Primary Endocrine Therapy Research Articles

Abstract P4-07-32: Prognostic factors among elderly patients with operable non-metastatic breast cancer treated with primary endocrine therapy

Abstract Background: The growing population of elderly patients with breast cancer imposes challenges for treatment when frailty and comorbidities may coexist. Age alone should not be a cutoff for cancer treatment decisions: benefit and risk should be taken into account, considering comorbidities burden, functionality, life expectancy and patient preferences. Primary endocrine therapy (PET) represents an alternative when primary surgery or neoadjuvant chemotherapy would not be adequate treatment choices for patients with hormonal receptor positive (HR+) non-metastatic breast cancer. We aimed to evaluate the prognostic factors associated with survival among elderly patients treated with PET with or without surgery. Methods: We retrospectively reviewed electronic medical records of a cohort of patients who were 70 years of age or older and were treated with PET for operable non-metastatic breast cancer in an academic cancer center from 2009 to 2021. Study endpoints were progression-free survival (PFS), overall survival (OS), and factors associated with PFS and OS. For PFS, the events considered were disease progression in patients treated with PET alone, disease recurrence in those who underwent surgery, or death from any cause. Survival was estimated using the Kaplan-Meir method and compared with the log-rank test. Prognostic factors evaluated were age, histological type, grade, Ki67 index, stage, ECOG-performance status (ECOG-PS) and comorbidities burden, according to Charlson index. Univariate and multivariable analysis were performed using Cox regression. Results: PET was the first treatment for 197 pts aged 70 years or older. The median age was 81 years (range 70-101). Most patients had ductal (N=149; 75%) or lobular carcinomas (N=22; 11%), grade 1 (N=48; 24%) or grade 2 (N=114; 58%), and stage II (N=67; 34%) or stage III (N=94; 48%) disease. Half of the patients had an ECOG-PS 3 (n=65) or 4 (n=35); 165 pts (83%) had an Charlson index < 6. Seventy-two pts (36%) underwent surgery. Thirty pts (15%) had a disease recurrence or progression and 60 pts (30.5%) died; most deaths (n=38; 63%) were not related to breast cancer. In a multivariable analysis, pts with grade 3 disease had higher risk of recurrence/progression/death (HR 3.31, 95% CI 1.45-7.58, P=0.005), while those treated with surgery had a decreased risk (HR 0.37, 95% CI 0.21-0.65; P=0.001). Median PFS was 55.2 mo for pts treated with PET alone and 99.7 mo in those treated with ET followed by surgery. Median OS was 63 mo and 111.9 mo, respectively. Conclusion: In this cohort, deaths observed were mostly unrelated to breast cancer, suggesting that PET is an appropriate choice for selected pts. Nevertheless, patients with grade 3 disease and those who were not treated with surgery after PET had a higher risk of disease progression/recurrence or death. Prognostic factors can be useful to select candidates for PET. Citation Format: Erika Andrade Rocha, Jessica Monteiro Vasconcellos, Sofia Vidaurre Mendes, Pedro José Galvão Freire, Ana Paula Messias, Leticia Vecchi Leis, Otavio Noschang Moreira, Mauricio Baptista Pereira, Bruna Zanin Orsi, Augusto Araujo Neto, Vanessa Petry, Renata Colombo Bonadio, Laura Testa. Prognostic factors among elderly patients with operable non-metastatic breast cancer treated with primary endocrine therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-32.

Revisiting primary endocrine therapy versus surgery in older women with breast cancer: meta-analysis.

Old age is associated with increased co-morbidities, resulting in reduced life expectancy. Primary endocrine therapy is an alternative to primary surgical therapy for patients with breast cancer and increased co-morbidities. The aim was to review outcomes of primary endocrine therapy versus primary surgical therapy in older women with breast cancer. PubMed, Embase (Ovid), Scopus, and the Cochrane Library were searched systematically from January 2000 to May 2022. Single-arm studies were excluded. Primary outcomes were overall survival and breast cancer-specific survival. Secondary outcomes were local and regional failure of primary endocrine therapy, recurrence after primary surgical therapy, and health-related quality of life. There were 14 studies including 14 254 patients (primary endocrine therapy 2829, 19.8 per cent; primary surgical therapy 11 425, 80.2 per cent), with the addition of four major studies (9538 patients) compared with the latest review in 2014. Seven studies defined primary surgical therapy as surgery plus adjuvant endocrine therapy, and six studies included patients with oestrogen receptor-positive tumours only. Patients in the primary endocrine therapy group were older than the primary surgical therapy group (mean difference 2.43 (95 per cent c.i. 0.73 to 4.13) years). Primary endocrine therapy led to worse overall survival than primary surgical therapy (HR 1.42, 95 per cent c.i. 1.06 to 1.91). Subgroup analysis of RCTs and prospective studies, however, showed comparable overall survival. Breast cancer-specific survival was also comparable (HR 1.28, 95 per cent c.i. 0.87 to 1.87). At 6 weeks, operated patients had significant arm symptoms and illness burden following major breast surgery compared with patients receiving primary endocrine therapy. Health-related quality of life, measured by the European Organization for Research and Treatment of Cancer QLQ-C30 and EuroQol EQ-5D-5L™, was comparable in the two treatment groups. Overall survival was worse among older women receiving primary endocrine therapy in an analysis including all studies, but comparable in RCTs and prospective studies. This may be due to confounding by age and co-morbidities in retrospective cohort studies of primary endocrine therapy.

