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The Oncologist May 2024Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) early breast cancer (EBC) with high-risk clinicopathological...
Adjuvant treatment strategy evolution and risk stratification for hormone receptor-positive, human epidermal growth factor receptor-2 negative early breast cancer in China.
BACKGROUND
Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) early breast cancer (EBC) with high-risk clinicopathological features face an increased risk of recurrence. This study explored the evolving treatment landscape and clinical outcomes in patients with EBC using a nationwide database.
PATIENTS AND METHODS
The study cohort comprised HR+/HER2-, stages 1-3, patients with EBC who underwent surgery and received adjuvant endocrine therapy (AET) from January 2013 to March 2021. High-risk patients were defined by ≥4 positive axillary lymph nodes, or 1-3 positive lymph node(s) with at least one high-risk feature (histologic grade 3, tumor size ≥5 cm, or Ki-67 ≥20%). A low-risk cohort included patients not meeting the criteria. Survival analysis was conducted with a cutoff of September 2021.
RESULTS
The study included 4088 eligible patients (1310 high-risk patients and 2778 low-risk patients). High-risk patients were more likely to receive adjuvant chemotherapy and radiotherapy compared to low-risk patients. From 2013 to 2021, an increasing proportion of patients received aromatase inhibitors and ovarian function suppression as part of their AET. The 2-, 5-, and 7-year invasive disease-free survival for high-risk cohort were 90.67%, 75.26%, and 57.10%, respectively, these rates were notably higher for low-risk cohort at 97.14%, 89.85%, and 84.83%. High-risk patients demonstrated a higher risk of recurrence or death compared with low-risk patients (hazard ratio, 2.38; 95% CI, 1.82-3.12).
CONCLUSION
In the setting of standard or even intensive AET, patients with EBC with high-risk features still present high recurrence risk, highlighting the urgent need for innovative adjuvant treatment strategies.
PubMed: 38780143
DOI: 10.1093/oncolo/oyae095 -
Ecancermedicalscience 2024Adjuvant treatment with aromatase inhibitors (AI) in oestrogen receptor-positive and/or progesterone receptor-positive breast cancer (BC) has been shown to increase...
INTRODUCTION
Adjuvant treatment with aromatase inhibitors (AI) in oestrogen receptor-positive and/or progesterone receptor-positive breast cancer (BC) has been shown to increase overall survival. However, arthralgias and myalgias are common adverse effects in patients treated with AI.
OBJECTIVE
To evaluate the frequency and characteristics of arthralgias and myalgias in patients with early BC-treated adjuvantly with AI in the Mastology Unit of the Oncology Service of the Hospital de Clínicas and the Departmental Hospital of Soriano.
MATERIALS AND METHODS
A prospective, cross-sectional and descriptive study was performed. A questionnaire was administered to patients to assess the presence and characteristics of arthralgias and myalgias associated with AI.
STATISTICAL ANALYSIS
'Age' was described with measures of central tendency and dispersion. Qualitative variables were presented in absolute and relative frequencies. Logistic models were used to evaluate the association between patient characteristics, tumour characteristics, treatment characteristics and the presence of pain. Results were presented by odds ratio and -value, using R software (version 4.1.2) with a significance threshold of 5%.
RESULTS
83 patients were included, with a median age of 69 years. 75.9% presented arthralgias and/or myalgias related to treatment, with an average intensity of 5-7. 80.9% received non-steroidal anti-inflammatory drugs (NSAIDs), achieving satisfactory analgesia. The presence of arthralgias and myalgias was significantly associated with age and time since the last menstrual period (LMP), being more frequent in patients older than 50 years and those with more than 5 years since the LMP.
CONCLUSION
Approximately 70% of the patients presented arthralgias or myalgias. These findings suggest a possible role of oestrogen withdrawal in its mechanism of development. Multidisciplinary and translational research is crucial to evaluate the ethology and therapeutic options for patients with AI-related arthralgia.
PubMed: 38774562
DOI: 10.3332/ecancer.2024.1697 -
Best Practice & Research. Clinical... May 2024Endometriosis-related infertility is one of the most debated topics in reproductive medicine. In recent years, prolonged pre-cycle hormonal regimens gained attention as... (Review)
Review
Endometriosis-related infertility is one of the most debated topics in reproductive medicine. In recent years, prolonged pre-cycle hormonal regimens gained attention as a mean of improving the assisted reproduction technologies (ART) success rates in endometriosis patients. GnRH agonists, dienogest, medroxyprogesterone acetate, and aromatase inhibitors are the most studied medications. Conflicting results and a high risk of bias exist in almost all of the conducted studies in the field. However, current evidence suggests that pre-cycle treatment with GnRH agonists may be beneficial for patients with stage III/IV endometriosis. Dienogest and medroxyprogesterone acetate-based progestin-primed ovarian stimulation protocol was shown to be comparable to the prolonged GnRH agonists protocol. Finally, aromatase inhibitors seem to be of limited benefit to the assisted reproductive outcomes of endometriosis patients. Although it is challenging to draw any clinical conclusions, pre-cycle hormonal treatments seem to be best indicated in endometriosis patients who had previously failed ART treatment.
