Negative Metastatic Breast Cancer Patients Research Articles

242P Impact of metastases directed radiation therapy on CDK4/6 inhibitors treatment for metastatic breast cancer

Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) represent the standard I-II line for hormonal receptors positive/human epidermal growth factor receptor 2 negative metastatic breast cancer (MBC) patients. Metastases directed radiotherapy (RT) for these patients is commonly used with palliative or ablative schedules during systemic treatment. There is still a lack of robust data on the safety concerning RT during CDK4/6i treatment.

Efficacy of everolimus-containing chemotherapy in HER2 negative metastatic breast cancer patients with PI3K/AKT/mTOR mutations: A retrospective study.

e13069 Background: The PI3K/AKT/mTOR pathway is frequently altered in breast cancer. Everolimus is a selective inhibitor of mammalian target of Rapamycin (mTOR).The benefit of everolimus in metastatic breast cancer patients with PI3K/AKT/mTOR mutations remains unclear, especially in TNBC patients. Our study aimed to investigate the efficacy of the everolimus-containing chemotherapy in metastatic breast cancer patients with PI3K/AKT/mTOR mutations. Methods: 13 cases of HER2- metastatic breast cancer with PI3K/AKT/mTOR mutations treated with everolimus-containing chemotherapy were analyzed. The genetic profile in PI3K/AKT/mTOR pathway was studied. Results: Overall, 4 cases were hormone receptor (HR) positive and 9 were TNBC. 7 patients only had PIK3CA mutations, 1 patient had only PIK3R1 mutations, and 5 patients had other mutations in the pathway in addition to PIK3CA, including PTEN, PIK3CB, CTNNB1, FGFR1 and TSC2. 5 cases were treated as first or second line chemotherapy, and 8 were as third line or above. The ORR (CR+PR) was 38.5% (5/13), and DCR (CR+PR+SD) was 84.6% (11/13), including 5 cases of PR, 6 cases of SD, and 2 cases of PD. The median PFS was 5.8 months (95% CI 3.7-9.7), and the median OS was 14.3 months (95% CI 6.47-null). However, the ORR of TNBC patients was higher than that of HR-positive, which were 44.4% (4/9) and 25% (1/4), respectively ( p = 0.070). The mPFS was also longer than that of HR-positive with 5.8 months versus 1.7 months, as well as the mOS with 14.3 versus 3.8 months. We also found that the patients carrying other mutations besides PIK3CA in the PI3K/AKT/mTOR pathway had a longer PFS compared to the patients without other mutations, which was 9.7 months and 4.3 months respectively ( p = 0.272). And the DCR of the two groups were 100% and 75% respectively ( p = 0.451). Conclusions: We found that everolimus-containing chemotherapy was effective in the treatment of HER2- metastatic breast cancer with PI3K/AKT/mTOR pathway activation. TNBC patients had a trend of longer mPFS than HR+ patients. And the patients carrying other mutations besides PIK3CA in the PI3K/AKT/mTOR pathway have a trend of longer PFS and higher DCR compared to the patients without other mutations. However, trails with larger samples are needed for further verification.

Real-world Indian scenario of CDK4/6 inhibitors (palbociclib and ribociclib) with endocrine therapy in upfront hormone positive metastatic breast cancer.

e13028 Background: CDK4/6 inhibitors (CDKi), in combination with endocrine therapy (ET), has become the standard of care in the treatment of hormone positive (HR+)/ HER2 neu negative metastatic breast cancer (MBC) patients. We evaluated clinical outcomes and toxicity in MBC patients, who have received ET with two CDKi, namely palbociclib and ribociclib. Methods: This is an ambispective, single institutional analysis of de-novo HR+ MBC patients treated with CDKi (palbociclib 125 mg and ribociclib 600 mg once a day for 21 days /28 days cycle) from November 2016- October 2020 at AIIMS, New Delhi, India. The primary endpoint was progression-free survival (PFS) and the secondary endpoint was response rate and toxicity. A total of 157 female patients were recruited in this study however the response and toxicity data were available in 120 cases. All premenopausal women received ovarian suppression or ovarian ablation. Results: A total of 120 patients were included in this study with a median age of 57 years (35-75) and 93 (77.5%) cases were postmenopausal. Twenty-three (19.1%) patients had a bone-only disease, 49 (40.9%) had bone and visceral disease and 48 (40%) had only visceral disease. In this study 91 (75.9%) patients received palbociclib and 29 (24.2%) received ribociclib. The median PFS was 18 months (4-36). Twenty four (20%) patients achieved a complete response, 69 (57.5%) patients attained partial response, 18(15%) patients had stable disease and 9 (7.5%) had disease progression. Grade 3–4 neutropenia, thrombocytopenia, and anaemia were observed in 18(15%), 8 (6.7%), and 4 (3.3%) cases respectively. None of the patients developed febrile neutropenia. Cutaneous, renal, hepatic, and gastrointestinal toxicity was observed in 1,1,3,4 cases respectively. Prolonged QTc was observed in one case. Grade 3 fatigue was observed in 7 cases. Dose interruption/delay (mean dose delay of 7 days), dose modification, and drug discontinuation were observed in 24 (20%), 12 (10%), and 10 (8.3%) of cases respectively. Conclusions: This is one of the largest real-world Indian data on CDK4/6 inhibitors on upfront HR+ MBC. Side effects are less than published literature with similar efficacy. Neutropenia was the most common side effect which was managed by brief dose interruption.

Local Laboratory Testing of Germline BRCA Mutations vs. Myriad: A Single-Institution Experience in Korea.

Genetic diagnosis for human epidermal growth factor receptor 2-negative metastatic breast cancer patients with the germline BRCA (gBRCA) mutation has been emphasized since the development of polyadenosine diphosphate-ribose polymerase inhibitors. Myriad Genetics, Inc.’s (Salt Lake City, UT, USA) companion diagnostics service is almost exclusively used for genetic testing. The aim of this study was to compare the results of germline BRCA mutation tests returned by a local laboratory and those performed by Myriad. Between April 2014 and February 2018, 31 patients with gBRCA 1/2 mutation test results from both Samsung Medical Center (Seoul, Korea) and Myriad were enrolled. “Discordant: Opposite classification” was observed for only one among 27 (3.7%). This discrepancy was due to the detection of a deleterious large genomic rearrangement of BRCA 1 by Myriad. Samsung Medical Center performed multiple ligation-dependent probe amplifications (MLPA) to detect large genomic rearrangements only in high-risk patients. This one case was not suspected as high risk and MLPA was not performed. The concordant rate was 74.1% for all 27 patients. “Discordant: Laboratory’s uncertain classification” was found in 22.2% of the sample (six patients). All discrepancies were generated during interpretation of BRCA 2 gene sequencing. Further studies and standardization of genetic testing for BRCA 1/2 genes are required.