Survival outcomes and tumor response to primary endocrine therapy in the non-operative management of early breast cancer: a retrospective observational study

Survival outcomes and tumor response to primary endocrine therapy in the non-operative management of early breast cancer: a retrospective observational study

Molecular Biomarker Expression in Window of Opportunity Studies for Oestrogen Receptor Positive Breast Cancer-A Systematic Review of the Literature.

Simple SummaryWindow of opportunity (WoO) trials allow the opportunity to assess the use of drugs in breast cancer research before treatment has commenced. The aim of this review of the literature is to review WoO trials in patients with oestrogen receptor-positive (ER+) breast cancer to help guide treatment. This will be useful for patients who receive drug treatment before surgery, or as an alternative to surgery in older, more frail adults.Window of opportunity (WoO) trials create the opportunity to demonstrate pharmacodynamic parameters of a drug in vivo and have increasing use in breast cancer research. Most breast cancer tumours are oestrogen receptor-positive (ER+), leading to the development of multiple treatment options tailored towards this particular tumour subtype. The aim of this literature review is to review WoO trials pertaining to the pharmacodynamic activity of drugs available for use in ER+ breast cancer in order to help guide treatment for patients receiving neoadjuvant and primary endocrine therapy. Five databases (EMBASE, Cochrane, MEDLINE, PubMed, Web of Science) were searched for eligible studies. Studies performed in treatment-naïve patients with histologically confirmed ER+ breast cancer were included if they acquired pre- and post-treatment biopsies, compared measurement of a proteomic biomarker between these two biopsies and delivered treatment for a maximum mean duration of 31 days. Fifteen studies were eligible for inclusion and covered six different drug classes: three endocrine therapies (ETs) including aromatase inhibitors (AIs), selective oestrogen receptor modulators (SERMs), selective oestrogen receptor degraders (SERDs) and three non-ETs including mTOR inhibitors, AKT inhibitors and synthetic oestrogens. Ki67 was the most frequently measured marker, appearing in all studies. Progesterone receptor (PR) and ER were the next most frequently measured markers, appearing five and four studies, respectively. All three of these markers were significantly downregulated in both AIs and SERDs; Ki67 alone was downregulated in SERMs. Less commonly assessed markers including pS6, pGSH3B, FSH and IGF1 were downregulated while CD34, pAKT and SHBG were significantly upregulated. There were no significant changes in the other biomarkers measured such as phosphate and tensin homolog (PTEN), Bax and Bcl-2.WoO studies have been widely utilised within the ER+ breast cancer subtype, demonstrating their worth in pharmacodynamic research. However, research remains focused upon routinely measured biomarkers such ER PR and Ki67, with an array of less common markers sporadically used.

Local recurrence of mammary Paget’s disease after nipple-sparing mastectomy and implant breast reconstruction: a case report and literature review

ObjectiveTo provide a rare case of local recurrent Paget’s disease after nipple-sparing mastectomy (NSM) with immediate breast reconstruction with 10 years of disease-free survival and to analyze the clinical and pathological characteristics.BackgroundMammary Paget’s disease can be considered a rare type of local recurrence after breast cancer treatment, both in cases of conservative surgery and NSM with immediate breast reconstruction (Lohsiriwat et al, Ann Surg Oncol 19:1850-1855, 2012). Recurrent patients who present with nipple-areolar Paget’s disease usually have unfavorable primary pathological characteristics and different latency periods. However, the recurrent status in patients with favorable primary pathological characteristics and the latency periods after NSM with immediate breast reconstruction are unclear.MethodsFirst, we present a case of local recurrent Paget’s disease in a young patient diagnosed with invasive breast carcinoma at age 30 who underwent NSM with primary silicone reconstruction. Then, the keywords “Paget’s disease” and “nipple-sparing mastectomy” were selected. Articles including the local recurrence of Paget’s disease after NSM were collected from the PubMed, Springer, and OVID databases, and the acquired relevant data were analyzed. We did not restrict our search by study design or publication date.ResultsFive studies describing 31 cases of local recurrent Paget’s disease after NSM with implant breast reconstruction were included. The mean patient age reported was 45 years, and the average latency period from NSM to the local recurrence of Paget’s disease was 40.2 months. Recurrent tumor histological features were Paget’s disease with ductal carcinoma in situ (DCIS) in 16 patients (50%), Paget’s disease without DCIS in 13 patients (40.6%), and Paget’s disease with ductal intraepithelial neoplasia (DIN) in 3 patients (9.4%). The primary tumor histological feature was estrogen receptor (ER)(−)/progesterone receptor (PR)(−)/human epidermal growth factor receptor (HER-2)(+) in 21 patients (77.8%). Neither locoregional relapse nor metastatic events were found in these recurrent patients who accepted NAC excision after 4–5 years of follow-up. Our reported case showed that the patient experienced pregnancy and lactation after primary adjuvant chemotherapy and endocrine therapy. However, she developed an eczematoid lesion in the NAC 120 months after breast surgery. The histopathological examination was consistent with Paget’s disease of the breast. Complete NAC and breast silicone prosthesis removal were performed. The patient accepted no systematic or local therapy and is currently alive. It is noteworthy that the biological features of the primary tumor were ER(+), PR(+), and HER-2(−); however, the recurrent tumor changed to ER(−), PR(−), and HER-2(+).ConclusionsThe local recurrence of Paget’s disease after NSM is uncommon; it may develop at a very early age and have a very long time to recurrence, as in our patient, who presented with recurrence 10 years after primary surgery. Surgeons should be wary of local recurrence of the nipple-areola complex after NSM in patients with ER-negative and HER-2-positive primary tumors. However, patients with ER/PR-positive and HER-2-negative tumors should not be neglected; we reported a case of an ER/PR-positive and HER-2-negative primary tumor, and ER-positive recurrent cases have the longest latency period. The local recurrence rate of Paget’s disease after NSM is low, and the prognosis is good in recurrent patients who accept further extensive NAC excision. Further systematic treatment was not considered for this patient.

