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PURPOSE The KRISTINE study compared neoadjuvant trastuzumab emtansine plus pertuzumab (T-DM1+P) with docetaxel, carboplatin, trastuzumab plus P (TCH+P) for the treatment human epidermal growth factor receptor 2–positive stage II to III breast cancer. T-DM1+P led to a lower pathologic complete response rate (44.4% v 55.7%; P = .016), but fewer grade 3 or greater and serious adverse events (AEs). Here, we present 3-year outcomes from KRISTINE. METHODS Patients were randomly assigned to neoadjuvant T-DM1+P or TCH+P every 3 weeks for six cycles. Patients who received T-DM1+P continued adjuvant T-DM1+P, and patients who received TCH+P received adjuvant trastuzumab plus pertuzumab. Secondary end points included event-free survival (EFS), overall survival, patient-reported outcomes (measured from random assignment), and invasive disease-free survival (IDFS; measured from surgery). RESULTS Of patients, 444 were randomly assigned (T-DM1+P, n = 223; TCH+P, n = 221). Median follow-up was 37 months. Risk of an EFS event was higher with TDM-1+P (hazard ratio [HR], 2.61 [95% CI, 1.36 to 4.98]) with more locoregional progression events before surgery (15 [6.7%] v 0). Risk of an IDFS event after surgery was similar between arms (HR, 1.11 [95% CI, 0.52 to 2.40]). Pathologic complete response was associated with a reduced risk of an IDFS event (HR, 0.24 [95% CI, 0.09 to 0.60]) regardless of treatment arm. Overall, grade 3 or greater AEs (31.8% v 67.7%) were less common with T-DM1+P. During adjuvant treatment, grade 3 or greater AEs (24.5% v 9.9%) and AEs leading to treatment discontinuation (18.4% v 3.8%) were more common with T-DM1+P. Patient-reported outcomes favored T-DM1+P during neoadjuvant treatment and were similar to trastuzumab plus pertuzumab during adjuvant treatment. CONCLUSION Compared with TCH+P, T-DM1+P resulted in a higher risk of an EFS event owing to locoregional progression events before surgery, a similar risk of an IDFS event, fewer grade 3 or greater AEs during neoadjuvant treatment, and more AEs leading to treatment discontinuation during adjuvant treatment.

Background In MONARCH 1 (NCT02102490), abemaciclib demonstrated promising single-agent activity and tolerability in a population of heavily pretreated women with refractory HR+, HER2- metastatic breast cancer (MBC).1 Confirmed objective response rate (ORR) was 19.7% (95% CI: 13.3, 27.5) and at 18 months minimum follow-up median overall survival (OS) was 22.3 months. Due to the single-arm trial design of MONARCH 1, there is a need to view these results in clinical context relative to available treatment options. This study compared the OS results of abemaciclib in MONARCH 1 vs that in a real-world single-agent chemotherapy cohort with similar patient and disease characteristics. Methods MONARCH 1 study design and key eligibility criteria were previously described.1 The real-world cohort was based on Flatiron Health electronic health records-derived, nationally representative (USA-based) database comprising patient-level structured and unstructured data, curated via technology-enabled abstraction, for patients with MBC between January 1, 2011 through February 28, 2018. A real-world single-agent chemotherapy cohort was created based on the key eligibility criteria of MONARCH 1 and included patients diagnosed with HR+, HER2- MBC who received single-agent chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) following 1-2 prior chemotherapy regimens in the metastatic setting, had an ECOG PS of 0-1, and no prior CDK4 & 6 therapy. The index date was the start of the eligible single-agent chemotherapy, and patients were followed from the index date until date of death, loss to follow-up, or end of the database, whichever occurred earlier. OS results were adjusted using 2 methods (Mahalanobis distance matching and entropy balancing with bootstrapping) to account for baseline demographic and clinical differences between the real-world and trial cohorts. Results A real-world cohort (n=281) with eligibility criteria similar to the MONARCH 1 population (n=132) was identified. A subsequent matching based on Mahalanobis distance was performed to match MONARCH 1 population (n=108) with the real-world cohort (n=108). The matched cohorts demonstrated similar patient and disease characteristics. Median OS was 22.3 months in the abemaciclib arm vs 13.6 months in the matched cohort with an estimated hazard ratio (HR) of 0.54 (95% CI: 0.37, 0.77). Results of a sensitivity analysis performed using entropy balancing were consistent with an adjusted median OS of 12.7 months in the real-world cohort (n=281)with HR of 0.57 (95% CI from bootstrapping: 0.44, 0.78). Conclusion Methodological advances to adjust for potential biases, and improvements in data quality, have evolved enabling the ability to leverage a real-world cohort as an external comparator arm. This study demonstrates the ability to create a real-world chemotherapy cohort suitable to serve as a comparator for MONARCH 1. These exploratory results suggest a survival advantage and adequately place the clinical benefit of abemaciclib monotherapy in clinical context. References Dickler et al, CCR 2017 Citation Format: Rugo H, Dieras V, Cortes J, Patt D, Wildiers H, O'Shaughnessy J, Zamora E, Yardley DY, Carter GC, Sheffield KM, Li L, Andre VA, Derbyshire RE, Li XI, Frenzel M, Huang Y-J, Dickler MN, Tolaney SM. Real-world survival of heavily pretreated patients with refractory HR+, HER2- metastatic breast cancer receiving single-agent chemotherapy - A comparison with MONARCH 1 [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 P6-18-19.

Background: Trop-2 is a transmembrane calcium signal transducer highly expressed in multiple solid tumors including breast cancer. Limited data exist about associations between Trop-2 protein expression, clinicopathological characteristics and outcome in triple-negative breast cancers (TNBC). Given the approval of sacituzumab govitecan in unselected TNBC, its evaluation in other breast cancer settings and the emergence of other Trop-2 targeted antibody-drug conjugates, Trop-2 emerges as an important drug target in solid tumors. Methods: Trop-2-expression of patients with TNBC diagnosed between 2000-2017 at UZ Leuven was determined with IHC (ab227689, Abcam) (continuous and categorical variables, high 201-300, medium 100-200 and low Results: Total of 658 patients with a median age at diagnosis of 53y (range 22-89y) were included, with median follow-up 9.6y. Low, medium and high Trop-2 expression was seen in 58.2%, 25.3% and 16.5% of cases. AR was positive in 25.5% of cases (10%-cutoff). Highest Trop-2 expression was observed in tumors with apocrine histology (median 180 score), and lowest expression in tumors with metaplastic histology (median 45 score) (p Conclusion: In patients with TNBC in a large tertiary center, higher Trop-2 expression was correlated with apocrine histology, higher AR expression, more associated DCIS, more LVI and nodal involvement. There was no correlation between Trop-2 expression and sTILs or outcome. Citation Format: Hava Izci, Kevin Punie, Lise Waumans, Annouschka Laenen, Hans Wildiers, Freija Verdoodt, Christine Desmedt, Jan Ardui, Ann Smeets, Sileny Han, Ines Nevelsteen, Patrick Neven, Giuseppe Floris. Trop-2 expression in triple-negative breast cancer according to histological subtype: correlations with tumor infiltrating lymphocytes (TILs) and survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 507.

1028 Background: N is an oral, irreversible pan-HER TKI with activity against HER2 mutations. Genomic analyses from the SUMMIT MBC cohort following N±F suggest that resistance to N may occur via mutant allele amplification or secondary HER2 mutations. Adding T to N+F in SUMMIT showed encouraging durable responses in patients (pts) with HR+, HER2-mutant MBC and prior CDK4/6 inhibitors (CDK4/6i). Methods: SUMMIT (NCT01953926) enrolled pts with HR+, HER2-negative MBC with activating HER2 mutation(s) and prior CDK4/6i. Pts received N+F+T (oral N 240 mg/d with loperamide prophylaxis, im F 500 mg d1&15 of cycle 1 then q4w, iv T 8 mg/kg initially then 6 mg/kg q3w). During the small, randomized portion of the trial, pts received N+F+T, F+T or F (1:1:1 ratio). Pts randomized to F+T or F could crossover to N+F+T at progression. Efficacy endpoints: investigator-assessed ORR and CBR (RECIST v1.1); DOR; best overall response. Pre-treatment tumor tissue was centrally assessed retrospectively by next-generation sequencing. ctDNA from patient samples was assessed by NGS. Results: SUMMIT has completed enrolment; we report efficacy from 45 pts in the N+F+T cohort, plus 10 pts who progressed on F (n=6) or F+T (n=4) and crossed over to N+F+T (Table). HER2 allelic variants in the 45 N+F+T pts and ORR (%) (pts may have >1 mutation) were: V777L (n=6, 50%), L755S/P (n=15, 40%), S310F (n=4, 50%), exon 20 insertion (n=11, 36%), other KD missense (n=6, 33%), TMD missense (n=2, 0%), exon 19 deletion (n=1, 0%). Conclusions: N+F+T is a promising combination for HR+, HER2-mutated MBC with prior exposure to CDK4/6i, across a range of activating HER2 mutations. Results from the upcoming Apr 2022 data cut, including biomarkers, safety, mechanisms of acquired resistance, and preclinical mechanism of N+T, will be presented. Clinical trial information: NCT01953926. [Table: see text]