Longitudinal Multi-Parametric Liquid Biopsy Approach Identifies Unique Features of Circulating Tumor Cell, Extracellular Vesicle, and Cell-Free DNA Characterization for Disease Monitoring in Metastatic Breast Cancer Patients.

Dynamics of mRNA from circulating tumor cells (CTCs), mRNA from extracellular vesicles (EVs), and cell-free DNA (cfDNA) were assessed to examine the relevance of a longitudinal multi-parametric liquid biopsy strategy. Eighteen milliliters of blood was drawn from 27 hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) patients at disease progression and at two subsequent radiologic staging time points. CTC mRNA and EV mRNA were analyzed using multi-marker qPCR, and cfDNA was analyzed using targeted next-generation sequencing (NGS). The presence of ERBB2 or ERBB3 overexpression signals in CTCs significantly correlated with disease progression (87% specificity, 36% sensitivity, p-value = 0.023), and the presence of either ERBB3 signals in CTCs or EVs or cfDNA variants in ERBB3 also showed a significant association with progressive MBC. Fluctuations during treatment were detected in the EV fraction with the appearance of hitherto undetected ERCC1 signals correlating with progressive disease (97% specificity, 18% sensitivity, p-value = 0.030). Allele frequency development of ESR1 and PIK3CA variants detected at subsequent staging time points could be used as a predictor for therapy success and, importantly, might help guide therapy decisions. The three analytes, each with their own unique features for disease monitoring, were shown to be complementary, underlining the usefulness of the longitudinal multi-parametric liquid biopsy approach.

Real-World Clinical Data of Palbociclib in Asian Metastatic Breast Cancer Patients: Experiences from Eight Institutions.

PurposeUse of cyclin-dependent kinase 4/6 inhibitors improved survival outcome of hormone receptor (HR) positive metastatic breast cancer (MBC) patients, including Asian population. However, Asian real-world data of palbociclib is limited. We analyzed the real-world clinical practice patterns and outcome in HR-positive, MBC Asian patients treated with palbociclib.Materials and MethodsBetween April 2017 to November 2019, 169 HR-positive, human epidermal growth factor-2–negative MBC patients treated with letrozole or fulvestrant plus palbocilib were enrolled from eight institutions. Survival outcome (progression-free survival [PFS]), treatment response and toxicity profiles were analyzed.ResultsMedian age of letrozole plus palbociclib (145 patients, 85.8%) and fulvestrant plus palbociclib (24 patients, 14.2%) was 58 and 53.5 years, with median follow-up duration of 14.63 months (range 0.2 to 33.9 months). Median PFS (mPFS) of letrozole plus palbociclib and fulvestrant plus palbociclib was 25.6 (95% confidence interval [CI], 19.1 to not reached) and 6.37 months (95% CI, 5.33 to not reached), comparable to previous phase 3 trials. In letrozole plus palbociclib arm, luminal A (hazard ratio, 2.86; 95% CI, 1.20 to 6.80; p=0.017) and patients with good performance (Eastern Cooperative Oncology Group 0–1 [hazard ratio, 3.68; 95% CI, 1.70 to 7.96]) showed better mPFS. In fulvestrant plus palbociclib group, chemotherapy naïve patients showed better mPFS (hazard ratio, 12.51, 95% CI, 1.59 to 99.17; p=0.017). The most common grade 3 or 4 adverse event was neutropenia (letrozole 86.3%, fulvestrant 88.3%).ConclusionTo our knowledge, this is the first real-world data of palbociclib reported in Asia. Palbociclib showed comparable benefit to previous phase 3 trials in Asian patients during daily clinical practice.

Impact of metastases directed radiation therapy on CDK4/6 inhibitors dose reduction and treatment discontinuation for metastatic HR+/HER2- breast cancer (MBC).

562 Background: Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) represent the standard I-II line for hormonal receptors positive/human epidermal growth factor receptor 2 negative metastatic breast cancer (MBC) patients. Metastases directed radiotherapy (RT) for these patients is commonly used with palliative or radical schedules during systemic treatment. Although encouraging preliminary results were published, there is still a lack of robust data on the safety concerning RT during CDK4/6i treatment. Methods: we analyzed at Our Institution 85 consecutive patients treated in I (n=47) and II line (n=38) for MBC with CDK4/6i between April 2017 and September 2019 (22 ribociclib, 63 palbociclib). Overall, 25 (29.4%) patients received metastases directed RT during CDK4/6i treatment, including 14 concomitant (16.5%) and 11 sequential (12.9%). Estimated CDK4/6i half-life is 26 and 30 hours for palbociclib and ribociclib, respectively. Five half-lives are required to reduce drug concentration by 95-97%; thus, we also analyzed CDK4/6i treatment as non-concomitant or sequential to RT. Main endpoints of our analysis were impact of RT on CDK4/6i dose reduction and discontinuation, overall adverse events rate (any grade and grade ≥2), and neutropenia grade ≥2 as per CTCAE scale version 5.0. Results: at a median follow up of 12 months (range 3-29), we observed a CDK4/6i dose reduction in 35 patients (41.2%) and 5 patients (5.9%) discontinued treatment due to adverse events; 82 patients (96.5%) experienced any grade of toxicity, 72 (84.7%) a grade ≥2 and 70 patients (82.4%) neutropenia grade ≥2. We did not observe significant difference in terms of CDK4/6i dose reduction or discontinuation, any grade or grade ≥2 toxicity, neutropenia grade ≥2 in the comparison between patients receiving RT versus no RT and between patients receiving concomitant RT versus sequential RT versus no-RT (Table). Conclusions: our results showed that the prescription of a metastases directed RT during treatment with a CDK4/6i as I-II line for MBC did not significantly impact on dose reduction or discontinuation caused by an exceeding in adverse event rate. Although these promising results, caution should be used and cooperative initiatives strongly encouraged. [Table: see text]

Glucose Metabolic Reprogramming of ER Breast Cancer in Acquired Resistance to the CDK4/6 Inhibitor Palbociclib.