The Breast Cancer Index Registry Study: Initial analysis of the first 1,000 patients.

e12513 Background: The Breast Cancer Index (BCI) is a gene expression-based biomarker that reports two results: BCI Predictive [BCI (H/I)], which predicts benefit from extended endocrine therapy (EET), and BCI Prognostic, which combines the Molecular Grade Index (MGI) with BCI (H/I) to provide individualized risk of both late (5-10 years) and overall (0-10 years) distant recurrence. The NCCN clinical practice guideline recommends use of BCI for prediction of benefit from EET in early stage, hormone receptor positive (HR+) breast cancer patients. Methods: The BCI Registry study was designed to prospectively evaluate the long-term clinical outcome, medication adherence and quality of life in HR+ early-stage breast cancer patients receiving BCI testing as part of routine clinical care. The BCI registry will enroll approximately 3,000 patients after completion of 4-7 years of primary adjuvant endocrine therapy. Patients will be followed for disease recurrence for at least 10 years from diagnosis. Patients extending endocrine therapy will be assessed annually for medication adherence. To evaluate the impact of BCI results on EET decision making, both the physician and patient will complete Decision Impact Questionnaires. Clinicopathological data are collected within the ClinCapture electronic data capture system. The BCI Registry Study is registered on ClinicalTrials.gov under NCT04875351. Results: The BCI Registry Study completed enrollment of the first 1,000 patients in January 2022. Clinical data were available for 942 patients (76.8% T1; 51.3% grade II; 75.4% N0). BCI test results were reported for 842 patients. 315 patients (37.4%) were classified as BCI (H/I)-High and 527 patients (62.6%) as BCI (H/I)-Low. Further, in node-negative (N0) patients, BCI classified 314 N0 patients (47.9%) with high risk for late distant recurrence and 342 patients (52.1%) with low risk. In node-positive (N1) patients, BCI classified 138 patients (74.2%) as high risk for late distant recurrence and 48 patients (25.8%) as low risk. The associated clinicopathological factors are shown in the table. Conclusions: The analysis of the first 1,000 BCI Registry patients confirms the expected distribution of clinicopathological factors. BCI by H/I status and prognostic risk groups are consistent with previous clinical validation studies. Clinical trial information: NCT04875351. [Table: see text]

AB168. SOH22ABS231. Does the change in mammographic breast density reflect the response to treatment in breast cancer treated with primary hormonal therapy?

AB168. SOH22ABS231. Does the change in mammographic breast density reflect the response to treatment in breast cancer treated with primary hormonal therapy?

Influence of local treatment on the biology of advanced prostate cancer : Treatment of the primary tumor may delay hormone resistance of metastases

