Dataset Information

Timing of adjuvant surgical oophorectomy in the menstrual cycle and disease-free and overall survival in premenopausal women with operable breast cancer.

ABSTRACT:

Background

For women with hormone receptor-positive, operable breast cancer, surgical oophorectomy plus tamoxifen is an effective adjuvant therapy. We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes.

Methods

Seven hundred forty premenopausal women entered a clinical trial in which those women estimated not to be in the luteal phase of their menstrual cycle for the next one to six days (n = 509) were randomly assigned to receive treatment with surgical oophorectomy either delayed to be during a five-day window in the history-estimated midluteal phase of the menstrual cycles, or in the next one to six days. Women who were estimated to be in the luteal phase of the menstrual cycle for the next one to six days (n = 231) were excluded from random assignment and received immediate surgical treatments. All patients began tamoxifen within 6 days of surgery and continued this for 5 years. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess differences in five-year disease-free survival (DFS) between the groups. All statistical tests were two-sided.

Results

The randomized midluteal phase surgery group had a five-year DFS of 64%, compared with 71% for the immediate surgery random assignment group (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 0.91 to 1.68, P = .18). Multivariable Cox regression models, which included important prognostic variables, gave similar results (aHR = 1.28, 95% CI = 0.94 to 1.76, P = .12). For overall survival, the univariate hazard ratio was 1.33 (95% CI = 0.94 to 1.89, P = .11) and the multivariable aHR was 1.43 (95% CI = 1.00 to 2.06, P = .05). Better DFS for follicular phase surgery, which was unanticipated, proved consistent across multiple exploratory analyses.

Conclusions

The hypothesized benefit of adjuvant luteal phase oophorectomy was not shown in this large trial.

SUBMITTER: Love RR

PROVIDER: S-EPMC4838061 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Timing of adjuvant surgical oophorectomy in the menstrual cycle and disease-free and overall survival in premenopausal women with operable breast cancer.

Love Richard R RR Laudico Adriano V AV Van Dinh Nguyen N Allred D Craig DC Uy Gemma B GB Quang Le Hong le H Salvador Jonathan Disraeli S JD Siguan Stephen Sixto S SS Mirasol-Lumague Maria Rica MR Tung Nguyen Dinh ND Benjaafar Noureddine N Navarro Narciso S NS Quy Tran Tu TT De La Peña Arturo S AS Dofitas Rodney B RB Bisquera Orlino C OC Linh Nguyen Dieu ND To Ta Van TV Young Gregory S GS Hade Erinn M EM Jarjoura David D

Journal of the National Cancer Institute 20150319 6

<h4>Background</h4>For women with hormone receptor-positive, operable breast cancer, surgical oophorectomy plus tamoxifen is an effective adjuvant therapy. We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes.<h4>Methods</h4>Seven hundred forty premenopausal women entered a clinical trial in which those women estimated not to be in the luteal phase of their ...[more]