PURPOSE: Using the EORTC Global Health Status (GHS) scale, we aimed to determine minimal clinically important differences (MCID) in health-related quality of life (HRQOL) changes for older cancer patients with a geriatric risk profile, as defined by the geriatric 8 (G8) health screening tool, undergoing treatment. Simultaneously, we assessed baseline patient characteristics prognostic for HRQOL changes. METHODS: Our analysis included 1424 (G8 ≤ 14) older patients with cancer scheduled to receive chemotherapy (n = 683) or surgery (n = 741). Anchor-based methods, linking the GHS score to clinical indicators, were used to determine MCID between baseline and follow-up at 3 months. A threshold of 0.2 standard deviation (SD) was used to exclude MCID estimates too small for interpretation. Logistic regressions analysed baseline patient characteristics prognostic for HRQOL changes. RESULTS: The 15-item Geriatric Depression Scale (GDS15), Visual Analogue Scale (VAS) for Fatigue and ECOG Performance Status (PS) were selected as clinical anchors. In the surgery group, MCID estimates for improvement and deterioration were ECOG PS (5*, 11*), GDS15 (5*, 2) and VAS Fatigue (3, 9*). In the chemotherapy group, MCID estimates for improvement and deterioration were ECOG PS (8*, 7*), GDS15 (5, 4) and VAS Fatigue (5, 5*). Estimates with * were > 0.2 SD threshold. Patients experiencing pain or malnutrition (surgery group) or fatigue (chemotherapy group) at baseline showed a significantly stable or improved HRQOL (p

Three patients with a medical history of breast carcinoma and metastatic carcinomatous liver disease associated with severe portal hypertension and refractory ascites are presented. Transjugular intrahepatic portosystemic shunt creation was considered as a palliative treatment option and a valuable alternative to regular paracenteses in these patients. In 2 of the 3 patients, the refractory ascites was controlled for several months without need for paracentesis, and subsequently transjugular intrahepatic portosystemic shunt may provide valuable palliation and ascites control in patients with refractory ascites due to breast cancer-induced pseudocirrhosis. ispartof: JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY vol:29 issue:12 pages:1713-1716 ispartof: location:United States status: published

Simple Summary Treating older patients with (breast) cancer is a major challenge. On the one hand, older persons are more vulnerable to side effects of therapy, and over-treatment should be avoided. On the other hand, under-treatment (which is common in the elderly) can lead to worse survival and quality of life as well. Benefits of therapy and risk of (sometimes life threatening) toxicity should be carefully balanced. There is an urgent need for robust markers that reflect the body’s biological age and could aid in outlining optimal individual treatment regimens. Here we investigated whether age/frailty and characteristics of the tumor immune infiltrate are mirrored in specific blood biomarker combinations. Several three-biomarker panels were able to categorize patients quite efficiently, especially in terms of their clinical frailty status. Abstract Background: Immune/senescence-related host factors play a pivotal role in numerous biological and pathological process like aging, frailty and cancer. The assessment of these host factors via robust, non-invasive, and easy-to-measure blood biomarkers could improve insights in these processes. Here, we investigated in a series of breast cancer patients in which way single circulating biomarkers or biomarker panels relate to chronological age, frailty status, and tumor-associated inflammatory microenvironment. Methods: An extensive panel of blood immune/senescence markers and the tumor immune infiltrate was studied in young, middle-aged, and old patients with an early invasive hormone-sensitive, HER2-negative breast cancer. In the old group, clinical frailty was estimated via the G8-scores. Results: Several three-blood biomarker panels proved to be able to separate old chronological age from young age very efficiently. Clinically more important, several three-blood biomarker panels were strongly associated with clinical frailty. Performance of blood biomarker panels for prediction of the tumor immune infiltrate was lower. Conclusion: Immune/senescence blood biomarker panels strongly correlate with chronological age, and clinically more importantly with frailty status in early breast cancer patients. They require further investigation on their ability to provide a more complete picture on clinical frailty status and direct personalized therapy in older persons.

BACKGROUND: This study aims to investigate the occurrence of unplanned hospitalizations in older patients with cancer and to determine predictive factors. METHODS: A prospective Belgian multicentre (n = 22), observational cohort study was performed. Patients ≥70 years with a malignant tumor were included. Patients underwent G8 screening followed by geriatric assessment (GA) if abnormal at baseline and were followed for unplanned hospitalizations at approximately three months. Uni- and multivariable regression models were performed to determine predictive factors associated with unplanned hospitalizations in older patients with an abnormal G8. RESULTS: In total, 7763 patients were included in the current analysis of which 2409 (31%) patients with a normal G8 score and 5354 (69%) with an abnormal G8 score. Patients with an abnormal G8 were hospitalized more frequently than patients with a normal G8 (22.9% versus 12.4%; p

Simple Summary As life expectancy is increasing, the older population is rapidly growing. However, older patients with cancer are still underrepresented in clinical trials, making treatment of these patients challenging for oncologists. Robust biomarkers that reflect the body’s biological age can be helpful to provide older patients with cancer with an optimal personalized treatment. However, to be able to identify such biomarkers, more in-depth research is needed in this underexplored population. In this review, we have put together the current knowledge concerning the mechanistic connections between aging and cancer, as well as aging biomarkers that could be useful in the field of geriatric oncology. Abstract Age is one of the main risk factors of cancer; several biological changes linked with the aging process can explain this. As our population is progressively aging, the proportion of older patients with cancer is increasing significantly. Due to the heterogeneity of general health and functional status amongst older persons, treatment of cancer is a major challenge in this vulnerable population. Older patients often experience more side effects of anticancer treatments. Over-treatment should be avoided to ensure an optimal quality of life. On the other hand, under-treatment due to fear of toxicity is a frequent problem and can lead to an increased risk of relapse and worse survival. There is a delicate balance between benefits of therapy and risk of toxicity. Robust biomarkers that reflect the body’s biological age may aid in outlining optimal individual treatment regimens for older patients with cancer. In particular, the impact of age on systemic immunity and the tumor immune infiltrate should be considered, given the expanding role of immunotherapy in cancer treatment. In this review, we summarize current knowledge concerning the mechanistic connections between aging and cancer, as well as aging biomarkers that could be helpful in the field of geriatric oncology.

Background: ESMO and SIOG created a joint WG in 2019. Their goals are to improve management of the older cancer patients through education, dedicated resources and guidelines and to raise awareness on their specific needs and requirements. Therefore, the WG initiated a survey to describe the practice patterns worldwide. Methods: All ESMO and SIOG members received a request by email to complete the survey online on 17 Feb 2020 with subsequent reminders. Questions were focused on clinical practices, perception of geriatric oncology (GO), use of screening tools such as geriatric-8 (G8), education and knowledge of guidelines. The survey was closed on 5 Apr 2020. Results: A total of 168 participants fully completed the survey. Most of them were female (65%), aged 30-39 (58%), medical oncologists (70%) and from Europe (50%). Professionals predominantly in charge of front-line care of older patients with cancer were medical oncologists (68%);however, only 19% had a physician coordinating a GO programme at their institution. According to respondents, GO brings to oncology: detection of frailty (83%), prediction of toxicity (77%), integrative management (70%), improving older patient’s understanding of treatment and adherence (64%), providing practice guidelines (46%) and prediction of survival (41%). Most of the respondents (95%) felt the need for other scales than ECOG Performance Status, 66% knew about the G8 scale and 52% used it in their clinical practice. Non-SIOG members were significantly less aware of the G8 screening tool (56% vs 97% for SIOG members;p

Since a detailed inventory of endothelial cell (EC) heterogeneity in breast cancer (BC) is lacking, here we perform single cell RNA-sequencing of 26,515 cells (including 8433 ECs) from 9 BC patients and compare them to published EC taxonomies from lung tumors. Angiogenic ECs are phenotypically similar, while other EC subtypes are different. Predictive interactome analysis reveals known but also previously unreported receptor-ligand interactions between ECs and immune cells, suggesting an involvement of breast EC subtypes in immune responses. We also identify a capillary EC subtype (LIPEC (Lipid Processing EC)), which expresses genes involved in lipid processing that are regulated by PPAR-gamma and is more abundant in peri-tumoral breast tissue. Retrospective analysis of 4648 BC patients reveals that treatment with metformin (an indirect PPAR-gamma signaling activator) provides long-lasting clinical benefit and is positively associated with LIPEC abundance. Our findings warrant further exploration of this LIPEC/PPAR-gamma link for BC treatment. Tumor blood vessels contribute to cancer growth, invasion and metastasis. Here, by using single cell transcriptomics, the authors report an inventory of endothelial cell heterogeneity in patients with breast cancer, including a subtype that expresses genes involved in lipid processing and is regulated by PPAR-gamma.