HintergrundIn den letzten 15 Jahren zeigt sich ein Trend hin zu einem längeren Überleben beim metastasierten Prostatakarzinom. Neben dem durch neue Medikamente bedingten Fortschritt deuten retrospektive Daten auch auf einen möglichen positiven Effekt einer früheren Primärtumorbehandlung hin.FragestellungKann eine Primärtumorbehandlung im Falle einer späteren Metastasierung die Prognose der betroffenen Patienten verbessern und wenn ja, über welche Mechanismen?Material und MethodeWir werteten die klinischen Langzeitergebnisse von 115 Patienten aus, die bei T4-Prostatakarzinomen nach induktiver Hormontherapie an unserer Klinik prostatektomiert worden waren. Weiterhin erfolgte eine kritische Durchsicht und Diskussion der zur oben genannten Fragestellung vorhandenen Literatur.ErgebnisseVon den 115 Patienten hatten 84 im weiteren Verlauf ein biochemisches Rezidiv erlitten, waren also definitiv durch die radikale Prostatektomie nicht geheilt. Das tumorspezifische und das Gesamtüberleben dieser 84 Patienten lag nach 150 Monaten bei 61 % bzw. 44 %. Bemerkenswert war die Beobachtung, dass diese Patienten ein überraschend gutes und langes Ansprechen auf eine Hormontherapie zeigten. Von den 84 Patienten waren nach durchschnittlich 95 Monaten Nachbeobachtungszeit noch 47 am Leben. 31 von ihnen, also ungefähr zwei Drittel, standen immer noch unter einer Standardhormontherapie. Nur 13 hatten eine Resistenz gegen die primäre Hormontherapie entwickelt und entsprechend eine tertiäre Hormontherapie erhalten, auf die sie teilweise aber auch wieder langfristig sensibel blieben.SchlussfolgerungenDie Primärtumorentfernung, zumindest unter den beschriebenen Begleitumständen, scheint die Entwicklung einer Hormonresistenz beim metastasierten Prostatakarzinom hinauszögern und in Einzelfällen sogar ganz verhindern zu können.

Abstract P1-18-08: Effect of duration of prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy (≤6 mo or >6 mo) on alpelisib benefit in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC) from BYLieve

Abstract Introduction: PIK3CA (encoding phosphatidylinositol 3-kinase alpha [PI3Kα]) is a driver oncogene mutated (mut) in ~40% of HR+, HER2- ABCs, leading to endocrine therapy (ET) resistance and poor prognosis. Alpelisib (ALP) is the first oral α-selective PI3K inhibitor and degrader approved in this patient (pt) population. Primary analyses of Cohorts A and B from BYLieve, an ongoing Phase II noncomparative study, demonstrated efficacy and a consistent safety profile of ALP + ET (fulvestrant [FUL] or letrozole [LET]) in pts with PIK3CA-mut, HR+, HER2- ABC in the post CDK4/6i setting. Post hoc analyses of ALP benefit in pts with centrally confirmed PIK3CA mut, based on median duration of prior CDK4/6i, supported the efficacy of ALP + ET in CDK4/6i-resistant, HR+, HER2- ABC. Here we assessed whether those who achieved a short duration of disease control (6-month [mo] cutoff), with prior CDK4/6i + ET received clinical benefit with ALP + ET. Methods: In Cohorts A and B, pts with PIK3CA-mut, HR+, HER2- ABC had received CDK4/6i + aromatase inhibitor (AI) or FUL, respectively, as immediate prior therapy (majority in first line). Pts in Cohort A received ALP 300 mg PO QD + FUL 500 mg IM Q28D + C1D15; pts in Cohort B received ALP 300 mg PO QD + LET 2.5 mg PO QD. Within each cohort, pts were divided based on duration of prior CDK4/6i therapy (≤6 mo or >6 mo), and the association of progression-free survival (PFS) with this covariate was analyzed using a stratified log-rank test and Cox Proportional Hazards model. A 6-mo cutoff was selected based on the ESO-ESMO ABC5 cutoff for primary ET resistance, as current guidelines do not specify cutoffs for CDK4/6i resistance. This analysis is based on the PFS endpoint and included pts for whom duration of prior CDK4/6i therapy was known. Results: Of the 121 pts in Cohort A with centrally confirmed PIK3CA-mut disease (modified full analysis set, mFAS), 120 had duration of prior CDK4/6i available; 26 had CDK4/6i for ≤6 mo and 94 for >6 mo, with similar demographics/disease characteristics between subgroups. The hazard ratio (HR) of median PFS (mPFS) between the ≤6-mo group and >6-mo group was 0.50 (95% confidence interval [CI], 0.27-0.94), indicating a lower risk of progression in the ≤6-mo group, with mPFS 10.0 mo (95% CI, 5.55-not estimable) and 6.0 mo (95% CI, 5.16-8.31), respectively. Grade ≥3 adverse events (AEs) were experienced by 67.5% (n=85) of all pts (safety set) in Cohort A and by 76.9% (n=20)/65.0% (n=65) in the ≤6-mo/>6-mo subgroups, respectively. Of the 115 pts in Cohort B with centrally confirmed PIK3CA-mut disease (mFAS), 113 had duration of prior CDK4/6i available; 31 had CDK4/6i for ≤6 mo and 82 for >6 mo, with similar demographics/disease characteristics between subgroups. The HR of mPFS between the ≤6-mo and >6-mo groups was 0.76 (95% CI, 0.47-1.23), with the wide CI indicating no difference in risk of progression between subgroups, and mPFS was 5.9 mo (95% CI, 3.55-10.97) and 5.6 mo (95% CI, 3.68-7.10), respectively. Grade ≥3 AEs were experienced by 69.9% (n=86) of all pts (safety set) in Cohort B and by 63.6% (n=21)/72.2% (n=65) in the ≤6-mo/>6-mo subgroups, respectively. Conclusions: This demonstrates that pts with PIK3CA-mut, HR+, HER2- ABC who achieved ≤6-mo duration of disease control with prior CDK4/6i had a numerically longer PFS in Cohort A, and almost the same clinical efficacy in Cohort B, to ALP + ET vs pts with >6-mo duration of disease control, with a comparable safety profile. This confirms targeting PI3Kα with ALP provides clinical benefit in pts with CDK4/6i-resistant ABC, including early progressors, and supports consideration of ALP + ET as an immediate next-line option in this setting, possibly delaying chemotherapy. Citation Format: Stephen Chia, Eva M Ciruelos, Hope S Rugo, Florence Lerebours, Manuel Ruiz-Borrego, Pamela Drullinsky, Aleix Prat, Thomas Bachelot, Nicholas Turner, Ennan Gu, Christina Arce, Murat Akdere, Dejan Juric. Effect of duration of prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy (≤6 mo or >6 mo) on alpelisib benefit in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC) from BYLieve [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 P1-18-08.