The majority of breast cancers express the estrogen receptor (ER) and are dependent on estrogen for their growth and survival. Endocrine therapy (ET) is the standard of care for these tumors. However, a superior outcome is achieved in a subset of ER positive (ER+)/human epidermal growth factor receptor 2 negative (HER2−) metastatic breast cancer patients when ET is administrated in combination with a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, such as palbociclib. Moreover, CDK4/6 inhibitors are currently being tested in ER+/HER2+ breast cancer and reported encouraging results. Despite the clinical advances of a combinatorial therapy using ET plus CDK4/6 inhibitors, potential limitations (i.e., resistance) could emerge and the metabolic adaptations underlying such resistance warrant further elucidation. Here we investigate the glucose-dependent catabolism in a series of isogenic ER+ breast cancer cell lines sensitive to palbociclib and in their derivatives with acquired resistance to the drug. Importantly, ER+/HER2− and ER+/HER2+ cell lines show a different degree of glucose dependency. While ER+/HER2− breast cancer cells are characterized by enhanced aerobic glycolysis at the time of palbociclib sensitivity, ER+/HER2+ cells enhance their glycolytic catabolism at resistance. This metabolic phenotype was shown to have prognostic value and was targeted with multiple approaches offering a series of potential scenarios that could be of clinical relevance.

Abstract P2-15-08: Efficacy and possible predictive factors of eribulin in a real-world population of HER-2 negative metastatic breast cancer patients in Japan

Abstract Background Eribulin mesylate, a non-taxane microtubule inhibitor, has unique characteristics that modify the tumor microenvironment by reversing epithelial-mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET). These effects might benefit the efficacy of chemotherapies, particularly those administered after eribulin. In fact, the EMBRACE study demonstrated that eribulin did not prolong progression-free survival (PFS) but rather overall survival (OS) when compared to the treatment of physician’s choice (TPC). However, the effects of eribulin on post-eribulin chemotherapy regimens remain unclear. Thus, this retrospective study aimed to assess PFS, OS, and post progression survival (PPS) of women with HER-2 negative metastatic breast cancer (MBC) as real-world data. In addition, clinical and pathological factors were analyzed as predictive factors for the survival measurements. Furthermore, the effect of eribulin on post-eribulin chemotherapies was also evaluated by assessing PFS of post-eribulin chemotherapy compared with PFS of eribulin and PFS of pre-eribulin chemotherapy. Methods A total of 75 women with HER-2 negative MBC who were treated with eribulin between January 2011 and June 2019 were included in this study. PFS, OS, and PPS were calculated according to the Kaplan-Meier method for each patient. The clinical and pathological factors analyzed in this study were hormone receptors, age, number of prior regimens, metastatic site, number of metastatic sites, and hematologic parameters such as neutrophil (NEU) counts, lymphocyte (LYM) counts, and neutrophil to lymphocyte ratio (NLR). A cox model was used to correlate these factors with survivals. In this study, PFS of the post-eribulin chemotherapy cohort divided by PFS of the eribulin-receiving cohort or PFS of the pre-eribulin chemotherapy cohort was analyzed as a unique parameter of the PFS ratio (PFSr, the former was PFSr A and the latter was PFSr B). A PFS ratio of 1.0 or higher may be the significantly favorable effect of eribulin on post-eribulin chemotherapy. Of a total of 75 patients, 46 and 36 were analyzed for assessing PFSr A and B, respectively, since patients who were not eligible for the calculation of PFSr were excluded. Single and multiple regression analyses were used to evaluate the associated factors with PFSr B. Results The median PFS, OS, and PPS were 3.5 months (95%CI 2.5-4.4), 13.1 (95% CI 9.4-16.7), and 13.1(95%CI 9.4-22.9), respectively. In univariate analysis, an age of 65 or older (p=0.001) and lower NLR (p=0.003) were associated with longer PFS. In multivariate analyses, an age of 65 or older (p=0.041) and lower NLR (p=0.008) were associated with superior PFS. NEU counts lower than 4500 (p=0.0028) and lower NLR (p=0.003) were correlated with longer OS in both univariate and multivariable analyses. There were no correlating factors with PPS. The median PFSr A and B were 0.86 and 0.65, respectively, and the percentages of PFSr A and B were 43% and 33%, respectively. Single and multiple regression analysis each showed that none of the factors are correlated with PFSr B. Conclusion The median PFS and OS in our study were comparable to those reported in the EMBRACE study which were 3.7 and 13.1 months, respectively. Age and NLR were associated with PFS and NEU count and NLR was associated with OS. The correlation of NEU count and NLR with PFS and OS suggests that the effects of eribulin might be diminished by a high inflammatory state but enhanced by higher oncologic immune status. In terms of eribulin’s effect on post-eribulin chemotherapy, no conclusive data were obtained in this study, and a larger number of patients should be analyzed. Citation Format: Sera Satoi, Hiroyuki Takei, Keiko Yanagihara, Tomoko Kurita, Maki Nakai, Meishi Hankyo, Rina Kanamaru, Ai Sato. Efficacy and possible predictive factors of eribulin in a real-world population of HER-2 negative metastatic breast cancer patients in Japan [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-08.

