OH)D and VDBP serum levels were related with survival and breast cancer recurrence and influenced by genetic variants of GC SNPs. An allele VDR dose-related decrease of breast cancer recurrence was achieved with the increasing number of allele C of BsmI rs1544410(C>T). Our study provides evidence for the pivotal role of vitamin D metabolism in breast cancer outcome of high risk patients with a positive family history, wild type for BRCA1 or BRCA2 genes. Citation Format: Valentina Aristarco, Davide Serrano, Monica Barile, Davide Bondavalli, Mariarosaria Calvello, Debora Macis, Harriet Johansson, Aliana Guerrieri Gonzaga, Irene Feroce, Valeria Pensotti, Sara Gandini, Bernardo Bonanni. Association of vitamin D related polymorphisms with hereditary breast cancer in 431 patients wild type for BRCA1 and BRCA2 mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 248.

Abstract P4-08-05: Impact of common polymorphisms of CYP19A1 and UGT2B17 gene deletion on early endocrine-responsive postmenopausal breast cancer

Background Polymorphisms of genes involved in estrogen production have been linked to breast cancer risk, prognosis and treatment response. Polymorphisms of the aromatase gene CYP19A1 influence its activity. The UGT2B17 catalyzes glucuronic acid transfer to a variety of substrates, including steroids and drugs like the aromatase inhibitor exemestane. We investigated the impact of two variants of CYP19A1 (rs10046, rs4646) and the UGT2B17 gene deletion on disease outcome in 125 postmenopausal women operated for ER-positive primary breast cancer enrolled in a randomized pre-surgical trial. Patients Briefly, upon informed consent, postmenopausal patients with ER-positive breast cancer (stage T1–2, N0–1, M0) eligible for surgery were randomized to receive either exemestane (25 mg/day), or celecoxib (800 mg/day), or placebo for 6 weeks prior to surgery at the European Institute of Oncology (2004-2008). Exemestane showed a significant 10% absolute reduction in Ki67 labeling index compared to the other two arms. Serum and whole blood was taken at baseline and the day before surgery and stored at -80°C until assayed. Methods DNA was extracted from blood by QIAamp DNA Blood Kits. The CYP19A1 rs1004/rs46466 were analyzed by Taqman genotyping assays in real-time PCR. The UGT2B17 deletion was estimated by copy number assay (Lifetechnologies). Serum estradiol (E2) and estrone (E1) levels were measured by gas chromatography tandem mass spectrometry detection (GS-MS/MS) after liquid-liquid extraction. The lower limit of quantitation were 0.625 pg/mL for estradiol and 1.56 pg/mL for estrone. The association of genetic polymorphisms with “any event” was assessed by the Cox proportional hazards models adjusted for confounders. Results The genetic polymorphisms did not deviate from Hardy-Weinberg equilibrium (P-value >0.41) and minor allele frequency of rs10046 (A/G), rs4646 (C/A), and UGT2B17 Del were 0.45, 0.22, and 0.31, respectively. The rs10046 A and rs4646 C alleles were associated with higher estrogen levels. Carriers of rs10046 AA had median levels of 7.57 pg/ml E2 and 35.9 pg/mL E1 versus 3,9 pg/mL E2 and 27.4 E1 pg/mL in CA/AA genotypes (P Conclusions Our analysis confirms previous findings of an association of CYP19A1 rs10046/rs4646 with estrogen levels in postmenopausal women. Interestingly, the carriers of the variants associated with lower estrogen levels at diagnosis had better prognosis. Further genomic profiling in larger trials aimed to enhance tailored treatment efficacy in endocrine-responsive postmenopausal breast cancer are warranted. Citation Format: Johansson H, Gandini S, Aristarco V, Macis D, Guerrieri-Gonzaga A, Serrano D, Pruneri G, Lazzeroni M, Viale G, Toesca A, Rajasekaran A, Bonanni B, DeCensi A. Impact of common polymorphisms of CYP19A1 and UGT2B17 gene deletion on early endocrine-responsive postmenopausal breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-08-05.

