Early Breast Cancer In Elderly Research Articles

Accelerated partial breast irradiation in the elderly: 8-year oncological outcomes and prognostic factors

PurposeThe purpose of the study is to evaluate long-term clinical outcomes and prognostic factors after accelerated partial breast irradiation (APBI) in the elderly using high-dose-rate interstitial multicatheter brachytherapy (HIBT). Methods and MaterialsBetween 2005 and 2018, 109 patients underwent APBI using HIBT (34 Gy/10f/5d or 32 Gy/8f/4d). Based on a prospective database, outcomes were retrospectively analyzed (local relapse-free survival, metastatic-free survival, specific survival (SS), and overall survival (OS)). Prognostic factors were investigated. Late toxicity and cosmetic evaluation were reported. ResultsWith a median followup of 97 months [7–159], median age was 81.7 years [58–89]. In accordance with the GEC-ESTRO APBI classification, 72.5%, 11.9%, and 15.6% were classified as low, intermediate, and high risk, respectively. The histological type was mainly invasive ductal carcinoma (87.1%). The median tumor size was 10 mm [range 1–35]. Eight-year local relapse-free survival, SS, and OS were 96.7% [95% confidence interval (CI) [0.923; 1]), 96.7% [95% CI [0.924; 1], and 72% [95% CI [0.616; 0.837], respectively. In univariate analysis, APBI classification was not considered as prognostic factor, whereas molecular classification was prognostic factor for OS (p < 0.0001), SS (p = 0.007), and metastatic-free survival (p = 0.009) but not for local recurrence (p = 0.586). No Grade ≥3 late toxicity was observed, whereas 61 patients (88.4%) and 8 patients (11.6%) presented Grade 1 and 2 toxicities, respectively. The cosmetic outcome was excellent/good for 96.4%. ConclusionsLong-term followup confirms that HIBT is safe and effective for elderly early breast cancer. Our results suggest that selected elderly women presenting with high-risk breast cancer could be also considered for APBI.

Phase II study of adjuvant endocrine therapy with CDK 4/6 inhibitor, ribociclib, for localized ER+/HER2- breast cancer (LEADER).

531 Background: Given the success of CDK 4/6 inhibitors for ER+/HER2- metastatic breast cancer, there is much interest in exploring these agents in early breast cancer to potentially reduce recurrence risk. However, tolerability and adherence are important considerations in the adjuvant setting. We evaluated the tolerability and adherence of adjuvant endocrine therapy with the CDK 4/6 inhibitor, ribociclib, in two different schedules, in a prospective phase II clinical trial. Methods: Eligible patients were those with localized stage I-III ER+ (≥ 10%), HER2- breast cancer who had completed surgery and were on adjuvant endocrine therapy with at least one year or more of treatment remaining. Patients were randomized to receive continuous ribociclib (400 mg daily of 28-day cycle; arm 1) or intermittent ribociclib (600 mg daily on days 1-21 of 28-day cycle; arm 2) for one year, in addition to an aromatase inhibitor (plus GnRH agonist if premenopausal). Toxicities were evaluated using CTCAE version 4.03. Adherence was monitored by review of patient diaries and pill count. Results: Of the 81 patients enrolled, 24 discontinued early. The table shows the current status of the patients based on treatment arm (data cut-off as of 1/31/20; updated results will be presented at meeting). A total of 8 serious adverse events (AEs) have occurred thus far: grade 3 transaminitis (1), grade 4 transaminitis (3), grade 3 colitis (1), grade 3 infection (2), and grade 4 lymphopenia (1). The most common grade 3 or greater AEs leading to study discontinuation thus far were transaminitis (8.6%), neutropenia (2.5%), and fatigue (2.5%). No patients discontinued early due to prolonged QTc. Adherence results will be reported at the meeting. Conclusions: Interim results demonstrate that while serious AEs with one year of adjuvant ribociclib are low, a number of patients discontinued adjuvant CDK 4/6 inhibitor. Tolerability and adherence patterns will need to be carefully considered with CDK 4/6 inhibitors in the adjuvant setting. Clinical trial information: NCT03285412 . [Table: see text]

