Personalising therapy for early-stage oestrogen receptor-positive breast cancer in older women.
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ABSTRACT:
SUBMITTER: Carleton N
PROVIDER: S-EPMC8765742 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveThe aim was to examine the real-world cost-effectiveness of breast-conserving surgery (BCS) plus hormonal therapy with radiotherapy, compared to hormonal therapy alone among women 66 and older with hormone receptor positive early-stage breast cancer in the United States (US).MethodsThis study was conducted from a U.S. Centers for Medicare and Medicaid Services perspective and an eight-year time horizon. Both costs (2020 US$) and health utilities (quality-adjusted life years, QALYs) were obtained from retrospective studies using the SEER linked with Medicare and Medicare Health Outcomes Survey, respectively. The incremental cost-effectiveness ratio (ICER) of the addition of radiotherapy to hormonal therapy versus hormonal therapy alone after BCS was estimated by an unbiased doubly robust estimator. Sensitivity analyses were conducted through bootstrapping to estimate credible intervals.ResultsThe addition of radiotherapy to hormonal therapy after BCS yielded the highest clinical benefits (2.66 QALYs) and costs ($19,424.27) compared to its hormonal therapy alone after BCS (0.77 QALYS; $2,028.58). The ICER was estimated to be $9,174.94/QALY. Sensitivity analyses did not change the direction of the findings.ConclusionsThe results implicated that the combination of radiotherapy and hormonal therapy is cost-effective in the US.
| S-EPMC10791147 | biostudies-literature
Project description:BackgroundBreast conserving surgery (BCS) and adjuvant hormonal therapy (HT) without radiation therapy (RT) is an acceptable approach for older women with early stage, estrogen receptor (ER) positive breast cancer. Toxicity and compliance remain issues with HT. Adjuvant RT alone may have better compliance, but its efficacy in the absence of HT is unclear. We aim to assess patterns of adjuvant therapy and survival outcomes among older women with early stage, ER positive (ER+) breast cancer.MethodsThe National Cancer Data Base (NCDB) was used to identify 130,194 women age ≥65 years with invasive ER+, node negative breast cancer diagnosed between 2004 and 2015. All patients underwent BCS. Kaplan-Meier survival curves were used to examine overall survival (OS). The association between adjuvant therapy and OS was assessed in multivariable Cox proportional hazards regression models.ResultsUnadjusted 5/10-year OS rates were 90.0%/64.3% for HT and RT, 84.2%/54.9% for RT alone, 78.7%/44.5% for HT alone, and 71.6%/38.0% for no treatment; p<0.001 for all. Compared to HT alone, the 10-year multivariable hazard ratio (HR) for death for RT alone was 0.86 (95% CI 0.82-0.91). In propensity-matched patients who received RT alone or HT alone (n=21,326), RT alone had significantly better survival at 5 (HRadj : 0.84) and 10 (HRadj : 0.87) years.ConclusionsOlder women with early stage ER+ breast cancer who undergo BCS and receive both HT and RT have the best survival, while RT as single-modality therapy had higher rates of OS at 5 and 10 years compared to HT alone.
| S-EPMC7666745 | biostudies-literature
Project description:ImportanceOvertreatment of early-stage breast cancer with favorable tumor biology in older patients may be harmful without affecting recurrence and survival. Guidelines that recommend deimplementation of sentinel lymph node biopsy (SLNB) (Choosing Wisely) and radiotherapy (RT) (National Comprehensive Cancer Network) have been published.ObjectiveTo describe the use rates and association with disease recurrence of SLNB and RT in older women with breast cancer.Design, setting, and participantsThis cohort study obtained patient and clinical data from an integrated cancer registry and electronic health record of a single health care system in Pennsylvania. The cohort was composed of consecutive female patients 70 years or older who were diagnosed with early-stage, estrogen receptor-positive, ERBB2 (formerly HER2)-negative, clinically node-negative breast cancer from January 1, 2010, to December 31, 2018, who were treated at 15 community and academic hospitals within the health system.ExposuresSentinel lymph node biopsy and adjuvant RT.Main outcomes and measuresPrimary outcomes were 5-year locoregional recurrence-free survival (LRFS) rate and disease-free survival (DFS) rate after SLNB and after RT. Secondary