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Background: Triple negative breast cancer (TNBC) is well known for its more aggressive course and poorer prognosis compared to other BC subtypes. RegistEM study provides real world data to understand the distribution of BC subtypes in the advanced setting, being its primary objective. Biological samples collection is part of its procedures. This is a non-interventional cohort study and 1,907 patients (pts) have been enrolled up to now (females and males) with advanced BC (ABC), diagnosed from Jan-2016 to Dec-2019, either after recurrence or as first BC diagnosis, in 38 Spanish sites. These pts will be followed for at least 5 years. Methods: In the current analysis (cut-off date 08/April/2022, database ongoing), we describe characteristics, treatment patterns and outcomes, including comparison between recurrent and de novo disease, of 157 pts with advanced TNBC included in the RegistEM study. Those pts represent the 10% of pts available in the database at the cut-off date and with ABC diagnosis up to December 2018 (n=1559). The BC clinical subtypes were histologically confirmed on the most recent tumor lesion (metastatic [M] or primary BC) before starting with the 1st-line therapy. Results: At first ABC diagnosis, 73% pts had recurrent early BC (EBC), 26% de novo MBC and 1% unresectable locally ABC (ULABC). Median age was 57 years (range 30-88), all pts were women, 98% Caucasian and 65% postmenopausal. Family history of BC and/or ovarian cancer was reported in 37% pts, and a hereditary-risk genetic test was performed in 59 of 147 pts. Germline BRCA1/2 and TP53 were the most frequently mutated genes, 21% (6/28) and 47% (8/17) pts, respectively. Visceral involvement was present in 69% pts (similar between recurrent EBC and de novo ABC, although brain metastases were only present in the recurrent EBC group), and ≤ 2 metastatic locations in 59%. In 61% (70/115) pts with recurrent EBC, the subtype was assessed in metastatic lesions, and 39 pts of them also had TN subtype in primary BC. In terms of the most frequent therapies by line: 1) 1st-line: chemotherapy (CT) (60%) and CT/biological therapy (BT) (39%). Of the 87 pts with CT alone, monotherapy was the preferred option in 57% pts (capecitabine 25%, taxanes 16%, and eribulin or vinorelbine, 5% each). Bevacizumab was the most frequent BT (79%) combined with CT (single agent in 56% pts, mostly taxanes and capecitabine). Progressive disease (PD) was reported in 85% pts (similar in pts with both recurrent and de novo MBC or ULABC); 2) 2nd-line: CT (79%) (monotherapy capecitabine, eribulin, taxanes) and CT/BT (17%) (CT-containing bevacizumab 82%). Progression was reported in 92% pts; 3) 3rd-line: CT (90%) (eribulin 33%, platinum-based 25%) and CT/BT (9%) (CT-containing bevacizumab 67%). Progression was reported in 88% pts. At database cut-off date, death was reported in 133 (85%) pts, mainly because of PD. Overall survival (OS) was similar between both groups, recurrent and de novo MBC. Conclusion: In this population of Spanish TNBC pts with ABC, three quarters had recurrent disease. De novo ABC pts had a higher proportion of non-visceral metastases, with absence of brain involvement at the first diagnosis. Single-agent CT and CT plus bevacizumab were the most frequent therapies, and OS was similar between recurrent and de novo MBC pts, although numerically higher in the later group. Citation Format: Silvia Antolin Novoa, César A Rodríguez, Josefina Cruz, Sara López-Tarruella, Ariadna Tibau, Encarna Adrover, Ana Miguel, Mireia Margelí, Purificación Martínez, María Hernández, Antonio Antón, Álvaro Rodríguez-Lescure, Catalina Falo, Isabel Álvarez, Diego Malón, Raquel Andrés, José L Alonso-Romero, César Gómez, J. José Illaramendi, Ruth Campo, Juan José Miralles, Susana Bezares, Federico Rojo, Angel Guerrero-Zotano. Treatment strategies for advanced triple negative breast cancer patients as per routine clinical practice: analysis from the observational study GEICAM/2014-03 (RegistEM) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-45.