Abstract P2-15-14: Triple negative (TNBC) metastatic breast cancer (MBC) patients (pts): Is chemotherapy (CHT) choice influenced by adjuvant (adj) treatments? Results from the GIM-13 AMBRA study

Abstract Background: TNBC shows a very bad prognosis: median time to relapse is 18 months and median overall survival (OS) is less than 24 months. Methods: AMBRA is a longitudinal cohort study, describing the choice of 1st- and subsequent treatments in HER2-ve MBC pts in the years 2012-2015. The present analysis is focused on TNBC pts (127 out of 879 evaluable; 14.4%) and CHT strategies, overall and according to adj treatment. Kaplan Meyer probability of survival from primary (DFS), 1st(PFS1) and 2nd(PFS2) progression and Time from last CHT and death were calculated for the whole population and according the main adj regimens. Results: Median age at primary diagnosis was 53 years. The most used regimens in the adj setting were anthra/taxane(tax) 50.7%, anthra 22.1% or others (CMF included) 20.6%. Median time to events was: DFS 23.2, PFS1 6.5 and PFS2 4.3 months, respectively. CHT choices in the metastatic setting according to adj treatment were: Adj Anthra-basedAdj Taxane-basedAdj other1st-lineTax* 57.6% - VRL/CAPE 18.2% - Plat 15.2% Other 3% - None 6.1%Tax* 46.2% - VRL/CAPE 24.6% Plat 24.6% - Other 4.6%Tax*52% - VRL/CAPE 16% - Anthra 16% - Anthra/Tax 8%2nd-lineTax**18.2% - Anthra 13.6% - VRL/CAPE 22.7% - Plat 27.3% - Erib 9.1% - Other 9.1%Tax**22% - VRL/CAPE 22% Plat 22% - Erib 14.6% - Other 17.1%VRL/CAPE 38.5% - Anthra 23.1% - Tax**23.1% - Plat 15.4%3rd lineVRL/CAPE 37.5% - Erib 25% - Anthra 18.8% - Tax***12.5% - Plat 6.3%Erib 26.9% - VRL/CAPE 23.1% - Plat 15.4% - Anthra 11.5% - Tax***11.5% - Other 11.5%VRL/CAPE 42.9% - Erib 28.6% - Plat 14.3% - Other 14.3%*docetaxel 8.4%, nab-paclitaxel 7%, paclitaxel 59%**docetaxel 7%, nab-paclitaxel 71.4%, paclitaxel 21%***docetaxel 20%, nab-paclitaxel 80%At a median follow up of 3.3 years 50% of pts are still alive. OS rates at 5 and 8 years from primary are 50% and 40%. OS rates from 1st progression are 50% and 20% at 22 and 40 months. Median OS (months) according to 1st line regimen was similar (ns) across the regimens (paclitaxel+bevacizumab: 17.8; Platinum-based: 14.1; CAPE/VRL: 16.3). Median time from last CHT and death was 1.5 months (29.6%< 1 month; 14% < 2 weeks) Conclusion: Our results show that taxanes play a crucial role in MBC even if used in 50% of Adj. CAPE/VRL, Platinum regimens and Eribuline are also widely used. Time from last CHT administration and Death is very short in 30% of cases Citation Format: Giorgio Mustacchi, Alessandra Beano, Alessandra Fabi, Lorenzo Livi, Antonio Bernardo, Ferdinando Riccardi, Paolo Marchetti, Ornella Garrone, Lucrezia Diodati, Laura Biganzoli, Monica Giordano, Anna Turletti, Livio Blasi, Andrea Milani, Clara Natoli, Marta Riemma, Alessia D'Alonzo, Grazia Arpino, Paolo Pronzato, Marina E Cazzaniga, on behalf of GIM-13 AMBRA Study Group. Triple negative (TNBC) metastatic breast cancer (MBC) patients (pts): Is chemotherapy (CHT) choice influenced by adjuvant (adj) treatments? Results from the GIM-13 AMBRA study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-14.

Abstract P5-11-18: Real-world evidence of efficacy and activity of palbociclib plus endocrine therapy and post-progression treatments in HR+/HER2- metastatic breast cancer patients: The PALPract study

Abstract Background: Several randomized clinical trials clearly demonstrated that adding palbociclib (P) to endocrine therapies (ET), such as letrozole (LT) or fulvestrant (FLV), significantly improves outcome both in first-line/endocrine sensitive and second-line/endocrine resistant hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2) metastatic breast cancer (MBC) patients (pts). The aims of the present study were to assess efficacy, activity and toxicity of P combined with either LT or FLV in a real world setting, and to study the efficacy and activity of treatments administered after progression to P + ET. Methods: Records of 245 consecutive HR+/HER2- MBC patients from 14 Italian cancer centers were reviewed in this observational study. Primary end-point was progression-free survival (PFS) obtained with P+ET; secondary end-points were overall response rates (ORR) and clinical benefit rate (CBR) obtained with P+ET and with post-progression treatments, as well as overall survival (OS), PFS to subsequent treatment lines and post-progression survival (PPS). Results: Overall 245 pts were treated with P+ET from April 2014. Of them, 116 (47%) received it in first-line setting, 70 (28%) in second-line and the rest (68 pts, 25%) in subsequent lines. Median age was 60 (35-80) years and median ECOG performance status was 0. Seventy-three pts (30%) had more than two metastatic sites and 75 (31%) had visceral metastasis. Ninenty-one (37%) pts received P+LT and 92 (37%) were treated with P+FLV. For 15 (6%) premenopausal pts an LHRH analogue was added to P+ET. In 77 (41%) patients a biopsy of a metastatic lesion was performed. Among the 116 pts treated in first-line setting, median PFS was 14.7 (95% CI 12.0-17.3) and 15.1 (95%CI 8.6-21.6) months for pts receiving P+LT and P+FLV, respectively. ORR was 48% (95% CI: 39-57%) and CBR was 75% (95% CI, 66-82%). Four (3%) complete responses (CR), 52 (45%) partial responses (PR), 31 (27%) stable disease (SD) and 11 (9%) progression disease (PD) were observed as best response; 18 pts were not yet evaluable. Among the 70 pts treated in second-line setting, median PFS was 10.8 (95%CI 0-24.3) and 7.9 (95%CI 3.3-12.5) months, for pts receiving P+LT and P+FLV, respectively. The ORR was 26% (95% CI: 16-38) and the CBR was 66% (95% CI, 53-76). One CR (1%), 17 PR (24%), 28 SD (40%) and 13 PD (18.5%) were observed as best response, while 9 were not yet evaluable. Best response was achieved after a median of 5 cycle. At time of the current analysis, 50 pts experienced PD during P+ET. Of them, 38 (76%) received chemotherapy (capecitabine, eribulin, nab-paclitaxel, paclitaxel+bevacizumab, vinoreline) and 12 (24%) ET. To date, only 5 pts progressed during these therapies, preventing us for evaluating secondary end-points regarding efficacy and activity. The most frequent adverse event (AE) was grade 3-4 neutropenia (31%), with febrile neutropenia reported in 5 (2%) cases. Main non-hematological AEs were fatigue and gastrointestinal symptoms (diarrhea and stypsis). Conclusions: Our findings confirm the efficacy and safety of P+ET as first/second-line treatment for HR+/HER2- MBC pts, even in a non-selected, real world population. Since data regarding the efficacy and activity of post-progression therapies were not mature at the time of the current analysis, they will be subsequently presented. Citation Format: Alessandra Fabi, Michelangelo Russillo, Mariangela Ciccarese, Simone Scagnoli, Francesco Schettini, Giuseppe Buono, Vito Lo Russo, Grazia Arpino, Rosalba Rossella, Giuseppina Sarobba, Marianna Giampaglia, Patrizia Pellegrini, Simonetta Stani, Michela Palleschi, Vincenzo Adamo, Francesca Morelli, Maria Agnese Fabbri, Cecilia Nistico, Gianluigi Ferretti, Giovanna Catania, Simona Pisegna, Diana Giannarelli, Francesco Cognetti. Real-world evidence of efficacy and activity of palbociclib plus endocrine therapy and post-progression treatments in HR+/HER2- metastatic breast cancer patients: The PALPract study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-18.