PURPOSE: In stage IV breast cancer, the efficacy of human epidermal growth factor receptor 2 (HER2) targeted therapies in cases with discordance in HER2 expression between primary and metastatic site is not well known. We studied progression free (PFS) and overall survival (OS) by HER2 concordance when treating women with taxane-trastuzumab (± pertuzumab) in first or second line and trastuzumab-emtansine (T-DM1) or capecitabine-lapatinib in later lines. PATIENTS AND METHODS: Retrospective monocentric study including all breast cancer patients receiving trastuzumab between January 2002 and September 2017 at the University Hospital in Leuven; we selected metastatic patients with an available HER2 status in primary and metastatic site. The Kaplan-Meier method was used for estimating PFS/OS and log-rank test for analyzing between group differences. A Cox model is used for testing difference between groups while correcting for Pertuzumab. Multivariable Cox regression is used to model overall survival as a function group, correcting for possible confounders. RESULTS: We included 74 patients; 46 had an unchanged HER2 status (positive/positive), 9 lost HER2 (positive/negative), while 19 acquired HER2 amplification (negative/positive). 25 out of 28 cases with a discordant HER2 status were positive for ER and/or PgR in the primary site. HER2 positive/negative cases had a significantly lower PFS for taxane-trastuzumab-(pertuzumab) (PFS = 5.5 months), compared to HER2 positive/positive (PFS 9 months, p = 0.01) and HER2 negative/positive (PFS 14 months, p = 0.01) patients. PFS for later line T-DM1 (n = 30) was significantly higher for the HER2 positive/positive group (PFS 6.0 months) than for the discordant groups HER2 negative/positive (PFS 1.0 month, p = 0.04) and HER2 positive/negative (PFS 1.5 month, p = 0.01). After correcting for possible confounders, the HER2 positive/negative group had a significantly worse OS compared to HER2 positive/positive (HR 0.19, 95% CI 0.08-0.44) and negative/positive (HR 0.15, 95% 0.06-0.38). CONCLUSION: Conversion of HER2 status was seen in 28 out of 74 cases and was mostly observed in hormone receptor-positive tumors. In contrast to patients with HER2 loss, patients with a positive conversion of HER2 status derived substantial benefit from first line treatment with taxane-trastuzumab-(pertuzumab). This study highlights the importance of re-biopsying the metastatic lesion and changing treatment according to the last HER2 result. ispartof: Breast Cancer Research And Treatment vol:185 issue:1 pages:183-194 ispartof: location:Netherlands status: Published online

Cancer and chronic kidney disease prevalence both increase with age. As a consequence, physicians are more frequently encountering older people with cancer who need dialysis, or patients on dialysis diagnosed with cancer. Decisions in this context are particularly complex and multifaceted. In this Review, we aim to provide an overview of the key points to address when making a treatment strategy in these patients. We provide information on what happens if dialysis is not started or is stopped, and how physicians should deal with such patients. Informed decisions about dialysis require a personalised care plan that considers the prognosis and treatment options for each condition while also respecting patient preferences. The concept of prognosis should include quality-of-life considerations, functional status, and burden of care. Close collaboration between oncologists, nephrologists, and geriatricians is crucial to making optimal treatment decisions, and several tools are available for estimating cancer prognosis, prognosis of renal disease, and general age-related prognosis. Emerging evidence shows that these geriatric assessment tools, which measure degrees of frailty, are useful in patients with chronic kidney disease. In this Review, we try to hand tools to practising physicians, to guide decision making regarding the initiation and termination of dialysis in patients with advanced cancer. ispartof: Lancet vol:2 issue:1 pages:e42-e52 ispartof: location:England status: Published online

Background: With the implementation of multidisciplinary treatment and development of multiple novel anticancer drugs in parallel with expanding knowledge of supportive and palliative care, a need for separate training and specialisation in medical oncology emerged. A Global Curriculum (GC) in medical oncology, developed and updated by a joint European Society for Medical Oncology/American Society of Clinical Oncology (ESMO/ASCO) GC Task Force/Working Group (GC WG), greatly contributed to the recognition of medical oncology worldwide. Material and methods: ESMO/ASCO GC WG carried out a global survey on medical oncology recognition and GC adoption in 2019. Results: Based on our survey, medical oncology is recognised as a separate specialty or sub-specialty in 47/62 (75%) countries participating in the survey; with a great majority of them (39/47, 83%) recognising medical oncology as a standalone specialty. Additionally, in 9 of 62 (15%) countries, medical oncology is trained together with haematology as a specialty in haemato-oncology or together with radiotherapy as a specialty in clinical oncology. As many as two-thirds of the responding countries reported that the ESMO/ASCO GC has been either fully or partially adopted or adapted in their curriculum. It has been adopted in a vast majority of countries with established training in medical oncology (28/41; 68%) and adapted in 12 countries with mixed training in haemato-oncology, clinical oncology or other specialty responsible for training on systemic anticancer treatment. Conclusions: With 75% of participating countries reporting medical oncology as a separate specialty or sub-specialty and as high as 68% of them reporting on GC adoption, the results of our survey on global landscape are reassuring. Despite a lack of data for some regions, this survey represents the most comprehensive and up-to-date information about recognition of medical oncology and GC adoption worldwide and will allow both societies to further improve the dissemination of the GC and global recognition of medical oncology, thus contributing to better cancer care worldwide., SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND: Only a few recent phase III trials with targeted therapies or immune checkpoint inhibitors (ICIs) in metastatic clear-cell renal cell carcinoma (m-ccRCC) demonstrated an overall survival (OS) benefit compared to standard of care. We aimed to study the evolution of OS since the start of systemic therapy from 2000 to 2020. PATIENTS AND METHODS: Retrospective study on all consecutively treated m-ccRCC patients in three Belgian hospitals starting with systemic therapy. The study outcome was OS since the start of systemic therapy. We used a univariable Cox model for OS with year of the start of therapy as a predictor, and a multivariable analysis including known prognostic factors. Linear and non-linear trends of time were tested. RESULTS: Five hundred patients were included. In a linear model, the HR for OS depending on the year of the start of therapy was 0.95 (95%CI 0.93-0.97; p

AURORA aims to study the processes of relapse in metastatic breast cancer (MBC) by performing multi-omics profiling on paired primary tumors and early-course metastases. Among 381 patients (primary tumor and metastasis pairs: 252 TGS, 152 RNA-Seq, 67 SNP Arrays), we found a driver role for GATA1 and MEN1 somatic mutations. Metastases were enriched in ESR1, PTEN, CDH1, PIK3CA and RB1 mutations; MDM4, MYC amplifications; ARID1A deletions. An increase in clonality was observed in driver genes like ERBB2 and RB1. Intrinsic subtype switching occurred in 36% of cases. Luminal A/B to HER2-Enriched switching was associated with TP53 and/or PIK3CA mutations. Metastases had lower immune score and increased immune permissive cells. High TMB correlated to shorter time to relapse in HR+/HER2- cancers. ESCAT tier I/II alterations were detected in 51% of patients and matched therapy was used in 7%. Integration of multi-omics analyses in clinical practice could impact treatment strategies in MBC., info:eu-repo/semantics/published

PURPOSE: In metastatic breast cancer (MBC) population treated with capecitabine monotherapy, we investigated clinical-pathological features as possible biomarkers for the oncological outcome. METHODS: Retrospective study of consecutive MBC patients treated at University Hospitals Leuven starting capecitabine between 1999 and 2017. The primary endpoint was the durable response (DR), defined as non-progressive disease for > 52 weeks. Other main endpoints were objective response rate (ORR), time to progression (TTP) and overall survival (OS). RESULTS: We included 506 patients; mean age at primary breast cancer diagnosis was 51.2 years; 18.2% had de novo MBC; 98.8% were pre-treated with taxanes and/or anthracycline. DR was reached in 11.6%. Patients with DR, as compared to those without DR, were more likely oestrogen receptor (ER) positive (91.5% vs. 76.8%, p = 0.010) at first diagnosis, had a lower incidence of lymph node (LN) involvement (35.6% vs. 49.9%, p = 0.039) before starting capecitabine, were more likely to present with metastases limited to ≤ 2 involved sites (54.2% vs. 38.5%, p = 0.020) and time from metastasis to start of capecitabine was longer (mean 3.5 vs. 2.7 years, p = 0.020). ORR was 22%. Median TTP and OS were 28 and 58 weeks, respectively. In multivariate analysis (only performed for TTP), ER positivity (hazard ratio (HR) = 0.529, p

Electronic systems for remotely monitoring symptoms during systemic anticancer treatment are increasingly being used. Some of these systems have features triggering alerts to healthcare professionals for worsening and/or severe symptoms, enabling real-time symptom management. This study aimed at exploring the characteristics and process of real-time alert management as well as its clinical relevance as perceived by healthcare professionals. From January until September 2019, a prospective process evaluation was set up to collect data on all alerts and their management. Also, an online survey presenting a selected number of cases was set up to explore oncologists’ and oncology nurses’ perceived clinical relevance of the real-time management of the alerts. The overall incidence rate of alerts was 1.4%. Of 253 alerts, pain, fever, dyspnea, and nausea were the most prevalent symptoms triggering an alert. The majority of alerts was managed by a nursing telephone consult alone. In 25.3% of cases, clinical examination was deemed necessary to manage the alert. In 148 of the ratings, oncologists and oncology nurses (totally) agreed with the clinical relevance of the real-time management (95.1%). The mean relevance score attached to the cases was 4.51 (±0.80). The majority of alerts triggered by a mobile tool for remote symptom monitoring during cancer treatment can be managed by a telephone nursing consult and real-time management is evaluated as (very) relevant by the majority of clinicians.

