Endocrine Therapy For Breast Cancer Research Articles

Prognostic influences of B-cell lymphoma 2-positive expression on late recurrence in breast cancer.

B-cell lymphoma 2 (BCL2) has an antiapoptotic role, however, has resulted in it being a powerful favorable prognostic factor in breast cancer. Several studies revealed BCL2 is strongly associated with a lower rate of early recurrence after initial treatment in breast cancer patients, but study of a prolonged effect after 5 years is lacking. We investigated BCL2 as a prognostic factor in breast cancer in comparison to early and late recurrence. We retrieved data from 2,198 patients with primary breast cancer who underwent surgical treatment and adjuvant treatment at the breast cancer center between 2005 and 2015. Each molecular subtype was classified, and Ki-67 and BCL2 were also assessed by immunohistochemistry. BCL2 and the association between molecular subtypes were assessed in early and late recurrences, respectively. Five-year postrecurrence survival and BCL2 were also assessed. The BCL2-positive group was associated with favorable clinicopathologic characteristics. The time to recurrence was significantly longer in the BCL2-positive group (P = 0.035). Late recurrence after 5 years was higher in the BCL2-positive group (P = 0.029). In multivariate survival analysis, tumor size and BCL2-positive expression were the only independent prognostic factors for late recurrence (P = 0.004). In the patients with recurrence, 5-year postrecurrence survival was significantly higher in the BCL2-positive group (P < 0.001). Our result showed that prognosis was better in BCL2-positive patients compared to BCL2-negative patients at late recurrence. We suggested that BCL2 expression could be used as a marker to help determine additional adjuvant therapy or extended hormone therapy in hormone-dependent breast cancer.

Prevention of Osteoporosis in Patients With Breast Cancer Treated With Aromatase Inhibitor Combined With Calcium/Vitamin D Supplements

Purpose: Tamoxifen and aromatase inhibitor (AI) are used for hormone therapy for hormone-positive breast cancer, and AI is well known to decrease bone mineral density (BMD). The authors compared the serial BMD of patients with hormone-positive breast cancer to evaluate the preventive effect of AI combined with calcium and vitamin D (Ca/Vit D) supplements.Methods: A total of 249 women with hormone-positive breast cancer who underwent serial BMD assessments between 2011 and 2015 were included. The patients were classified as the tamoxifen alone group (n=23), AI with Ca/Vit D group (n=139), and extended regimen from tamoxifen to AI with Ca/Vit D group (n=87). Moreover, osteoporosis was diagnosed based on the World Health Organization guideline.Results: The incidence of osteoporosis was highest in the AI with Ca/Vit D group (n=50, 36.0%) and lowest in the tamoxifen only group (n=4, 17.4%). Furthermore, it showed statistical difference between the three groups (p=0.003). However, considering the baseline of initial BMD in each patient, the mean change value did not show any statistical difference between the three groups (p=0.498). Moreover, the lumbar T-scores were lower than that of the total hip T-scores in each patient.Conclusion: Although it has been reported that osteoporosis is common in patients treated with AI, the decreased BMD was not significantly severe compared to that in the tamoxifen alone group if Ca/Vit D was administrated with AI. Therefore, Ca/Vit D has some preventive effect for osteoporosis in patients treated with AI.

Patients' Experience of Medication Brand Changes during Hormone Therapy for Breast Cancer-An Interpretative Phenomenological Analysis.

Medication adherence to hormone therapy (HT) in breast cancer survivors is often suboptimal and is affected by a range of factors. Patients are usually prescribed different generic formulations of HT drugs and their impact on side effects and on adherence and persistence is poorly understood. This study aimed to explore women's lived experience of HT medication brand changes (generic substitution) and its impact on side effects, quality of life and medication-taking behaviors, as well as on adherence and persistence. Nine female breast cancer survivors who had previous experience of HT medication brand changes participated in the study. Individual, online, semi-structured interviews were conducted and analyzed using interpretative phenomenological analysis. The findings identified three superordinate themes and nine subordinate themes that influenced the lived experience of medication brand changes for these patients: (i) experiencing brand changes, (ii) responsiveness of health care providers and (iii) future expectations. Women reported negative physical and emotional experiences of brand changes, which is often compounded by healthcare professionals' lack of information and reassurances, disbelief in the worsening of side effects and inconsistent advice regarding generics. These have implications for women's self-efficacy for medication-taking behaviors, ability to manage side effects and HT adherence and persistence.