Abstract CT122: A presurgical study of lecithin formulation of green tea extract in women with early breast cancer

Background: Epidemiologic data support an inverse association between green tea intake and breast cancer (BC) risk. Greenselect® Phytosome® (GSP) is a lecithin formulation of a caffeine-free green tea catechin extract. The purpose of the study was to determine the tissue distribution of Epigallocatechin 3-O-gallate (EGCG) and its effect on cell proliferation and other biomarkers in BC patients undergoing surgery. Methods: Twelve early BC patients received GSP, 300 mg daily for 4 weeks prior to surgery. The EGCG levels were measured before (free-) and after (total-) enzymatic hydrolysis by HPLC-MS/MS in plasma, urine, BC tissue and surrounding normal tissue. Fasting blood samples were taken at baseline, before the last administration and 2 hours later. Women were asked to avoid any tea for at least 14 days prior the beginning of the study and for the entire duration of the study. Results: All patients were fully compliant and completed the treatment program. No toxicity was observed. Free-EGCG and Total-EGCG were undetectable in baseline samples except for 1 patient with total-EGCG of 1 ng/mL in plasma. Despite a high between-subject variability, total EGCG was detectable in all tumor tissue samples collected (n = 8). Repeated administration of GSP achieved levels of total-EGCG ranging from 17 to 121 ng/mL in plasma, and up to 8 ng/g in BC tissue. Median total-EGCG concentration was higher in the tumor as compared to the adjacent normal tissue (P = 0.01).Urine EGCG levels correlated inversely with concentration in normal tissue (P = 0.01). Free-EGCG concentrations ranged from 8 to 65 ng/mL in plasma, but were under the limit of quantitation in tumor tissue and present in traces in adjacent normal breast tissue. Conclusions: Compared to other green tea extracts, GSP taken orally, appears to increase bioavailability of EGCG which selectively accumulates in breast tumor tissue. Biomarkers of activity will be presented at the conference. Citation Format: Matteo Lazzeroni, Aliana Guerrieri-Gonzaga, Sara Gandini, Harriet Johansson, Davide Serrano, Pietro Caldarella, Gianmatteo Pagani, Paolo Arnone, Giancarlo Pruneri, Valentina Aristarco, Antonella Puccio, Serena Mora, Antonella Riva, Giovanna Petrangolini, Paolo Morazzoni, Bernardo Bonanni. A presurgical study of lecithin formulation of green tea extract in women with early breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT122.

Abstract P4-11-16: Low serum adiponectin level is an independent risk factor of DCIS in postmenopausal women at increased risk of breast cancer

Background:The assessment of breast cancer (BC) risk is a key step for an effective preventive treatment. Besides the established risk assessment models, validation of independent predictive factors such as circulating biomarkers would improve patient selection and treatment efficacy. Obesity and metabolic imbalance play an important role in BC risk in menopausal women. The role of adipocytes in energy homeostasis is currently under investigation for their emerging relationship with BC. Adipokines (such as leptin and adiponectin) are linked to insulin sensitivity and have been related to BC risk and prognosis. Adiponectin, a peptide hormone secreted by the adipose tissue, has been inversely related to BC risk both in observational studies and in a phase II chemoprevention trial in premenopausal women at increased risk. Aim:We measured baseline serum adiponectin and leptin levels as well as HOMA index, in 534 postmenopausal women enrolled in 16 Italian centers and randomized in one of the two international phase III trials for BC prevention -the IBIS-II(Prevention) and IBIS-II(DCIS) trials- to assess whether these biomarkers were different in the healthy women at increased risk for BC cohort compared to the DCIS cohort. Methods:Healthy postmenopausal women (aged 40-70) at increased risk for BC (on an age-dependent risk model; n=186) or DCIS patients who underwent radical surgery in the previous 6 months (n=348) were eligible according to the two separate protocol entry criteria. At baseline, fasting blood was collected, processed and stored at -80°C till biomarkers measurement. Insulin and glucose levels were measured with the Architect system (Abbott Laboratories, Abbott Park, IL 60064 USA). Serum adiponectin and leptin levels were determined with Immunoassays by RD OR=2.49; 95% CI, 1.39-4.44, p= 0.0003) adjusting for center, BMI, HOMA index and age. Conclusions:Low serum adiponectin levels in postmenopausal women are more frequent in DCIS patients compared to healthy at risk subjects independently of BMI, HOMA index and age and results are similar to premenopausal women. Future investigations in both trials will assess whether adiponectin is also associated with BC events. Acknowledgments: J.Forbes and T.Howell, Co-Chairmen,IBIS-II Steering Committee. Citation Format: Aliana Guerrieri-Gonzaga, Debora Macis, Sara Gandini, Valentina Aristarco, Harriet Johansson, Giorgia Bollani, Teresa Roth, Maria-Teresa Sandri, Jill Knox, Jack Cuzick, Bernardo Bonanni. Low serum adiponectin level is an independent risk factor of DCIS in postmenopausal women at increased risk of 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 P4-11-16.