Abstract P2-16-05: Efficacy of response- and toxicity-guided neoadjuvant chemotherapy in elderly early breast cancer patients: Results of WSG ADAPT elderly sub-trial

Abstract Introduction: More than 1/3 of early breast cancers (EBC) are diagnosed in women ≥ 70 years. Although polychemotherapy has been shown to be more effective than monochemotherapy also in these patients, only limited prospective data on efficacy of neoadjuvant therapy are available so far. Here, we present results of the prospective ADAPT Elderly sub-study from the WSG ADAPT umbrella protocol. Methods: Patients ≥70 years with high-risk HR+/HER2- EBC (i.e. Recurrence Score (RS)&amp;gt;25 or RS 12-25 with post-endocrine Ki67 of &amp;gt;10% or ≥cN2) or HR-/HER2- EBC were treated by 2 cycles of liposomal doxorubicin (Myocet® 60 mg/m2)/cyclophosphamide 600 mg/m2 (MC). In case of clinical response by ultrasound (&amp;gt;50% reduction in the sum of two largest diameters) and no AE grade 3-4, patients received an additional 2 cycles MC, otherwise they were switched to 6 cycles of paclitaxel (80 mg/m2) weekly. A sample size of n=150 was planned to demonstrate non-inferiority of the response- and toxicity-guided regimen vs. 4 cycles MC in responding patients (25% assumed pCR). The study was stopped early due to slow recruitment. Results: Between 09/2014 and 10/2015, 83 EBC patients from 31 centers were registered; 78 started with therapy (40 HR+/HER2-; 38 HR-/HER2-). Median age was 74 years. 64% had G3 tumors, 66% cT24, and 34% cN+. Median Ki67 was 40%. 75/78 pts underwent stratification after 2 cycles; 1 pt withdrew consent: 45(61%) were responders with no severe toxicities, 29 (39%) non-responders or suffered toxicity grade 3-4. Surgical information is available in 72 patients (43 responder/no toxicity, 29 no response/toxicity groups respectively). pCR was observed in 7 patients in the responder/no toxicity group (i.e. 16% irrespective of HR status) and in n=3 patients in the no response/toxicity group (10%). Updated efficacy and safety data will be presented at the meeting. Discussion: In one of the largest neoadjuvant chemotherapy-studies specifically for elderly pts with HER2- EBC, we observed a lower than expected pCR rate after 4 cycles of anthracycline-containing neoadjuvant chemotherapy. Taxane-based standard chemotherapy may thus be preferable in this population. Nevertheless, neoadjuvant chemotherapy seems feasible in elderly pts with high-risk HER2- EBC and should further be explored in the context of potential pCR-based (de)escalation strategies. Citation Format: Sherko Kuemmel, Oleg Gluz, Matthias Christgen, Jochem Potenberg, John Hackmann, Raquel von Schumann, Monika Graeser, Marina Mangold, Rachel Wuerstlein, Ronald Kates, Hans H. Kreipe, Ulrike Nitz, Nadia Harbeck, West German Study Group. Efficacy of response- and toxicity-guided neoadjuvant chemotherapy in elderly early breast cancer patients: Results of WSG ADAPT elderly sub-trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-05.

Accelerated partial breast irradiation in elderly breast cancer patients.