Background: HER2-low breast cancer (BC) is a new therapeutic entity, but it is uncertain if this subgroup of BC differs from HER2-negative tumors in clinical characteristics, prognosis, and response to therapy. The objective is to describe the clinical characteristics and outcomes of 422 patients (pts) with HER2-low BC documented before 1st line, having been diagnosed with advanced BC (ABC) before 2019 and included in the RegistEM study (n=1,663). Methods: In this analysis (cut-off date 08/April/2022; database is ongoing), two subgroups of pts have been considered based on HER2 results: HER2-low (n=422) (immunohistochemistry [IHC] 1+ or IHC 2+ and in situ hybridization [ISH] negative) and HER2-IHC 0 (n=590), as reference. Hormone Receptor (HR) expression has also been considered for subgroup analysis. Results: At first ABC diagnosis, < 1% pts had unresectable locally advanced BC (ULABC) in both groups, 31% de novo metastatic BC in HER2-low and 20% in HER2-IHC0 groups. Less than 1% were male, 99% Caucasian and ~71% postmenopausal. Median age was 60 years, being similar between both groups (range 26-96). Family history of BC and/or ovarian cancer was reported in 32% pts in HER2-low and 29% in HER2-IHC0. Germline BRCA1/2 mutation was higher in HER2-low (14/40=35%) in reference to HER2-IHC0 (14/64=22%) (p=0.14). Relevant information summarized by HR expression and HER2 status are detailed in the table below. Visceral disease was similar in both total groups (58% in HER2-low vs HER2-IHC0 56%), but slightly higher in HR- HER2-low pts (81% vs 64%), and 84% and 90% pts had ≤3 metastatic locations, in HER2-low and HER2-IHC0 groups, respectively. Distribution of 1st-line therapies was also similar between both groups, being endocrine therapy (ET) plus biological therapy (BT) (HER2-low 39% vs HER2-IHC0 36%) and ET (HER2-low 30% vs HER2-IHC0 28%), while chemotherapy (CT) (HER2-low 13% vs HER2-IHC0 16%) and CT plus BT (HER2-low 9% vs HER2-IHC0 10%) were more frequent in HR- pts. A 2nd-line therapy was reported in 70% HER2-low pts and 67% HER2-IHC0 pts. The median time to progression (TTP) at 1st-line therapy in HER2-low pts was 11 mo (0-66), being similar in HER2-IHC0 pts, but the higher difference was observed in relation to HR expression. Treatments in 2nd-line were similar in both groups, CT and ET/BT were the most frequent totally. Median duration of 2nd-line therapy was ~6 mo; progressive disease (PD) was reported in 85% pts. A 3rd-line therapy was reported in 74% HER2-low and 69% HER2-IHC0 pts. The median time to progression (TTP) to 3rd-line therapy was 6 mo, being similar in HER2-low and HER2-IHC0 pts .The most frequent 3rd-line therapies were CT and ET/BT in both groups, as in 2nd-line. Median duration of 3rd-line therapy was 4 mo; PD was reported in 84% HER2-low pts and 82% HER2-IHC0 pts. Median (95% confidence interval [CI]) PFS at 1st, 2nd and 3rd lines (mo) were 14 (12-16), 6 (5-7) and 6 (5-6) in HER2-low pts, being similar in HER2-IHC0. OS was comparable in all soubgroups analyzed, however, differences were observed regarding HR status. Conclusions: Our results show that HER2-low BC pts have similar characteristics than HER2-IHC0 BC pts. There are differences in therapy outcomes in terms of survival and prognosis, particularly in HR- tumors, being better in HER2-low BC pts. It could be related to the fact that these tumors have a specific biology, but more evidence is needed. Citation Format: Isabel Álvarez, Angel Guerrero-Zotano, Ariadna Tibau, Catalina Falo, María Hernández, Ana Miguel, Raquel Andrés, Álvaro Rodríguez-Lescure, Miguel Corbellas, Sara López-Tarruella, Purificación Martínez, Cesar A Rodríguez, Diego Malón, María Marin, Mª José Echarri, Antonio Antón, Josefina Cruz, Diana Moreno, J. Ignacio Chacón, Ruth Campo, Andrea Blasco, Susana Bezares, Federico Rojo, Silvia Antolin. Features and survival outcomes of HER2-low patients from a prospective registry of unresectable locally advanced or metastatic breast cancer: GEICAM/2014-03 (RegistEM) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-30.