Abstract 1909: Associations of Vitamin D related polymorphisms with hereditary breast cancer in 1025 subjects undergoing BRCA 1/2 testing

Background: Vitamin D plays an important role in many normal body functions, including regulation of cell growth, bone formation, inflammation, neuromuscular and immune function. Lower serum levels of 25-hydroxyvitamin D, an index of vitamin D status, are associated with greater risk of cancer. Genetic variants in vitamin D related genes have been linked to breast cancer (BC) risk. These include the vitamin D receptor (VDR) and the GC gene that encodes for the vitamin D binding protein. Aims: To determinate the frequency of 5 single nucleotide polymorphisms (SNPs) of VDR and GC in a large cohort of subjects candidate to BRCA 1/2 genetic testing and to assess any interaction between vitamin D and BRCA pathways on disease outcome. Methods: From 2002 to 2012 blood samples from 1025 subjects with family history of ovarian cancer (OC) or BC were collected after informed consent was signed during the genetic counseling. DNA was extracted from whole EDTA treated blood and Allelic Discrimination (Applied Biosystems’ Taqman assays) of VDR (BsmI, FokI, TaqI, ApaI) and GC SNPs is ongoing. Results: At last follow-up in February 2014 our cohort included 272 unaffected subjects (117 BRCA carriers, 37 WT and 118 true negative) and 753 affected subjects (276 BRCA1/2 carriers, 469 WT and 1 true negative subjects). Amongst BC patients (N = 675), 221 were BRCA carriers, 446 WT, and 8 true negative. Those affected ofBC and OC (N = 27), included 23 BRCA carriers and 4 WT, while OC patients (N = 51) included 32 BRCA carriers and 19 WT. Here we present the preliminary data obtained for VDR and GC SNPs in 833 and 710 subjects, respectively. None of the genotypes deviated from the Hardy-Weinberg equilibrium. At the AACR meeting the genotyping of all subjects will be completed. Conclusions: Our results of vitamin D genotyping will be correlated with BC tumor molecular subtype in affected subjects, and any association with BRCA mutation and outcome will be assessed. The study was funded by IEO Foundation and AVON. Citation Format: Valentina Aristarco, Harriet Johansson, Debora Macis, Aliana Guerrieri Gonzaga, Sara Gandini, Davide Serrano, Irene Feroce, Monica Barile, Antonella Puccio, Lorenzo Brocca, Bernardo Bonanni. Associations of Vitamin D related polymorphisms with hereditary breast cancer in 1025 subjects undergoing BRCA 1/2 testing. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1909. doi:10.1158/1538-7445.AM2015-1909

Abstract P1-12-01: CYP19A1 and ESR1 polymorphisms and selected early-onset side effects during combined endocrine therapy in the IBCSG TEXT trial for premenopausal women with hormone receptor-positive (HR+) early breast cancer