BackgroundExact numbers of breast cancer recurrences are currently unknown at the population level, because they are challenging to actively collect. Previously, real-world data such as administrative claims have been used within expert- or data-driven (machine learning) algorithms for estimating cancer recurrence. We present the first systematic review and meta-analysis, to our knowledge, of publications estimating breast cancer recurrence at the population level using algorithms based on administrative data.MethodsThe systematic literature search followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We evaluated and compared sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of algorithms. A random-effects meta-analysis was performed using a generalized linear mixed model to obtain a pooled estimate of accuracy.ResultsSeventeen articles met the inclusion criteria. Most articles used information from medical files as the gold standard, defined as any recurrence. Two studies included bone metastases only in the definition of recurrence. Fewer studies used a model-based approach (decision trees or logistic regression) (41.2%) compared with studies using detection rules without specified model (58.8%). The generalized linear mixed model for all recurrence types reported an accuracy of 92.2% (95% confidence interval = 88.4% to 94.8%).ConclusionsPublications reporting algorithms for detecting breast cancer recurrence are limited in number and heterogeneous. A thorough analysis of the existing algorithms demonstrated the need for more standardization and validation. The meta-analysis reported a high accuracy overall, which indicates algorithms as promising tools to identify breast cancer recurrence at the population level. The rule-based approach combined with emerging machine learning algorithms could be interesting to explore in the future.

BACKGROUND: BRCA1 or BRCA2-mutated breast cancers are sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors and platinum agents owing to deficiency in homologous recombination repair of DNA damage. In this trial, we compared veliparib versus placebo in combination with carboplatin and paclitaxel, and continued as monotherapy if carboplatin and paclitaxel were discontinued before progression, in patients with HER2-negative advanced breast cancer and a germline BRCA1 or BRCA2 mutation.METHODS: BROCADE3 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 147 hospitals in 36 countries. Eligible patients (aged ≥18 years) had deleterious germline BRCA1 or BRCA2 mutation-associated, histologically or cytologically confirmed advanced HER2-negative breast cancer, an Eastern Cooperative Oncology Group performance status of 0-2, and had received up to two previous lines of chemotherapy for metastatic disease. Patients were randomly assigned (2:1) by interactive response technology by means of permuted blocks within strata (block size of 3 or 6) to carboplatin (area under the concentration curve 6 mg/mL per min intravenously) on day 1 and paclitaxel (80 mg/m2 intravenously) on days 1, 8, and 15 of 21-day cycles combined with either veliparib (120 mg orally twice daily, on days -2 to 5) or matching placebo. If patients discontinued carboplatin and paclitaxel before progression, they could continue veliparib or placebo at an intensified dose (300 mg twice daily continuously, escalating to 400 mg twice daily if tolerated) until disease progression. Patients in the control group could receive open-label veliparib monotherapy after disease progression. Randomisation was stratified by previous platinum use, history of CNS metastases, and oestrogen and progesterone receptor status. The primary endpoint was investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy analyses were done by intention to treat, which included all randomly assigned patients with a centrally confirmed BRCA mutation, and safety analyses included all patients who received at least one dose of velilparib or placebo. This study is ongoing and is registered with ClinicalTrials.gov, NCT02163694.FINDINGS: Between July 30, 2014, and Jan 17, 2018, 2202 patients were screened, of whom 513 eligible patients were enrolled and randomly assigned. In the intention-to-treat population (n=509), 337 patients were assigned to receive veliparib plus carboplatin-paclitaxel (veliparib group) and 172 were assigned to receive placebo plus carboplatin-paclitaxel (control group). Median follow-up at data cutoff (April 5, 2019) was 35·7 months (IQR 24·9-43·6) in the veliparib group and 35·5 months (23·1-45·9) in the control group. Median progression-free survival was 14·5 months (95% CI 12·5-17·7) in the veliparib group versus 12·6 months (10·6-14·4) in the control group (hazard ratio 0·71 [95% CI 0·57-0·88], p=0·0016). The most common grade 3 or worse adverse events were neutropenia (272 [81%] of 336 patients in the veliparib group vs 143 [84%] of 171 patients in the control group), anaemia (142 [42%] vs 68 [40%]), and thrombocytopenia (134 [40%] vs 48 [28%]). Serious adverse events occurred in 115 (34%) patients in the veliparib group versus 49 (29%) patients in the control group. There were no study drug-related deaths.INTERPRETATION: The addition of veliparib to a highly active platinum doublet, with continuation as monotherapy if the doublet were discontinued, resulted in significant and durable improvement in progression-free survival in patients with germline BRCA mutation-associated advanced breast cancer. These data indicate the utility of combining platinum and PARP inhibitors in this patient population.FUNDING: AbbVie.

PURPOSE NALA (ClinicalTrials.gov identifier: NCT01808573 ) is a randomized, active-controlled, phase III trial comparing neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capecitabine (N+C) against lapatinib, a reversible dual TKI, plus capecitabine (L+C) in patients with centrally confirmed HER2-positive, metastatic breast cancer (MBC) with ≥ 2 previous HER2-directed MBC regimens. METHODS Patients, including those with stable, asymptomatic CNS disease, were randomly assigned 1:1 to neratinib (240 mg once every day) plus capecitabine (750 mg/m2 twice a day 14 d/21 d) with loperamide prophylaxis, or to lapatinib (1,250 mg once every day) plus capecitabine (1,000 mg/m2 twice a day 14 d/21 d). Coprimary end points were centrally confirmed progression-free survival (PFS) and overall survival (OS). NALA was considered positive if either primary end point was met (α split between end points). Secondary end points were time to CNS disease intervention, investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), clinical benefit rate, safety, and health-related quality of life (HRQoL). RESULTS A total of 621 patients from 28 countries were randomly assigned (N+C, n = 307; L+C, n = 314). Centrally reviewed PFS was improved with N+C (hazard ratio [HR], 0.76; 95% CI, 0.63 to 0.93; stratified log-rank P = .0059). The OS HR was 0.88 (95% CI, 0.72 to 1.07; P = .2098). Fewer interventions for CNS disease occurred with N+C versus L+C (cumulative incidence, 22.8% v 29.2%; P = .043). ORRs were N+C 32.8% (95% CI, 27.1 to 38.9) and L+C 26.7% (95% CI, 21.5 to 32.4; P = .1201); median DoR was 8.5 versus 5.6 months, respectively (HR, 0.50; 95% CI, 0.33 to 0.74; P = .0004). The most common all-grade adverse events were diarrhea (N+C 83% v L+C 66%) and nausea (53% v 42%). Discontinuation rates and HRQoL were similar between groups. CONCLUSION N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed.

PURPOSE: We studied the long-term outcomes of invasive micropapillary carcinoma (IMPCs) of the breast in relation to stromal tumor infiltrating lymphocytes (sTILs), prognostic biomarkers and clinicopathological features. METHODS: Stage I-III IMPCs treated with upfront surgery at our institution (January 2000 and December 2016) were included. Central pathology review was performed and sTILs (including zonal distribution and hot spot analysis) and tumor-associated plasma cells (TAPC) were evaluated. Expression of P53, BCL2, FOXP3, and WT1, which are variably linked to breast cancer prognosis, was measured by immunohistochemistry using tissue microarrays. Time-to-event endpoints were distant recurrence free interval (DRFI) and breast cancer-specific survival (BCSS). RESULTS: We included 111 patients of whom 59% were pure IMPCs. Standard clinicopathological features were comparable between pure and non-pure IMPCs. Overall, the mean sTILs level was 20% with higher proportion of sTILs present at the invasive front. There were no significant differences between pure- and non-pure IMPCs in sTILs levels, nor in the spatial distribution of the hot spot regions or in the distribution of TAPC. Higher sTILs correlated with worse DRFI (HR = 1.55; p = 0.0172) and BCSS (HR = 2.10; p

BACKGROUND: Cancer seems to have an independent adverse prognostic effect on COVID-19-related mortality, but uncertainty exists regarding its effect across different patient subgroups. We report a population-based analysis of patients hospitalised with COVID-19 with prior or current solid cancer versus those without cancer. METHODS: We analysed data of adult patients registered until 24 May 2020 in the Belgian nationwide database of Sciensano. The primary objective was in-hospital mortality within 30 days of COVID-19 diagnosis among patients with solid cancer versus patients without cancer. Severe event occurrence, a composite of intensive care unit admission, invasive ventilation and/or death, was a secondary objective. These endpoints were analysed across different patient subgroups. Multivariable logistic regression models were used to analyse the association between cancer and clinical characteristics (baseline analysis) and the effect of cancer on in-hospital mortality and on severe event occurrence, adjusting for clinical characteristics (in-hospital analysis). RESULTS: A total of 13 594 patients (of whom 1187 with solid cancer (8.7%)) were evaluable for the baseline analysis and 10 486 (892 with solid cancer (8.5%)) for the in-hospital analysis. Patients with cancer were older and presented with less symptoms/signs and lung imaging alterations. The 30-day in-hospital mortality was higher in patients with solid cancer compared with patients without cancer (31.7% vs 20.0%, respectively; adjusted OR (aOR) 1.34; 95% CI 1.13 to 1.58). The aOR was 3.84 (95% CI 1.94 to 7.59) among younger patients (

This study aims to develop and validate a simple score to estimate survival in the older population suffering from malignant hemopathies.We prospectively recruited 285 patients, aged ≥65 years, admitted to receive chemotherapy. At inclusion, a geriatric assessment was performed. Cox proportional hazards models were performed to assess correlations between vulnerabilities and one-year survival. We developed a frailty score, HEMA-4, based on the most powerful prognostic factors. It was externally confirmed with an independent cohort.In the development cohort, 206 patients were evaluable. Mean age was 76 years (range 65-90). The HEMA-4 score was created based on four independent predictive factors for survival: cognitive impairment (MMSE27), comorbidities (≥2 on Charlson comorbidity index), CRP (≥10 mg/L) and low albumin level (35 g/L). The population was stratified into three groups: good prognosis (score = 0-1, n = 141), intermediate prognosis (score = 2, n = 37) and poor prognosis (score = 3-4, n = 28). Their respective one-year survival was 74%, 51% (HR = 2.30; 95% CI =1.31-4.05; p 0.01) and 36% (HR = 3.95; 95% CI =2.23-6.98; p 0.01). In the validation cohort (n = 25), the one-year survival was 78% in the good prognosis group (n = 9) and 50% in the intermediate prognosis group (n = 6). The poor prognosis group had a median survival of four months in the development cohort and six months in the validation cohort (n = 10).The HEMA-4 score is a simple score that combines cognitive impairment, comorbidities, inflammation and low albumin level. Our data suggest that it predicts survival among older patients suffering from malignant hemopathies referred to receive chemotherapy regardless of their chronological age.

