Core concomitant symptoms reported by the patients with breast cancer in postoperative endocrine treatment and the demand for acupuncture therapy： a network-based cross-sectional study. / ä¹³è ºç™Œæœ¯åŽå† åˆ†æ³Œæ²»ç–—æ‚£è€ æŠ¥å‘Šçš„æ ¸å¿ƒä¼´éšç—‡çŠ¶åŠå¯¹é’ˆç¸æ²»ç–—çš„éœ€æ±‚ï¼šä¸€é¡¹åŸºäºŽç½‘ç»œçš„æ¨ªæ–­é¢ç ”ç©¶.

OBJECTIVES: To investigate the most common concomitant symptoms and the urgent demand of solution in the breast cancer patients undergoing postoperative endocrine treatment, as well as the acceptance and expectation of acupuncture in the patients so as to provide the scientific data for promoting the application of acupuncture in the breast cancer patients. METHODS: Breast cancer patients treated in Tianjin Medical University Cancer Institute and Hospital from January 2022 to March 2023 were randomly selected as the subjects. Using "questionnaire star" website, the questionnaire was conducted to investigate the relevant concomitant symptoms of the patients in postoperative endocrine treatment and the questions related to acupuncture treatment. RESULTS: In this study, 229 questionnaires were distributed and 211 valid ones were collected, with the response rate of 92.1%. Among these patients, the first three common symptoms were sleep disorders (157 cases, 74.4%), hot flashes (138 cases, 65.4%) and joint / muscle pain (118 cases, 55.9%)；the top three symptoms to be solved the most urgently were sleep disorders (131 cases, 62.1%), joint / muscle pain (62 cases, 29.4%) and hot flashes (45 cases, 21.3%). 79.1% of the patients (167 cases) were willing to receive acupuncture treatment because of the high expectations on its potential effect (93%). 20.9% of them (44 cases) refused acupuncture because they were worried not to be treated by the experienced physicians of TCM (52%) or afraid of needling feelings (48%). The average expectation value of acupuncture treatment was 4.02 points (5 points for the total score) among patients willing to receive acupuncture treatment. The main purposes of receiring acupuncture for the patients undergoing endocrine treatment were to strengthen the immune function (92%), reduce the adverse reactions (83%), and improve the physical condition (75%), et al. CONCLUSIONS: Sleep disorder is one of the most concerned symptoms in endocrine treatment for the patients after breast cancer surgery. The patients highly expect for acupuncture treatment even though some patients dislike the needling sensation. How to provide the acceptable and high-quality acupuncture services for cancer patients will be one of the major directions of acupuncture research in the future.

Utilisation of endocrine therapy for cancer in Indigenous peoples: a systematic review and meta-analysis.

BACKGROUND: Indigenous peoples worldwide experience inequitable cancer outcomes, and it is unclear if this is underpinned by differences in or inadequate use of endocrine treatment (ET), often used in conjunction with other cancer treatments. Previous studies examining ET use in Indigenous peoples have predominately focused on the sub-national level, often resulting in small sample sizes with limited statistical power. This systematic review aimed to collate the findings ofarticles on ET utilisation for Indigenous cancer patients and describe relevant factors that may influence ET use. METHODS: We conducted a systematic review and meta-analysis of studies reporting ET use for cancer among Indigenous populations worldwide. PubMed, Scopus, CINAHL, Web of Science, and Embase were searched for relevant articles. A random-effect meta-analysis was used to pool proportions of ET use. We also performed a subgroup analysis (such as with sample sizes) and a meta-regression to explore the potential sources of heterogeneity. A socio-ecological model was used to present relevant factors that could impact ET use. RESULTS: Thirteen articles reported ET utilisation among Indigenous populations, yielding a pooled estimate of 67% (95% CI:54 - 80), which is comparable to that of Indigenous populations 67% (95% CI: 53 - 81). However, among studies with sufficiently sized study sample/cohorts (≥ 500), Indigenous populations had a 14% (62%; 95% CI:43 - 82) lower ET utilisation than non-Indigenous populations (76%; 95% CI: 60 - 92). The ET rate in Indigenous peoples of the USA (e.g., American Indian) and New Zealand (e.g., Maori) was 72% (95% CI:56-88) and 60% (95% CI:49-71), respectively. Compared to non-Indigenous populations, a higher proportion of Indigenous populations were diagnosed with advanced cancer, at younger age, had limited access to health services, lower socio-economic status, and a higher prevalence of comorbidities. CONCLUSIONS: Indigenous cancer patients have lower ET utilisation than non-Indigenous cancer patients, despite the higher rate of advanced cancer at diagnosis. While reasons for these disparities are unclear, they are likely reflecting, at least to some degree, inequitable access to cancer treatment services. Strengthening the provision of and access to culturally appropriate cancer care and treatment services may enhance ET utilisation in Indigenous population. This study protocol was registered on Prospero (CRD42023403562).