PubMed: 38772765
DOI: 10.1016/j.bpobgyn.2024.102500 -
The Oncologist May 2024In women, ovarian cancer is the eighth most frequent cancer in incidence and mortality. It is often diagnosed at advanced stages; relapses are frequent, with a poor...
BACKGROUND
In women, ovarian cancer is the eighth most frequent cancer in incidence and mortality. It is often diagnosed at advanced stages; relapses are frequent, with a poor prognosis. When platinum resistant, subsequent lines of chemotherapy are of limited effect and often poorly tolerated, leading to quality of life deterioration. Various studies suggest a hormonal role in ovarian carcinogenesis, with a rationale for endocrine therapy in these cancers.
PATIENTS AND METHODS
This multicenter, retrospective study assessed the use of endocrine treatment for high-grade ovarian epithelial carcinomas treated between 2010 and 2020.
RESULTS
Eighty-one patients with ovarian cancers were included. The median duration of platinum sensitivity was 29 months. We observed a 35% disease control rate with endocrine therapy, and 10% reported symptom improvement. For 19 patients (23.5%), the disease was stabilized for more than 6 months. Median overall survival from diagnosis was 62.6 months. Regarding endocrine therapy predictive factors of response, in a multivariate analysis, 3 factors were statistically significant in favoring progression-free survival: platinum sensitivity (P = .021), an R0 surgical resection (P = .020), and the indication for hormone therapy being maintenance therapy (P = .002).
CONCLUSION
This study shows real-life data on endocrine therapy in ovarian cancer. As it is a low-cost treatment with many advantages such as its oral administration and its safety, it may be an option to consider. A perspective lies in the search for cofactors to aim as future therapeutic targets to improve the effectiveness of hormone treatment by means of combination therapy.
PubMed: 38768082
DOI: 10.1093/oncolo/oyae093 -
Nutrition Research (New York, N.Y.) Apr 2024The influence of gut microbiota on gut health is well-documented, but it remains obscure for extraintestinal diseases such as breast cancer. Moreover, it is entirely...
The influence of gut microbiota on gut health is well-documented, but it remains obscure for extraintestinal diseases such as breast cancer. Moreover, it is entirely unknown how gut dysbiosis during early life contributes to breast tumorigenesis later in life. In this study, we hypothesized that a high-fat diet during early life leads to alterations in the gut microbiome and is associated with disruptions in the mammary microenvironment. Female C57BL/6 mice were fed a low-fat diet (10% kcal fat) or a high-fat diet (HF, 60% kcal fat) for 8 weeks from the age of 4 to 12 weeks, which is equivalent to human childhood and adolescence. Twelve mice were sacrificed immediately after the 8-week feeding, the remainder were euthanized after switching to a normal lifecycle-supporting diet for an additional 12 weeks; the gut microbiome was then sequenced. The 8-week HF diet feeding altered the beta-diversity (Bray & Jaccard P < .01), and the difference remained significant after switching the diet (Bray & Jaccard P < .05). Immediately after HF feeding, a greater number of microbial taxa (>50) were altered, and about half of the taxa (25) remained significantly changed after switching the diet. The abundance of Alistipes, Bilophila, and Rikenellaceae stood out as significantly associated with multiple metabolic and inflammatory biomarkers in mammary tissue, including aromatase, Ccl2, and Cox2. In conclusion, an 8-week early-life HF feeding reshaped the gut microbiome, which connected with disrupted mammary microenvironments.
PubMed: 38763113
DOI: 10.1016/j.nutres.2024.04.006 -
Cancer Treatment and Research... May 2024Hormone Receptor-positive (HR+) and Human Epidermal Growth Factor Receptor 2-negative (HER2-) breast cancer is the most common subtype, predominantly treated with...
INTRODUCTION/BACKGROUND
Hormone Receptor-positive (HR+) and Human Epidermal Growth Factor Receptor 2-negative (HER2-) breast cancer is the most common subtype, predominantly treated with endocrine therapy. The efficacy of CDK4/6 inhibitors combined with endocrine therapy in this context remains to be fully evaluated.
MATERIALS (OR PATIENTS) AND METHODS
This study compared the effectiveness of CDK4/6 inhibitors (palbociclib and ribociclib) in combination with an aromatase inhibitor or fulvestrant against endocrine therapy alone in patients with HR+/HER2- advanced breast cancer. The main focus was on progression-free survival (PFS) and overall survival (OS). The study involved a population treated exclusively with endocrine therapy for bone involvement, examining median OS and PFS, and adjusting for variables like stage, visceral metastasis, age, and treatment line.
RESULTS
The study found no significant OS difference between treatments with palbociclib, ribociclib, and endocrine therapy alone. However, ribociclib combined with letrozole significantly improved PFS over letrozole alone. Propensity score weighting indicated a potential 50 % reduction in death risk with ribociclib compared to palbociclib, though this was not confirmed by cox regression.
CONCLUSION
CDK4/6 inhibitors, particularly ribociclib in combination with letrozole, show promise in improving outcomes for HR+/HER2- breast cancer patients. While palbociclib may not be superior to traditional endocrine therapy, the results underscore the need for further research. These findings could influence future treatment protocols, emphasizing the importance of personalized therapy in this patient group.