PMID: 25794890

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Project description:Menstrual cycle characteristics are markers of endocrine milieu. However, associations between age at menarche and adulthood sex steroid hormone levels have been inconsistent, and data on menstrual characteristics and non-sex steroid hormones are sparse.We assessed the relations of menstrual characteristics with premenopausal plasma sex steroid hormones, sex hormone binding globulin (SHBG), prolactin, and growth factors among 2,745 premenopausal women (age 32-52) from the Nurses' Health Study II. Geometric means and tests for trend were calculated using multivariable general linear models.Early age at menarche was associated with higher premenopausal early-follicular free estradiol (percent difference <?12 vs.?>?13 years?=?11%), early-follicular estrone (7%), luteal estrone (7%), and free testosterone (8%) (all p trend?<?0.05). Short menstrual cycle length at age 18-22 was associated with higher early-follicular total (<?26 vs.?>?39 days?=?18%) and free estradiol (16%), early-follicular estrone (9%), SHBG (7%), lower luteal free estradiol (-?14%), total (-?6%), and free testosterone (-?15%) (all p trend?<?0.05). Short adult menstrual length was associated with higher early-follicular total estradiol (<?26 vs.?>?31 days?=?14%), SHBG (10%), lower luteal estrone (-?8%), progesterone (-?9%), total (-?11%) and free testosterone (-?25%), and androstenedione (-?14%) (all p trend?<?0.05). Irregularity of menses at 18-22 was associated with lower early-follicular total (irregular vs. very regular?=?-?14%) and free estradiol (-?14%), and early-follicular estrone (-?8%) (All p trend?<?0.05). Irregularity of adult menstrual cycle was associated with lower luteal total estradiol (irregular vs. very regular?=?-?8%), SHBG (-?3%), higher total (8%), and free testosterone (11%) (all p trend?<?0.05).Early-life and adulthood menstrual characteristics are moderately associated with mid-to-late reproductive year's hormone concentrations. These relations of menstrual characteristics with endogenous hormone levels could partially account for associations between menstrual characteristics and reproductive cancers or other chronic diseases.

Project description:ImportanceRestless legs syndrome is a common neurologic disorder that is more prevalent in women than in men, and it has been suggested that female hormones may be involved in the disorder's pathophysiology.ObjectiveTo determine whether women who underwent premenopausal bilateral oophorectomy were at increased risk of restless legs syndrome.Design, setting, and participantsThis cohort study was performed using data from the Mayo Clinic Cohort Study of Oophorectomy and Aging-2 for a population in Olmsted County, Minnesota. There were 1653 women who underwent premenopausal bilateral oophorectomy before the age of 50 years for a benign indication between 1988 and 2007 and 1653 age-matched women (of same age plus or minus 1 year) in a reference group. Follow-up was conducted until the end of the study period (ie, December 31, 2014). Data were analyzed from January to July 2020.ExposuresUndergoing bilateral oophorectomy, as shown in medical record documentation.Main outcomes and measuresDiagnosis of restless legs syndrome, as defined using Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria, was recorded.ResultsAmong 3306 women, the median (interquartile range) age at baseline was 44.0 (40.0-47.0) years. Women who underwent bilateral oophorectomy, compared with women who did not undergo this procedure, had a greater number of chronic conditions at the index date (eg, 300 women [18.1%] vs 171 women [10.3%] with ≥3 chronic conditions; overall P < .001), were more likely to have obesity (576 women [34.8%] vs 442 women [27.1%]; overall P < .001), and were more likely to have a history of anemia of any type (573 women [34.7%] vs 225 women [13.6%]; P < .001), iron deficiency anemia (347 women [21.0%] vs 135 women [8.2%]; P < .001), and restless legs syndrome before the index date (32 women [1.9%] vs 14 women [0.8%]; P = .008). Women who underwent bilateral oophorectomy prior to natural menopause had a higher risk of restless legs syndrome after the index date compared with women in the reference group (120 diagnoses vs 74 diagnoses), with an adjusted hazard ratio (HR) of 1.44 (95% CI, 1.08-1.92; P = .01). After stratification by indication for the bilateral oophorectomy, there was an increased risk of restless legs syndrome among women without a benign ovarian condition (HR, 1.52; 95% CI, 1.03-2.25; P = .04) but not among women with a benign condition (HR, 1.25; 95% CI, 0.80-1.96; P = .34). Treatment with estrogen therapy through the age of 46 years in women who underwent bilateral oophorectomy at younger ages was not associated with a difference in risk.Conclusions and relevanceThis cohort study found that risk of restless legs syndrome was increased among women who underwent bilateral oophorectomy prior to menopause, especially those without a benign ovarian indication.