Breast-conserving surgery with adjuvant whole-breast irradiation has become the standard treatment for early breast cancer (EBC) patients. Partial breast irradiation, which targets only the postoperative cavity, has been established as an alternative to whole-breast therapy in selected patients. The treatment of elderly breast cancer patients differs from the therapeutic approach in younger ones, as elderly patients are prone to geriatric frailty and comorbid conditions, the incidence and severity of which increase with age. A review of the evidence, process, techniques, and results of accelerated partial breast irradiation (APBI) in elderly EBC patients, seems to indicate that APBI is an advisable postoperative approach in properly selected elderly EBC patients, combining advantages of a radical approach that minimizes the risk of undertreatment with efficient reduction of redundant irradiated volume, treatment toxicity, overall treatment time, staff workload, radiation technique workflow, patient transportation, and the potential for non-compliance. There is no “one size fits all” technique of APBI, the best technique always depending on willing patients, individual anatomy, performance status, patient frailty and comorbid conditions, and tumour location.

Clinical benefits of bone targeted agents in early breast cancer

Through their profound effects on the bone microenvironment, bone targeted treatments can potentially modify the process of metastasis and have important effects on disease outcomes as well as on bone health. The Early Breast Cancer Trialists Collaborative Group (EBCTCG) evaluated the effect of adjuvant bisphosphonates in early breast cancer by performing a meta-analysis of individual patient data (n = 18,766) from all available randomized trials initiated between the early 1990s until 2006. In postmenopausal women, bisphosphonates reduced bone recurrence (RR = 0.72; 95%CI 0.60-0.86, 2p = 0.0002) and breast cancer mortality (0.82; 95%CI 0.73-0.93, 2p = 0.002); no effects on disease outcomes could be identified in premenopausal women. Somewhat surprisingly, these effects could not be reproduced in the large adjuvant trial of denosumab (DCARE). In this study, neither bone metastasis free survival (the primary endpoint) or disease-free survival were improved by the addition of this targeted antibody inhibitor of osteoclast activity. Efforts are ongoing to try to understand the biologic implications of these results. For now, the use of denosumab in early cancers is limited to its use for fracture prevention using the 60mg every 6 months dosing schedule.

Accelerated partial breast irradiation for suitable elderly women using a single fraction of multicatheter interstitial high-dose-rate brachytherapy: Early results of the Single-Fraction Elderly Breast Irradiation (SiFEBI) Phase I/II trial

Purpose/ObjectiveTo evaluate feasibility and early clinical outcomes of a single fraction of multi-catheter interstitial high-dose rate brachytherapy for accelerated partial breast irradiation (APBI) in the elderly. Material/MethodsFrom November 2012 to September 2014, 26 patients (≥70) with early breast cancer were enrolled in a prospective phase II trial (NCT01727011). After lumpectomy, intra-operative catheter implant was performed for post-operative APBI (single fraction 16 Gy). Surveillance was achieved at 1, 3 and 6 months after APBI, then twice a year. Acute toxicity was investigated. Early cosmetic outcome was analyzed (patient, radiation oncologist, 2 observers). Local and regional relapse-free survival, cancer specific survival and overall survival were analyzed. ResultsMedian age was 77 years [69–89]. Median CTV was 41 cc [22-95]. Acute toxicity was observed in 18 pts (70%) with a total of 44 events: G1: 75.7%; G2: 22.8%; G3: 4.5%. Breast fibrosis (31.8%), puncture site inflammation (13.6%) and skin hyperpigmentation (11.4%) were the most frequent side effects. Cosmetic evaluation at 6 months was excellent/good in 88%, 92%, 85% and 88% for patient, radiation oncologist, observer #1 and #2 respectively. With a median follow-up of 37.2 months [35.6-42.3], side effects were G1: 4 pts (15%) and G2: 1 pt (4%). Three-year Local and regional relapse-free survival, cancer specific survival and overall survival rates were 100%, 100%, 100% and 95.2% respectively. ConclusionsFor elderly early breast cancer, a post-operative multi-catheter interstitial high-dose rate brachytherapy single dose (16 Gy) appears feasible. Acute toxicity is acceptable as well as early cosmetic outcome. Oncologic outcome seems encouraging and allows going forward with new clinical trials focusing on single fraction APBI.