PubMed: 38761788
DOI: 10.1016/j.ctarc.2024.100818 -
Journal of Neuroendocrinology May 2024Neuroestrogens locally synthesized in the brain are known to play a role in sexual behaviors. However, the question of whether neuroestrogens are involved in the...
Neuroestrogens locally synthesized in the brain are known to play a role in sexual behaviors. However, the question of whether neuroestrogens are involved in the regulation of the gonadotropin-releasing hormone (GnRH) release is just emerging. Because previous studies in this lab indicate that neuroestradiol is also important for the pulsatile release as well as the surge release of GnRH in female rhesus monkeys, in the present study, we examined whether neuroestradiol plays a role in the estrogen-induced LH surge in orchidectomized (ORX) male rhesus monkeys. Unlike in rodents, it is known that a high dose of estrogen treatment can result in the LH surge in ORX male rhesus monkeys. Results that the administration of the aromatase inhibitor, letrozole, failed to attenuate the estrogen-induced LH surge, suggest that unlike in ovariectomized females, neuroestrogens do not play a role in the LH surge experimentally induced by the exogenous estrogen treatment in ORX male monkeys.
PubMed: 38760983
DOI: 10.1111/jne.13413 -
American Journal of Respiratory and... May 2024Inhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models.
RATIONALE
Inhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models.
OBJECTIVES
We aimed to determine whether anastrozole improved six-minute walk distance (6MWD) at six months in pulmonary arterial hypertension (PAH).
METHODS
We performed a randomized, double-blind, placebo-controlled Phase II clinical trial of anastrozole in subjects with PAH at seven centers. Eighty-four post-menopausal women and men with PAH were randomized in a 1:1 ratio to receive anastrozole 1 mg or placebo by mouth daily, stratified by sex using permuted blocks of variable sizes. All subjects and study staff were masked. The primary outcome was the change from baseline in 6MWD at six months. Using intent-to-treat analysis, we estimated the treatment effect of anastrozole using linear regression models adjusted for sex and baseline 6MWD. Assuming 10% loss to follow-up, we anticipated having 80% power to detect a difference in the change in 6MWD of 22 meters.
MEASUREMENTS AND MAIN RESULTS
Forty-one subjects were randomized to placebo and 43 to anastrozole and all received the allocated treatment. Three subjects in the placebo group and two in the anastrozole group discontinued study drug. There was no significant difference in the change in 6MWD at six months (placebo-corrected treatment effect -7.9 m, 95%CI -32.7 - 16.9, p = 0.53). There was no difference in adverse events between the groups.
CONCLUSIONS
Anastrozole did not show a significant effect on 6MWD compared to placebo in post-menopausal women and men with PAH. Anastrozole was safe and did not show adverse effects. Clinical trial registration available at www.
CLINICALTRIALS
gov, ID: NCT03229499.
PubMed: 38747680
DOI: 10.1164/rccm.202402-0371OC -
Bulletin Du Cancer May 2024
PubMed: 38744543
DOI: 10.1016/j.bulcan.2024.03.005 -
The Journal of Endocrinology Jul 2024We recently showed that the ratio of capillaries to myofibers in skeletal muscle, which accounts for 80% of insulin-directed glucose uptake and metabolism, was reduced...
We recently showed that the ratio of capillaries to myofibers in skeletal muscle, which accounts for 80% of insulin-directed glucose uptake and metabolism, was reduced in baboon fetuses in which estrogen was suppressed by maternal letrozole administration. Since vascular endothelial growth factor (VEGF) promotes angiogenesis, the present study determined the impact of estrogen deprivation on fetal skeletal muscle VEGF expression, capillary development, and long-term vascular and metabolic function in 4- to 8-year-old adult offspring. Maternal baboons were untreated or treated with letrozole or letrozole plus estradiol on days 100-164 of gestation (term = 184 days). Skeletal muscle VEGF protein expression was suppressed by 45% (P < 0.05) and correlated (P = 0.01) with a 47% reduction (P < 0.05) in the number of capillaries per myofiber area in fetuses of baboons in which serum estradiol levels were suppressed 95% (P < 0.01) by letrozole administration. The reduction in fetal skeletal muscle microvascularization was associated with a 52% decline (P = 0.02) in acetylcholine-induced brachial artery dilation and a 23% increase (P = 0.01) in mean arterial blood pressure in adult progeny of letrozole-treated baboons, which was restored to normal by letrozole plus estradiol. The present study indicates that estrogen upregulates skeletal muscle VEGF expression and systemic microvessel development within the fetus as an essential programming event critical for ontogenesis of systemic vascular function and insulin sensitivity/glucose homeostasis after birth in primate offspring.
Topics: Animals; Female; Letrozole; Muscle, Skeletal; Vascular Endothelial Growth Factor A; Pregnancy; Nitriles; Estrogens; Estradiol; Triazoles; Neovascularization, Physiologic; Papio; Male; Fetus; Capillaries; Aromatase Inhibitors
PubMed: 38738915
DOI: 10.1530/JOE-23-0364