239 VASOSPASTIC ANGINA: A CASE OF COMPLETE FUNCTIONAL ASSESSMENT

Abstract Introduction Vasospastic angina is defined as a focal or diffuse spasm of the arterial wall of an epicardial coronary artery due to muscle cells hyperreactivity caused by an increased calcium sensitivity. Clinical presentation typically consists in chronic story of rest and/or effort typical chest pain, episodes of ST elevated or not ST elevated myocardial infarction, arrhythmias or cardiac arrest; an increased vagal tone, drugs, allergic reactions or the exposure to extreme cold also can trigger vasospasm. Clinical case 73 years old dyslipidemic woman; in past medical history thyroidectomy and radiotherapy for carcinoma and right quadrantectomy with radiotherapy and hormonal therapy for breast cancer. In 2017 admission to cath-lab for non-ST elevation myocardial infarction (NSTEMI) with the evidence of mild left coronary artery disease without critical obstructive stenosis (MINOCA). For the persisting of effort angina and dyspnea (NYHA and CCS II-III), started Diltiazem therapy (60 mg x3) with clinical benefit. In 2020, due to the onset of new episodes of angina, started Ranolazine therapy. In June 2022, for the worsening of clinical symptoms, was evaluated with a Coronary CT, that showed a 65% stenosis at right coronary-acute marginal bifurcation and mild disease on left coronary artery, and then was admitted for an elective coronary angiography, with no evidence of epicardial artery critical stenosis. At the functional evaluation FFR, CFR and IMR (&amp;gt;0.80, 2.5 and 18) demonstrated normal coronary flow reserve and good microcirculation function. For the suspicion of vasospastic angina, acetylcholine test was performed with the evidence of mid-distal left anterior descending artery total occlusion, angina onset and ECG changes, promptly regressed with nitrates administration (Figure 1). Patient was discharged with the optimization of medical therapy with Diltiazem 120 mg x3, with clinical benefit. Conclusions To date vasospastic angina remains underdiagnosed. Functional evaluation of coronary arteries plays a fundamental role in the diagnostic algorithm of the disease and should always be investigated in case of patients with typical symptoms and the absence of critical epicardial stenosis. Further investigations are required to better explain pathogenesis and to identify affected patients in shorter times to ensure early optimized medical therapy.

Why are they not coming back? A single-center follow-up study on oncological women oocyte's storing for fertility preservation.

Oocyte cryopreservation is a valid option for female cancer patients to preserve fertility. The number of patients undergoing fertility preservation (FP) cycles has increased over the past years. Nevertheless, the rates of patients returning to use their cryopreserved material have shown to be considerably low, ranging from 5-8%, but significant data regarding the reasons of such low return rates are scarce. This study is a single-center follow-up retrospective study evaluating the return rate of oncological women who underwent FP at a tertiary care Fertility Center and assessing the reasons influencing the patients who did not return. Data about patients who returned to attempt pregnancy were retrieved from internal registries. Non-returned patients were assessed with a standardized phone survey investigating health condition, marital status and family projects, spontaneous conceptions, and the reasons why they had not returned to use their gametes. A univariate analysis between returned and non-returned patients was performed. Of the 397 patients who received counseling about FP, 171 (43.1%) underwent oocyte cryopreservation between 2001 and 2017. Nine (5%) died, and 17 (10%) were lost at follow-up. A total of 20 patients (11.7%) returned and 125 did not. In the non-returned group, 37 (29.6%) did not have a partner, 10 (8%) had a previous spontaneous conception, and 15 (12%) had recurrent malignancy at the time of follow-up. In the univariate analysis, younger age at freezing (31.8±6.2 vs. 35.2±4.7; p 0.018), lack of a partner (p 0.002), type of cancer (other than breast cancer; p 0.024) were the significant factors in the non-returned group. As for the personal reason for not coming back, patients mainly answered as follows: lack of a partner (29, 23.2%), the desire for spontaneous motherhood (24, 19.2%), previous spontaneous pregnancies after FP procedures (16, 12.8%), and still ongoing hormonal therapy for breast cancer (13, 10.4%). All patients confirmed their will to keep the storage of their oocytes. The impact of a cancer diagnosis on a woman's maternal desire, sentimental status and life priorities should be studied more thoroughly. Studies investigating hormonal therapy suppression in breast cancer patients seeking pregnancy should be encouraged. https://clinicaltrials.gov, identifier NCT05223764.