outcomes included recurrence rate, subgroups that may benefit from SLNB or RT, and use rate of SLNB and RT over time. Propensity scores were used to create 2 cohorts to separately evaluate the association of SLNB and RT with recurrence outcomes. Cox proportional hazards regression model was used to estimate hazard ratios (HRs).ResultsFrom 2010 to 2018, a total of 3361 women 70 years or older (median [interquartile range {IQR}] age, 77.0 [73.0-82.0] years) with estrogen receptor-positive, ERBB2-negative, clinically node-negative breast cancer were included in the study. Of these women, 2195 (65.3%) received SLNB and 1828 (54.4%) received adjuvant RT. Rates of SLNB steadily increased (1.0% per year), a trend that persisted after the 2016 adoption of the Choosing Wisely guideline. Rates of RT decreased slightly (3.4% per year). To examine patient outcomes and maximize follow-up time, the analysis was limited to cases from 2010 to 2014, identifying 2109 patients with a median (IQR) follow-up time of 4.1 (2.5-5.7) years. In the propensity score-matched cohorts, no association was found between SLNB and either LRFS (HR, 1.26; 95% CI, 0.37-4.30; P = .71) or DFS (HR, 1.92; 95% CI, 0.86-4.32; P = .11). In addition, RT was not associated with LRFS (HR, 0.33; 95% CI, 0.09-1.24; P = .10) or DFS (HR, 0.99; 95% CI, 0.46-2.10; P = .97). Subgroup analysis showed that stratification by tumor grade or comorbidity was not associated with LRFS or DFS. Low absolute rates of recurrence were observed when comparing the groups that received SLNB (3.5%) and those that did not (4.5%) as well as the groups that received RT (2.7%) and those that did not (5.5%).Conclusions and relevanceThis study found that receipt of SLNB or RT was not associated with improved LRFS or DFS in older patients with ER-positive, clinically node-negative breast cancer. Despite limited follow-up time and wide 95% CIs, this study supports the continued deimplementation of both SLNB and RT in accordance with the Choosing Wisely and National Comprehensive Cancer Network guidelines.
| S-EPMC8050744 | biostudies-literature
Project description:BackgroundOlder women are at the greatest risk of breast cancer development and a considerable number present with comorbidities. Although the majority of breast cancers in this age group express oestrogen receptor (ER), which makes endocrine therapy (primary or adjuvant) feasible, given the huge size of the elderly population, there remains a significant number of patients, in absolute term, whose tumours do not express ER and their management is challenging.MethodsOf a consecutive series of 1,758 older (≥70 years) women with early operable primary breast cancer managed in a dedicated service from 1973-2010, 252(14.3%) had ER-negative (histochemical (H) score ≤50) tumours. Their clinical outcome was retrospectively reviewed and tumour samples collected from diagnostic core biopsies were analysed for progesterone receptor (PgR), HER2 and Ki67 using immunohistochemistry.ResultsThe commonest primary treatment was surgery (N = 194, 77%) followed by primary endocrine therapy (14.3%), primary radiotherapy (5.6%) and supportive treatment only (3.1%). Among the patients undergoing surgery, most of them had grade 3 (78.1%) and node-negative disease (62.2%). Some of them (21.1%) received postoperative radiotherapy. At a median follow-up of 37.5 months, 117 patients had died, out of which 48.6% were due to breast cancer. For those who underwent surgery, the regional and local recurrence rates were 2% and 1.1% per annum respectively. For those who received primary endocrine therapy, 38% progressed at 6 months, however all patients who had primary radiotherapy achieved clinical benefit at 6 months. Regardless of treatment given, the 5-year breast cancer specific and overall survival rates were 70% and 50% respectively. Biological analysis based on good quality needle core biopsy specimensfrom181 patients showed that 26.8% (N = 49), 16.9% (N = 31) and 70.7% (N = 70)expressed positivity for PgR, HER2 and Ki67 respectively. No correlation between these biomarkers and breast cancer specific survival was demonstrated.ConclusionOestrogen receptor negative early operable primary breast cancer in older women is associated with poor prognostic features in terms of biology and clinical outcome. Surgery appears to produce the best outcome as a primary treatment, however for those where neither surgery nor chemotherapy is appropriate, primary radiotherapy can be beneficial.
