e22150 Background: Distinction of primary ovarian tumors from metastatic tumors involving the ovary is in some cases challenging for final pathologic diagnosis and for treatment with efficient chemotherapy Methods: We gathered from our biobank 16 pairs of breast/ovarian tumors for some of which the diagnosis was uncertain. We investigated the possibility to improve diagnosis using genomic and transcriptomic tools. The pangenomic profiles of 16 pairs of primary breast carcinoma and ovary tumors (primary tumors or metastases from breast carcinoma) from the same patients were analyzed using the Affymetrix GeneChip Mapping 50K (XbaI) SNP arrays. The data were normalized with ITALICS algorithm. We analyzed the transcriptome of the paired samples using Affymetrix U133plus2 arrays. The data were normalized with GCRMA algorithm and a hierarchical clustering of these samples was performed, together with a dataset of primary and secondary ovary tumors. Results: Primary infiltrating lobular carcinoma (ILC) was observed in 6 patients, infiltrating ductal carcinoma (IDC) in 7 patients, 1 patient had one ILC and one IDC, 1 patient had a mixed IDC+ILC and 1 patient an undifferentiated cancer. All patients received adequate loco-regional and systemic therapies. Median time to diagnosis of ovarian tumor was 54 months. Ovarian tumors were considered as primary in 7 patients, and metastatic in 9 patients, and diagnosis was ambiguous in 4 of them. Four patients developed extra-abdominal metastases. Median survival from breast cancer diagnosis was 78 months, and from ovarian tumor diagnosis was 29 months. CGH array: In 12 pairs, the comparison of genomic profiles one with each other, confirmed the pathological characteristics of the tumors. In 4 cases, the genomic profiles established clearly the status of the ovary tumor whereas the pathological analysis did not. Transcriptome: The status established by the transcriptomic analysis was for each sample in total agreement with the status established by the genomic analysis. Conclusions: We clearly established in this training series that CGH array analysis could help to discriminate between primary and secondary ovarian tumors from breast cancer. Transcriptomic data confirmed these results. Further validation data are warranted. No significant financial relationships to disclose.
Abstract Background: Bone-only (BO) metastatic breast cancer (MBC), defined as bone as unique site of metastasis at MBC diagnosis, is thought to carry a better prognosis among MBC. However, only small retrospective series and data from selected randomized controlled trials have been reported so far. Based on a national database, we aimed at providing a large comprehensive analysis of BO MBC, and at evaluating its impact on clinical outcome. Methods: The ESME MBC platform (NCT03275311) is a French multicenter retrospective real-life database using a clinical trial-like methodology to collect data from 18 French Comprehensive Cancer Centers. It includes data from each newly diagnosed MBC patient having initiated at least one treatment between 2008 and 2016. BO cases occurring in women were retrieved and compared to the overall non-BO population, regarding treatment effects and survival. Results: Of the 22,463 women selected in the database, 5,041 (22.4%) patients with BO disease were identified. Most (N=4,102, 81.4%) had HR+/HER2- disease while 644 (12.8%) and 295 (5.9%) patients had HER2+ or HR-/HER2- disease, respectively. Compared to non-BO MBC, BO MBC patients were older in the global cohort and in HR-/HER2- patients (mean age 61.0y versus 59.5y, and 59.3y vs 56.4y, all p<0.0001, respectively), and tumor histology was more frequently a lobular carcinoma in the global cohort, in HR+/HER2- and in HR-/HER2- patients (18.6% vs 10.8%, 20.6% vs 15.2%, 13.8% vs 3.2%, all p<0.0001, respectively). In addition, metastatic disease occurred de novo more frequently in BO MBC patients (37.9% versus 29.2%) (p<0.0001), and a statistically significant difference was also observed within each tumor subtype group. The management of bone disease included bisphosphonates or denosumab, radiotherapy, and invasive bone metastasis procedures in 3,913 (77.6%), 2,929 (58.1%), and 1,154 (22.9%) patients, respectively. Median follow up was 52.4 months (95% CI [50.8-54.2]) in BO population and 50.9 months (95% CI [49.7-51.8]) in non-BO population. BO MBC patients had improved median progression-free survival (PFS) 1, regarding first-line treatment, and overall survival (OS) compared to non-BO MBC, globally and within each tumor subtype group (Table). Indeed, 5-year OS rates reached up to 43%, 54% and 16% in HR+/HER2-, HER2+ and HR-/HER2- BO MBC groups, respectively. This suggests that a substantial number of these patients could be considered as long survivors. In the BO MBC cohort, de novo BO MBC patients had a higher 5-year OS rate than relapsed BO MBC patients. BO disease was an independent prognostic factor of OS (hazard ratio 0.68 (95% CI [0.65-0.72]), p<0.0001) together with age, tumor subtype, grade, adjuvant treatment and metastatic-free interval. Conclusion: This large comprehensive study is the largest cohort of BO MBC to date. BO MBC has a distinct presentation from non-BO MBC and carry a better prognosis compared to non-BO MBC. A significant proportion