Background: Single nucleotide polymorphisms (SNPs) of the aromatase enzyme (CYP19A1) and estrogen receptor alpha (ESR1) may be associated with breast cancer susceptibility and endocrine-mediated side effects. The IBCSG Tamoxifen (Tam) and Exemestane (Exe) Trial (TEXT) includes a translational research project to assess whether selected SNPs may influence treatment efficacy and toxicity. We report on early-onset hot flashes and sweating (HF/S) and musculoskeletal symptoms (MS; myalgia, arthralgia, stiffness) with respect to CYP19A1 and ESR1 SNPs under combined endocrine therapy. Patients and Methods: 2,672 premenopausal women with HR+ early breast cancer were randomized to treatment with the GnRH-agonist triptorelin (Trip)+Tam or Trip+Exe for 5 years. Randomization was stratified according to intended use of chemotherapy (yes/no) and lymph node status (N- vs N+). Estrogen-depletion side effects (HF/S and MS) were recorded at baseline, 3-monthly during the first year and 6-monthly thereafter using the NCI CTCAE v3.0. DNA was centrally extracted from whole blood with Qiagen kits. SNPs of CYP19A1 (rs4646 and rs10046) and ESR1 (rs207764, rs2234693 and rs9340799) were analyzed by a pyrosequencing method (Diatech Pharmacogenetics S.r.l., Jesi, Italy). Control genotypes (wt/wt; wt/v; v/v) for all SNPs were processed in each run. Logistic regression was used to analyze two endpoints: presence or absence of grade (gr) 2-3 HF/S during first 6 months and gr 2-4 MS during first 12 months. Four genetic models were used to explore associations with side effects: genetic (wt/wt; wt/v; v/v), additive, dominant and recessive. Results: DNA was isolated and genotyped for 1970 (74%) consenting women. Clinical characteristics and outcomes of this cohort were consistent with the overall trial. At baseline median age was 44, median BMI 24 kg/m2 and 86% had regular menses. During follow-up, 43% reported gr 2-3 HF/S and 27% reported gr 2-4 MS. The 5 SNPs did not deviate from Hardy-Weinberg equilibrium (p>0.30) and minor allele frequency ranged from 29%-48%. The CYP19A1 SNP rs10046 (C>T) was associated with gr 2-3 HF/S. Specifically, women with variant homozygote genotype (T/T) had a reduced risk of HF/S (39% T/T vs 45%). The univariate odds ratio (OR) was 0.77 (95%CI: 0.62-0.96; p=0.02) compared with other variant groups. The multivariate model showed consistent results after adjusting for age, BMI, menstrual status, chemo use, treatment allocation (Tam vs Exe) and baseline HF/S. The other 4 SNPs were not associated with the selected side effects. Conclusions: Our analysis indicates association of HF/S with CYP19A1 rs10046 genetic variants. The lack of association between early-onset of selected estrogen-depletion side effects and the other 4 SNPs may be masked by the concurrent Trip. Ovarian reserve before treatment may also influence the impact of SNP genotypes on early-onset side effects. Further analysis with details of concurrent medications and treatment adherence will contribute to the interpretation of these results. Funded by Susan G. Komen for the Cure. Citation Format: Harriet Johansson, Kathryn P Gray, Olivia Pagani, Meredith M Regan, Giuseppe Viale, Valentina Aristarco, Debora Macis, Antonella Puccio, Susanne Roux, Rudolf Maibach, Marco Colleoni, Manuela Rabaglio-Poretti, Alan S Coates, Richard D Gelber, Aron Goldhirsch, Roswitha Kammler, Bernardo Bonanni, Barbara A Walley. CYP19A1 and ESR1 polymorphisms and selected early-onset side effects during combined endocrine therapy in the IBCSG TEXT trial for premenopausal women with hormone receptor-positive (HR+) early 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 P1-12-01.