Association of Adherence to Endocrine Therapy Among Patients With Breast Cancer and Potential Drug-Drug Interactions

Suboptimal adherence to endocrine therapy (ET) among patients with hormone-receptor-positive breast cancer significantly affects survival outcomes and is associated with higher hospitalization rates and health care costs. Weak adherence to long-term treatments has multiple determinants, including disease characteristics, treatment adverse effects, and patients' attributes, such as age and comorbidities. To examine whether potential drug-drug interactions (PDDI) with tamoxifen or aromatase inhibitor were associated with adherence to ET in patients with early and advanced breast cancer. This cohort study used anonymized health record data of women with breast cancer who received ET in a private observational primary care database. Patients eligible for analysis included women aged 18 years or older who had a reported diagnosis of breast cancer and received ET with tamoxifen or aromatase inhibitor between 1994 and 2021. Data were analyzed 2021. Adherence to ET during a given year was defined by a medication possession ratio of 80% or greater over 1-year prescription periods. PDDI were categorized into absent, minor (a combination to take into account), moderate (combination requiring precautions for use), major (combination not recommended), and contraindicated according to guidelines in the Claude Bernard Drug Database. We used regression models to estimate odds ratios (ORs) and 95% CIs for the associations between adherence and age, baseline comorbidities, PDDI, and adherence to ET during the previous year. A total of 10 863 patients who were prescribed ET for breast cancer were eligible for the analysis (age 70 years or older, 3509 patients [32.3%]). In the tamoxifen cohort (3564 patients), PDDI were reported in 497 of 3670 patients (13.5%) at baseline (moderate, 254 patients [51.1%]; major, 227 patients [45.7%]), 2047 of 4831 patients (42.4%) at year 1, 1127 of 2751 patients (41.0%) at year 2, 761 of 1861 patients (40.9%) at year 3, 376 of 1058 patients (35.5%) at year 4, and 201 of 593 patients (33.9%) at year 5. In the aromatase inhibitor cohort (7299 patients), PDDI were reported in 592 of 7437 patients (8.0%) at baseline (moderate in 588 of 592 patients [99.3%]), which reached 2875 of 9031 patients (31.8%) at year 1 and ranged between 31.4% (1802 of 5730 patients in year 2) and 32.8% (791 of 2411 in year 4) throughout the study period. No association between adherence and PDDI was found in the tamoxifen (OR, 0.99; 95% CI, 0.91-1.08) or aromatase inhibitor (OR, 1.05; 95% CI, 0.95-1.15) cohort. In this cohort of patients with hormone-receptor-positive breast cancer, PDDI with tamoxifen and aromatase inhibitors were not associated with adherence to ET.

ERBB2 mutation is associated with sustained tumor cell proliferation after short-term preoperative endocrine therapy in early lobular breast cancer

Invasive lobular breast cancer (ILC) is a special breast cancer (BC) subtype and is mostly hormone receptor (HR)-positive and ERBB2 non-amplified. Endocrine therapy restrains tumor proliferation and is the mainstay of lobular BC treatment. Mutation of ERBB2 has been associated with recurrent ILC. However, it is unknown whether ERBB2 mutation impacts on the otherwise exquisite responsiveness of early ILC to endocrine therapy. We have recently profiled n = 622 HR-positive early BCs from the ADAPT trial for mutations in candidate genes involved in endocrine resistance, including ERBB2. All patients were treated with short-term preoperative endocrine therapy (pET, tamoxifen or aromatase inhibitors) before tumor resection. Tumor proliferation after endocrine therapy (post-pET Ki67 index) was determined prospectively by standardized central pathology assessment supported by computer-assisted image analysis. Sustained or suppressed proliferation were defined as post-pET Ki67 ≥10% or <10%. Here, we report a subgroup analysis pertaining to ILCs in this cohort. ILCs accounted for 179/622 (28.8%) cases. ILCs were enriched in mutations in CDH1 (124/179, 69.3%, P < 0.0001) and ERBB2 (14/179, 7.8%, P < 0.0001), but showed fewer mutations in TP53 (7/179, 3.9%, P = 0.0048) and GATA3 (11/179, 6.1%, P < 0.0001). Considering all BCs irrespective of subtypes, ERBB2 mutation was not associated with proliferation. In ILCs, however, ERBB2 mutations were 3.5-fold more common in cases with sustained post-pET proliferation compared to cases with suppressed post-pET proliferation (10/75, 13.3% versus 4/104, 3.8%, P = 0.0248). Moreover, ERBB2 mutation was associated with high Oncotype DX recurrence scores (P = 0.0087). In summary, our findings support that ERBB2 mutation influences endocrine responsiveness in early lobular BC.