Background High levels of stromal tumor-infiltrating lymphocytes (sTIL) are associated with increased pathological complete response (pCR) rate and longer survival after neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients. Here, we evaluated the value of sTIL in predicting pCR and explored prognosis in TNBC patients treated with neoadjuvant chemotherapy according to body mass index (BMI). Methods sTIL were scored centrally on pretreatment biopsies from 2 retrospective series of nonunderweight TNBC patients (n = 445). sTIL and BMI were considered as binary (sTIL: Results 236 (53.0%) patients were lean and 209 (47.0%) overweight and obese. pCR was achieved in 181 of 445 (41.7%) patients. Median sTIL was 11.0%, and 99 of 445 (22.2%) tumors had high sTIL. A statistically significant interaction between sTIL and BMI, considered as categorical or continuous variables, for predicting pCR was observed in the multivariable analysis (Pinteraction = .03 and .04, respectively). High sTIL were statistically significantly associated with pCR in lean (odds ratio [OR] = 4.24, 95% confidence interval [CI] = 2.10 to 8.56; P < .001) but not in heavier patients (OR = 1.48, 95% CI = 0.75 to 2.91; P = .26) in the multivariable analysis. High sTIL were further associated with increased event-free survival in lean (hazard ratio [HR] = 0.22, 95% CI = 0.08 to 0.62; P = .004) but not in heavier patients (HR = 0.53, 95% CI = 0.26 to 1.08; P = .08). Similar results were obtained for overall survival. Conclusion BMI is modifying the effect of sTIL on pCR and prognosis in TNBC patients treated with neoadjuvant chemotherapy.

AIMS: As important prognostic and predictive information can be obtained from the composition, functionality and spatial arrangement of different immune cell subtypes, this study aims at characterizing the immune infiltrate in breast tumours. METHODS AND RESULTS: Tumour-infiltrating lymphocytes (TILs) in 62 patients with luminal B-like breast cancer were characterised by immunohistochemical staining with standard markers, and were subsequently classified and quantified by the use of QuPath software. In different delineated tumour regions, the proportion and density of CD3+ , CD4+ , CD5+ , CD8+ , CD20+ and FOXP3+ cells were assessed. The results of the software analysis were compared with those of manual counting for CD8 and CD20 staining. The QuPath scoring protocol slightly overestimated positive, negative and total lymphocyte counts and density, while minimally underestimating the proportion of positively stained lymphocytes. However, for density and proportion, no real differences from manual counting were observed. For all markers, the density of positively stained immune cells was higher in the invasive front than in the tumour centre, pointing to an accumulation of immune cells near the tumour boundaries. When we looked at the proportion of immunohistochemically positive immune cells, we observed enrichment of CD5 (P = 0.025) and CD20 (P

The COVID-19 pandemic poses a barrier to equal and evidence-based management of cancer in older adults. The International Society of Geriatric Oncology (SIOG) formed a panel of experts to develop consensus recommendations on the implications of the pandemic on several aspects of cancer care in this age group including geriatric assessment (GA), surgery, radiotherapy, systemic treatment, palliative care and research. Age and cancer diagnosis are significant predictors of adverse outcomes of the COVID-19 infection. In this setting, GA is particularly valuable to drive decision-making. GA may aid estimating physiologic reserve and adaptive capability, assessing risk-benefits of either providing or temporarily withholding treatments, and determining patient preferences to help inform treatment decisions. In a resource-constrained setting, geriatric screening tools may be administered remotely to identify patients requiring comprehensive GA. Tele-health is also crucial to ensure adequate continuity of care and minimize the risk of infection exposure. In general, therapeutic decisions should favor the most effective and least invasive approach with the lowest risk of adverse outcomes. In selected cases, this might require deferring or omitting surgery, radiotherapy or systemic treatments especially where benefits are marginal and alternative safe therapeutic options are available. Ongoing research is necessary to expand knowledge of the management of cancer in older adults. However, the pandemic presents a significant barrier and efforts should be made to ensure equitable access to clinical trials and prospective data collection to elucidate the outcomes of COVID-19 in this population. ispartof: JOURNAL OF GERIATRIC ONCOLOGY vol:11 issue:8 pages:1190-1198 ispartof: location:Netherlands status: published

In 2011, the International Society of Geriatric Oncology (SIOG) published the SIOG 10 Priorities Initiative, which defined top priorities for the improvement of the care of older adults with cancer worldwide.1 Substantial scientific, clinical, and educational progress has been made in line with these priorities and international health policy developments have occurred, such as the shift of emphasis by WHO from communicable to non-communicable diseases and the adoption by the UN of its Sustainable Development Goals 2030. Therefore, SIOG has updated its priority list. The present document addresses four priority domains: education, clinical practice, research, and strengthening collaborations and partnerships. In this Policy Review, we reflect on how these priorities would apply in different economic settings, namely in high-income countries versus low-income and middle-income countries. SIOG hopes that it will offer guidance for international and national endeavours to provide adequate universal health coverage for older adults with cancer, who represent a major and rapidly growing group in global epidemiology. ispartof: The Lancet Oncology vol:22 issue:1 pages:e29-e36 ispartof: location:England status: Published online

Background The aim of the study was to evaluate the safety and feasibility of intra-arterial mitomycin C (MMC) infusion after selective internal radiation therapy (SIRT) using Yttrium-90 (90Y) resin microspheres in liver metastatic breast cancer (LMBC) patients. Patients and methods The prospective pilot study included LMBC patients from 2012–2018. Patients first received infusion of 90Y resin microspheres, after 6–8 weeks response to treatment was assessed by MRI, 18F-FDG PET/CT and laboratory tests. After exclusion of progressive disease, MMC infusion was administrated 8 weeks later in different dose cohorts; A: 6 mg in 1 cycle, B: 12 mg in 2 cycles, C: 24 mg in 2 cycles and D: maximum of 72 mg in 6 cycles. In cohort D the response was evaluated after every 2 cycles and continued after exclusion of progressive disease. Adverse events (AE) were reported according to CTCAE version 5.0. Results Sixteen patients received 90Y treatment. Four patients were excluded for MMC infusion, because of extra hepatic disease progression (n = 3) and clinical and biochemical instability (n = 1). That resulted in the following number of patient per cohort; A: 2, B: 1, C: 3 and D: 6. In 4 of the 12 patients (all cohort D) the maximum dose of MMC was adjusted due biochemical toxicities (n = 2) and progressive disease (n = 2). One grade 3 AE occurred after 90Y treatment consisting of a gastrointestinal ulcer whereby prolonged hospitalization was needed. Conclusions Sequential treatment of intra-arterial infusion of MMC after 90Y SIRT was feasible in 75% of the patients when MMC was administrated in different escalating dose cohorts. However, caution is needed to prevent reflux after 90Y SIRT in LMBC patients.

Objectives Aging is associated with altered immune function and chronic low‐grade inflammation, referred to as immunosenescence. As breast cancer is an age‐related disease, the impact of aging on tumor immune responses may have important consequences. However, effects of immunosenescence on breast tumor immune infiltration remain largely unknown. Methods This exploratory study investigated a broad panel of immune/senescence markers in peripheral blood and in the tumor microenvironment of young, middle‐aged and old patients diagnosed with early invasive luminal (hormone‐sensitive, HER2‐negative) breast cancer. In the old group, G8‐scores were computed as a correlate for clinical frailty. Results Significant age‐related changes in plasma levels of several inflammatory mediators (IL‐1α, IP‐10, IL‐8, MCP‐1, CRP), immune checkpoint markers (Gal‐9, sCD25, TIM‐3, PD‐L1), IGF‐1 and circulating miRs (miR‐18a, miR‐19b, miR‐20, miR‐155, miR‐195 and miR‐326) were observed. Shifts were observed in distinct peripheral blood mononuclear cell populations, particularly naive CD8+ T‐cells. At the tumor level, aging was associated with lower total lymphocytic infiltration, together with decreased abundance of several immune cell markers, especially CD8. The relative fractions of cell subsets in the immune infiltrate were also altered. Clinical frailty was associated with higher frequencies of exhausted/senescent (CD27−CD28− and/or CD57+) terminally differentiated CD8+ cells in the blood and with increased tumor infiltration by FOXP3+ cells. Conclusion Aging and frailty are associated with profound changes of the blood and tumor immune profile in luminal breast cancer, pointing to a different interplay between tumor cells, immune cells and inflammatory mediators at higher age., In this study, apart from age‐related changes in the immune profile of patients with luminal breast cancer, remarkable frailty‐related changes within the subgroup of older patients were observed. Our data support age‐dependent remodelling of both systemic immunity features and anti‐tumor immune responses.