Favorable outcome of neoadjuvant endocrine treatment than surgery-first in female HR-positive/HER2-negative breast cancer patients-A NCDB analysis (2010-2016).

PURPOSE: To assess the efficacy of neoadjuvant endocrine therapy in female HR-positive/HER2-negative breast cancer patients. DATA AND METHODS: We identified female patients aged ≥18 years with cT1-4N0-XM0, HR(+), and HER2(-) breast cancer from the National Cancer Database. The patients who underwent surgery first were categorized as "surgery-first," while those who received NET before surgery were classified as "NET." Propensity score-matching, Cox proportional-hazard model, variance inflation factors, and interaction analysis were employed to estimate the correlation between NET and survival outcomes. RESULTS: Among 432,387 cases, 2914 NET patients and 2914 surgery-first patients were matched. Compared with the surgery-first group, the NET group received less adjuvant chemotherapy (p < 0.001). Furthermore, the NET group exhibited higher survival probabilities compared with the surgery-first group (3 years: 91.4% vs. 82.1%; 5 years: 82.1% vs. 66.8%). Multivariate Cox analysis indicated that NET was associated with improved OS (surgery-first vs. NET: HR 2.17, 95% CI: 1.93-2.44). Age over 55 years old, having public insurance, higher CDCC score, higher NSBR grade, ER(+)PR(-), and advanced clinical stage were related to worse OS (all p < 0.05). There was an interaction between age, race, income, and home and treatment regimen (all p < 0.05). CONCLUSION: NET may be a more effective treatment procedure than surgery-first in female HR-positive/HER2-negative, non-metastatic breast cancer patients. Future clinical studies with more detailed data will provide higher-level evidence-based data.

Impact of Prosigna test on adjuvant treatment decision in lymph node-negative early breast cancer-a prospective national multicentre study (EMIT-1).

BACKGROUND: EMIT-1 is a national, observational, single-arm trial designed to assess the value of the Prosigna, Prediction Analysis of Microarray using the 50 gene classifier (PAM50)/Risk of Recurrence (ROR), test as a routine diagnostic tool, examining its impact on adjuvant treatment decisions, clinical outcomes, side-effects and cost-effectiveness. Here we present the impact on treatment decisions. PATIENTS AND METHODS: Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative pT1-pT2 lymph node-negative early breast cancer (EBC) were included. The Prosigna test and standard histopathology assessments were carried out. Clinicians' treatment decisions were recorded before (pre-Prosigna) and after (post-Prosigna) the Prosigna test results were disclosed. RESULTS: Of 2217 patients included, 2178 had conclusive Prosigna results. The pre-Prosigna treatment decisions were: no systemic treatment (NT) in 27% of patients, endocrine treatment alone (ET) in 38% and chemotherapy (CT) followed by ET (CT + ET) in 35%. Post-Prosigna treatment decisions were 25% NT, 51% ET and 24% CT + ET, respectively. Adjuvant treatment changed in 28% of patients, including 21% change in CT use. Among patients assigned to CT + ET pre-Prosigna, 45% were de-escalated to ET post-Prosigna. Of patients assigned to ET, 12% were escalated to CT + ET and 8% were de-escalated to NT; of those assigned to NT, 18% were escalated to ET/CT + ET. CT was more frequently recommended for patients aged ≤50 years. In the subgroup with pT1c-pT2 G2 and intermediate Ki67 (0.5-1.5× local laboratory median Ki67 score), the pre-Prosigna CT treatment decision varied widely across hospitals (3%-51%). Post-Prosigna, the variability of CT use was markedly reduced (8%-24%). The correlation between Ki67 and ROR score within this subgroup was poor (r = 0.25-0.39). The median ROR score increased by increasing histological grade, but the ROR score ranges were wide (for G1 0-79, G2 0-90, G3 16-94). CONCLUSION: The Prosigna test result changed adjuvant treatment decisions in all EBC clinical risk groups, markedly decreased the CT use for patients categorized as higher clinical risk pre-Prosigna and reduced treatment decision discrepancies between hospitals.