| S-EPMC5746234 | biostudies-literature
Project description:Background Weight gain is commonly observed during and after breast cancer treatment and is associated with poorer survival outcomes, particularly in women with oestrogen receptor-positive (ER +) disease. The aim of this study was to co-design (with patients) a programme of tailored, personalised support (intervention), including high-quality support materials, to help female breast cancer patients (BCPs) with ER + disease to develop the skills and confidence needed for sustainable weight loss. Methods ER + BCPs were recruited from two UK National Health Service (NHS) Trusts. The selection criteria included (i) recent experience of breast cancer treatment (within 36 months of completing primary treatment); (ii) participation in a recent focus group study investigating weight management perceptions and experiences; (iii) willingness to share experiences and contribute to discussions on the support structures needed for sustainable dietary and physical activity behaviour change. Co-design workshops included presentations and interactive activities and were facilitated by an experienced co-design researcher (HH), assisted by other members of the research team (KP, SW and JS). Results Two groups of BCPs from the North of England (N = 4) and South Yorkshire (N = 5) participated in a two-stage co-design process. The stage 1 and stage 2 co-design workshops were held two weeks apart and took place between Jan–March 2019, with each workshop being approximately 2 h in duration. Guided by the Behaviour Change Wheel, a theoretically-informed weight management intervention was developed on the basis of co-designed strategies to overcome physical and emotional barriers to dietary and physical activity behaviour change. BCPs were instrumental in designing all key features of the intervention, in terms of Capability (e.g., evidence-based information, peer-support and shared experiences), Opportunity (e.g., flexible approach to weight management based on core principles) and Motivation (e.g., appropriate use of goal-setting and high-quality resources, including motivational factsheets) for behaviour change. Conclusion This co-design approach enabled the development of a theoretically-informed intervention with a content, structure and delivery model that has the potential to address the weight management challenges faced by BCPs diagnosed with ER + disease. Future research is required to evaluate the effectiveness of the intervention for eliciting clinically-important and sustainable weight loss in this population. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-10287-y.
| S-EPMC9682743 | biostudies-literature
Project description:PurposeTo identify the information older women with early-stage breast cancer need when making radiation therapy decisions, and who patients identify as the main decision maker.Methods and materialsWe surveyed (through face-to-face interview, telephone, or mail) women aged ≥65 years who received lumpectomy and were considering or receiving adjuvant radiation therapy for early-stage breast cancer. The survey instrument was constructed with input from patient and professional advisory committees, including breast cancer survivors, advocates of breast cancer care and aging, clinicians, and researchers. Participants rated the importance (on a 4-point scale) of 24 statements describing the benefits, side effects, impact on daily life, and other issues of radiation therapy in relation to radiation therapy decision making. Participants also designated who was considered the key decision maker.ResultsThe response rate was 56.4% (93 of 165). Mean age was 72.5 years, ranging from 65 to 93 years. More than 96% of participants indicated they were the main decision maker on receiving radiation therapy. There was wide variation in information needs regarding radiation therapy decision making. Participants rated a mean of 18 (range, 3-24) items as "essential." Participants rated items related to benefits highest, followed by side effects. Participants who were older than 75 years rated 13.9 questions as essential, whereas participants aged ≤74 years rated 18.7 as essential (P=.018).ConclusionsOlder women desire information and have more agency and input in the decision-making process than prior literature would suggest. The variation in information needs indicates that future decision support tools should provide options to select what information would be of interest to the participants.
| S-EPMC5468466 | biostudies-literature
Project description:BackgroundDespite data demonstrating the safety of omitting axillary surgery in older women with early-stage breast cancer, the incidence of axillary surgery remains high. It was hypothesized that the prevalence of nodal positivity would decrease with advancing age.MethodsThe National Cancer Data Base was used to construct a cohort of adult women with early-stage, clinically node-negative, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative breast cancer treated between 2013 and 2015. Multivariable logistic regression was used to assess the relationship between age and nodal positivity, and this was stratified by the axillary surgery category. Modified Poisson regression was used to estimate the proportion of women receiving adjuvant therapy according to age and nodal status.ResultsThe incidence of axillary surgery among women aged 70 and older (n = 51,917) remained high nationwide (86%). There was a significant decrease in nodal positivity with advancing age in women with early-stage, ER+, clinically node-negative breast cancer from the youngest cohort up to patients aged 70 to 89 years, and this was independent of histologic subtype (ductal vs lobular), race, comorbidities, and socioeconomic factors. Overall, less than 10% of women aged 70 or older who underwent surgery had node-positive disease, regardless of axillary surgery type, and almost 95% of node-positive patients aged 70 or older were at pathological stage N1mi or N1.ConclusionsAxillary surgery may be safely omitted for many older women with ER+, clinically node-negative, early-stage breast cancer. Nodal positivity declines with advancing age, and this suggests varied biology in older patients versus younger patients.