Abstract OT2-02-05: A randomized trial of abemaciclib in combination with fulvestrant compared to chemotherapy in women with HR+, HER2- advanced breast cancer with visceral metastases

Abstract Background: Abemaciclib is a potent oral cyclin-dependent kinase (CDK) 4 and 6 inhibitor that demonstrated statistically significant improvement in progression-free survival (PFS) and objective response rate (ORR) in combination with endocrine therapy (ET) in hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced and metastatic breast cancer patients in Phase 3 studies. In contrast to NCCN guidelines, cytotoxic chemotherapy is still often initiated early in the course of HR+, HER2- advanced breast cancer despite absence of visceral crises, potentially denying patients effective and tolerable standard-of-care regimens containing ET. The current study aims to compare the efficacy and safety of abemaciclib in combination with ET to chemotherapy in patients with HR+, HER2- advanced breast cancer with ≥1 site of visceral metastases. Trial design: I3Y-MC-JPCU is a multicenter, open-label, randomized, controlled study of abemaciclib in combination with fulvestrant compared to physician’s choice of chemotherapy in women with HR+, HER2- locally advanced or metastatic breast cancer who have poor prognosis due to visceral metastases. Approximately 300 patients will be randomized 1:1 to Arm A (abemaciclib, 150 mg BID, in combination with fulvestrant, n=150) or Arm B (physician’s choice of chemotherapy [capecitabine, docetaxel, nab-paclitaxel, or paclitaxel], n=150). Stratification factors will include liver metastasis, sensitivity to endocrine therapy (sensitive vs primary resistance vs secondary resistance, and postmenopausal status (natural/surgical/therapeutic radiation vs GnRH use). It will be conducted in the USA. Accrual is planned to start in 2019. Eligibility: Key inclusion criteria are postmenopausal HR+, HER2- patients with locally advanced recurrent and unresectable or metastatic HR+, HER2- breast cancer and ≥1 site of visceral metastasis as well as disease progression after ≥1 line of ET in (neo)adjuvant or metastatic setting. Individuals will be excluded if they have visceral crisis, have received prior systemic therapy other than ET for metastatic disease, have received >1 prior ET for metastatic disease, and/or have been treated with fulvestrant or any CDK 4 and F6 inhibitor for any duration. Objectives: The primary objective is ORR. Secondary objectives include PFS, time to response, duration of response, time to second disease progression (PFS2), and safety. Exploratory objectives include healthcare resource utilization, patient reported outcomes, and relationship of pharmacogenomics/biomarkers to clinical outcomes. Statistical Methods: Comparability of abemaciclib in combination with fulvestrant to chemotherapy will be evaluated with respect to ORR and PFS. The study is designed to demonstrate comparability using a 10% ORR margin and a 20% PFS margin. Comparability will declared if the posterior probability the true difference is less than the comparability margin is at least 80%. PFS comparability will be assessed only if ORR comparability is declared after a gatekeeping testing strategy. The tested hypotheses will be 1) ORR comparability: ≥80% posterior probability that true ORRArm B - true ORRArm A <10% with 10% the defined margin for ORR comparability; and 2) PFS comparability (gated secondary endpoint): ≥80% posterior probability that true PFS hazard ratioArm A/Arm B - 1 <0.2, with 0.2 being the defined margin for PFS comparability. Citation Format: Peter Kaufman, John Glaspy, Wei Zhang, Andrew Koustenis, Yanyun Chen, Adam Brufsky. A randomized trial of abemaciclib in combination with fulvestrant compared to chemotherapy in women with HR+, HER2- advanced breast cancer with visceral metastases [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-02-05.

Present issues regarding BRCA genetic testing and genetic counseling in medical care for HBOC patients in Japan

Abstract One of 400 to 500 general people has a germ-line pathogenic variant in BRCA 1 or 2, and those with such variants are diagnosed as HBOC. Since women with HBOC have extremely high risk of breast and ovarian cancer, they need to take action to avoid death due to those cancers. But how can we find them? We should screen suspicious people by their personal and family histories. We most frequently use NCCN guidelines to find them. They recommend BRCA genetic testing for all patients with personal history of ovarian, male breast, pancreatic or metastatic prostate cancer, and breast cancer patients with young onset, and/or family history of breast, ovarian, prostate, and/or pancreatic cancer. And after the approval of Olaparib for breast cancer, all HER2 negative metastatic breast cancer patients have become candidates for the BRCA genetic testing to check if Olaparib is usable or not. If we consider patients’ ages of breast cancer diagnosis and/or family histories of cancers mentioned above, the positive rate will be high, but if we do the testing for all HER2 negative metastatic breast cancer patients, it will be around 5%. Genetic counseling is quite important to do the BRCA genetic testing in suspicious people and recommend women with HBOC to take cancer surveillance and/or risk-reducing surgery. For now, we have a big problem in genetic counseling in most Japanese hospitals. Specialists in genetics, especially genetic counselors, are expected to play an important role in genetic counseling. But there are only 243 certified genetic counselors in Japan. This number is not only small, but the majority of them are not good at hereditary cancers. Physicians and surgeons are also required to do genetic counseling in medical care of HBOC. To improve their knowledge and skills that are required in performing genetic counseling of hereditary cancer syndromes including HBOC, educational workshops have been held by several societies. I will present them briefly.