Cost-effectiveness of adjuvant endocrine treatment with tamoxifen for male breast cancer.

BACKGROUND: Tamoxifen (TAM) is recommended as the first-line strategy for men with estrogen receptor (ER)-positive early breast cancer who are candidates for adjuvant endocrine therapy in ASCO guideline. Our study aims to analyze the cost-effectiveness of receiving adjuvant endocrine therapy with TAM compared to no TAM, and to assess the cost-effectiveness of using TAM with high adherence over low adherence for ER-positive early male breast cancer in the USA. METHODS: Two Markov models comprising three mutually exclusive health states were constructed: (1) the first Markov model compared the cost-effectiveness of adding TAM with not using TAM (TAM versus Not-TAM); (2) the second model compared the cost-effectiveness of receiving TAM with high adherence and low adherence (High-adherence-TAM versus Low-adherence-TAM). The simulation time horizon for both models was the lifetime of patients. The efficacy and safety data of two models were elicited from the real-world studies. Model inputs were derived from the US website and published literature. The main outcomes of two models both included the total cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: In the first model, TAM yielded an ICER of $5707.29 per QALY compared to Not-TAM, which was substantially below the WTP threshold of $50,000.00 per QALY in the USA. Probabilistic sensitivity analysis results demonstrated a 100.00% probability of cost-effectiveness for this strategy. In the second model, High-adherence-TAM was dominated absolutely compared to Low-adherence-TAM. The High-adherence-TAM was cost-effective with a 99.70% probability over Low-adherence-TAM when WTP was set as $50,000.00/QALY. All of these parameters within their plausible ranges did not reversely change the results of our models. CONCLUSIONS: Our study will offer valuable guidance for physicians or patients when making treatment decisions and provide an effective reference for decision-making to consider the appropriate allocation of funds to this special group.

Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2- advanced breast cancer: a real-world evidence cohort.

PURPOSE: Everolimus in combination with endocrine therapy (ET) was formerly approved as 2nd-line therapy in HR(+)/HER2(-) advanced breast cancer (aBC) patients (pts) progressing during or after a non-steroidal aromatase inhibitor (NSAI). Since this approval, the treatment landscape of aBC has changed dramatically, particularly with the arrival of CDK 4-6 inhibitors. Endocrine monotherapy after progression to CDK4/6 inhibitors has shown a limited progression-free survival (PFS), below 3 months. Evidence of the efficacy of everolimus plus ET after CDK4/6 inhibitors is scarce. METHODS: A retrospective observational study of patients with aBC treated with everolimus and ET beyond CDK4/6-i progression compiled from February 2015 to December 2022 in 4 Spanish hospitals was performed. Clinical and demographic data were collected from medical records. The main objective was to estimate the median progression-free survival (mPFS). Everolimus adverse events (AE) were registered. Quantitative variables were summarized with medians; qualitative variables with proportions and the Kaplan-Meier method were used for survival estimates. RESULTS: One hundred sixty-one patients received everolimus plus ET (exemestane: 96, fulvestrant: 54, tamoxifen: 10, unknown: 1) after progressing on a CDK4/6 inhibitor. The median follow-up time was 15 months (interquartile range: 1-56 months). The median age at diagnosis was 49 years (range: 35-90 years). The estimated mPFS was 6.0 months (95%CI 5.3-7.8 months). PFS was longer in patients with previous CDK4/6 inhibitor therapy lasting for > 18 months (8.7 months, 95%CI 6.6-11.3 months), in patients w/o visceral metastases (8.0 months, 95%CI 5.8-10.5 months), and chemotherapy-naïve in the metastatic setting (7.2 months, 95%CI 5.9-8.4 months). CONCLUSION: This retrospective analysis cohort of everolimus plus ET in mBC patients previously treated with a CDK4/6 inhibitor suggests a longer estimated mPFS when compared with the mPFS with ET monotherapy obtained from current randomized clinical data. Everolimus plus ET may be considered as a valid control arm in novel clinical trial designs.