Abstract OT1-10-01: The Breast Cancer Index registry study: A prospective multi-center observational study to evaluate patient outcome, clinical impact, and medication adherence in HR+ breast cancer patients considering treatment with extended endocrine therapy

Abstract Background: Hormone receptor-positive (HR+) is the most common molecular subtype of breast cancer accounting for approximately 2 out of every 3 patients. Adjuvant anti-estrogen therapy is the cornerstone of systemic therapy, underscoring the critical role of endocrine treatment which affects the majority of women with breast cancer. Furthering efforts to better understand endocrine response and resistance and implementing genomic tools to help individualize patient selection for endocrine therapy are of ongoing importance to improve outcomes. Breast Cancer Index (BCI) is a gene expression signature composed of the Molecular Grade Index (MGI) and HOXB13/IL17BR (H/I) that predicts the likelihood of extended endocrine benefit and quantifies the risk of both late (5-10 years) and overall (0-10 years) distant recurrence. BCI has recently been incorporated into the NCCN clinical practice guideline as a biomarker for prediction of benefit from extended endocrine therapy in patients with early-stage, HR+ breast cancer. The objective of the BCI Registry Study is to collect real-world evidence at a national level aimed at advancing patient care and optimizing duration of endocrine treatment and will be conducted in two phases. First, long-term patient outcomes and the impact of BCI on decision-making based on physician and patient reported outcomes as well as medication adherence to extended endocrine therapy will be assessed. Secondly, individual patient data on over 40 clinical variables will be collected and partnered with molecular profiling and genomic data for each patient to enable correlative analysis and novel biomarker research of endocrine sensitivity and resistance. Study Description: The BCI Registry Study is a prospective, multi-center, observational data registry and biospecimen repository for stage I-III HR+ breast cancer patients. The main objective of the Registry Study is prospective characterization of BCI predictive and prognostic performance. The primary endpoint is time to distant recurrence (TTDR), defined as the interval between the time of BCI testing and the first metastasis at distant organs. Secondary endpoints include time to any recurrences and medication adherence score over time. Eligibility criteria includes confirmed diagnosis of HR+ early-stage invasive breast carcinoma (ductal, lobular, or mixed ductal/lobular), either HER2 negative or positive and either node-negative or node-positive tumors with 1-3 positive lymph nodes (N1). Patients must have completed 4 to 7 years of primary adjuvant endocrine therapy and have pre-treatment tumor tissue available from a previous breast surgery or biopsy. Both physicians and patients will complete a pre- and post-test Decision Impact Questionnaire to assess the impact of BCI results on extended endocrine therapy decision-making. Patients who elect to complete 10 years of endocrine therapy will answer a Medication Adherence Questionnaire during annual follow-up visits. Follow-up of patients will end 10 years from initial breast cancer diagnosis. The Registry plans to enroll approximately 3,000 patients across approximately 40 study sites in the United States. Enrollment for the study began in Q2 2021, and 324 patients have been enrolled as of July 2021. For more information, please visit the ClinicalTrials.gov registration: NCT04875351. Citation Format: Joyce A O'Shaughnessy, Jenny R Fox, Carlos A Encarnación, Brandon O'Neal, Kai Treuner, Tara Sanft, Rachel C Jankowitz, Mark D Pegram, Catherine A Schnabel, Sami G Diab. The Breast Cancer Index registry study: A prospective multi-center observational study to evaluate patient outcome, clinical impact, and medication adherence in HR+ breast cancer patients considering treatment with extended endocrine therapy [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 OT1-10-01.

Breast Cancer Management in the over 80’s population: are we being fair?