Project description:ObjectiveOvarian suppression is recommended to complement endocrine therapy in premenopausal women with breast cancer and high-risk features. It can be achieved by either medical ovarian suppression or therapeutic bilateral salpingo-oophorectomy. Our objective was to evaluate characteristics of patients with stage I-III hormone receptor positive primary breast cancer who underwent bilateral salpingo-oophorectomy at our institution.Materials and methodsPremenopausal women with stage I-III hormone receptor positive primary breast cancer diagnosed between January 2010 and December 2014 were identified from a database. Patients with confirmed BRCA1/2 mutations were excluded. Distribution of characteristics between treatment groups was assessed using χ2 test and univariate logistic regression. A multivariate model was based on factors significant on univariate analysis.ResultsOf 2740 women identified, 2018 (74%) received endocrine treatment without ovarian ablation, 516 (19%) received endocrine treatment plus ovarian ablation, and 206 (7.5%) did not receive endocrine treatment. Among patients undergoing ovarian ablation 282/516 (55%) received medical ovarian suppression, while 234 (45%) underwent bilateral salpingo-oophorectomy. By univariate logistic analyses, predictors for ovarian ablation were younger age (OR 0.97), histology (other vs ductal: OR 0.23), lymph node involvement (OR 1.89), higher International Federation of Gynecology and Obstetrics (FIGO) stage (stage II vs I: OR 1.48; stage III vs I: OR 2.86), higher grade (grade 3 vs 1: OR 3.41; grade 2 vs 1: OR 2.99), chemotherapy (OR 1.52), and more recent year of diagnosis (2014 vs 2010; OR 1.713). Only year of diagnosis, stage, and human epidermal growth factor receptor 2 (HER-2) treatment remained significant in the multivariate model. Within the cohort undergoing ovarian ablation, older age (OR 1.05) was associated with therapeutic bilateral salpingo-oophorectomy. Of 234 undergoing bilateral salpingo-oophorectomy, 12 (5%) mild to moderate adverse surgical events were recorded.ConclusionsBilateral salpingo-oophorectomy is used frequently as an endocrine ablation strategy. Older age was associated with bilateral salpingo-oophorectomy. Perioperative morbidity was acceptable. Evaluation of long-term effects and quality of life associated with endocrine ablation will help guide patient/provider decision-making.

Project description:ImportanceThe associations of bilateral oophorectomy among premenopausal women, age at oophorectomy, and use of estrogen therapy after oophorectomy with cognitive performance later in life remain controversial.ObjectiveTo investigate whether women who underwent premenopausal bilateral oophorectomy were at increased risk of mild cognitive impairment (MCI) and experienced decreased global or domain-specific cognitive performance.Design, setting, and participantsThis case-control study and cross-sectional study were made possible by combining data from the Mayo Clinic Study of Aging (MCSA) and the Rochester Epidemiology Project (REP) medical record-linkage system. The studies were conducted among a population-based sample in Olmsted County, Minnesota, consisting of 2732 women aged 50 to 89 years who participated in the MCSA study from 2004 to 2019 and underwent a clinical evaluation and comprehensive cognitive testing. Data were analyzed from January to May 2021.ExposuresMedical record documentation of bilateral oophorectomy abstracted from a medical record-linkage system (ie, REP).Main outcomes and measuresOdds of MCI and global or domain-specific z scores on cognitive tests were measured at the first MCSA visit. The median (IQR) lag time between bilateral oophorectomy performed before menopause and before age 50 years and cognitive evaluation was 30 (22-38) years.ResultsAmong 2732 women aged 50 to 89 years (median [IQR] age at evaluation, 74 [66-81] years) who participated in the MCSA, the case-control study included 283 women with MCI (10.4%) and 2449 women without cognitive impairment (89.6%). Bilateral oophorectomy before menopause and before age 46 years was associated with clinically diagnosed MCI (adjusted odds ratio [aOR], 2.21; 95% CI, 1.41-3.45; P < .001) compared with no bilateral oophorectomy. The presence of an association with MCI varied by surgical indication, with an association among 259 women with bilateral oophorectomy before menopause and before age 50 years for the indication of benign ovarian condition (aOR, 2.43; 95% CI, 1.36-4.33; P = .003) but not for cancer or no ovarian condition. The presence of an association did not vary by estrogen therapy after bilateral oophorectomy, with associations among women aged less than 46 years with estrogen therapy (aOR, 2.56; 95% CI, 1.24-5.31; P = .01) and without estrogen therapy (aOR, 2.05; 95% CI, 1.18-3.52; P = .01). The cross-sectional study included 625 women with a history of bilateral oophorectomy (median [IQR] age, 75 [70-82] years) and 2107 women without a history of bilateral oophorectomy (median [IQR] age, 73 [65-80] years). Premenopausal bilateral oophorectomy was performed before age 46 years among 161 women and was associated with decreased global cognition z score (β, -0.17; 95% CI, -0.32 to -0.03; P = .02), attention and executive domain z score (β, -0.21; 95% CI, -0.36 to -0.05; P = .009), and Short Test of Mental Status score (β, -0.51; 95% CI, -0.95 to -0.08; P = .02) compared with no bilateral oophorectomy.Conclusions and relevanceThis study found that women who underwent bilateral oophorectomy before menopause had increased odds of MCI and poorer performance on cognitive tests approximately 30 years later compared with women who did not undergo bilateral oophorectomy.