Obstructive sleep apnea predicts pathologic response to neoadjuvant therapy in resected pancreatic ductal adenocarcinoma.

Obstructive sleep apnea predicts pathologic response to neoadjuvant therapy in resected pancreatic ductal adenocarcinoma.

Medication delivery factors and adjuvant endocrine therapy adherence in breast cancer.

Over 50% of breast cancer patients prescribed a 5-year course of daily oral adjuvant endocrine therapy (ET) are nonadherent. We investigated the role of costs and cancer medication delivery mode and other medication delivery factors on adherence. We conducted a retrospective cohort study of commercially insured and Medicare advantage patients with newly diagnosed breast cancer in 2007-2015 who initiated ET. We examined the association between 12-month ET adherence (proportion of days covered by fills ≥ 0.80) and ET copayments, 90-day prescription refill use, mail order pharmacy use, number of pharmacies, and synchronization of medications. We used regression models to estimate nonadherence risk ratios adjusted for demographics (age, income, race, urbanicity), comorbidities, total medications, primary cancer treatments, and generic AI availability. Sensitivity analyses were conducted using alternative specifications for independent variables. Mail order users had higher adherence in both commercial and Medicare-insured cohorts. Commercially insured patients who used mail order were more likely to be adherent if they had low copayments (< $5) and 90-day prescription refills. For commercially insured patients who used local pharmacies, use of one pharmacy and better synchronized refills were also associated with adherence. Among Medicare patients who used mail order pharmacies, only low copayments were associated with adherence, while among Medicare patients using local pharmacies both low copayments and 90-day prescriptions were associated with ET adherence. Out-of-pocket costs, medication delivery mode, and other pharmacy-related medication delivery factors are associated with adherence to breast cancer ET. Future work should investigate whether interventions aimed at streamlining medication delivery could improve adherence for breast cancer patients.

PSAT160 The Dangers of Long-term Aromatase Inhibitor use in an Elderly Hispanic Population

Abstract The most common endocrine therapies for breast cancer are Aromatase Inhibitors (AIs), which can help reduce the recurrence of the disease and its mortality rate. However, because aromatase inhibitors prevent the aromatization of androgens into estrogen, they can have serious effects on bone health. This can lead to accelerated bone loss and an increased risk for fractures, especially among postmenopausal women. In 2017, the Journal of Bone Oncology (JBO) released a joint position statement advising that all patients with breast cancer on endocrine treatment, such as AIs which are known to accelerate bone loss, be placed on bisphosphonate therapy should they present 2 or more risk factors for fracture (1). The purpose of this study was to evaluate patients on AIs at a 5-star Medicare Advantage plan facility and document any discrepancies with regards to whether appropriate treatment is being given to prevent fractures. We hypothesized that we may have a large percentage of patients on AI that have 2 or more risk factors and are not on treatment. An electronic chart review was conducted of 398 patients on AIs between 6/9/2020 and 8/25/2020. Patients were evaluated for the following risk factors: current smoking, personal history of hip/vertebral fracture, current use of glucocorticoids, age &amp;gt; 65, BMD T-score &amp;lt; -1.5, and BMI &amp;lt; 20. Surprisingly, 1 out of every 2 patients treated with an AI was not being treated in accordance with the JBO's recommendations. Of the 398 patients evaluated, 191 presented 2 or more risk factors and were not on antiresorptive treatment. There are a few steps that can be taken to better manage these at-risk patients. First is raising awareness to providers about the dangers of long-term AI use. Additional changes to the EMR system may help as well, such as prompting the ordering provider to consider bisphosphonate therapy if risk factors are present. Lastly, the addition of a fracture reduction clinic can help streamline the referral process to an endocrinologist upon the prescribing of AI therapy. This would allow patients to be fully evaluated for fracture risks and prescribed treatment should they qualify. With the low costs of generic bisphosphonate therapy, if a fracture is prevented, providers can hope to save a significant amount in indirect costs. Through improved awareness of providers of the risks, a more intuitive EMR system, and the creation of a new automatic referral process, we believe that we can vastly improve patient morbidity and quality of life by reducing the chances of fracture in patients on long-term AIs.Reference: (1) Hadji et al., J Bone Oncol. 2017 Mar 23;7: 1-12. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Patient experiences and views on pharmaceutical care during adjuvant endocrine therapy for breast cancer: A qualitative study.