Ovarian Suppression: Early Menopause and Late Effects.

OPINION STATEMENT: Around 90% of breast tumours are diagnosed in the early stage, with approximately 70% being hormone receptor-positive. The cornerstone of adjuvant therapy for early-stage hormone receptor-positive breast cancer is endocrine therapy, tailored according to disease stage, biological characteristics of the tumour, patient's comorbidities, preferences and age. In premenopausal patients with hormone receptor-positive breast cancer, ovarian function suppression is a key component of the adjuvant endocrine treatment in combination with an aromatase inhibitor or tamoxifen. Moreover, it can be used during chemotherapy as a standard strategy for ovarian function preservation in all breast cancer subtypes. In the metastatic setting, ovarian function suppression should be used in all premenopausal patients with hormone receptor-positive breast cancer to achieve a post-menopausal status. Despite its efficacy, ovarian function suppression may lead to several side effects that can have a major negative impact on patients' quality of life if not properly managed (e.g. hot flashes, depression, cognitive impairment, osteoporosis, sexual dysfunction, weight gain). A deep knowledge of the side effects of ovarian function suppression is necessary for clinicians. A correct counselling in this regard and proactive management should be considered a fundamental part of survivorship care to improve treatment adherence and patients' quality of life.

Pre- and Postoperative Antioxidant Use, Aryl Hydrocarbon Receptor (AhR) Activation and Clinical Outcome in Different Treatment Groups of Breast Cancer Patients.

BACKGROUND: Cancer patients often use antioxidants that may interact with adjuvant treatments. The purpose was to investigate pre- and postoperative antioxidant use in relation to clinicopathological characteristics and prognosis in different breast cancer treatment groups. METHODS AND PATIENTS: Pre- and postoperative antioxidant (vitamin A, C, E, carotenoids, or Q10) or multivitamin use was self-reported by patients from Lund (n = 1855) and Helsingborg (n=478), Sweden. Patients were followed for up to 15 years. Clinical data were obtained from patient charts. The aryl hydrocarbon receptor (AhR) was evaluated in tumor tissue arrays from 915 patients from Lund and with Western blot in MCF-7 and MDA-MB-231 cells. RESULTS: About 10% of patients used antioxidants. Nuclear AhR (AhRnuc) positivity was twice as common in preoperative antioxidant users compared to non-users. In mechanistic studies vitamin C increased AhR levels and its downstream target CYP1B1, indicating AhR activation. There were significant interactions between tumor AhRnuc status and preoperative antioxidant use in relation to clinical outcome. In all patients, antioxidant use (other than multivitamins) at both visits was associated with poorer prognosis, while use only at the follow-up visit was associated with better prognosis, compared with no use at either visit. CONCLUSION: The clinical impact of antioxidants depended on antioxidant type, timing of use, and tumor AhR activation. Antioxidants may influence clinical outcome by activation of the master regulator AhR in addition to interference with free radicals. Further studies are needed to identify breast patients that might improve or worsen their prognosis when using antioxidants postoperatively.

Neoadjuvant endocrine treatment in hormone receptor-positive breast cancer: Does it result in more breast-conserving surgery?