Analyses of the Clinical Outcomes and Cardiovascular Events in Elderly Early Breast Cancer Patients After Breast-Conserving Surgery: A Nationwide Population-Based Study

Analyses of the Clinical Outcomes and Cardiovascular Events in Elderly Early Breast Cancer Patients After Breast-Conserving Surgery: A Nationwide Population-Based Study

Bisphosphonates as anticancer agents in early breast cancer: preclinical and clinical evidence.

Bisphosphonates (BPs) are approved as standard therapy in breast cancer for the treatment of bone metastases, since they were demonstrated to reduce the prevalence of skeletal-related events including fractures and hypercalcemia. In the adjuvant setting, BPs can be given to prevent and treat tumor therapy-induced bone loss in premenopausal and postmenopausal women and, owing to their beneficial effect on bone turnover, have also been evaluated for prevention of bone metastases occurrence. In this article we will review the mechanisms through which BPs have been demonstrated to prevent premetastatic niche formation and cell proliferation in bone lesions. Moreover, preclinical evidence of antitumoral effects of BPs will be presented and results from the most important clinical trials will be described critically. BPs may clearly play a clinically important role in early breast cancer in a postmenopausal adjuvant setting.

256O - Weekly Docetaxel (Wd) Vs Cmf As Adjuvant Chemotherapy for Elderly Early Breast Cancer (Ebc) Patients (Pts): Final Results from the Randomised Phase 3 Elda Trial

ABSTRACT Aim: Evidence on adjuvant chemotherapy in elderly EBC pts is poor. The ELDA trial tested whether wD is more effective than CMF (NCT00331097). Methods: EBC pts, 65 to 79 years old, were eligible if they had metastatic nodes or average to high risk of recurrence according to 2001 St.Gallen criteria. Pts were randomly assigned to wD (35 mg/m2 dd 1, 8, 15) or CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, fluorouracil 600 mg/m2, dd 1, 8), both every 4 wks and given for 4 cycles in ER+ pts and 6 cycles in ER- ones. With 178 events, the study would have 80% power to detect a 0.65 hazard ratio (HR) of disease-free survival (DFS) with bilateral alpha = 0.05. Quality of life (QoL) was assessed with EORTC C30 and BR23 tools; activity of daily living (ADL), instrumental ADL (IADL) and Charlson score for comorbidities were assessed. ER+ and HER2+ pts received endocrine treatment and trastuzumab after chemotherapy, respectively. Results: From July 2003 to April 2011, 302 pts were randomized and 299 (152 CMF, 147 wD) were evaluable. Median age was 71. Hypertension (62%), arthropathy (34%) osteoporosis (17%) and controlled diabetes (16%) were the most frequent comorbidities. At baseline: pT1 44%, pN0 37%, G3 64%, ER+ 75%, HER2+ 19%. After 5.5 years median follow-up, with a plateau of DFS after 108 events (50 with CMF and 58 with wD), the Independent Data Monitoring Committee recommended to anticipate final analysis. HR of DFS for wD vs CMF was 1.20 (95% CI: 0.82-1.75, p = 0.35); HR of death was 1.23 (95% CI: 0.73-2.07, p = 0.42); outcome is similar at multivariable analysis, also including ADL, IADL and Charlson scores. QoL was significantly worse with wD for emesis, appetite loss, diarrhoea, body image, future perspective, side effects and hair loss items. Hematologic toxicity, mucositis and nausea were significantly worse with CMF, while allergy, fatigue, hair loss, onicopathy, dysgeusia, diarrhoea, abdominal pain, neuropathy, cardiac and skin toxicity were significantly worse with wD. There were 1 toxic death with CMF and 2 with wD. Conclusions: The ELDA trial shows that wD is not more effective than CMF, and produces worse QoL and toxicity. CMF remains a standard for elderly EBC pts. (Partially supported by Sanofi-Aventis). Disclosure: All authors have declared no conflicts of interest.