The use of adjuvant endocrine therapy (AET) after primary treatment of hormone receptor-positive breast cancer reduces the risk of recurrence and mortality. However, non-adherence is still common. Limited consideration has been given to how users deal with AET and the role of pharmaceutical care. Therefore, this study aims to obtain insight into the needs and wishes of women using AET regarding pharmaceutical care and eHealth. This is a qualitative explorative study comprising semi-structured interviews (n = 16) and a focus group (n = 5) among women who use or used AET after primary early-stage breast cancer (EBC) treatment using a thematic analysis approach. Three themes emerged from the interviews and focus group: (1) experiences with AET use, (2) experiences with provided information and (3) needs and wishes regarding pharmaceutical care. Most women were highly motivated to use AET and indicated to have received useful information on AET. However, many expressed a strong need for more elaborate tailored and timely provided information on AET. They acknowledged the accessibility of pharmacists but reported that currently, pharmacists are hardly involved in AET care. Several women considered eHealth useful to obtain counselling and reliable information. Women need more comprehensive information and follow-up in primary setting after initial cancer treatments. A more elaborate role for the pharmacy and eHealth/mHealth, especially with regard to counselling on side effects and side effect management, could potentially improve pharmaceutical care.

The frequencies of CYP2D6 alleles and their impact on clinical outcomes of adjuvant tamoxifen therapy in Syrian breast cancer patients

BackgroundTamoxifen is one of the fundamental pillars of adjuvant endocrine therapy for hormone receptor-positive breast cancer; however, 30–50% of patients receiving tamoxifen experience tumor relapse. CYP2D6, encoded by an extremely polymorphic CYP2D6 gene, is the rate-limiting enzyme of tamoxifen bioactivation. This study aimed at determining the frequencies of the most clinically relevant CYP2D6 alleles and evaluating their impact on the responsiveness to tamoxifen in a cohort of Syrian breast cancer patients.MethodsThis case–control study encompassed positive estrogen and/or progesterone receptor, stage 1–3 breast cancer female patients receiving tamoxifen at Al-Bairouni University Hospital, the major National Oncology Center in Syria. Successfully genotyped eligible patients (n = 97) were classified according to their response into; no recurrence group (n = 39) who had completed a five-year recurrence-free adjuvant tamoxifen therapy, and recurrence group (n = 58) who had experienced recurrence. Several star alleles including CYP2D6*4, CYP2D6*10, CYP2D6*41, and CYP2D6*69 were identified via targeted sequencing of specific polymerase chain reaction (PCR) products and phenotypes were assigned according to activity score (AS). The correlation between genotypes and disease-free survival (DFS) was assessed using Kaplan–Meier method and log-rank test. Hazard ratios were estimated using Cox proportional hazards regression models.ResultsThe allelic frequencies of CYP2D6*41, CYP2D6*10, CYP2D6*4, and CYP2D6*69 were found to be 9.28%, 7.22%, 7.22%, and 2.58%, respectively. No statistically significant differences were observed in the frequencies of CYP2D6 phenotypes between the two arms (P = 0.24), nor the incidence of tamoxifen-induced hot flashes (P = 0.109). Poor metabolizers (PMs) tended to display shorter DFS than intermediate metabolizers (IMs) and normal metabolizers (NMs) combined (adjusted HR = 2.34, 95% CI = 0.84–6.55, P = 0.104). Notably, patients homozygous for the null CYP2D6*4 allele (1847A/A) had an elevated risk of disease recurrence compared to patients with 1847G/G genotype (adjusted HR = 5.23, 95% CI = 1.22–22.49, P = 0.026).ConclusionsOur findings show no association between CYP2D6 phenotype and treatment outcomes of tamoxifen in Syrian breast cancer patients. Nevertheless, a worse DFS was revealed in patients with 1847A/A genotype (*4/*4).

Factors associated with worsening sexual function during adjuvant endocrine therapy in a prospective clinic-based cohort of women with early-stage breast cancer.