BACKGROUND: Patients with locally advanced endocrine positive tumors who will not benefit from chemotherapy can be treated by either primary surgery or neoadjuvant endocrine therapy (NET). How often does NET result in breast-conserving surgery (BCS)? METHODS: We conducted a literature search in PubMed and Embase, to identify articles on surgical treatment after NET. RESULTS: In 19 studies the pathological complete response (pCR) rate was reported after NET; an overall pCR rate of 1% was found. Compared with neoadjuvant chemotherapy (NCT), the BCS rate was significantly higher after NET (OR 0.60; 95% CI, 0.51-0.69; P < 0.00001). The surgical conversion rate was reported in eight studies [4-75.9%], with a mean of 30.2%. CONCLUSION: This review found that one out of three patients becomes eligible for BCS after treatment with NET.

Adjuvant treatment in hormone receptor-positive early breast cancer: New approaches of endocrine therapy.

Breast cancer is the most common cancer in women, and luminal breast cancer is the predominant subtype, characterized by the presence of estrogen receptors and/or progesterone receptors in tumor cells. Adjuvant endocrine therapy is the pivotal approach in the management of luminal early breast cancer. Hence, new therapeutic approaches have been studied during the last few years, especially in patients with high risk of recurrence.Here we provide a summary of the most recent clinical trials evaluating adjuvant treatment in hormone-receptors-positive early breast cancer. First, the main cornerstone is related to the role of extended endocrine treatment, which has been widely investigated to access a benefit in disease-free survival and overall survival (only the GIM4 trial has positive feedback about survival) and to tailor the treatment according to patient compliance. The results highlighted an advantage in extending the use of endocrine treatment for at least seven full years, considering aromatase inhibitors as principal drugs. Second, the shift of CDK4/6 inhibitors (CDK4/6i) from advanced to early setting reported positive outcomes, with favorable results from MonarchE and NATALEE trials, using Abemaciclib and Ribociclib respectively, even if non-negligible toxicities have been reported. Last, the use of PARP inhibitors for BRCA1/2 mutated patients has been evaluated in the OlympiA trial (Olaparib), observing a comparable benefit between hormone-receptors-positive and triple-negative early breast cancer.However, more data are still required to better select patients that could benefit more from CDK4/6i considering side effects too, and sequential treatments are still not codified.

The Endocrine Treatment Landscape for Patients with HR+ HER2- Early-stage Breast Cancer in Germany Before the Introduction of CDK4/6 Inhibitor Therapy - A Real-World Analysis.

Introduction: While premenopausal patients with HR+ HER2- early breast cancer are treated with tamoxifen +/- ovarian suppression with a GnRH analog or an aromatase inhibitor (AI) + GnRH, the majority of postmenopausal women receive an AI due to its higher efficacy compared to tamoxifen. As the introduction of CDK4/6 inhibitors into the treatment of early-stage breast cancer with a higher risk of recurrence will probably result in a shift in the endocrine treatment landscape, the question is what treatment did potential candidates for CDK4/6 inhibitors in Germany receive before CDK4/6 inhibitors were available. Patients and Methods: As part of a retrospective multicenter analysis, anonymized data were collected of patients with HR+ HER2- early-stage breast cancer who received endocrine therapy in the period between 10/2021 and 03/2022. Potential candidates for CDK4/6 inhibitor treatment were classified into different risk cohorts using the inclusion criteria of the NATALEE and monarchE trials. Results: The data of 238 patients from 29 different centers were analyzed. While 20.6% of patients met the monarchE criteria, the subgroup which met the NATALEE inclusion criteria consisted of 46.2% of patients. 53.8% of patients did not meet the inclusion criteria for either the NATALEE or the monarchE trial. More than half of the patients did not receive chemotherapy. 28.6% of patients in the whole cohort were premenopausal. 67.6% of premenopausal women received neo-/adjuvant chemotherapy. 61.8% of premenopausal patients received tamoxifen as adjuvant endocrine therapy, 19.1% received an AI + GnRH and 10.3% were treated with tamoxifen + GnRH. Conclusion: Despite the high percentage of premenopausal patients who received aggressive treatment in the form of chemotherapy, only one third of premenopausal patients received GnRH in addition to their standard endocrine therapy. Studies carried out at a later point in time and registry studies will be necessary to see how the endocrine therapy landscape in Germany has changed following the introduction of CDK4/6 inhibitors.