of BO MBC patients have a very long survival and may benefit from aggressive local therapy, as stereotactic radiotherapy. Dedicated studies are warranted to tailor the management of these patients. Funding: This work was supported by UNICANCER. The ESME MBC database is supported by an industrial consortium (Roche, Pfizer, AstraZeneca, MSD, Eisai and Daiichi Sankyo). Data collection, analyses and publications are totally managed by R&D UNICANCER independently of the industrial consortium. TableBOBOBOBOnon-BOnon-BOnon-BOnon-BON (%)median OS monthsmedian PFS1 months5-year OS rate %N (%)median OS monthsmedian PFS1 months5-year OS rate %(95% CI)(95% CI)(95% CI)(95% CI)(95% CI)(95% CI)Overall population5,041 (100%)52.1 (50.3-54.1) 13.1 (12.6-13.8) 43.41 (41.66-45.15)15,054 (100%)34.7 (34.0-35.6) 8.5 (8.3-8.7) 30.55 (29.62-31.48)HR+/HER-4,102 (81.4%)52.6 (50.5-54.8)13.6 (13.0-14.3)43.52 (41.56-45.46)9,127 (60.6%) 39.0 (37.8-40.1)9.6 (9.3-9.9)32.69 (31.47-33.93)HER2+644 (12.8%)66.4 (59.8-71.9) 14.9 (12.9-17.3) 54.49 (49.54-59.16)3,265 (21.7%) 46.5 (44.2-48.9)10.6 (10.1-11.3)39.88 (37.77-41.98)HR-/HER2-295 (5.9%)20.8 (18.3-27.4) 5.6 (4.9-7.5)16.21 (11.21-22.02)2,662 (17.7%) 14.3 (13.6-15.1)4.8 (4.6-5.0)10.89 (9.4-12.5)De novo MBC patients1,909 (37.9%)58.6 (55.4-62.1)17.9 (17.0-18.9)48.24 (45.28-51.14)4,399 (29.2%) ---Relapsed MBC patients3,132 (62.1%)48.3 (46.5-50.5)10.7 (10.2-11.2)40.51 (38.34-42.67)10,655 (70.8%)--- Citation Format: Marion Bertho, Julien Fraisse, Anne Patsouris, Paul Cottu, Suzette Delaloge, David Pérol, Anne Jaffré, Anthony Goncalves, Marie-Paule Lebitasy, Véronique D'Hondt, Florence Dalenc, Jean-Marc Ferrero, Christelle Levy, Patrick Arveux, Roman Rouzier, Frédérique Penault-Llorca, Lionel Uwer, Jean-Christophe Eymard, Mathias Breton, Michaël Chevrot, Marianne Leheurteur, Michel Velten, Gaëtane Simon, Jean-Sébastien Frenel. Impact of bone-only metastatic breast cancer on outcome in a real-life setting: A comprehensive analysis of 5,041 women from the ESME database [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 P2-19-01.
The use of serum alkaline phosphatase (ALP) isoenzymes as markers of breast cancer metastases and treatment efficacy has received little attention. Twenty-six breast cancer women (56+/-13 years, all post-menopausal) were prospectively evaluated during their first and third course of chemotherapy (4-week interval). Serum samples were analyzed for ALP isoenzymes (bone, liver, and intestine) using a lectin affinity electrophoresis kit (Hydragel 15 ISO-PAL, Sebia) adapted on a semi-automated Hydrasys system (Sebia). Results were compared with imaging techniques for the presence of metastases; bone ALP isoenzyme (B-ALP) results were compared with C-Terminal degradation products of type I collagen (S-CTX) (CrossLaps, IDS Nordic). Serum B-ALP, but not S-CTX, confirmed the presence of bone metastases (BM) (n=15) with 67/100% sensitivity/specificity (using a 69 UI/L ROC cut-off); ROC AUC was 0.806 (P=0.0004) (NS for S-CTX). Chemotherapy reduced serum B-ALP by 24% over 4 weeks (P=0.0012); there was no change for S-CTX. There was no specific clinical pattern for other ALP isoenzymes (liver and intestine). In conclusion, serum B-ALP, but not S-CTX, could help confirm the presence of BM in breast cancer patients.
The purpose of this study was to evaluate the prognostic value of the multigene EndoPredict test in prospectively collected data of patients screened for the randomized, double-blind, phase III UNIRAD trial, which evaluated the addition of everolimus to adjuvant endocrine therapy in high-risk, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer.
In nonmetastatic triple-negative breast cancer (TNBC) patients, we investigated whether circulating tumor DNA (ctDNA) detection can reflect the tumor response to neoadjuvant chemotherapy (NCT) and detect minimal residual disease after surgery.Ten milliliters of plasma were collected at 4 time points: before NCT; after 1 cycle; before surgery; after surgery. Customized droplet digital PCR (ddPCR) assays were used to track tumor protein p53 (TP53) mutations previously characterized in tumor tissue by massively parallel sequencing (MPS).Forty-six patients with nonmetastatic TNBC were enrolled. TP53 mutations were identified in 40 of them. Customized ddPCR probes were validated for 38 patients, with excellent correlation with MPS (r = 0.99), specificity (≥2 droplets/assay), and sensitivity (at least 0.1%). At baseline, ctDNA was detected in 27/36 patients (75%). Its detection was associated with mitotic index (P = 0.003), tumor grade (P = 0.003), and stage (P = 0.03). During treatment, we observed a drop of ctDNA levels in all patients but 1. No patient had detectable ctDNA after surgery. The patient with rising ctDNA levels experienced tumor progression during NCT. Pathological complete response (16/38 patients) was not correlated with ctDNA detection at any time point. ctDNA positivity after 1 cycle of NCT was correlated with shorter disease-free (P < 0.001) and overall (P = 0.006) survival.Customized ctDNA detection by ddPCR achieved a 75% detection rate at baseline. During NCT, ctDNA levels decreased quickly and minimal residual disease was not detected after surgery. However, a slow decrease of ctDNA level during NCT was strongly associated with shorter survival.