Sexual function problems are common but under-reported among women receiving adjuvant endocrine therapy for breast cancer. Worsening scores on patient-reported outcomes (PROs) may identify those at risk for sexual function problems during treatment. We performed a secondary analysis of prospectively collected PROs in women receiving adjuvant endocrine therapy to identify factors associated with worsening sexual function. Women with stage 0-III breast cancer initiating adjuvant endocrine therapy participating in a prospective cohort completed PROs at baseline, 3, 6, 12, 24, 36, 48, and 60months. Sexual function was evaluated by the MOS-SP measure. Other measures included PROMIS pain interference, fatigue, depression, anxiety, physical function, and sleep disturbance and the Endocrine Symptom Subscale of the FACT-ES. We evaluated associations between score worsening of at least the minimal important difference (MID) in PROMIS T-scores (4 points) and FACT-ES scores (5 points) with score worsening of at least the MID in MOS-SP scores (8 points) using logistic regression. Among 300 participants, 45.7% experienced ≥ 8-point worsening of MOS-SP score at any time point compared to baseline. Worsening endocrine symptoms (OR 1.34, 95% CI 1.22-1.49, p < 0.001), worsening physical function (OR 1.09, 95% CI 1.00-1.18, p = 0.06), and prior mastectomy (OR 1.45, 95% CI 0.94-2.23, p = 0.09) were associated with MOS-SP score worsening by at least the MID. Worsening endocrine symptoms and physical function identified on PROs are associated with worsening sexual function during adjuvant endocrine therapy. Routine assessment of these domains with PROs may identify women at risk for sexual function problems. NCT01937052; Date of Registration: 09/09/2013.

Efficacy of minodronic acid for the prevention of osteoporosis in premenopausal women with gynaecologic disease who undergo bilateral oophorectomy: a single-centre, non-randomised controlled, experimental study

We evaluated the efficacy of minodronic acid for osteoporosis prevention after bilateral oophorectomy for gynaecologic disease in premenopausal women. Bone mineral density (BMD) and young adult mean (YAM) data from the lumbar vertebrae and femur and bone alkaline phosphatase (BAP)/tartrate-resistant acid phosphatase 5 b (TRACP 5 b) data were obtained for 101 patients. The primary endpoint was the efficacy of minodronic acid for osteoporosis prevention. Fifty-five and 31 patients were assigned to medication and no medication groups, respectively. The decrease in BMD and YAM and the increase in BAP/TRACP-5b were significantly more suppressed in the medication group. There were no significant between-group differences in age at oophorectomy, cancer type, body mass index (BMI), and adjuvant therapy. There were no adverse events due to minodronic acid. Minodronic acid may prevent osteoporosis after oophorectomy in premenopausal women with gynaecologic disease, independent of age at oophorectomy, cancer type, BMI, or adjuvant therapy. Impact statement What is already known on this subject? Although the current strategy for osteoporosis prevention after premenopausal bilateral oophorectomy (b-OVX) is hormone therapy (HT), there is no consensus on the treatment duration or adverse events. What do the results of this study add? Therefore, we planned a prospective study to evaluate the efficacy of prophylactic treatment for osteoporosis after b-OVX in premenopausal women with gynaecologic disease using minodronic acid, an oral bisphosphonate, which have a strong evidence of the treatment for osteoporosis. The result showed minodronic acid significantly suppressed the decrease in bone mineral density (BMD) and young adult mean (YAM) and the increase in bone alkaline phosphatase (BAP)/tartrate-resistant acid phosphatase 5b (TRACP 5b). Minodronic acid may prevent osteoporosis after oophorectomy in premenopausal women with gynaecologic disease, independent of age at oophorectomy, cancer type, BMI, or adjuvant therapy. What are the implications of these findings for clinical practice and/or further research? Minodronic acid treatment for osteoporosis prevention after premenopausal b-OVX may be effective as a therapeutic agent after the cessation of HT, or alternative for patients who are contraindicated for HT in breast cancer and thrombosis and should be administered with caution with a history of uterine or ovarian cancer.