Endocrine treatment near the end of life among older women with metastatic breast cancer: a nationwide cohort study.

Background: The appropriate time to discontinue chemotherapy at the end of life has been widely discussed. In contrast, few studies have investigated the patterns of endocrine treatment near death. In this study, we aimed to investigate the end-of-life endocrine treatment patterns of older women with metastatic breast cancer and explore characteristics associated with treatment. Methods: A retrospective cohort study of all older women (age ≥65 years) with hormone receptor-positive breast cancer who died in Sweden, 2016 - 2020. We used routinely collected administrative and health data with national coverage. Treatment initiation was defined as dispensing during the last three months of life with a nine-month washout period, while continuation and discontinuation were assessed by previous use during the same period. We used log-binomial models to explore factors associated with the continuation and initiation of endocrine treatments. Results: We included 3098 deceased older women with hormone receptor-positive breast cancer (median age 78). Overall, endocrine treatment was continued by 39% and initiated by 5% and of women during their last three months of life, while 31% discontinued and 24% did not use endocrine treatment during their last year of life. Endocrine treatment continuation was more likely among older and less educated women, and among women who had multi-dose drug dispensing, chemotherapy, and CDK4/6 use. Only treatment-related factors were associated with treatment initiation. Conclusion: More than a third of women with metastatic breast cancer continue endocrine treatments potentially past the point of benefit, whereas late initiation is less frequent. Further research is warranted to determine whether our results reflect overtreatment at the end of life once patients' preferences and survival prognosis are considered.

Clinical Treatment Score Post-5 Years as a Tool for Risk Estimation of Late Recurrence in Thai Patients With Estrogen-Receptor-Positive, Early Breast Cancer: A Validation Study.

Background: The risk of late distant recurrence (LDR) of estrogen receptor (ER)-positive breast cancer continues even after 5 years of endocrine treatment. Clinical Treatment Score after 5 years (CTS5) was developed and validated as a tool to assess the risk of LDR using data from Tamoxifen, Arimidex Alone or in Combinations (ATAC) and Breast International Group 1-98 (BIG1-98) trials. This study aimed to externally validate CTS5 in a real-world cohort of patients treated at an academic center in Thailand. Methods: The study was a retrospective analytical research study of early-stage, ER-positive breast cancer patients. The primary endpoint was LDR. The risk of LDR was determined using the CTS5 calculator. Cox regression model and Kaplan-Meier survival analysis were applied for prognostic validation of CTS5. Calibration was performed by comparing observed LDR to expected LDR using the Hosmer-Lemeshow (H-L) test. Results: A total of 323 women were included with a median follow-up period of 11.6 years. The rate of LDR was 10.8%. The CTS5 was prognostic for LDR. C-index of the area under the ROC curve was 0.672. There was no significant difference between actual and expected numbers of LDR with an observed (O) LDR events to expected (E) number of LDR events ratio of 0.99 (0.86-1.12) (H-L P = .79) indicating a proper calibration in this cohort. Conclusions: Our study validated that CTS5 is accurate in predicting the risk of LDR in ER-positive breast cancer cases in Thai patients. Its performance seemed to be better in postmenopausal patients. CTS5 could be applied in routine clinical practice to improve decisions regarding prolonged endocrine therapy, particularly in resource-limited countries where molecular profiling are inaccessible.

Frequent upregulation of HER2 protein in hormone-receptor-positive HER2-negative breast cancer after short-term neoadjuvant endocrine therapy.