Project description:Bisphosphonates are thought to act through the osteoclast by changing bone microenvironment. Previous findings of adjuvant clodronate trials in different populations with operable breast cancer have been mixed. The National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-34 aims to ascertain whether oral clodronate can improve outcomes in women with primary breast cancer.NSABP B-34 is a multicentre, randomised, double-blind, placebo-controlled study in 3323 women with stage 1-3 breast cancer. After surgery to remove the tumour, patients were stratified by age, axillary nodes, and oestrogen and progesterone receptor status and randomly assigned in a 1:1 ratio to either oral clodronate 1600 mg daily for 3 years (n=1662) or placebo (1661). The primary endpoint was disease-free survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00009945.Median follow-up was 90·7 months (IQR 82·7-100·0) and 3311 patients had data for this period. Disease-free survival did not differ between groups (286 events in the clodronate group vs 312 in the placebo group; hazard ratio 0·91, 95% CI 0·78-1·07; p=0·27). Moreover, no differences were recorded for overall survival (0·84, 0·67-1·05; p=0·13), recurrence-free interval (0·83, 0·67-1·04; p=0·10), or bone metastasis-free interval (0·77, 0·55-1·07; p=0·12). Non-bone metastasis-free interval was slightly increased with clodronate (0·74, 0·55-1·00; p=0·047). Analyses in women age 50 years or older on study entry showed benefits of clodronate for recurrence-free interval (0·75, 0·57-0·99; p=0·045), bone metastasis-free interval (0·62, 0·40-0·95; p=0·027), and non-bone metastasis-free interval (0·63, 0·43-0·91; p=0·014), but not for overall survival (0·80, 0·61-1·04, p=0·094). Adherence to treatment at 3 years was 56% for the clodronate group and 60% for the placebo group. Grade 3 or higher liver dysfunction was noted in 23 of 1612 patients in the clodronate group and 12 of 1623 patients in the placebo group; grade 3-4 diarrhoea was noted in 28 patients in the clodronate group and in ten in the placebo group. There was one possible case of osteonecrosis of the jaw in the clodronate group.Findings of NSABP B-34 suggest that bisphosphonates might have anticancer benefits for older postmenopausal women. A meta-analysis of adjuvant bisphosphonate trials is suggested before recommendations for use in non-osteoporotic postmenopausal women with primary breast cancer are made.National Cancer Institute, Bayer Oy (formerly Schering Oy).

Dataset Information

Timing of adjuvant surgical oophorectomy in the menstrual cycle and disease-free and overall survival in premenopausal women with operable breast cancer.

Background

Methods

Results

Conclusions

Publications

Timing of adjuvant surgical oophorectomy in the menstrual cycle and disease-free and overall survival in premenopausal women with operable breast cancer.

Similar Datasets

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