Cell-Free DNA Variant Sequencing Using CTC-Depleted Blood for Comprehensive Liquid Biopsy Testing in Metastatic Breast Cancer.

Liquid biopsy analytes such as cell-free DNA (cfDNA) and circulating tumor cells (CTCs) exhibit great potential for personalized treatment. Since cfDNA and CTCs are considered to give additive information and blood specimens are limited, isolation of cfDNA and CTC in an “all from one tube” format is desired. We investigated whether cfDNA variant sequencing from CTC-depleted blood (CTC-depl. B; obtained after positive immunomagnetic isolation of CTCs (AdnaTest EMT-2/Stem Cell Select, QIAGEN)) impacts the results compared to cfDNA variant sequencing from matched whole blood (WB). Cell-free DNA was isolated using matched WB and CTC-depl. B from 17 hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) metastatic breast cancer patients (QIAamp MinElute ccfDNA Kit, QIAGEN). Cell-free DNA libraries were constructed (customized QIAseq Targeted DNA Panel for Illumina, QIAGEN) with integrated unique molecular indices. Sequencing (on the NextSeq 550 platform, Illumina) and data analysis (Ingenuity Variant Analysis) were performed. RNA expression in CTCs was analyzed by multimarker quantitative PCR. Cell-free DNA concentration and size distribution in the matched plasma samples were not significantly different. Seventy percent of all variants were identical in matched WB and CTC-depl. B, but 115/125 variants were exclusively found in WB/CTC-depl. B. The number of detected variants per patient and the number of exclusively detected variants per patient in only one cfDNA source did not differ between the two matched cfDNA sources. Even the characteristics of the exclusively detected cfDNA variants in either WB or CTC-depl. B were comparable. Thus, cfDNA variants from matched WB and CTC-depl. B exhibited no relevant differences, and parallel isolation of cfDNA and CTCs from only 10 mL of blood in an “all from one tube” format was feasible. Matched cfDNA mutational and CTC transcriptional analyses might empower a comprehensive liquid biopsy analysis to enhance the identification of actionable targets for individual therapy strategies.

Abstract PD2-03: Circulating tumor DNA (ctDNA) and circulating tumor cells (CTC) predictive value in HER2 negative metastatic breast cancer patients treated with first line weekly paclitaxel and bevacizumab: Results of a prospective cohort from the French Breast Cancer InterGroup Unicancer (UCBG): COMET study

Abstract Background: Increased levels of CTC and a persistent elevated level after just one cycle of chemotherapy are very strong and independent markers of worse progression-free survival (PFS) and overall survival (OS) in patients (pts) with metastatic breast cancer (MBC) (Bidard et al, Lancet Oncol 2014). ctDNA can be used to detect mutation associated with resistance to treatment. It has also been shown that dynamic changes in ctDNA levels closely reflect changes in tumor burden. We prospectively monitored CTC and ctDNA early variations during first line chemotherapy for MBC. Patients & methods: The French cohort COMET is a prospective study including first line HER2 negative patients (pts) receiving weekly paclitaxel and bevacizumab according to EMA approved combination. The aim of this cohort is to evaluate clinical, biological and radiological parameters associated with pts outcome (CTC, serum markers, ctDNA, pharmacogenomic polymorphisms, metabolomic parameters, visceral fat, serum estradiol level and quality of life). We present here the first planned analysis on pts evaluated for CTC (CellSearch) and ctDNA using targeted sequencing (Roche SeqCap technology) of a panel of 46 genes and 8 promoters, using unique molecular identifiers to increase ctDNA detection sensitivity. Blood samples were obtained at baseline (BL) and before the second cycle of chemotherapy (C2). Results: From 09/2012 to 5/2014, 218 pts were included in this substudy. Median age was 55 years and 22% of pts had triple negative BC. At BL, 70% of pts had ≥1 detectable CTC per 7.5 ml of blood (median 4 CTC, range 1- 30,000) and 37% at C2. With a threshold of ≥5 CTC, 47% of pts were positive at BL and 22% at C2. For ctDNA, out of the first 141 pts analyzed, 105 had at least one somatic mutation detected in plasma (74%). The average number of mutations per pt was 2.7 and most commonly mutated genes were TP53 and PIK3CA. ESR1 was found mutated in 9% of all cases and restricted to the ER+ subgroup. Median Allelic Frequency was 10% (range 0.6-83%). Only 33% of pts had detectable ctDNA at C2. At BL, CTC and ctDNA levels were correlated (r=0.46, p<0.0001). Despite no complete overlap, 11% of pts had no CTC nor ctDNA detected. Median follow-up was 53 months and median OS was 32 months. Increased level of CTC and ctDNA were significantly associated with decreased PFS and OS. At C2, ≥5 CTC or still detectable ctDNA were strong markers of reduced OS: HR 4.6 (CI95 3.1-7) and HR 3.2 (CI95 1.8 – 5.5), respectively (both p< 0.0001). At multivariate analysis for PFS, detectable ctDNA at C2 and triple negative status were the only significant prognostic factors. None of serum marker level at BL or their early variations had prognostic value. Conclusion: This is the largest prospective cohort assessing the respective prognostic values of early CTC and ctDNA changes in homogenously treated first line MBC patients. Analysis of mutations profile variations and comparison with primary tumor and metastasis biopsies are ongoing and may reveal early mechanisms of resistance. Citation Format: Pierga J-Y, Silveira A, Lorgis V, Tanguy M-L, Tredan O, Dubot C, Jacot W, Goncalves A, Debled M, Levy C, Ferrero J-M, Jouannaud C, Luporsi E, Mouret-Reynier M-A, Dalenc F, Lemonnier J, Berger F, Proudon C, Bidard F-C. Circulating tumor DNA (ctDNA) and circulating tumor cells (CTC) predictive value in HER2 negative metastatic breast cancer patients treated with first line weekly paclitaxel and bevacizumab: Results of a prospective cohort from the French Breast Cancer InterGroup Unicancer (UCBG): COMET 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 PD2-03.