Objectives: We aimed to determine the prognostic value of baseline Health-Related Quality Of Life (HRQOL) and geriatric assessment (GA) to predict three-month mortality in older patients with cancer undergoing treatment. Methods: Logistic regressions analysed HRQOL, as measured with the EORTC Global Health Status (GHS) scale, and geriatric information prognostic for early mortality controlling for oncology variables. The assessment was established with the odds ratio (OR), 95% confidence interval (CI) and level of significance set at p < 0.05. Discriminative power was evaluated with area under the curve (AUC). Results: In total, 6769 patients were included in the study, of whom 1259 (18.60%) died at three months. Our model showed higher odds of early death for patients with lower HRQOL (GHS, OR 0.98, 95% CI 0.98-0.99; p < 0.001), a geriatric risk profile (G8 Screening Tool, 1.94, 1.14-3.29; p = 0.014), cognitive decline (Mini Mental State Examination, 1.41, 1.15-1.72; p 0.001), being at risk for malnutrition (Mini Nutritional Assessment-Short Form, 1.54, 1.21-1.98; p = 0.001), fatigue (Visual Analogue Scale for Fatigue, 1.45, 1.16-1.82; p = 0.012) and comorbidities (Charlson Comorbidity index, 1.23, 1.02-1.49: p = 0.033). Additionally, older age, poor ECOG PS and being male increased the odds of early death, although the magnitude differed depending on tumor site and stage, and treatment (all p < 0.05). Predictive accuracy increased with 3.7% when including HRQOL and GA in the model. Conclusion: The results suggest that, in addition to traditional clinical measures, HRQOL and GA provide additional prognostic information for early death, but the odds differ by patient and tumor characteristics. (C) 2020 Elsevier Ltd. All rights reserved.

Germline pathogenic alterations in the breast cancer susceptibility genes 1 (BRCA1) and 2 (BRCA2) are the most prevalent causes of hereditary breast and ovarian cancer. The increasing trend in proportion of cancer patients undergoing genetic testing, followed by predictive testing in families of new index patients, results in a significant increase of healthy germline BRCA1/2 mutation carriers who are at increased risk for breast, ovarian, and other BRCA-related cancers. This review aims to give an overview of available screening guidelines for female and male carriers of pathogenic or likely pathogenic germline BRCA1/2 variants per cancer type, incorporating malignancies that are more or less recently well correlated with BRCA1/2. We selected guidelines from national/international organizations and/or professional associations that were published or updated between January 1, 2015, and February 1, 2020. In total, 12 guidelines were included. This review reveals several significant discordances between the different guidelines. Optimal surveillance strategies depend on accurate age-specific cancer risk estimates, which are not reliably available for all BRCA-related cancers. Up-to-date national or international consensus guidelines are of utmost importance to harmonize counseling and proposed surveillance strategies for BRCA1/2 carriers.

Background: Lymph node positivity (LNP) is among the most important prognostic factors in breast cancer. Counterintuitively, a negative association of LNP with age has been shown in different cancers. The goal of this study is to determine the influence of age and tumor size on lymph node positivity in breast cancer in a large real-world population setting. Methods: Patients aged 0-85 years with primary invasive breast cancer who underwent primary surgery and lymph node dissection between 2010 and 2018 were selected using the U.S. Surveillance, Epidemiology, and End Results (SEER) database. Patients with systemic therapy before surgery or patients not receiving surgery for the breast tumor and/or lymph nodes were excluded. We used a multivariate logistic regression model to determine the association of age with regional LNP. We corrected for grade, tumor size, ER-, PR- and HER2-positivity and race. Based on previous studies and exploratory analysis on the current database, we used a piecewise effect of age with cutoff at 70y, and an interaction term between age and tumor size. We also introduced a piecewise linear effect for tumor size, with cut-off at 50mm. Results: (see table) 177,866 patients were included. The multivariate model suggests that LNP strongly decreases with age in patients with breast cancer ≤ 70y. This effect is stronger for smaller tumor sizes. The effects in patients >70 years are less clear, and may be more biased by delay in diagnosis or selection bias as older patients with small tumors are less likely to undergo surgery (of both breast tumor and lymph nodes).Concerning impact of tumor size, our analysis shows that LNP strongly increases with tumor size in tumors ≤ 50 mm as expected, but that this association is not present anymore in tumors > 50 mm. Conclusion: We found a clear negative association of LNP with age in patients ≤ 70 years, when corrected for grade, tumor size, ER-, PR- and HER2-positivity and race. This points to differences in biological mechanisms of lymph node invasion in young versus older persons that are counterintuitive and poorly understood. We also found that LNP strongly increases with tumor size in tumors ≤ 50 mm, but not in larger tumors. The impact of age on tumor biology, micro-environment and the lymphatic system may each play a role. However, these areas are understudied and further research is needed to understand the mechanism behind the current results. Impact of age on Lymph node positivity (LNP), according to tumor sizeAge expressed per 10-year increaseTumor sizeOdds Ratio (95% CI)≤70y15mm0.852 (0.841;0.863)25mm0.871 (0.860;0.881)40mm0.900 (0.885;0.914)>70y15mm0.980 (0.939;1.023)25mm1.002 (0.960;1.046)40mm1.035 (0.990;1.082)Impact of tumor size on Lymph node positivity (LNP), according to ageTumor size expressed by 1 cm increaseAgeOdds Ratio (95% CI)≤50mm50y2.041 (2.016;2.066)60y2.086 (2.063;2.109)70y2.132 (2.105;2.159)80y2.179 (2.143;2.215)>50mm50y0.957 (0.945;0.970)60y0.978 (0.967;0.990)70y1.000 (0.987;1.013)80y1.022 (1.005;1.039)OR: odds ratio, CI: confidence interval OR>( Citation Format: Michael Pinchuk, Annouschka Laenen, Sigrid Hatse, Kevin Punie, Patrick Neven, Ines Nevelsteen, Hans Wildiers. Influence of age and tumor size on lymph node positivity in breast cancer: A retrospective population study on the US SEER database [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 P1-01-05.

BACKGROUND: The number of patients requesting autologous breast reconstruction (ABR) after mastectomy for breast cancer has increased over the past decades. However, concern has been expressed about the oncological safety of ABR. The aim of our study was to assess the effect of ABR on distant relapse. METHODS: In this retrospective cohort study, data was analysed from patients who underwent mastectomy for invasive breast cancer in University Hospitals Leuven between 2000 and 2011. In total, 2326 consecutive patients were included, 485 who underwent mastectomy with ABR and 1841 who underwent mastectomy alone. The risk of relapse in both groups was calculated using a Cox proportional hazards analysis, adjusted for established prognostic factors. ABR was considered as a time-dependent variable. Additionally, the evolution of the risk over follow-up time was calculated. RESULTS: With a median follow-up of 68 months, 8% of patients in the reconstruction group developed distant metastases compared to 15% in the mastectomy alone group (univariate HR 0.70, 95% CI 0.50-0.97, p = 0.0323). However, after adjustment for potential confounding factors in a Cox multivariable analysis, the risk of distant relapse was no longer significantly different between groups (multivariate HR 0.82, 95% CI 0.55-1.22, p = 0.3301). Moreover, the risk of metastasis after reconstruction was not time-dependent. CONCLUSIONS: These findings suggest that there is no effect of ABR on distant relapse rate and thus that ABR is an oncological safe procedure. The rate of local recurrence was too low to make any significant conclusions. ispartof: BMC CANCER vol:18 issue:1 ispartof: location:England status: published

Background The aim of this study was to determine and compare the added prognostic value of screening tools, geriatric assessment (GA) components, and GA summaries to clinical information for overall survival (OS) in older patients with cancer. Methods A screening and a 10-item GA were systematically performed in patients ≥70 years old with cancer. Cox regression analyses were conducted to evaluate the added prognostic value for OS of screening tools, GA, and GA summaries to clinical information (age, stage, and tumor type) in 2 cohorts (A and B). Cox models were compared on the basis of the Akaike information criterion and the concordance probability estimate. The 2 cohorts for the analyses were similar but independent. Results A complete case analysis was available for 763 patients (median age, 76 years) in cohort A and for 402 patients (median age, 77 years) in cohort B. In both cohorts, most individual GA components were independent prognostic factors for OS. Nutritional status (assessed with the Mini Nutritional Assessment Short Form) and functional status (assessed with the Instrumental Activities of Daily Living) consistently displayed a strong capacity to predict OS. Less consistent results were found for screening tools. GA summaries performed the best in comparison with the screening tools and the individual GA components. Conclusions Most individual GA components, especially nutritional status and functional status, are prognostic factors for OS in older patients with cancer. GA summaries provide more prognostic information than individual GA components but only moderately improve the prognostic baseline model with clinical information.