Background: 24% of all new breast cancers are diagnosed in patient’s aged over 75. The recent 2020 National Audit of Breast Cancer in the Older Population (NABCOP) report highlighted a large variation in the treatment offered geographically within the UK. The report recommended surgery should be offered where possible given its survival benefit over primary endocrine therapy (PET). However, this is not the case for many patients in the UK and the reasons why are not clear. An individual patient’s overall survival benefit can be calculated using the Age Gap Decision Tool which performs a multivariant analysis based on co-morbidities, tumour characteristics and a patient’s ability to undertake certain activities of daily living.

Differences in treatment and survival of older patients with operable breast cancer between the United Kingdom and the Netherlands – A comparison of two national prospective longitudinal multi-centre cohort studies

BackgroundPrevious studies have shown that survival outcomes for older patients with breast cancer vary substantially across Europe, with worse survival reported in the United Kingdom. It has been hypothesised that these differences in survival outcomes could be related to treatment variation. ObjectivesWe aimed to compare patient and tumour characteristics, treatment selection and survival outcomes between two large prospective cohorts of older patients with operable breast cancer from the United Kingdom (UK) and The Netherlands. MethodsWomen diagnosed with operable breast cancer aged ≥70 years were included. A baseline comprehensive geriatric assessment was performed in both cohorts, with data collected on age, comorbidities, cognition, nutritional and functional status. Baseline tumour characteristics and treatment type were collected. Univariable and multivariable Cox regression models were used to compare overall survival between the cohorts. Results3262 patients from the UK Age Gap cohort and 618 patients from the Dutch Climb cohort were included, with median ages of 77.0 (IQR: 72.0–81.0) and 75.0 (IQR: 72.0–81.0) years, respectively. The cohorts were generally comparable, with slight differences in rates of comorbidity and frailty. Median follow-up for overall survival was 4.1 years (IQR 2.9–5.4) in Age Gap and 4.3 years (IQR 2.9–5.5) in Climb. In Age Gap, both the rates of primary endocrine therapy and adjuvant hormonal therapy after surgery were approximately twice those in Climb (16.6% versus 7.3%, p < 0.001 for primary endocrine therapy, and 62.2% versus 38.8%, p < 0.001 for adjuvant hormonal therapy). There was no evidence of a difference in overall survival between the cohorts (adjusted HR 0.94, 95% CI 0.74–1.17, p = 0.568). ConclusionsIn contrast to previous studies, this comparison of two large national prospective longitudinal multi-centre cohort studies demonstrated comparable survival outcomes between older patients with breast cancer treated in the UK and The Netherlands, despite differences in treatment allocation.

Quality of Life of Elderly and Senile Patients with Hormone Receptor Positive Breast Cancer Using Primary Endocrine Therapy

Introduction. Elderly and senile patients are a special category of patients and standard methods in breast cancer treatment are not suitable due to the frequent presence of serious comorbidities and personal preferences and concerns about treatment options. Аn available treatment option for these patients with hormone-receptor positive breast cancer may be the primary endocrine therapy (PET).The objectivewas to assess the quality of life of patients treated by PET or surgical treatment with adjuvant endocrine therapy (ET) and identifying the reasons of choosing a conservative treatment strategy.Methods and materials.Our study included 65–89-year-old patients with hormone-receptor positive breast cancer with stages I–II, some of whom received only endocrine therapy (ET) (n=20), and others are prescribed adjuvant ET after surgical treatment (n=20). Quality of life was assessed by analyzing the EORTC QLQ C-30 and QLQ-BR23 questionnaires filled in by patients at different stages of treatment. An analysis of outpatient records was carried out to identify the reasons for choosing a conservative treatment strategy.Results. The choice of conservative treatment strategy was justified by the presence of a serious concomitant pathology in 65 % of cases. Performing breast surgery was associated with a decline in the quality of life in the postoperative period.Conclusions. PET is an alternative treatment option for some of the elderly patients with hormone-receptor positive breast cancer, since it has similar results in overall survival compared to standard complex treatment (surgery + adjuvant ET), but also does not make the quality of life worst during treatment.

ESR1 PvuII polymorphism: from risk factor to prognostic and predictive factor of the success of primary systemic therapy in advanced breast cancer

BackgroundThe ESR1 gene encodes Estrogen Receptor alpha (ERα), which plays a role in the tumourigenesis of breast cancer. A single nucleotide polymorphism (SNP) in intron 1 of this gene called ESR1 PvuII (rs2234693) has been reported to increase the risk of breast cancer. This study aimed to investigate the ESR1 PvuII polymorphism as a prognostic and predictive factor guiding the choice of therapy for advanced breast cancer.MethodsThis retrospective study was conducted in 104 advanced breast cancer patients at Dharmais Cancer Hospital from 2011 to 2018. The ESR1 PvuII polymorphism was analysed by Sanger sequencing of DNA from primary breast tumour samples.ResultsThe percentages of patients with ESR1 PvuII genotypes TT, TC, and CC were 42.3, 39.4, and 18.3%, respectively. Looking at prognosis, patients with ESR1 PvuII TC + CC had shorter overall survival than those with the TT genotype [HR = 1.79; 95% CI 1.05–3.04; p = 0.032]. As a predictive marker, TC + CC was associated with shorter survival (p = 0.041), but TC + CC patients on primary hormonal therapy had a median overall survival longer than TC + CC patients on primary chemotherapy (1072 vs 599 days).ConclusionThe ESR1 PvuII TC + CC genotypes confer poor prognosis in advanced breast cancer, but these genotypes could be regarded as a good predictor of the therapeutic effect of hormonal treatment.