BACKGROUND: Endocrine resistant metastatic disease develops in ~ 20-25% of hormone-receptor-positive (HR+) breast cancer (BC) patients despite endocrine therapy (ET) use. Upregulation of HER family receptor tyrosine kinases (RTKs) represent escape mechanisms in response to ET in some HR+ tumors. Short-term neoadjuvant ET (NET) offers the opportunity to identify early endocrine escape mechanisms initiated in individual tumors. METHODS: This was a single arm, interventional phase II clinical trial evaluating 4 weeks (± 1 week) of NET in patients with early-stage HR+/HER2-negative (HER2-) BC. The primary objective was to assess NET-induced changes in HER1-4 proteins by immunohistochemistry (IHC) score. Protein upregulation was defined as an increase of ≥ 1 in IHC score following NET. RESULTS: Thirty-seven patients with cT1-T3, cN0, HR+/HER2- BC were enrolled. In 35 patients with evaluable tumor HER protein after NET, HER2 was upregulated in 48.6% (17/35; p = 0.025), with HER2-positive status (IHC 3+ or FISH-amplified) detected in three patients at surgery, who were recommended adjuvant trastuzumab-based therapy. Downregulation of HER3 and/or HER4 protein was detected in 54.2% of tumors, whereas HER1 protein remained low and unchanged in all cases. While no significant volumetric reduction was detected radiographically after short-term NET, significant reduction in tumor proliferation rates were observed. No significant associations were identified between any clinicopathologic covariates and changes in HER1-4 protein expression on multivariable analysis. CONCLUSION: Short-term NET frequently and preferentially upregulates HER2 over other HER family RTKs in early-stage HR+/HER2- BC and may be a promising strategy to identify tumors that utilize HER2 as an early endocrine escape pathway. CLINICAL TRIAL REGISTRY: Trial registration number: NCT03219476.

Oestrogen receptor low positive breast cancer: associations with prognosis.

PURPOSE: In this study of oestrogen receptor (ER) Low Positive breast cancers (BC) in three large cohorts of BC patients, we assess associations between levels of ER expression and tumour characteristics and prognosis. METHODS: Cases were stratified into patients unlikely to have received adjuvant therapy according to treatment guidelines at time of diagnosis (before 1995), and those who could have received adjuvant therapy (diagnosed in 1995 or later). ER status was divided into < 1%; ≥ 1 < 10%; ≥ 10%. Results were correlated with time of diagnosis, histopathological grade, proliferation status, and molecular subtypes, using Pearson's Chi-square test. For prognosis, hazard ratios and cumulative incidence of death from BC were used. RESULTS: Of the 1955 tumours, 65 (3.3%) were ER Low Positive (ER ≥ 1 < 10%). Overall, the highest proportion of ER Low Positive tumours was observed among Luminal B (HER2 +) subtype (9.4%) and grade 3 tumours (4.3%). The risk of death from BC was lower in ER Low Positive and ER ≥ 10% compared to ER-negative cases. Compared to patients diagnosed before 1995, women diagnosed in 1995 or later showed a higher proportion of ER Low Positive BCs, and their tumours were of smaller size, lower grade, and lower proliferative status. There was no significant difference in prognosis compared to those with ER ≥ 10% tumours. CONCLUSION: Women with ER Low Positive tumours diagnosed in a time period when adjuvant therapy was available had tumours of smaller size, lower grade, and lower proliferative status, and similar prognosis to those with ER ≥ 10% compared to women diagnosed earlier.

Compliance to adjuvant endocrine therapy and survival in breast cancer patients.