Preclinical and Clinical Evaluation of Intraductally Administered Agents in Early Breast Cancer

Most breast cancers originate in the epithelial cells lining the breast ducts. Intraductal administration of cancer therapeutics would lead to high drug exposure to ductal cells and eliminate preinvasive neoplasms while limiting systemic exposure. We performed preclinical studies in N-methyl-N'-nitrosourea-treated rats to compare the effects of 5-fluorouracil, carboplatin, nanoparticle albumin-bound paclitaxel, and methotrexate to the previously reported efficacy of pegylated liposomal doxorubicin (PLD) on treatment of early and established mammary tumors. Protection from tumor growth was observed with all five agents, with extensive epithelial destruction present only in PLD-treated rats. Concurrently, we initiated a clinical trial to establish the feasibility, safety, and maximum tolerated dose of intraductal PLD. In each eligible woman awaiting mastectomy, we visualized one ductal system and administered dextrose or PLD using a dose-escalation schema (2 to 10 mg). Intraductal administration was successful in 15 of 17 women with no serious adverse events. Our preclinical studies suggest that several agents are candidates for intraductal therapy. Our clinical trial supports the feasibility of intraductal administration of agents in the outpatient setting. If successful, administration of agents directly into the ductal system may allow for "breast-sparing mastectomy" in select women.

Treatment of early breast cancer in women over 65: what is important? Retrospective trial.

Abstract Abstract #1125 Introduction-Background-Objective&amp;#x2028; There are some demonstrations for the under-treatment of elderly (age 65 or older) women with early breast cancer. However, a few reports are available for overall survival as well as treatment patterns. To characterize treatment patterns and to determine the impact of under-treatment of early breast cancer in the elderly population compared to younger population.&amp;#x2028; Methods&amp;#x2028; We analyzed data of 4,990 early (stage I, II) breast cancer patients aged ≥ 50 years old postmenopausal women, registered in the Korean Breast Cancer Society Registration Program (KBCSRP) between 1992 and 2001 retrospectively. We compared elderly group (age 65 or older) with younger group (age 50 or older, and under age 65) in cancer stage, hormonal receptor status, p53 status, HER-2 status, breast conservation rate, radiation therapy omission rate after breast conservation surgery, chemotherapy rate, hormonal therapy rate and overall survival.&amp;#x2028; Results&amp;#x2028; 942(19%) patients were in the elderly group and 4,048(81%) patients were in the younger group. We followed up to 2004 and median follow up period were 5.7 years. There were no differences in cancer stage, HER-2 status, and hormonal therapy rate.&amp;#x2028; In elderly group, tumor had two better prognostic factors: more hormonal receptor positivity (63.3% vs. 59.3%; p=0.001) and less p53 positivity (37.3% vs. 49.5%: p&amp;lt;0.001). Overall survival, however, was lower than younger group: 83% vs. 91% in 5 year survival rate, 68% vs. 81% in 10 year survival rate, respectively. Elderly group had less breast conservation rate (16.4% vs. 20.4%; p&amp;lt;0.001), more radiation omission rate after breast conservation surgery (59.8% vs. 15.3%; p&amp;lt;0.001) and less chemotherapy rate (43% vs. 70.6%; p&amp;lt;0.001). Using log-rank analysis, overall survival was affected by under-treatment of disease: women who underwent breast conservation surgery without radiation therapy experienced a significant decreased survival compared to women with radiation therapy (68% vs. 84% in 10 year survival rate; p&amp;lt;0.001). Total mastectomy was not superior to breast conservation surgery plus radiation therapy (p=0.2856). Women who underwent chemotherapy, however, revealed no survival gains, but women with hormonal therapy showed superior survival rate (p=0.0019).&amp;#x2028; Conclusions&amp;#x2028; Our data revealed that elderly patients had better prognostic tumor characteristics, but lower survival rate. Deviated under-treatment patterns in elderly early breast cancer patient could be dangerous choice to patients, therefore, radiation therapy after breast conservation surgery should not be omitted and hormonal therapy should be recommended especially. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1125.