Background: Over the last years, the treatment of HER2-positive (HER2+) breast cancer (BC) patients (pts) has been changing because of the development of new anti-HER2 agents. In the current analysis, we describe the features, treatment patterns, progression-free survivall (PFS) and overall survival (OS) outcomes of BC pts with HER2 + (immunohistochemistry [IHC] 3+ or IHC 2+ and in situ hybridization [ISH]+), following ASCO/CAP 2018 guidelines in the most recent tumor lesion before the 2nd-line. Methods: The RegistEM study is an ongoing BC registry study that is providing prospective data from around 1900 pts diagnosed with advanced BC (ABC) between 01/Jan/2016 and 31/Dec/2019, in 38 Spanish institutions from GEICAM network. In this analysis, 296 HER2+ BC pts have been included, representing the 18% of pts available in the database at the cut-off date (08/Apr/2022), with ABC diagnosis before 2019 (n=1559). Results: At first ABC diagnosis, 58% (n=173) pts had recurrent disease (>36 months [mo] from initial BC diagnosis in 62%), 41% (n=120) de novo metastatic BC and 1% (n=3) unresectable locally ABC (ULABC); the median age was 58 years, 68% were postmenopausal and there was only 1 male pt. From total 296 pts, 66% had hormone receptor expression [HR+]; the BC subtype was assessed in tumor tissue from the breast (58%) or a metastatic lesion (34%), and in 8% pts, HER2 positivity was observed after the 1st-line. Family history of BC and/or ovarian cancer was reported in 28% pts, and a hereditary-risk genetic test was performed in 26% pts (n=74/282). Germline BRCA1/2 and TP53 genetic testing were reported in 14 and 26 pts respectively, being mutated in 3/14 (21%) and 5/26 (19%) pts. Bone (50%), lymph nodes (49%), liver (35%), lung (31%), soft tissue (8%) and central nervous system (CNS), mostly in brain (8%), were the main metastatic sites. One hundred pts were diagnosed with CNS metastases: 24 at baseline, 48 during the 1st-line and 28 in subsequent lines. Additional data according to HR status and type of ABC are detailed in the table below, showing a worse prognosis in absence of HR expression. In HR- pts, bone metastases were less frequent and lymph nodes metastases more frequent compared to HR+ pts. Visceral disease was present in 69% (66% in HR+ and 74% in HR-; non-statistically significant) pts and ≈80% had ≤3 (54%, ≤2) locations involved. The most common therapies by line were: 1) 1st-line: Chemotherapy (CT) + biological therapy (BT) (38%), CT + BT+ endocrine therapy (ET) (35%), and ET + BT [11%]; 2) 2nd-line: BT (55%), CT + BT (20%) and ET + BT (15%); 3) 3rd-line: CT + BT (49%) and BT (31%). The median (95% confidence interval [CI]) progression-free survival (PFS) on 1st, 2nd and 3rd line was 18 (15-22), 8 (7-9) and 6 (5-8) mo, respectively. The median (95% CI) overall survival (OS) from ABC diagnosis was 43 (40-49) mo. These survival outcomes were higher in HR+ pts, however, the differences were only statistically significant in OS (p=0.006; log-rank). At database cut-off date, death was reported in 47% pts. Conclusions: In spite of the anti-HER2 therapies administered in the advanced setting, the HR expression is a relevant prognostic factor, with a clinically and statistically significant impact in OS, improving the outcomes of HR+ pts. Citation Format: Sara López-Tarruella, Angel Guerrero-Zotano, Josefina Cruz, Silvia Antolin Novoa, Purificación Martínez, María Hernández, César A Rodríguez, J. Ignacio Chacón, Ariadna Tibau, Catalina Falo, Álvaro Rodríguez-Lescure, Mireia Margelí, Sonia Servitja, Raquel Andrés, María Galán-Gramaje, Encarna Adrover, Ana Miguel, Rafael Villanueva, Silvia Varela, Ruth Campo, Mª José Escudero, Susana Bezares, Federico Rojo, Isabel Álvarez. Real-world data of Advanced Breast Cancer (ABC) patients with HER2-positivity before the second-line therapy: data from the observational study GEICAM/2014-03 (RegistEM) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-38.