BACKGROUND: Data on compliance to adjuvant endocrine treatment (ET) is mainly reported from prospective clinical trials or from smaller retrospective cohorts without correlation to outcome. AIMS: To determine compliance to adjuvant ET and the impact on survival in a population-based series of patients with early breast cancer (BC) advised ET. PATIENTS AND METHODS: 1090 consecutive patients with hormone receptor positive (HR+) stage I-III BC diagnosed from 1 January 1997 to 31 December 2003 from one health care region of Sweden were included. Data on tumour, type of ET, compliance, reason for termination and outcome were collected. Statistical analyses were calculated with patients in three groups. RESULTS: 72 patients were excluded leaving 1018 patients with a HR+ stage I to III BC for analyses. The most common ET was tamoxifen (n = 751, 73.8%). At the last follow up (31 Dec 2019) with a median follow-up of 18 years (interquartile range 16-22) 228 (22.4%) patients had a relapse. 71.1% of the included patients were compliant to endocrine therapy. Older patients ≥74 years had lower compliance, 61% compared with 75% in the other age groups (≤50 years and 51-73 years) (p < 0001), other parameters including type of ET were not associated with compliance. Low compliance remained as an independent risk factor in multivariate analyses for lower relapse-free survival, HR=1.83, 95% Confidence Interval (CI) 1.52-2.19, p < 0.001 and for time to BC death, HR=2.69, 95%CI 1.82-3.98, p < 0.001. CONCLUSIONS: Patients compliant to adjuvant ET have an improved survival.

CDK4/6 Inhibitors-Overcoming Endocrine Resistance Is the Standard in Patients with Hormone Receptor-Positive Breast Cancer.

PURPOSE OF REVIEW: Tamoxifen and aromatase inhibitors can be considered as some of the first targeted therapies. For the past 30 years, they were the endocrine treatment standard in the advanced and early breast cancer setting. CDK4/6 inhibitors, however, are the first substances in almost two decades to broadly improve the therapeutic landscape of hormone receptor-positive breast cancer patients for the upcoming years. This review is designed to discuss the recent history, current role, future directions and opportunities of this substance class. RECENT FINDINGS: The CDK4/6 inhibitors abemaciclib, dalpiciclib, palbociclib and ribociclib have all demonstrated a statistically significant improvement in progression-free survival in advanced disease. However, to date, abemaciclib and ribociclib are the only CDK4/6 inhibitors to have shown an improvement in overall survival in patients with metastatic breast cancer. Moreover, abemaciclib is the first CDK4/6 inhibitor to also reduce the risk of recurrence in those with early-stage disease. Further CDK inhibitors, treatment combinations with other drugs and different therapy sequences are in development. SUMMARY: Achieving significant improvements in survival rates in the advanced and early breast cancer treatment setting, CDK4/6 inhibitors have set a new standard of care for patients with advanced breast cancer. It remains important to better understand resistance mechanisms to be able to develop novel substances and treatment sequences.

Adherence to endocrine therapy in early breast cancer in relation to Cytochrome P450 2D6 genotype: a comparison between pharmacy dispensation data and medical records.

PURPOSE: Suboptimal adherence to adjuvant endocrine treatment (AET) is an important clinical concern. A correlation between CYP2D6 activity and tamoxifen discontinuation has been described. The main aim of this study was to investigate the consistency between pharmacy dispensation data and medical records on adherence to AET. METHODS: Adherence was calculated for patients with at least 4.5 years of follow up and was defined as Medical Possession Rate ≥ 80%. Subgroup analyses were performed based on menopausal status, recurrence risk and CYP2D6 activity. RESULTS: In 86% of the 1235 included patients the consistency between the two sources of information was within 80-125%. Poor consistency, < 80%, was most frequent in the premenopausal/ high-risk group and CYP2D6 Poor Metabolizers (PMs). Among 899 patients with at least 4.5 years follow up, 72% were adherent to tamoxifen based on pharmacy dispensation data, compared with 77% as reported by medical records. When including patients who switched to aromatase inhibitors after tamoxifen, adherence increased to 82% and 88%, respectively. Adherence did not differ by menopausal status or risk for recurrence. CYP2D6 PMs had poorer adherence (54%) to tamoxifen compared to patients with the highest CYP2D6 activity (83%). CONCLUSIONS: There was a good consistency between medical records and pharmacy dispensing data on the use of AET. Adherence to AET was adequate, especially when including switch to aromatase inhibitors. Surprisingly, CYP2D6 PMs had low adherence to tamoxifen, despite a likely reduced risk of side effects according to previous data.

Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy.

BACKGROUND: There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). METHODS: A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. RESULTS: The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. CONCLUSION: Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.