Defer surgery in operable breast cancer: how long is too long?

PurposeThe aim of this meta-analysis was to evaluate outcomes of surgery compared to primary endocrine therapy (PET) in patients with non-advanced, operable invasive breast cancer, and to determine if PET as initial therapy may safely postpone surgery.MethodsThe MEDLINE, EMBASE, PubMed, and Cochrane Library were searched from database inception to July 2020 to identify eligible studies. Inclusion criteria were experimental or observational studies with at least one arm treated with PET and a second arm treated with surgery with or without PET. Local recurrence or progression of disease was defined as either failure of non-operative management (tumor failing to decrease in size and/or continuous local or distant tumor growth) or relapse of breast tumor after tumor downsizing following PET. Effect estimates were expressed in hazard ratio and 95% confidence intervals (HR (95% CI)).ResultsThe analysis included six studies with 1499 unique patients. The median time to local progression of disease was 2.3 years. Patients treated with PET alone without surgery had a higher risk of local recurrence and or progression [HR (95% CI): 1.76 (1.33, 2.31); I2 = 84%; p < 0.001]. Patients treated with PET had more favorable outcomes in terms of overall survival [HR (95% CI): 1.24 (1.06, 1.46); I2 = 70%; p = 0.008] and less favorable outcomes in breast cancer-specific survival [HR (95% CI): 1.13 (0.98, 1.31); I2 = 41%; p = 0.10]. The risk of publication bias was assessed to be high in reporting local recurrence rates and low in reporting distant recurrence rates.ConclusionPET alone is inferior to surgery in the treatment of operable invasive breast cancer.However, it may be acceptable to postpone curative breast cancer surgery without risk of progression for 1.1 years or longer.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12282-021-01302-4.

376 Management of Breast Cancer in elderly patients

Abstract Aim To evaluate the care and outcomes for women with breast cancer over the age of 70 and to compare our performance at AUH against the national outcomes. Method Using the online database at AUH we gathered the following data: age, TNM status, surgical management, histology, adjuvant treatment (radiotherapy, chemotherapy, hormone therapy, targeted therapy) and reasons for alterations in planned therapy. Results We audited 176 patients between 2018 and 2019. Age varied between 70 and 95 years old. 10 patients suffered from DCIS, 152 from invasive breast cancer and 14 from de novo metastatic breast cancer. 40% of patients with DCIS with underwent WLE, 40% underwent mastectomy and 20% were not offered an operation as they were unfit. Invasive breast cancer accounted for the majority of cases. 86% were ER/PR positive and 12.2% were Her-2 positive. 35.7% underwent mastectomy, 64.4% underwent WLE and 0.8% VAB excision. 51.7% had Sentinel node biopsy, 15.3% underwent axillary clearance and 1.7 % had axillary sampling. 7.9% of patients presented with metastatic disease. 2.6% of those patients had palliative radiotherapy. Primary endocrine therapy was commenced on 21.1% of patients. Factors that lead to PET were that 47% of patients were unfit for an operation, 20.6% refused surgical intervention, 11.7% had concurrent aggressive malignancy and 8.8% were inoperable. Conclusions Overall, successful results were achieved for this group of patients compared to the national outcomes. 99.4% of patients in our centre had triple assessment prior to MDT. Further review of functional status and service outcomes will be required to be audited.

86 Adequate Assessment Can Affect the Management of Breast Cancer in The Geriatric Population

Abstract Background Breast cancer (BC) risk increases with age; about a third of patients are diagnosed in age older than 70. Treatment of this age group remains a thorny issue leading to inferior outcome with lower survival rate compared to younger patients. Aim We aimed to evaluate performance status tools as well as the outcome of management of breast cancer in the geriatric population. Method We have conducted a retrospective database analysis looking into the management of breast cancer patients older than 65 years old presenting to our unit during the period between June 2015 to June 2019. All patients had triple assessment as well as multimodality performance status assessment with their treatment modalities and outcomes recorded and assessed. Results We have included 578 patients, 0.8% male and 99.2 % female, and our patients mean age was 71 years. Most of our patients scored one or two on the WHO/ ECOG performance status score, Clinical Frailty Score, as well as ASA-PS score. 3.2% had no treatment, 4.3% had endocrine therapy only, 0.5% had primary endocrine therapy followed by surgery, 92.3 % underwent surgery with 4.1% complication rate. Patients who underwent breast-conserving surgery had adjuvant breast radiotherapy, and 23.7% had adjuvant chest wall radiotherapy, 78.8% had adjuvant endocrine treatment and 4.8% had adjuvant chemotherapy out of which 30.7% had adjuvant chemotherapy and Herceptin. Conclusions Patients’ age should trigger the use of objective assessment tools while assessing elderly patients with a new breast cancer diagnosis, and treatment modalities offered should be individualised to reach the optimum outcome.