Adjuvant therapy; Breast cancer; Olaparib Terapia adyuvante; Cáncer de mama; Olaparib Teràpia adjuvant; Càncer de mama; Olaparib Background The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI −0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals. Funding for this work, which was conducted as a collaborative partnership among the Breast International Group, NRG Oncology, Frontier Science, AstraZeneca, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A. (MSD), was provided by the National Institutes of Health (grant numbers: U10CA 180868, UG1CA 189867, and U10CA 180822) and by AstraZeneca as part of an alliance between AstraZeneca and MSD. Provision of olaparib and placebo was from AstraZeneca.

We do not know the precise figure for solid organ tumors diagnosed each year in Spain and it is therefore difficult to calculate whether there has been a decrease in cancer diagnoses as a consequence of the pandemic. Some indirect data suggest that the pandemic has worsened the stage at which some non-hematological neoplasms are diagnosed. Despite the lack of robust evidence, oncology patients seem more likely to have a poor outcome when they contract COVID-19. The antibody response to infection in cancer patients will be fundamentally conditioned by the type of neoplasia present, the treatment received and the time of its administration. In patients with hematological malignancies, the incidence of infection is probably similar or lower than in the general population, due to the better protective measures adopted by the patients and their environment. The severity and mortality of COVID-19 in patients with hematologic malignancies is clearly higher than the general population. Since the immune response to vaccination in hematologic patients is generally worse than in comparable populations, alternative methods of prevention must be established in these patients, as well as actions for earlier diagnosis and treatment. Campaigns for the early diagnosis of malignant neoplasms must be urgently resumed, post-COVID manifestations should be monitored, collaboration with patient associations is indisputable and it is urgent to draw the right conclusions to improve our preparedness to fight against possible future catastrophes.

Resumen El cancer de mama metastasico (CMM) constituye la primera causa de muerte por cancer entre las mujeres y plantea importantes retos en la practica clinica y en la convivencia con la enfermedad para pacientes y familiares. Con la participacion de un amplio panel de oncologos medicos y representantes de pacientes, en este proyecto se analizaron los recursos (herramientas de planificacion, registros de cancer), proceso asistencial (diagnostico, tratamiento, cuidados paliativos) y procesos transversales (atencion psicosocial, habitos de vida saludables, rol de las asociaciones de pacientes) en el abordaje del CMM en el contexto sanitario espanol. El trabajo realizado permitio identificar una serie de areas de mejora y proponer 42 recomendaciones orientadas a mejorar la calidad asistencial y la atencion de los pacientes con CMM y sus cuidadores organizadas en las siguientes areas de accion: registros de cancer, coordinacion entre niveles asistenciales, diagnostico de la metastasis, comunicacion y habilidades interpersonales, accesibilidad a farmacos, ensayos clinicos, el papel de la enfermeria en el CMM, cuidados paliativos, atencion psicosocial y promocion de estilos de vida saludables. Estas recomendaciones, elaboradas desde una perspectiva integral y centradas en las caracteristicas del entorno sanitario en Espana, ofrecen un punto de partida para la mejora de la calidad asistencial y pueden ser de gran valor en otros entornos sanitarios que se enfrenten a las mismas necesidades en el abordaje del CMM.