BACKGROUND The current study was performed to evaluate the prognostic value of laboratory parameters and geriatric assessment (GA) in addition to a baseline model with clinical information regarding overall survival (OS) in patients with cancer. METHODS GA was systematically performed in patients aged ≥70 years. The baseline model consisted of age, tumor type, and stage of disease. The incremental prognostic values of the GA as a whole (10-item GA) and laboratory parameters were assessed separately and combined. The parameters included hemoglobin (Hb), albumin, C-reactive protein (CRP), and the Glasgow Prognostic Score (GPS). Analyses were conducted with continuous and dichotomized variables. Cox models were compared based on Akaike information criterion (ΔAIC) and their discriminatory ability was assessed using the concordance probability estimate (CPE). RESULTS A total of 328 patients were considered for this analysis. The baseline model had a CPE of 0.725. The addition of CRP, albumin, and Hb combined resulted in the best performing model (ΔAIC: 40.12 and CPE: 0.757) among the laboratory parameters. However, the 10-item GA improved the baseline model even more (ΔAIC: 46.03 and CPE: 0.769). Similar results were observed in the analysis with dichotomous variables. The addition of the 3 laboratory parameters (CRP, albumin, and Hb) improved the CPE by 1.4% compared with the baseline model already extended with the 10-item GA. The CPE increase (1.7%) was the highest with the GPS in the analysis with dichotomous variables. CONCLUSIONS GA appears to add slightly more prognostic information than laboratory parameters in addition to clinical information. The laboratory parameters have an additional prognostic value beyond clinical and geriatric information.

We present the case of a postmenopausal patient with a secondary metastatic ER-positive, HER2-negative breast cancer who was successfully treated with fulvestrant and alpelisib following six lines of therapy. The tumour showed two uncommon PIK3CA mutations, and with the combination of alpelisib and fulvestrant the patient went from ECOG grade 3, before the start of this therapy, to ECOG grade 1 during treatment until progressive disease after 6 months. This unexpected benefit emphasizes the importance of performing a Next Generation Sequencing (NGS)-based assay to screen for several cancer genes in the metastatic setting, even after more than four lines of therapy and a high ECOG grade. Moreover, the use of alpelisib may be beneficial for uncommon PIK3CA mutations.

We aimed to investigate the role of palbociclib, a first-in-class cyclin-dependent kinase 4 and 6 inhibitor, in postmenopausal women with highly pretreated endocrine therapy-resistant metastatic breast cancer (MBC). Between 28 September 2015 and 14 March 2017, a compassionate use program was established in the University Hospitals Leuven in which 82 postmenopausal women with estrogen receptor-positive, HER2-negative MBC were included after at least four lines of systemic treatment. The efficacy and safety analysis was performed in 82 patients who had received at least one dose of palbociclib and who had at least 6-month follow-up at the data cut-off point. The primary objective was the evaluation of efficacy of the combination of palbociclib and endocrine therapy with clinical benefit as primary endpoint, defined as the absence of progressive disease and being on treatment for at least 6 months. Secondary objectives were the evaluation of toxicity and the identification of potential predictors for clinical benefit. The median age of the patients was 67.1 years (range 34.8–85.9) at the time of inclusion. The average duration of treatment was 5.6 months (range 1–19), with a median progression-free survival of 3.17 (95% CI 2.76–4.70) months. At the data cut-off point, 10 patients were still on treatment with palbociclib. In this highly pretreated setting, 34 patients experienced no progressive disease within 6 months, resulting in an overall clinical benefit rate (CBR) of 41.5%. 20.7% (17/82) showed stable disease for ≥ 9 months and 13.4% for ≥ 12 months. None of the investigated predicting factors were significantly associated with clinical benefit at 6 months. For 43.9% of the patients, treatment delay or dose reduction was indicated. Palbociclib in combination with endocrine therapy shows an unexpectedly high CBR and favorable safety profile in heavily pretreated endocrine-resistant estrogen receptor-positive, HER2-negative MBC patients.

Summary Background Despite the high incidence of metastatic breast cancer and its related mortality in the elderly population, our knowledge about optimal treatment for older patients with cancer is far from adequate. We aimed to evaluate the efficacy of dual anti-HER2 treatment with or without metronomic chemotherapy in older patients with HER2-positive metastatic breast cancer. Methods We did a multicentre, open-label, randomised, phase 2 trial in 30 centres from eight countries in Europe, in patients with histologically proven, HER2-positive metastatic breast cancer, without previous chemotherapy for metastatic disease, who were 70 years or older, or 60 years or older with confirmed functional restrictions defined by protocol, and had a life expectancy of more than 12 weeks and a performance status according to WHO scale of 0–3. Eligible patients were randomly assigned (1:1) by an online randomisation system based on the minimisation method to receive metronomic oral cyclophosphamide 50 mg per day plus trastuzumab and pertuzumab, or trastuzumab and pertuzumab alone. Trastuzumab was given intravenously with a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks. Pertuzumab was given intravenously with a loading dose of 840 mg, followed by 420 mg every 3 weeks. Patients were stratified by hormone receptor positivity, previous HER2 treatment, and baseline geriatric screening. The primary endpoint was investigator-assessed progression-free survival at 6 months as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A difference of 10% or greater between the two groups was sought. Efficacy analyses were by intention to treat; safety was assessed in all patients who received at least one dose of study treatment. In case of progression, all patients were offered trastuzumab emtansine. This trial is registered with ClinicalTrials.gov, number NCT01597414, and is completed. Findings Between July 2, 2013, and May 10, 2016, 80 patients, of whom 56 (70%) had a potential frailty profile according to the geriatric screening G8 score (≤14), were randomly assigned to receive trastuzumab and pertuzumab (n=39) or trastuzumab and pertuzumab plus metronomic oral cyclophosphamide (n=41). Estimated progression-free survival at 6 months was 46·2% (95% CI 30·2–60·7) with trastuzumab and pertuzumab versus 73·4% (56·6–84·6) with trastuzumab and pertuzumab plus metronomic oral cyclophosphamide (hazard ratio [HR] 0·65 [95% CI 0·37–1·12], p=0·12). At a median follow-up of 20·7 months (IQR 12·5–30·4), the median progression-free survival was 5·6 months (95% CI 3·6–16·8) with trastuzumab and pertuzumab versus 12·7 months (6·7–24·8) with the addition of metronomic oral cyclophosphamide. The most frequent grade 3–4 adverse events were hypertension (in six [15%] of 39 patients in the trastuzumab and pertuzumab group vs five [12%] of 41 in the trastuzumab and pertuzumab plus metronomic oral cyclophosphamide group), diarrhoea (four [10%] vs five [12%]), dyspnoea (two [5%] vs four [10%]), fatigue (three [8%] vs two [5%]), pain (two [5%] vs two [5%]), and a thromboembolic event (0 [0%] vs four [10%]). Severe cardiac toxicities were occasionally observed in both groups. In the trastuzumab and pertuzumab group four patients died without progression, due to cardiac arrest during treatment (n=1), peritoneal infection (n=1), respiratory failure (n=1), and sudden death without a specified cause (n=1). In the trastuzumab and pertuzumab plus metronomic oral cyclophosphamide group, one patient died from heart failure. Interpretation Addition of metronomic oral cyclophosphamide to trastuzumab plus pertuzumab in older and frail patients with HER2-positive metastatic breast cancer increased median progression-free survival by 7 months compared with dual HER2 blockade alone, with an acceptable safety profile. Trastuzumab and pertuzumab plus metronomic oral cyclophosphamide, followed by trastuzumab emtansine after disease progression, might delay or supersede the need for taxane chemotherapy in this population. Funding F Hoffmann-La Roche.

We aim to assess short and long term effects of chemotherapy on patient-reported quality of life (QOL) and patient versus clinician symptom reporting in older patients with breast cancer adjusted for tumour and aging parameters.In this prospective, multicentre, non-interventional, observational study, women aged ≥70years were enrolled after surgery and assigned to a TC chemotherapy (docetaxel and cyclophosphamide) group or a control group depending on their planned adjuvant treatment. Longitudinal multivariate models were used to assess the statistical and minimal clinically important difference (MCID) in the impact of TC chemotherapy over time on QOL and symptom burden adjusted for baseline aging and tumour parameters. Statistical significance was set at 5% and MCID at 10 points.In total, 57 patients were enrolled in the chemotherapy and 52 patients in the control group. Within the chemotherapy group, clinical deterioration was reported at 3months for Fatigue (17.73), Dyspnoea (17.05), Diarrhoea (12.06) and Appetite Loss (17.05) scores (all p0.001). However, the scores had returned to baseline (or even better for Role Functioning) at year 1. No clinical deterioration was reported in the control group. Symptom scores as reported by patients were significantly (p0.05) higher than those reported by the clinicians, even more so for Fatigue, Dyspnoea, and Pain.Our results show that symptom burden and diminished QOL in an older breast cancer population receiving adjuvant TC chemotherapy are short-lived and disappear after a while with no long-term differences compared to a similar population not receiving chemotherapy.