The Emerging Role of Aromatase Inhibitors in the Adjuvant Management of Breast Cancer

Adjuvant hormonal therapy for patients with endocrine sensitive breast cancer has been dominated for several decades by the gold standard tamoxifen. Promising data on third generation aromatase inhibitors (AI), anastrozole, letrozole and exemestane, in metastatic setting led to the development of these agents in early breast cancer. If recent results consistently show the superiority of these agents over tamoxifen, the therapeutic strategies of AIs in adjuvant setting remain discussed. Various approaches have been evaluated ranging from: 1. Front line 5 year use of AI instead of tamoxifen for newly diagnosed patients, to 2. Switching to AI after 2 or 3 years of tamoxifen for patients presently on tamoxifen (total of 5 years), or 3. Continuing with an AI after completion of 5 years of adjuvant tamoxifen. However, it is unclear today whether one of these AI strategies is superior to the other ones. The overall therapeutic index of AIs appears superior to that of tamoxifen with proven improved efficacy and better toxicity profile. AIs are all less toxic than tamoxifen in terms of thromboembolic disease and gynaecological complications while musculoskeletal disorders and joint pains are more frequent seen with AIs. This review will explore the results from the available adjuvant AIs trials and will define the present role of AIs in the adjuvant management of postmenopausal patients with breast cancer.

Aromatase inhibitors as adjuvant therapy for breast cancer

The aromatase inhibitors are regarded as standard approaches to first- or second-line endocrine therapy in women with hormone-responsive metastatic breast cancer. Their efficacy and apparent lack of toxicity have led to their evaluation as adjuvant therapy. Although initial results with these agents in early breast cancer are promising, our collective long-term experience documenting tamoxifen's benefits and our uncertainty about the long-term effects of aromatase inhibitors suggest that it is too early to recommend their routine use in the adjuvant setting. However, anastrozole is also a reasonable therapeutic option in the adjuvant setting, particularly in individuals with a contraindication to tamoxifen such as those with thromboembolic disease or those who develop breast cancer while receiving tamoxifen or raloxifene (Evista) therapy. Anastrozole (Arimidex) was recently approved by the Food and Drug Administration for the adjuvant treatment of postmenopausal women with hormone-receptor-positive early breast cancer. Ongoing trials are assessing the potential role of aromatase inhibitors in the adjuvant, neoadjuvant, and preventive settings.

The Aromatase Inhibitors as Adjuvant Therapy for Hormone Receptor-Positive Breast Cancer

Adjuvant hormonal therapy has been shown to decrease the risk of breast cancer recurrence and overall mortality in patients with hormone receptor-positive breast cancer. Tamoxifen has been used in this setting for many years, both in premenopausal and postmenopausal patients. Tamoxifen is not devoid of toxicity, and attempts have been made to develop newer hormonal agents with better efficacy and less toxicity. The aromatase inhibitors have shown equivalent or superior efficacy to tamoxifen in the treatment of metastatic breast cancer, and efforts are underway to determine the role of these agents in early breast cancer. The ATAC trial recently showed that use of the third-generation aromatase inhibitor anastrozole in the adjuvant setting led to a modest improvement in relapse-free survival as compared with tamoxifen. Patients treated with anastrozole were also less likely to develop uterine cancer or experience a thromboembolic event. However, patients treated with anastrozole were more likely than those treated with tamoxifen to suffer a fracture or other musculosketal problem. An ASCO technology assessment panel reviewed the relevant data and issued a consensus statement regarding the use of aromatase inhibitors in the adjuvant setting. In general, the panel favored the continued use of tamoxifen as adjuvant hormonal therapy for most postmenopausal women. Within the next few years, further data from the ATAC trial and from other trials of aromatase inhibitors in the adjuvant setting should be available to guide treatment recommendations for this patient population.