Cancer and cancer therapies are a major factor risk for osteoporosis due to bone loss and deterioration of bone microarchitecture. Both factors contribute to a decrease in bone strength and, consequently, increased bone fragility and risk of fracture. Cancer-associated bone loss is a multifactorial process, and optimal interdisciplinary management of skeletal health, accurate assessment of bone density, and early diagnosis are essential when making decisions aimed at reducing bone loss and fracture risk in patients who have received or are receiving treatment for cancer. In this document, a multidisciplinary group of experts collected the latest evidence on the pathophysiology of osteoporosis and its prevention, diagnosis, and treatment with the support of the Spanish scientific society SEOM. The aim was to provide an up-to-date and in-depth view of osteoporotic risk and its consequences, and to present a series of recommendations aimed at optimizing the management of bone health in the context of cancer.

ImportanceBiomarkers to guide the use of pertuzumab in the treatment of early-stage ERBB2 (formerly HER2)-positive breast cancer beyond simple ERBB2 status are needed.ObjectiveTo determine if use of the HER2DX genomic assay (Reveal Genomics) in pretreatment baseline tissue samples of patients with ERBB2-positive breast cancer is associated with response to neoadjuvant trastuzumab-based chemotherapy with or without pertuzumab.Design, Setting, and ParticipantsThis is a retrospective diagnostic/prognostic analysis of a multicenter academic observational study in Spain performed during 2018 to 2022 (GOM-HGUGM-2018-05). In addition, a combined analysis with 2 previously reported trials of neoadjuvant cohorts with results from the assay (DAPHNe and I-SPY2) was performed. All patients had stage I to III ERBB2-positive breast cancer, signed informed consent, and had available formalin-fixed paraffin-embedded tumor specimens obtained prior to starting therapy.ExposuresPatients received intravenous trastuzumab, 8 mg/kg, loading dose, followed by 6 mg/kg every 3 weeks in combination with intravenous docetaxel, 75 mg/m2, every 3 weeks and intravenous carboplatin area under the curve of 6 every 3 weeks for 6 cycles, or this regimen plus intravenous pertuzumab, 840 mg, loading dose, followed by an intravenous 420-mg dose every 3 weeks for 6 cycles.Main Outcome and MeasuresAssociation of baseline assay-reported pathologic complete response (pCR) score with pCR in the breast and axilla, as well as association of baseline assay-reported pCR score with response to pertuzumab.ResultsThe assay was evaluated in 155 patients with ERBB2-positive breast cancer (mean [range] age, 50.3 [26-78] years). Clinical T1 to T2 and node-positive disease was present in 113 (72.9%) and 99 (63.9%) patients, respectively, and 105 (67.7%) tumors were hormone receptor positive. The overall pCR rate was 57.4% (95% CI, 49.2%-65.2%). The proportion of patients in the assay-reported pCR-low, pCR-medium, and pCR-high groups was 53 (34.2%), 54 (34.8%), and 48 (31.0%), respectively. In the multivariable analysis, the assay-reported pCR score (as a continuous variable from 0-100) showed a statistically significant association with pCR (odds ratio [OR] per 10-unit increase, 1.43; 95% CI, 1.22-1.70; P P P P = .77). A statistically significant interaction between the assay-reported pCR score and the effect of pertuzumab in pCR was observed.Conclusions and RelevanceThis diagnostic/prognostic study demonstrated that the genomic assay predicted pCR following neoadjuvant trastuzumab-based chemotherapy with or without pertuzumab. This assay could guide therapeutic decisions regarding the use of neoadjuvant pertuzumab.

Purpose We conducted a systematic review to analyse the performance of the sentinel lymph-node biopsy (SLNB) after the neoadjuvant chemotherapy, compared to axillary lymph-node dissection, in terms of false-negative rate (FNR) and sentinel lymph-node identification rate (SLNIR), sensitivity, negative predictive value (NPV), need for axillary lymph-node dissection (ALND), morbidity, preferences, and costs. Methods MEDLINE, Embase, Scopus, and The Cochrane Library were searched. We assessed the quality of the included systematic reviews using AMSTAR2 tool, and estimated the degree of overlapping of the individual studies on the included reviews. Results Six systematic reviews with variable quality were selected. We observed a very high overlapping degree across the included reviews. The FNR and the SLNIR were quite consistent (FNR 13-14%; SLNIR- 90% or higher). In women with initially clinically node-negative breast cancer, the FNR was better (6%), with similar SLNIR (96%). The included reviews did not consider the other prespecified outcomes. Conclusions It would be reasonable to suggest performing an SLNB in patients treated with NACT, adjusting the procedure to the previous marking of the affected lymph node, using double tracer, and biopsy of at least three sentinel lymph nodes. More well-designed research is needed.