Adjuvant endocrine therapy in patients with estrogen receptor-low positive breast cancer: A prospective cohort study

BackgroundLittle is known about the benefits of adjuvant endocrine therapy (ET) in low ER-positive breast cancer (1%–10%) patients. We analyzed the association between ET and breast cancer-specific survival (BCSS) in these patients with respect to the regimen and the duration of ET. MethodsPatients were classified into three groups based on the regimen and duration of ET. The regimens included aromatase inhibitor (AI) monotherapy or sequential tamoxifen followed by an AI (AI/T + AI), or only tamoxifen and no ET. The duration of ET included 2–3 years and >3 years. Multivariate Cox regression analysis was employed to calculate the hazard ratios (HRs) with 95% confidence intervals (CIs). ResultsOf the 10,696 patients diagnosed with breast cancer between 2010 and 2020, 407 women were identified with ER-low positive disease and met the inclusion criteria. During a median follow-up of 5.2 years, patients who received ET improved BCSS. Of them, those with AI/T + AI had increased BCSS compared to patients without ET, after adjusting for demographics and tumor characteristics, especially in ER-low/HER-2-positive breast cancer. After additional adjustment for treatment mode, the association maintained a similar trend. Patients who received >3 years of ET was associated with a better DFS. There was no significant difference in BCSS between patients with 2–3 years and >3 years of ET. ConclusionFor ER-low patients, findings suggest that ET with AI/T + AI may be a reasonable treatment alternative. This effect should be assessed in randomized studies.

Comprehensive Transcriptomic and Proteomic Analyses Identify a Candidate Gene Set in Cross-Resistance for Endocrine Therapy in Breast Cancer.

Endocrine therapy (ET) of selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs), and aromatase inhibitors (AIs) has been used as the gold standard treatment for hormone-receptor-positive (HR+) breast cancer. Despite its clinical benefits, approximately 30% of patients develop ET resistance, which remains a major clinical challenge in patients with HR+ breast cancer. The mechanisms of ET resistance mainly focus on mutations in the ER and related pathways; however, other targets still exist from ligand-independent ER reactivation. Moreover, mutations in the ER that confer resistance to SERMs or AIs seldom appear in SERDs. To date, little research has been conducted to identify a critical target that appears in both SERMs/SERDs and AIs. In this study, we conducted comprehensive transcriptomic and proteomic analyses from two cohorts of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) to identify the critical targets for both SERMs/SERDs and AIs of ET resistance. From a treatment response cohort with treatment response for the initial ET regimen and an endocrine therapy cohort with survival outcomes, we identified candidate gene sets that appeared in both SERMs/SERDs and AIs of ET resistance. The candidate gene sets successfully differentiated progress/resistant groups (PD) from complete response groups (CR) and were significantly correlated with survival outcomes in both cohorts. In summary, this study provides valuable clinical implications for the critical roles played by candidate gene sets in the diagnosis, mechanism, and therapeutic strategy for both SERMs/SERDs and AIs of ET resistance for the future.

Arthralgia induced by endocrine therapy with or without cyclin-dependent kinase 4/6 inhibitors in breast cancer: A systematic review and meta-analysis.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) have been approved for breast cancer (BC) treatment. Several trials suggested that arthralgia was reduced in patients treated with ET plus CDK4/6i compared with that in those with ET-alone. We aimed to compare arthralgia rates in BC patients treated with/without CDK4/6i. We reviewed randomized controlled phase II/III trials investigating CDK4/6i with ET in hormone receptor-positive and epidermal growth factor 2-negative BC. Publications were retrieved from PubMed from January 2014 to April 2021. We compared arthralgia rates between patients who were administered ET plus CDK4/6i (CDK4/6i group) and those treated with ET-alone (control group). We reviewed 12 trials that reported data on adverse effects for arthralgia. These trials included 17,440 patients (9255 in the CDK4/6i group and 8185 in the control group). The arthralgia rate in the CDK4/6i group was significantly lower than that in the control group (27.6%vs. 34.8%, p<.001), especially in early BC (28.8%vs. 37.3%, p<.001). These suggested that the arthralgia rate in patients treated with ET plus CDK4/6i was lower than that in patients treated with ET-alone and that CDK4/6i may decrease the arthralgia rate in BC patients treated with ET, especially in early BC.

Role of β1-integrin in promoting cell motility and tamoxifen resistance of human breast cancer MCF-7 cells.