Abstract P6-09-02: Effects of palbociclib on thymidine kinase-1 (TK1) in hormone receptor positive (HR+) breast cancer cell lines

Abstract Introduction: TK1 plays a crucial role in DNA synthesis and is a well-established marker of cell proliferation. We and others have previously described the potential role of TK1 activity (TKa) as predictive biomarker of response to endocrine therapy in HR+/HER2 negative metastatic breast cancer patients. TK1 synthesis is regulated by the E2F pathway, the target pathway of CDK4/6 inhibitors, and TKa has recently been reported as a potential circulating pharmacodynamic marker of CDK4/6 inhibition in breast cancer. However, modulations of TK1 levels and activity during palbociclib treatment and in the development of treatment resistance are unknown. Here, we report how TK1 expression and TKa are modulated in response to palbociclib in a panel of HR+ breast cancer cell lines: both palbociclib-sensitive (PDS) and with acquired resistance to (PDR). Material and methods: We used a panel of 7 PDR HR+ breast cancer models previously developed in our lab via chronic exposure of parental cells (MCF7, T47D, ZR75-1, BT474, MDAMB361 and two MCF7 endocrine resistant derivatives) to escalating doses of palbociclib, from a Starting Treatment Concentration (STC) of 50 nM or 350 nM according to the cell line, up to 1 μM. We analyzed gene expression profiles of PDS cells treated with drug vehicle (DMSO) as a control or palbociclib at STC for 3 days, and PDR cells grown with palbociclib 1 μM. Cell proliferation was assessed by methylene blue assay in MCF7 and BT474 PDS and PDR treated for 3, 6 and 9 days with DMSO, palbociclib STC and 1 μM. In parallel, TKa was measured in cell lysates at 3 days of treatment using the DiviTumTM assay (Biovica, Sweden). Results: Among E2F target genes, gene expression data demonstrated that TK1 was one of the most differentially expressed genes between PDR and PDS treated cells. In PDS cells compared to control, treatment with palbociclib resulted in reduced TK1 expression, with the HER2 positive models (BT474 and MDAMB361) showing the highest reduction. In PDR cells, TK1 expression was higher, but remained slightly inhibited compared to untreated PDS cells. TKa was significantly reduced in PDS cells treated with palbociclib for 3 days compared to vehicle (p<0.05). TKa response to palbociclib was more dramatic in BT474 cells as compared to MCF7. As expected, palbociclib inhibited cell proliferation in PDS models, with a significant reduction observed only after 6 days of treatment, suggesting that TKa may be an early marker of growth inhibition in response to palbociclib. No significant alterations in TKa were observed in PDR cells, at any dose of palbociclib. Similarly, proliferation rate was not affected by palbociclib in PDR cells. Conclusions: TK1 expression and activity are regulated by palbociclib in HR+ breast cancer cell lines, particularly in HER2 positive models. Ongoing studies of TKa in patients treated with palbociclib will assess the role of TKa as a circulating biomarker for predicting and monitoring response to CDK4/6 inhibitors. Citation Format: Bonechi M, Migliaccio I, Benelli M, Romagnoli D, Bergqvist M, Mattsson K, Boccalini G, Capaccioli G, De Luca F, Galardi F, Biagioni C, Risi E, McCartney A, Rossi L, Osborne CK, Schiff R, De Angelis C, Guarducci C, Di Leo A, Malorni L. Effects of palbociclib on thymidine kinase-1 (TK1) in hormone receptor positive (HR+) breast cancer cell lines [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 P6-09-02.

The prognostic and therapeutic implications of circulating tumor cell phenotype detection based on epithelial\u2013mesenchymal transition markers in the first-line chemotherapy of HER2-negative metastatic breast cancer

BackgroundEpithelial–mesenchymal transition (EMT) is implicated in the metastatic process and presents a challenge to epithelial cell adhesion molecule-based detection of circulating tumor cells (CTCs), which have been demonstrated to be a prognostic indicator in metastatic breast cancer. Although evidence has indicated that heterogeneity of CTCs based on EMT markers is associated with disease progression, no standard recommendations have been established for clinical practice. This study aimed to evaluate the prognostic significance of dynamic CTC detection based on EMT for metastatic breast cancer patients.MethodsWe enrolled 108 human epidermal growth factor receptor 2-negative metastatic breast cancer patients from the prospective phase III CAMELLIA study and applied the CanPatrol CTC enrichment technique to identify CTC phenotypes (including epithelial CTCs, biphenotypic epithelial/mesenchymal CTCs, and mesenchymal CTCs) in peripheral blood samples. Receiver operating characteristic curve analyses of total CTC count and the proportion of mesenchymal CTCs for predicting the 1-year progression-free survival (PFS) rate were conducted to determine the optimal cut-off values, and Kaplan–Meier analysis and Cox proportional hazards regression analysis were performed to investigate the prognostic value of the cut-off values of both total CTC count and the proportion of mesenchymal CTCs in combination.ResultsFor predicting the 1-year PFS rate, the optimal cut-off value of total CTC count was 9.5 (Area under the curve [AUC] = 0.538, 95% confidence interval [CI] = 0.418–0.657), and that of the proportion of mesenchymal CTCs was 10.7% (AUC = 0.581, 95% CI = 0.463–0.699). We used the two cut-off values in combination to forecast PFS in which the total CTC count was equaled to or exceeded 10/5 mL with the proportion of mesenchymal CTCs surpassed 10.7%. Patients who met the combined criteria had significantly shorter median PFS than did those who did not meet the criteria (6.2 vs. 9.9 months, P =0.010). A nomogram was constructed based on the criteria and significant clinicopathological characteristics with a C-index of 0.613 (P = 0.010).ConclusionsThe criteria, which combine the total CTC count and the proportion of mesenchymal CTCs, may be used to monitor therapeutic resistance and predict prognosis in patients with metastatic breast cancer.Trial registrationClinicalTrials.gov. NCT01917279. Registered on 19 July 2013, https://clinicaltrials.gov/ct2/show/NCT01917279?term=NCT01917279&rank=1.