Background: The RegistEM study is a non-interventional study that is providing prospective data from around 1900 ABC pts (females and males) diagnosed with advanced disease between 01/Jan/2016 and 31/Dec/2019, either after recurrence or at 1st diagnosis, in 38 Spanish sites representative of the national territory and whose investigators are GEICAM members. Methods: In the current analysis (cut-off date 10/May/2021, ongoing database), we describe the features of 279 pts included in the RegistEM study, with HER2+ (immunohistochemistry [IHQ] 3+, IHQ 2+ and in situ hybridization [ISH]+) tumors at any time of their ABC (5% after the 1st-line therapy). This subgroup has been evaluated because of the interest from a clinical perspective. Multivariate Cox analysis aiming to identify factors associated with overall survival (OS) were built. Results: 279 pts were identified, representing the 15% pts available in the database at the cut-off date. At first ABC diagnosis, 48% pts had recurrent BC (>12 months [mo] from initial BC diagnosis in 93%), 51% de novo metastatic BC and 1% unresectable locally advanced BC (ULABC). The median age was 59 years, 98% were white , 71% postmenopausal and only 1 male was part of this subset. Considering the BC subtype assessed in the most recent tumor lesion before the 1st-line therapy, 264 pts wereHER2 positive (67% with hormone receptor [HR]+). Family history of BC and/or ovarian cancer was reported in 31% pts, and an hereditary-risk genetic test was performed in 25% (66/267 pts). BRCA1/2 and TP53 mutations were reported in 4/20 and 4/19 pts, respectively, and p53 overexpression in 20/46 pts. Lymph nodes (56%), bone (49%), liver (34%), lung (33%), soft tissue (10%) and brain (8%) were the main metastatic sites. Additional data according to HR status and type of ABC are detailed in the table below. In HR- pts, bone metastases were less frequent and lymph nodes metastases more frequent compared to HR+ pts. Visceral disease was present in 68% pts and ≈75% had ≤3 (47% ≤2) locations involved. The most common therapies by line were: 1) 1st-line: CT + dual anti-HER2 blockade (3%), chemotherapy (CT) (almost in all pts taxane-based)+dual anti-HER2 blockade + endocrine therapy (ET) (mainly aromatase inhibitors) (35%), and ET + anti-HER2 blockade or ET + cyclin-dependent kinases 4/6 inhibitors (11%); 2) 2nd-line: anti-HER2 blockade (56%) [mostly an antibody-drug conjugate (90%)], CT + anti-HER2 blockade (18%) and ET + anti-HER2 blockade (14%); 3) 3rd-line: CT + anti-HER2 blockade (55%) and anti-HER2 blockade (22%). The median time-to-progressions to 1st-, 2nd- and 3rd-line were 14, 5, and 4 mo, respectively. A 4th-line therapy was reported in 52% of pts who received a 3rd-line. At database cut-off date, death was reported in 34% of pts. The median OS of this subset of pts was 41 mo (36-49). In a multivariate Cox regression analysis, the following variables were significantly related with worse survival (from ABC diagnosis): Brain (HR=2.62; 95% CI, 1.02-6.73) and Visceral no Brain involvement (HR=2.15; 95% CI, 1.02-4.53) compare to only soft tissue lesions; early stage at first diagnosis (HR=1.77; 95% CI, 1.15-2.73); HR- (HR=1.70; 95% CI, 1.11-2.60) and age (HR=1.04; 95% CI, 1.02-1.07). Conclusions: In this cohort of HER2+ pts with advanced disease, half of them had de novo ABC which was associated with better OS. The median PFS in 1st- and 3rd-line were slightly better in HR+ pts, and in 2nd-line was similar between HR+ and HR- cohorts. HR+181 (67%)HR- 