| S-EPMC7369168 | biostudies-literature
Project description:BackgroundOlder women with breast cancer are underrepresented in clinical trials, and data on the effects of adjuvant chemotherapy in such patients are scant. We tested for the noninferiority of capecitabine as compared with standard chemotherapy in women with breast cancer who were 65 years of age or older.MethodsWe randomly assigned patients with stage I, II, IIIA, or IIIB breast cancer to standard chemotherapy (either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide plus doxorubicin) or capecitabine. Endocrine therapy was recommended after chemotherapy in patients with hormone-receptor-positive tumors. A Bayesian statistical design was used with a range in sample size from 600 to 1800 patients. The primary end point was relapse-free survival.ResultsWhen the 600th patient was enrolled, the probability that, with longer follow-up, capecitabine therapy was highly likely to be inferior to standard chemotherapy met a prescribed level, and enrollment was discontinued. After an additional year of follow-up, the hazard ratio for disease recurrence or death in the capecitabine group was 2.09 (95% confidence interval, 1.38 to 3.17; P<0.001). Patients who were randomly assigned to capecitabine were twice as likely to have a relapse and almost twice as likely to die as patients who were randomly assigned to standard chemotherapy (P=0.02). At 3 years, the rate of relapse-free survival was 68% in the capecitabine group versus 85% in the standard-chemotherapy group, and the overall survival rate was 86% versus 91%. Two patients in the capecitabine group died of treatment-related complications; as compared with patients receiving capecitabine, twice as many patients receiving standard chemotherapy had moderate-to-severe toxic effects (64% vs. 33%).ConclusionsStandard adjuvant chemotherapy is superior to capecitabine in patients with early-stage breast cancer who are 65 years of age or older. (ClinicalTrials.gov number, NCT00024102.)
| S-EPMC3082436 | biostudies-literature
Project description:For premenopausal women with primary ER?+?breast cancer, oophorectomy (OvX) is an evidence-based cost-effective option and is standard treatment in many countries. However, there is virtually no data describing the effects of OvX on breast tumour biology. We therefore, characterised the endocrine and genome-wide transcriptional impact of OvX in 56 premenopausal women with ER?+?breast cancer for 2 weeks prior to mastectomy. Plasma estradiol concentrations decreased from 406?±?41 to 20.7?±?2.6?pmol/l (mean?±?sem) 24?h after OvX, and to 8.1?±?0.8?pmol/l 2 weeks later at mastectomy. Ki67 decreased in 33/36 (91.7%) tumours. The expression of 655 genes changed significantly (FDR?<?1%) with an absolute mean fold-change (FC)???1.25 (257 up, 398 down). Archetypal oestrogen-regulated genes (TFF1, GREB1, PGR and PDZK1) showed large decreases in expression (FC?=?0.20-0.69; p?<?1e-6-1e-7). Proliferation-associated genes (e.g. TOP2A, AURKA and UBE2C) were also strongly downregulated (FC?=?0.38-0.56; p?<?1e-7) along with putative progesterone-regulated genes (e.g. FKBP4, MYB; FC?=?0.64-0.68; p?<?1e-4-1e-7). The gene expression changes did not differ according to HER2 status and correlated strongly with the changes reported previously after aromatase inhibitor (AI) treatment in postmenopausal women (rho?=?0.55, p?<?1e-04). However, after OvX the mean FC was significantly higher compared to AI (p?<?1e-04). In conclusion, changes in tumoural gene expression after OvX were largely similar, but of a greater magnitude to those observed after AI in postmenopausal patients; however, OvX appeared to have a greater effect on progesterone-regulated genes than AI.
| S-EPMC5703856 | biostudies-literature
Project description:IntroductionThe purpose was to evaluate the effect of adjuvant radiation therapy on the survival prognosis of older women with early-stage breast cancer under different surgical treatments.MethodsWe collected patients from the Surveillance, Epidemiology and End Results (SEER) database. Elderly female patients (≥ 70 years) with stage I-IIB diagnosed with invasive carcinoma in 1988-2017 were included. After propensity score matching (PSM), the prognosis of patients who underwent breast-conserving surgery or mastectomy was calculated separately. The effects of radiotherapy on the survival of three special population groups (breast-conserving surgery + T1N0M0 + ER positive, mastectomy + T3N0M0 and mastectomy + T1-2N1M0) were analyzed selectively.ResultsOf 106,553 older women with early-stage breast cancer were identified. 48,630 patients had received radiotherapy, while 57,923 patients had not. After PSM, older women undergoing breast-conserving surgery benefited significantly from radiotherapy (both OS and BCSS p < 0.001), for patients with T1N0M0 and ER-positive breast cancer (both OS and BCSS p < 0.001). In the subgroup of T1-2N1M0 breast cancer treated by mastectomy, patients undergoing radiotherapy had a worse survival as well (OS p < 0.001; BCSS p = 0.0907). While in the subgroup of T3N0M0 breast cancer treated by mastectomy, survival analyses showed no statistical differences between patients receiving radiation or not (OS p = 0.1778, BCSS p = 0.6957).ConclusionsThis study indicated the clinical effects of radiation on older women who received different surgical treatments. Our study suggested that radiotherapy should be omitted in older women undergoing mastectomy + T3N0M0 or T1-2N1M0 and radiotherapy could be considered in women with T1N0M0 + ER-positive undergoing breast-conserving surgery.
| S-EPMC9873780 | biostudies-literature