Primary umbilical endometriosis – A rare presentation of cutaneous endometriosis

Primary umbilical endometriosis is a rare condition with an overall incidence of around 0.5% to 1% among all the endometriosis cases, but at times it poses a diagnostic dilemma. In our institution we encountered a case of primary umbilical endometriosis presented to multiple surgical speciality departments. A prompt clinical examination with surgical biopsy was the key tool which lead to the diagnosis and providing a complete cure for the patient. Pelvic endometriosis affects 5-10% of women in the child bearing age group. The most pronounced symptoms are dyspareunia, pelvic pain, and infertility. Clinical presentations of umbilical endometriosis are as a nodule with or without associated umbilical pain and bleeding. This patient was given primary hormonal therapy and later underwent a biopsy which paved way for an accurate diagnosis of primary umbilical endometriosis. In this case of umbilical swelling, conditions like a benign nevus, lipoma, abscess, cyst, hernia, as well as metastatic deposit from a systemic malignancy were considered in the clinical differential diagnosis. However surgical excision helped us arrive at a definitive diagnosis and cure for the patient.

Adequate Assessment Can Affect the Management of Breast Cancer in Geriatric Population.

Breast cancer (BC) risk increases with age; about a third of patients are diagnosed in age older than 65. Treatment of this age group remains controversial, leading to inferior outcomes with lower survival rates than younger patients. We aimed to evaluate performance status tools as well as the outcome of management of breast cancer in the geriatric population. We have conducted a retrospective database analysis looking into the management of breast cancer patients older than 65years old presenting to our unit during the period between June 2015 and June 2019. All patients had triple assessment as well as multimodality performance status assessment with their treatment modalities, and outcomes are recorded and assessed. We have included 578 patients, 0.8% male and 99.2% female, and our patients' mean age was 71years. Most of our patients scored one or two on the WHO/ECOG performance status score and Clinical Frailty Score, as well as ASA-PS score. 3.2% had no treatment, 4.3% had endocrine therapy only, 0.5% had primary endocrine therapy followed by surgery, and 92.3% underwent surgery with 4.1% complication rate. Patients who underwent breast-conserving surgery had adjuvant breast radiotherapy, and 23.7% had adjuvant chest wall radiotherapy, 78.8% had adjuvant endocrine treatment, and 4.8% had adjuvant chemotherapy out of which 30.7% had adjuvant chemotherapy and Herceptin. Objective assessment tools should be used for patients older than 65years diagnosed with primary breast cancer to be able to scarify patients' individualised treatment options to reach the optimum outcome.

Process evaluation of the Bridging the Age Gap in Breast Cancer decision support intervention cluster randomised trial

BackgroundThe Bridging the Age Gap in Breast Cancer research programme sought to improve treatment decision-making for older women with breast cancer by developing and testing, in a cluster randomised trial (n = 1339 patients), two decision support interventions (DESIs). Both DESIs were used in the intervention arm and each comprised an online risk prediction model, brief decision aid and information booklet. One DESI supported the decision to have either primary endocrine therapy (PET) or surgery with adjuvant therapies and the second supported the decision to have adjuvant chemotherapy after surgery or not.MethodsSixteen sites were randomly selected to take part in the process evaluation. Multiple methods of data collection were used. Medical Research Council (MRC) guidelines for the evaluation of complex interventions were used.ResultsEighty-two patients, mean age 75.5 (range 70–93), provided data for the process evaluation. Seventy-three interviews were completed with patients. Ten clinicians from six intervention sites took part in telephone interviews. Dose: Ninety-one members of staff in the intervention arm received intervention training. Reach: The online tool was accessed on 324 occasions by 27 clinicians. Reasons for non-use of the online tool were commonly that the patient had already made a decision or that there was no online access in the clinic. Of the 32 women for whom there were data available, fifteen from the intervention arm and six from the usual care arm were offered a choice of treatment. Fidelity: Clinicians used the online tool in different ways, with some using it during the consultation and others checking the online survival estimates before the consultation. Adaptation: There was evidence of adaptation when using the DESIs. A lack of infrastructure, e.g. internet access, was a barrier to the use of the online tool. The brief decision aid was rarely used. Mediators: Shared decision-making: Most patients felt able to contribute to decision-making and expressed high levels of satisfaction with the process. Participants’ responses to intervention: Six patients reported the DESIs to be very useful, one somewhat useful and two moderately useful.ConclusionsClinicians who participated were mainly supportive of the interventions and had attempted some adaptations to make the interventions applicable, but there were practical and engagement barriers that led to sub-optimal adoption in routine practice.Trial registrationISRCTN46099296. Registered on 11 August 2016—retrospectively registered