91 (33%)Recurrent EBC134 (48%)ULABC or de novo M1 145 (52%)Time to recurrence >12 mo in EBC pts., n8435125NALocation of metastaticsites, nBoneBrainLiverLungLymph nodesSoft tissue104 10 62 57 90 1829 9 3232 64 1059 15 36 47 51 2278 6 59 46 1056Líne123123123123n180935690492613385521446333Deaths, n211112111161715141584Therapies by line, nET/BT261922101910212100ET12441011022323CT/BT/ET935031038305830CT/BT4017307581552182366924CT3572353711211BT6431373651145143385The most frequent therapies, nCT + dual anti-HER2 blockade + ET8623331551CT + single-agent HER2 blockade + ET522CT + dual anti-HER2 blockade3493644391016252CT + single-agent HER2 blockade4825641588211521CT5573354711411ET*22105212162644ET + HER2 blockade1213411662782Anti-HER2 blockade6431073651145143382Median duration of treatment, mo125585310441064TTP (mo), median (range)15(1-47)5(1-32)5(0-18)11(2-38)5(1-27)4(2-12)12 (1-47)5(1-26)4(0-17)17(2-45)7(1-32)4(1-18)Median PFS, mo14561154------HR: hormone receptor; EBC: early breast cancer; ULABC: unresectable locally advanced breast cancer; M1: metastatic; mo: month; ET: endrocrine therapy; BT: biological therapy; CT: chemotherapy; TTP: time-to-progression; PFS: progression-free survival. *ET includes aromatase inhibitors or selective estrogen receptor degraders, as single-agents or combined with cyclin-dependent kinases 4/6 inhibitors. Citation Format: Isabel Álvarez, Ángel Guerrero-Zotano, Josefina Cruz, Purificación Martínez, María Hernández, César A Rodríguez, Álvaro Rodríguez-Lescure, Silvia Antolín, Encarna Adrover, Raquel Andrés, Catalina Falo, Jose Ignacio Chacón, Ana Miguel, Sonia Servitja, Maria Galán Gramaje, Mireia Margelí Vila, César Gómez Raposo, María Jose Echarri, Rafael Villanueva, Ariadna TIbau Martorell, Silvia Varela Ferreiro, Ruth Campo, Juan Jose Miralles, Susana Bezares, Federico Rojo, Sara López-Tarruella. Features of HER2+ metastasic patients (pts) from a prospective registry of advanced breast cancer (ABC), GEICAM/2014-03 (RegistEM) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-15-04.

Background: The incidence of breast cancer brain metastases (BCBM) is estimated to be around 5-15%, but necropsies show a much higher incidence (30-50%). Frecuency of BCBM has gradually increase likely as a result from advances in systemic treatment that allow more patients to live long enough to develop BCBM. In general, outcome for patients with BCBM is poor, with 1-year survival of approximately 20%, but some patient and tumor characteristics are associated with improved behaviour. The RegistEM study is a non-interventional cohort study providing prospective data from around 1,867 advanced breast cancer (ABC) patients (pts.). This study offers a unique opportunity to assess the incidence, potential risk factors, and outcomes for patients with BCBM. Methods: In this analysis (cut-off date 26/April/2021 and ongoing database), we describe the features of 218 pts. with BCBM included in the RegistEM study, which represent the 11% of current total number of pts. in the study. BC clinical subtypes are based on the most recent tumor lesion (distant metastasis or primary BC). The most frequent therapies by BC subtypes are detailed in the table below. At the database cut-off date, death had been reported in 74% pts with BCBM. Results: All pts. were female, 97% caucasian, and at ABC diagnosis, 66% were postmenopausal and their median age was 55 years. The subtype distribution was: Luminal (ER+/HER2-) 41%, HER2+ 35%, Triple Negative (TN) 19%, unknown 5%. Eighty