The mechanism of acquired resistance of tamoxifen in endocrine therapy of breast cancer is not fully understood. In this study, we investigated the genomic changes in acquired tamoxifen-resistant cell lines. Tamoxifen-resistantsubclones (MCF-7R) derived from parent MCF-7 cells, which is an ER(+) breast cancer cell line, cultured with 4-hydrotamoxifen more than 6 months were used to obtain genomic alterations. Cell growth, microarray, and quantitative real-time PCR (q-RTPCR) assays were conducted. Additionally, the ITGB1 function was investigated in MCF-7R cells and MCF-7R ITGB1-silenced subclones using MTT and Transwell assays. Online pathway analysis was performed to assess the genetic characteristics of tamoxifen resistance. The gene expression profile of the tamoxifen-resistant cell line was considerably changed compared to the tamoxifen-sensitive cell line. Of 4102 genes with altered expressions, 1986 genes were upregulated, whereas 2116 were downregulated. The ITGB1 expression in MCF-7R cells was higher than that in MCF-7 cells. Interestingly, ITGB1 silencing partially rescued the sensitivity of MCF-7R cells to tamoxifen and reduced their motility. The activation of the β1-integrin signaling pathway was probably responsible for this phenomenon. Our data confirm the presence of alterations in the genes of tamoxifen-resistance breast cancer cells. ITGB1 probably partially contributes to tamoxifen resistance and cell motility via the β1-integrin signaling pathway. Thus, ITGB1 may be a potential target for the improvement of anti-hormone therapy reaction in ER(+) breast cancer patients.

The Development of Schematics to Illustrate Women's Experiences with Adjuvant Hormone Therapy in the Treatment of Breast Cancer.

ObjectiveNon-adherence to adjuvant hormone therapy prescribed orally in the treatment of breast cancer is complex as the literature has shown. Many women find it hard to adhere to the hormonal medicines they are prescribed and expected to take for at least 5 years following the initial management of their breast cancer. Arguably, communicating other women’s ‘trials, tribulations, and triumphs’ with medication-taking could help newly-diagnosed patients to better prepare for the journey ahead. Our objective was to visually represent women’s experiences with these medicines using data synthesized in the literature.MethodsThree schematics were drawn for each phase of medication-taking, namely, starting out, adherence, and cessation. The schematics were validated by interviewing a panel of healthcare professionals (n=10) and calculating a Content Validity Index (CVI). The edited drawings were discussed with a separate panel of breast cancer survivors (n=14) whose responses were elicited qualitatively in one-to-one interviews.ResultsA total of 76 individual pictograms were drawn across the three schematics. The 13 pictograms that had an item-level CVI<0.8 were modified according to feedback resulting in three final schematics with an overall CVI of 87%, 87% and 80%, respectively.ConclusionSynthesised summaries of women’s experiences with oral hormone therapy for breast cancer were visualised via three validated schematics. The schematics could aid patient-professional communication to help anticipate and tackle negative experiences and support decisions to take hormone medication in breast cancer.

Impact of cytochrome P450 2D6 polymorphisms on decision-making and clinical outcomes in adjuvant hormonal therapy for breast cancer

BACKGROUNDThere are concerns that tamoxifen is less effective in Asian women because of the high prevalence of impaired function cytochrome P450 2D6 (CYP2D6) polymor-phisms.AIMTo evaluate how knowledge of CYP2D6 genotype impacted the choice of hormonal agent and how CYP2D6 genotype and agent were associated with clinical outcomes.METHODSEighty-two women were recruited. Seventy-eight completed CYP2D6 genotyping and were categorized into poor, intermediate (IM) and extensive or ultra metabolizer phenotypes. Women with poor metabolizer and IM phenotypes were recommended aromatase inhibitors as the preferred agent.RESULTSMore than 70% of the women had an IM phenotype, 32% an extensive or ultra metabolizer phenotype, and 0% had a poor metabolizer phenotype. Regardless of genotype, more women opted for aromatase inhibitors. Overall, 80% of women completed 5 years of hormonal therapy. Five women developed recurrence, 3 contralateral breast cancer, 5 died, and 1 was diagnosed with a second primary cancer. Five-year recurrence-free and overall survival were slightly better in women with the extensive or ultra metabolizer phenotype compared to those with the IM phenotype, though not statistically significant [P = 0.743, hazard ratio (HR): 1.441, 95% confidence interval (CI): 0.191 to 10.17 and P = 0.798, HR: 1.327, 95%CI: 0.172 to 9.915, respectively]. Women receiving aromatase inhibitors also appeared to have a better, but also nonsignificant, 5-year recurrence-free and overall survival (P = 0.253, HR: 0.368, 95%CI: 0.031 to 0.258 and P = 0.292, HR: 0.252, 95%CI: 0.005 to 4.951, respectively).CONCLUSIONThe IM phenotype was highly prevalent but was not associated with clinical outcome.