Time to treatment failure of palbociclib and letrozole as second-line therapy or beyond in hormone receptor-positive advanced breast cancer.

The management of endocrine therapy resistance is one of the most challenging facets of advanced breast cancer treatment. Palbociclib is an inhibitor of cyclin-dependent kinases 4 and 6 approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer in combination with fulvestrant in postmenopausal women with disease progression following endocrine therapy. However, treatment responsiveness of tumors to palbociclib after multiple lines of endocrine therapy is not clearly established. The purpose of this study was to determine the efficacy of palbociclib and letrozole in patients pretreated with one or more lines of endocrine therapy. This was a single-center, retrospective cohort study of all postmenopausal hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer patients who received palbociclib and letrozole as a second-line endocrine therapy or beyond (and no prior cyclin-dependent kinases 4 and 6 inhibitor therapy) between February 1, 2015, and July 31, 2016. The primary objective was to evaluate time to treatment failure of palbociclib in combination with letrozole as a second-line of therapy or beyond. Fifty-three patients meeting eligibility criteria were included in the analysis. For the primary outcome, the median time to treatment failure of palbociclib and letrozole was 6.3 months (95% CI 3.1-7.4 months). Progression-free survival of palbociclib and letrozole therapy was 6.4 months (95% CI 4.9-8.3 months). Palbociclib and letrozole therapy is a viable, effective treatment option for metastatic breast cancer patients who were not exposed to cyclin-dependent kinases 4 and 6 inhibitors as a first-line endocrine therapy. The benefits of palbociclib and letrozole therapy were seen without excessive toxicity, and although neutropenia was common, it may be managed with dose reduction.

Abstract CT152: A phase II study of pembrolizumab and eribulin in patients with HR-positive/HER2-negative metastatic breast cancer previously treated with anthracyclines and taxanes (KELLY study)

Abstract BACKGROUND: Preliminary results with MK3475 (pembrolizumab) in heavily pretreated Estrogen Receptor (ER)-positive/ Human Epidermal Growth Factor Receptor 2 (HER2)-negative metastatic breast cancer (MBC) patients have shown promising antitumor activity. However, no data are available with anti-Programmed Death-Ligand 1 (PD-L1) agents in combination with chemotherapy in this tumor subtype in the metastatic setting. The aim of this trial is to evaluate the efficacy of pembrolizumab in combination with eribulin in patients with Hormone Receptor (HR)-positive/HER2-negative MBC who have been previously treated with an anthracycline and a taxane. TRIAL DESIGN: This is an open-label, non-randomized, multicenter phase IIA clinical trial. Patients will receive intravenously pembrolizumab (200 mg) followed by eribulin (1.23 mg/m2) on day 1 of each cycle (every three weeks). Eribulin will also be administered alone on day 8 of each cycle until progression or unacceptable toxicity. The end of study will be 12 months after last study dose or progressive disease experienced in all patients. The principal selection criteria are: (1) HR-positive/HER2-negative inoperable locally recurrent or MBC; (2) prior therapy with an anthracycline and a taxane in the early or metastatic disease setting unless contraindicated; (3) at least one, but not more than two, previous chemotherapeutic regimens for locally recurrent and/or MBC; (4) measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1; (5) available tumor tissue for PD-L1 biomarker analysis. The primary objective of the study is to assess the efficacy of this combination as determined by the clinical benefit rate (CBR) defined as the percentage of patients who achieve complete response, partial response, or stable disease ≥24 weeks based on RECIST v.1.1. Secondary objectives evaluate: (1) safety-related outcomes and (2) efficacy measures as progression-free survival (PFS), overall survival, overall response rate (ORR), and duration of response in the intention-to-treat population and in patients with PD-L1 positive tumors. Exploratory objectives include: (1) the analysis of PFS and ORR based on irRECIST; and (2) the identification of new predictive factors of response to the combination of pembrolizumab and eribulin based on gene signatures, mutational load, and circulating tumor cells. The trial uses an exact single-stage design. We hypothesized that excluding a CBR ≤30% while targeting an improvement of the CBR to ≥50% would be an optimal approach to evaluation of the study strategy. At least 17 patients with clinical benefit among 39 evaluable patients will be adequate to justify the investigation of this strategy in further clinical trials. Considering a drop-out rate of 10%, a sample size of 44 patients will be needed to attain 80% power at nominal level of one-sided alpha of 0.05. TRIAL REGISTRATION: NCT03222856. Date of registration: July 19th, 2017. First Patient First Visit: December 14th, 2017. Citation Format: José Manuel Pérez García, Antonio Llombart, José Luis Alonso, Begoña Bermejo, Lourdes Calvo, Vicente Carañana, Giuseppe Curigliano, Susana de la Cruz Sánchez, María Gión Cortés, Raúl Márquez Vázquez, Aleix Prat, Manuel Ruiz Borrego, Miguel Sampayo, Peter Schmid, Miguel Ángel Seguí, Javier Cortés, Esther Holgado. A phase II study of pembrolizumab and eribulin in patients with HR-positive/HER2-negative metastatic breast cancer previously treated with anthracyclines and taxanes (KELLY study) [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 CT152.

Fulvestrant efficacy in artificial menopausal hormone receptor positive and HER 2 negative metastatic breast cancer patients under 50 years old.

e13000Background: This study investigated the efficacy of fulvestrant in premenopausal patients with metastatic breast cancer who developed artificial menopause using a luteinizing hormone releasing hormone analogue. Methods: This retrospective study was conducted at the Istanbul Okmeydani Education and Research Hospital. Those patients receiving 3.6 mg of goserelin acetate for 28 days and 500 mg of intramuscular fulvestrant for 28 days were included. Results: A total of 37 patients were evaluated, with a median age of 39 years old (range 27–49) and a median follow-up time of 20 months (0–78). The estrogen receptor positivity was 83.8%, and the progesterone receptor positivity was 86.5%. Of these patients, 86.5% had invasive ductal carcinoma, 5.4% had invasive lobular carcinoma, and 8.1% had other histological types. Bone metastasis was found in 83.8% of the patients, lung metastasis in 21.6%, lymph node metastasis in 16.2%, liver metastasis in 13.5%, and brain metastasis in 5.4%. On average, the fulvestr...