pts. (37%) had BM at diagnosis of ABC, and in 17 of them BM was the only site of relapse. The median time from diagnosis of primary BC to BM at initial diagnosis of ABC was 34 months (mo), being shorter for TN (18 mo). In patients without BM at diagnosis of ABC, the median time from ABC diagnosis to onset of BM for de novo metastatic disease was: Luminal 27 mo, HER2+ 28 mo, TN 10 mo; while for EBC disease was: Luminal 18 mo, HER2+ 14 mo, TN 10 mo. De novo metastatic BC was associated with longer time to BM appearance (HR:0.527, CI 95%: 0.358-0.776) while TN subtype with shorter time (HR:4.122, CI 95%: 2.318-7.329) compared to Luminal subtype. The median survival from the onset of BM, according to BC subtype was: Luminal 6 mo, HER2 11 mo and TN 4 mo. Risk factors for worse survival were: BM at ABC (HR:1.677, CI 95%:1.169-2.406) and TN subtype (HR:3.631, CI 95%: 2.353-5.603) compared to Luminal subtype. Conclusions: TN breast cancer is associated with a shorter time to brain metastases and poorer outcome than other breast cancer subtype. Patients with de novo metastatic BC develop metastases later than patients with metastatic recurrence after primary BC. New treatment approach to avoid the onset of brain metastases in patients with ABC warrants further research. Luminaln=90 (41%)HER2+n=77 (35%)Triple Negativen=41 (19%)HRHER2+-Any+–First BC diagnosis, nEBC (stages I-III)ULABC or de novo metastatic65. 2555. 2227. 14Only CNS metastases at ABC diagnosis584Number of line (L)1L2L3L1L2L3L1L2L3Ln877158745936352515Type of therapy, nET/BT26167443---ET239531----CT/BT/ET58-15-----CT/BT10924014211331CT/ET623------CT172635321222214BT1693811---Most frequent therapies by mechanism of action, nAI/CDK4/6i 20SERD 12CT single agent 12AI single agent 11CT + antiangiogenic 9CT single agent 24SERD +/- CDK4/6i 8AI + CDK4/6i 7CT + antiangiogenic 7CT single agent 27CT combination 8SERD +/- CDK4/6i 6CT + dual anti-HER2 blockade 46CT + anti-HER2 blockade single agent 7Anti-HER2 single agent 35CT + anti-HER2 blockade single agent 12CT + anti-HER2 blockade single agent 18Anti-HER2 blockade single agent 9CT combination 12CT + antiangiogenic 12CT single agent 10CT single agent 16CT combination 6CT + antiangiogenic 4CT single agent 9CT combination 5Median Treatment duration, months (range)7 (0-31)6 (0-41)4 (0-16)12 (0-43)5 (0-47)3 (0-17)5 (0-18)3 (0-7)2 (0-6)TTP in months, median (range)8 (2-35)--12 (3-46)--6 (2-19)--Death, n635139Abbreviations: HR=hormone receptor; HER2=human epidermal growth factor receptor 2; BC=breast cancer; EBC=early breast cancer; ULABC=unresectable locally advanced breast cancer; ET=endrocrine therapy; BT=biological therapy; CT=chemotherapy; TTP=time to progression; AI=aromatase inhibitor; SERD=selective estrogen receptor degrader; CDK4/6i=cyclin dependent kinases 4 and 6 inhibitor Citation Format: Sara López-Tarruella, Ángel Guerrero-Zotano, César A Rodríguez, Josefina Cruz, María Hernández, Encarna Adrover, Álvaro Rodríguez-Lescure, Catalina Falo, Purificación Martínez, Ana Miguel, Raquel Andrés, Silvia Antolín, J. Ignacio Chacón, Jose Luis Alonso Romero, Rafael Villanueva Vázquez, Ana Isabel Ballesteros García, María Galán Gramaje, Diego Malón Jiménez, Silvia Varela Ferreiro, Diana Moreno Muñoz, Ruth Campo, María José Escudero, Susana Bezares, Federico Rojo, Isabel Alvarez. Breast cancer clinical subtypes in brain metastases patients from a prospective registry of advanced breast cancer, GEICAM/2014-03 (RegistEM) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD4-08.