Introduction: Overall prognosis of early TNBC remains inferior to that of other breast cancer subtypes. Neoadjuvant platinum added to taxanes-anthracycline regimen has been reported to potentially improve pathologic complete response (pCR) and survival in TNBC pts. Aim: To report the final results of the efficacy and toxicity of the addition of weekly Cp to P and dose dense (dd) EC on the pCR rate in an open-label phase II study in stage II/III TNBC pts. Patients and methods: In the BSMO study sixty three pts received dd P (80mg/m2/wk) concurrent with Cp (AUC=2) for 12 weeks, added to bi-weekly E (90mg/m2) and C (600mg/m2) for 4 cycles, followed by surgery and radiotherapy. The primary endpoint was pCR in the breast and axilla. Additionally actual drug dosing and toxicities were registered. A correlative assessment of germline mutations in HRD genes is ongoing. Pts were monitored for clinical response by magnetic resonance and mammography, and also for relapse free survival and time to treatment failure. The study sample size has been calculated according to the optimal Simon's two-stage design method. The target sample size was 63 patients with 80% power to detect a pCR rate of > or=47% (α= 0.05). Results: Sixty three eligible pts with operable, non-inflammatory stage II/III TNBC were included. Most pts were between 40 and 59 yrs old and had clinical stage II disease. Forty percent were clinically node + and 68% were G3. Seventy three percent received breast conserving surgery. Sixty percent (38 out of 63 pts) achieved a pCR breast/axilla. Sixteen percent (10pts) missed three or more doses of wP, whereas at least 1 EC cycle was skipped in 19% (12pts). Sixty five percent had G3/4 neutropenia. Investigator reported febrile neutropenia occurred in 18 pts (28.5%) of which more than eighty percent during the EC part despite primary prophylaxis. Thrombocytopenia G3/4 was noticed in 10 pts (16%). Only four pts (6%) developed grade 3 peripheral neuropathy. Conclusion: The addition of weekly carboplatinum to neoadjuvant paclitaxel and ddEC is feasible and a pCR rate in the breast and axilla as high as 60% compares nicely with the results achieved with the similar 3 weekly carboplatinum arm of the CALBG 40603 trial. Febrile neutropenia rate was higher than the 3-weekly carboplatin arm in CALGB40603 trial, but occurred mainly during the EC part, while other toxicities are comparable. Future research could focus on this combination in the reverse sequence (first ECdd), which may lead to a better global haematological profile. Citation Format: Fontaine C, Cappoen N, Renard V, Van Den Bulck H, Vuylsteke P, Glorieux P, Dopchie C, Decoster L, De Grève J, Awada A, Wildiers H. Final results of weekly (w) neoadjuvant carboplatin (Cp) added to paclitaxel (P) followed by epirubicin (E) and cyclophosphamide (C) in triple negative breast cancer (TNBC) patients (pts): A BSMO breast cancer task force phase II study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-15-09.

Pregnancy affects breast cancer risk but how it affects the subtype and prognosis remain controversial. We studied the effect of parity and time since last birth on breast cancer subtype and outcome. We conducted a retrospective multivariate cohort study including all premenopausal women with early breast cancer aged ≤ 50 years (N = 1306) at diagnosis at the University Hospitals Leuven (Jan. 2000–Dec. 2009). Primary study endpoints were the breast cancer subtype, disease-free survival, and distant disease-free survival by parity and time since last birth. Statistical methods used were baseline-category logits models and Cox proportional hazard models. Multivariable models were used to correct for possible confounders. Breast cancer subtypes did not differ between nulliparous (N = 266) and parous women (N = 1040) but subtypes differed significantly in parous women by time since last birth (p

Aging is a heterogeneous process. Most newly diagnosed cancers occur in older adults, and it is important to understand a patient’s underlying health status when making treatment decisions. A geriatric assessment provides a detailed evaluation of medical, psychosocial, and functional problems in older patients with cancer. Specifically, it can identify areas of vulnerability, predict survival and toxicity, assist in clinical treatment decisions, and guide interventions in routine oncology practice; however, the uptake is hampered by limitations in both time and resources, as well as by a lack of expert interpretation. In this review, we describe the utility of geriatric assessment by using an illustrative case and provide a practical approach to geriatric assessment in oncology.

Summary Background HER2-targeted treatments have improved outcomes in patients with HER2-positive breast cancer in the neoadjuvant, adjuvant, and metastatic settings; however, some patients remain at risk of relapse or death for many years after treatment of early-stage disease. Therefore, new strategies are needed. We did a phase 3 trial to assess a neoadjuvant regimen for HER2-positive breast cancer that replaces traditional systemic chemotherapy with targeted treatment. Methods We did a randomised, open-label phase 3 KRISTINE trial in 68 Translational Research In Oncology centres (hospitals and specialty cancer centres in Asia, Europe, USA, and Canada). Eligible participants were aged 18 years or older with centrally confirmed HER2-positive stage II–III operable breast cancer (>2 cm tumour size), an Eastern Cooperative Oncology Group performance status of 0–1, and a baseline left ventricular ejection fraction of at least 55% (by echocardiogram or multiple-gated acquisition scan). We randomly assigned participants (1:1) to receive either trastuzumab emtansine plus pertuzumab or docetaxel, carboplatin, and trastuzumab plus pertuzumab. We did the randomisation via an interactive response system under a permuted block randomisation scheme (block size of four), stratified by hormone receptor status, stage at diagnosis, and geographical location. Patients received six cycles (every 3 weeks) of neoadjuvant trastuzumab emtansine plus pertuzumab (trastuzumab emtansine 3·6 mg/kg; pertuzumab 840 mg loading dose, 420 mg maintenance doses) or docetaxel, carboplatin, and trastuzumab plus pertuzumab (docetaxel 75 mg/m 2 ; carboplatin area under the concentration–time curve 6 mg/mL × min; trastuzumab 8 mg/kg loading dose, 6 mg/kg maintenance doses) plus pertuzumab [same dosing as in the other group]). All treatments were administered intravenously. The primary objective was to compare the number of patients who achieved a pathological complete response (ypT0/is, ypN0), between groups in the intention-to-treat population (two-sided assessment), based on local evaluation of tumour samples taken at breast cancer surgery done between 14 days and 6 weeks after completion of neoadjuvant therapy. Safety was analysed in patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT02131064, and follow-up of the adjuvant phase is ongoing. Findings Between June 25, 2014, and June 15, 2015, we randomly assigned 444 patients to neoadjuvant treatment with trastuzumab emtansine plus pertuzumab (n=223) or docetaxel, carboplatin, and trastuzumab plus pertuzumab (n=221). A pathological complete response was achieved by 99 (44·4%) of 223 patients in the trastuzumab emtansine plus pertuzumab group and 123 (55·7%) of 221 patients in the docetaxel, carboplatin, and trastuzumab plus pertuzumab group (absolute difference −11·3 percentage points, 95% CI −20·5 to −2·0; p=0·016). During neoadjuvant treatment, compared with patients receiving docetaxel, carboplatin, and trastuzumab plus pertuzumab, fewer patients receiving trastuzumab emtansine plus pertuzumab had a grade 3–4 adverse event (29 [13%] of 223 vs 141 [64%] of 219) or a serious adverse event (11 [5%] of 223 vs 63 [29%] of 219). The most common grade 3–4 adverse events in the trastuzumab emtansine plus pertuzumab group were decreased platelet count (three [1%] of 223 patients vs 11 [5%] of 219 with docetaxel, carboplatin, and trastuzumab plus pertuzumab), fatigue (three [1%] vs seven [3%]), alanine aminotransferase increase (three [1%] vs four [2%]), and hypokalaemia (three [1%] vs five [2%]). The most common grade 3–4 adverse events in the docetaxel, carboplatin, and trastuzumab plus pertuzumab group were neutropenia (55 [25%] of 219 vs one [ vs 2 [ vs 0). No deaths were reported during neoadjuvant treatment. Interpretation Traditional neoadjuvant systemic chemotherapy plus dual HER2-targeted blockade (docetaxel, carboplatin, and trastuzumab plus pertuzumab) resulted in significantly more patients achieving a pathological complete response than HER2-targeted chemotherapy plus HER2-targeted blockade (trastuzumab emtansine plus pertuzumab); however, numerically more grade 3–4 and serious adverse events occurred in the chemotherapy plus trastuzumab and pertuzumab group. Further efforts to improve the efficacy of chemotherapy without imparting more toxicity are warranted. Funding F Hoffmann-La Roche and Genentech.

Objective: To evaluate dispositional coping strategies as predictors for changes in well-being after 1 year in older patients with cancer (OCP) and 2 control groups. Methods: OCP were compared with 2 control groups: middle-aged patients with cancer (MCP) (aging effect) and older patients without cancer (ONC) (cancer effect). Patients were interviewed shortly after a cancer diagnosis and 1 year later. Dispositional coping was measured with the Short Utrecht Coping List. For well-being, we considered psychological well-being (depression, loneliness, distress) and physical health (fatigue, ADL, IADL). Logistic regression analyses were performed to study baseline coping as predictor for subsequent well-being while controlling for important baseline covariates. Results: A total of 1245 patients were included in the analysis at baseline: 263 OCP, 590 ONC, and 392 MCP. Overall, active tackling was employed most often. With the exception of palliative reacting, OCP utilized each coping strategy less frequently than MCP. At 1-year follow-up, 833 patients (66.9%) were interviewed. Active coping strategies (active tackling and seeking social support) predicted subsequent well-being only in MCP. Avoidance coping strategies did not predict well-being in any of the patient groups. Palliative reacting predicted distress in OCP; depression and dependency for ADL in MCP. Conclusions: Coping strategies influence subsequent well-being in patients with cancer, but the impact is different in the age groups. Palliative reacting was the only coping strategy that predicted well-being (ie, distress) in OCP and is therefore, especially in this population, a target for coping skill interventions.